Bariatric surgery has a positive impact on mental health.

Psychological Outcome 4 Years after Restrictive Bariatric Surgery

Extreme obesity is associated with severe psychiatric and somatic comorbidity and impairment of psychosocial functioning. Bariatric surgery is the most effective treatment not only with regard to weight loss but also with obesity-associated illnesses. Health-related psychological and psychosocial variables have been increasingly considered as important outcome variables of bariatric surgery. However, the long-term impact of bariatric surgery on psychological and psychosocial functioning is largely unclear. The aim of this study was to evaluate the relationship between the course of weight and psychological variables including depression, anxiety, health-related quality of life (HRQOL), and self-esteem up to 4 years after obesity surgery. By standardized questionnaires prior to (T1) and 1 year (T2), 2 years (T3), and 4 years (T4) after surgery, 148 patients (47 males (31.8 %), 101 females (68.2 %), mean age 38.8 ± 10.2 years) were assessed. On average, participants lost 24.6 % of their initial weight 1 year after surgery, 25.1 % after 2 years, and 22.3 % after 4 years. Statistical analysis revealed significant improvements in depressive symptoms, physical dimension of quality of life, and self-esteem with peak improvements 1 year after surgery. These improvements were largely maintained. Significant correlations between weight loss and improvements in depression, physical aspects of HRQOL (T2, T3, and T4), and self-esteem (T3) were observed. Corresponding to the considerable weight loss after bariatric surgery, important aspects of mental health improved significantly during the 4-year follow-up period. However, parallel to weight regain, psychological improvements showed a slow but not significant decline over time.

Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis.

IMPORTANCE Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown. OBJECTIVE To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions. DATA SOURCES We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. FINDINGS We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease). CONCLUSIONS AND RELEVANCE Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.

Mental Health Support Provided Throughout the Bariatric Surgery Clinical Pathway in French Specialized Care Centers for Obesity

Pre-operative psychological assessment is recommended by international guidelines for bariatric surgery candidates. Thereby, service teams caring for bariatric patients should include at least one mental health provider (e.g., a psychologist or psychiatrist). The objective of this study was to evaluate the psychology and psychiatry resources and practices in the 37 specialized obesity centers (CSOs) created by the French Ministry of Health. CSO coordinators were contacted by e-mail to collect general information on the centers (e.g., number of bariatric operations). Secondly, psychologists and psychiatrists of each center completed an anonymous questionnaire assessing their professional practices and their organization of care pathways. The vast majority of CSO coordinators (81%, n = 26/32) answered our survey. These results show significant differences and shortages in terms of the psychology/psychiatry resources available. Most of the psychologists (n = 26/31) and psychiatrists (n = 10/10) stated that they systematically meet new patients only before surgery (56%) or both before and after the operation (30%); however, some psychologists and psychiatrists (14%) do not systematically meet all the patients (before and/or after surgery). Nevertheless, all the professionals provide psychology assessments, and about 75% of them offer a psychological follow-up, indicating a similarity regarding the practices of psychologists and psychiatrists. Our results highlight the place of psychological/psychiatric evaluations in French CSOs and emphasize the absence of mental health providers in several of these services. Post-operative psychological follow-up is not usually provided. It would be appropriate to create clear recommendations for post-operative psychological or psychiatric long-term follow-up.

Recommendations for the presurgical psychosocial evaluation of bariatric surgery patients.

Psychosocial factors have significant potential to affect long-term outcomes of bariatric surgery, including emotional adjustment, adherence to the recommended postoperative lifestyle regimen, weight loss outcomes, and co-morbidity improvement and or resolution. Thus, it is recommended that bariatric behavioral health clinicians with specialized knowledge and experience be involved in the evaluation and care of patients both before and after surgery. The evaluating clinician plays a number of important roles in the multidisciplinary treatment of the bariatric patient. Central among these is the role of identifying factors that may pose challenges to optimal surgical outcome and providing recommendations to the patient and bariatric team on how to address these issues. This document outlines recommendations for the psychosocial evaluation of bariatric surgery patients, appropriate qualifications of those conducting these evaluations, communication of evaluation results and suggested treatment plan, and the extension of behavioral healthcare of the bariatric patient to the entire span of the surgical and postsurgical process.

Brief, four-session group CBT reduces binge eating behaviors among bariatric surgery candidates.

BACKGROUND The objective of this study was to evaluate the effectiveness of a brief, 4-session cognitive behavioral, group psychotherapy for binge eating among bariatric surgery candidates at an academic medical center. Binge eating behaviors have been linked to poorer outcomes among bariatric surgery patients, and binge eating disorder have be considered a contraindication in surgery programs, some of which have mandated preoperative binge eating treatment. However, no previous studies have examined whether a preoperative binge eating intervention could successfully reduce binge eating behaviors among severely obese bariatric surgery candidates. METHODS A total of 243 bariatric surgery candidates completed a brief cognitive behavioral group treatment for binge eating behaviors and were administered the Binge Eating Scale and reported the number of weekly binge eating episodes at the initial psychological evaluation and again after the group sessions. The study used a pre-post intervention design. RESULTS The results suggested significant reductions in both binge eating behaviors and cognitions and binge eating episodes after the group intervention. The intervention's effectiveness did not differ according to gender or ethnicity (black versus white). CONCLUSION A brief cognitive behavioral intervention can reduce binge eating behaviors among bariatric surgery candidates. Given the potential influence of binge eating on outcomes, bariatric surgery programs could benefit by treating binge eating before surgery.

Preoperative Predictors of Weight Loss Following Bariatric Surgery: Systematic Review

Obesity affects 32% of adults in the USA. Surgery generates substantial weight loss, but 20–30% fails to achieve successful weight loss. Our objective was to identify preoperative psychosocial factors associated with weight loss following bariatric surgery. We performed a literature search of PubMed® and the Cochrane Database of Reviews of Effectiveness between 1988 and April 2010. Articles were screened for bariatric surgery and weight loss if they included a preoperative predictor of weight loss: body mass index (BMI), preoperative weight loss, eating disorders, or psychiatric disorder/substance abuse. One thousand seven titles were reviewed, 534 articles screened, and 115 included in the review. Factors that may be positively associated with weight loss after surgery include mandatory preoperative weight loss (7 of 14 studies with positive association). Factors that may be negatively associated with weight loss include preoperative BMI (37 out of 62 studies with negative association), super-obesity (24 out of 33 studies), and personality disorders (7 out of 14 studies). Meta-analysis revealed a decrease of 10.1% excess weight loss (EWL) for super-obese patients (95% confidence interval (CI) [3.7–16.5%]), though there was significant heterogeneity in the meta-analysis, and an increase of 5.9% EWL for patients with binge eating at 12 months after surgery (95% CI [1.9–9.8%]). Further studies are necessary to investigate whether preoperative factors can predict a clinically meaningful difference in weight loss after bariatric surgery. The identification of predictive factors may improve patient selection and help develop interventions targeting specific needs of patients.

"Grazing": a high-risk behavior.

BACKGROUND Gastric bypass patients with a range of disturbed eating patterns before surgery may be at risk of returning to old patterns postoperatively. Recent research has shown that binge eating is common among the obese before surgery as well as in the postoperative maintenance phase and appears to be linked to poorer outcome. Although "grazing" behavior has not been specifically studied, it is also a high-risk pattern. This paper is a descriptive investigation summarizing postoperative eating patterns in a group of patients. METHODS Patients completed self-report questionnaires before surgery and were seen for a preoperative mental health evaluation with particular focus on assessing eating patterns. Patients with high-risk eating patterns, both binge eating and "grazing", were identified, invited to attend a post-surgery therapy group, and were given additional follow-up questionnaires regarding postoperative eating patterns. RESULTS Consistent with recent studies, many high-risk patients reported recurrent loss of control over eating and, in some cases, subsequent weight gain. Although no longer able to eat large amounts, "grazing" became a more common pattern, appearing >or=6 months following surgery. CONCLUSION Different forms of overeating need to be assessed in this population, focusing on the subjective loss of control rather than on the quantity consumed. Although many patients do not meet strict criteria for binge eating disorder before surgery, these "grazers" are also high-risk. Former binge eaters often turn into "grazers" following surgery. Interventions are needed for at-risk patients.

Integration of mental health into primary healthcare in low-income countries: avoiding medicalization.

Since 2008 the World Health Organization (WHO), through its mental health Gap Action Programme, has attempted to revitalize efforts to integrate mental health into non-specialized (e.g. primary) healthcare. While this has led to renewed interest in this potential method of mental health service delivery, it has also prompted criticism. Some concerns raised are that it would contribute to the medicalization of social and psychological problems, and narrowly focus on primary care without sufficient attention given to strengthening other levels of the healthcare system, notably community-based care and care on district levels. This paper discusses seven elements that may be critical to preventing inadvertently contributing to increasing a narrow biomedical approach to mental healthcare when integrating mental health into non-specialized healthcare: (1) using task shifting approaches within a system of stepped care, (2) ensuring primary mental healthcare also includes brief psychotherapeutic interventions, (3) promote community-based recovery-oriented interventions for people with disabling chronic mental disorders, (4) conceptualizing training as a continuous process of strengthening clinical competencies through supervision, (5) engaging communities as partners in psychosocial interventions, (6) embedding shifts to primary mental healthcare within wider health policy reforms, and (7) promoting inter-sectoral approaches to address social determinants of mental health.

Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care.

BACKGROUND Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.

Anxiety

OBJECTIVES To examine the effect of routinely administered psychiatric questionnaires on the recognition, management, and outcome of psychiatric disorders in non-psychiatric settings. DATA SOURCES Embase, Medline, PsycLIT, Cinahl, Cochrane Controlled Trials Register, and hand searches of key journals. METHODS A systematic review of randomised controlled trials of the administration and routine feedback of psychiatric screening and outcome questionnaires to clinicians in non-psychiatric settings. Narrative overview of key design features and end points, together with a random effects quantitative synthesis of comparable studies. MAIN OUTCOME MEASURES Recognition of psychiatric disorders after feedback of questionnaire results; interventions for psychiatric disorders; and outcome of psychiatric disorders. RESULTS Nine randomised studies were identified that examined the use of common psychiatric instruments in primary care and general hospital settings. Studies compared the effect of the administration of these instruments followed by the feedback of the results to clinicians, with administration with no feedback. Meta-analytic pooling was possible for four of these studies (2457 participants), which measured the effect of feedback on the recognition of depressive disorders. Routine administration and feedback of scores for all patients (irrespective of score) did not increase the overall rate of recognition of mental disorders such as anxiety and depression (relative risk of detection of depression by clinician after feedback 0.95, 95% confidence interval 0.83 to 1.09). Two studies showed that routine administration followed by selective feedback for only high scorers increased the rate of recognition of depression (relative risk of detection of depression after feedback 2.64, 1.62 to 4.31). This increased recognition, however, did not translate into an increased rate of intervention. Overall, studies of routine administration of psychiatric measures did not show an effect on patient outcome. CONCLUSIONS The routine measurement of outcome is a costly exercise. Little evidence shows that it is of benefit in improving psychosocial outcomes of those with psychiatric disorder managed in non-psychiatric settings.

Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression

The brain interprets experiences and translates them into behavioral and physiological responses. Stressful events are those which are threatening or, at the very least, unexpected and surprising, and the physiological and behavioral responses are intended to promote adaptation via a process called "allostasis. " Chemical mediators of allostasis include cortisol and adrenalin from the adrenal glands, other hormones, and neurotransmitters, the parasympathetic and sympathetic nervous systems, and cytokines and chemokines from the immune system. Two brain structures, the amygdala and hippocampus, play key roles in interpreting what is stressful and determining appropriate responses. The hippocampus, a key structure for memories of events and contexts, expresses receptors that enable it to respond to glucocorticoid hormones in the blood, it undergoes atrophy in a number of psychiatric disorders; it also responds to stressors with changes in excitability, decreased dendritic branching, and reduction in number of neurons in the dentate gyrus. The amygdala, which is important for "emotional memories, " becomes hyperactive in posttraumatic stress disorder and depressive illness, in animal models of stress, there is evidence for growth and hypertrophy of nerve cells in the amygdala. Changes in the brain after acute and chronic stressors mirror the pattern seen in the metabolic, cardiovascular, and immune systems, that is, short-term adaptation (allostasis) followed by long-term damage (allostatic load), eg, atherosclerosis, fat deposition obesity, bone demineralization, and impaired immune function. Allostatic load of this kind is seen in major depressive illness and may also be expressed in other chronic anxiety and mood disorders.

Collective trauma in northern Sri Lanka: a qualitative psychosocial-ecological study

BACKGROUND Complex situations that follow war and natural disasters have a psychosocial impact on not only the individual but also on the family, community and society. Just as the mental health effects on the individual psyche can result in non pathological distress as well as a variety of psychiatric disorders; massive and widespread trauma and loss can impact on family and social processes causing changes at the family, community and societal levels. METHOD This qualitative, ecological study is a naturalistic, psychosocial ethnography in Northern Sri Lanka, while actively involved in psychosocial and community mental health programmes among the Tamil community. Participatory observation, key informant interviews and focus group discussion with community level relief and rehabilitation workers and government and non-governmental officials were used to gather data. The effects on the community of the chronic, man-made disaster, war, in Northern Sri Lanka were compared with the contexts found before the war and after the tsunami. RESULTS Fundamental changes in the functioning of the family and the community were observed. While the changes after the tsunami were not so prominent, the chronic war situation caused more fundamental social transformations. At the family level, the dynamics of single parent families, lack of trust among members, and changes in significant relationships, and child rearing practices were seen. Communities tended to be more dependent, passive, silent, without leadership, mistrustful, and suspicious. Additional adverse effects included the breakdown in traditional structures, institutions and familiar ways of life, and deterioration in social norms and ethics. A variety of community level interventions were tried. CONCLUSION Exposure to conflict, war and disaster situations impact on fundamental family and community dynamics resulting in changes at a collective level. Relief, rehabilitation and development programmes to be effective will need to address the problem of collective trauma, particularly using integrated multi-level approaches.

The psychiatric manifestations of mitochondrial disorders: a case and review of the literature.

OBJECTIVE Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271. We also searched the literature for all case reports of patients with mitochondrial disorders who initially present with prominent psychiatric symptoms by using MEDLINE (from 1948-February 2011), Embase (from 1980-February 2011), PsycINFO (from 1806-February 2011), and the search terms mitochondrial disorder, mitochondria, psychiatry, mental disorders, major depression, anxiety, schizophrenia, and psychosis. STUDY SELECTION Fifty cases of mitochondrial disorders with prominent psychiatric symptomatology were identified. DATA EXTRACTION Information about the psychiatric presentation of the cases was extracted. This information was combined with our case, the most common psychiatric manifestations of mitochondrial disorders were identified, and the important diagnostic and treatment implications for patients with psychiatric illness were reviewed. RESULTS The most common psychiatric presentations in the cases of mitochondrial disorders included mood disorder, cognitive deterioration, psychosis, and anxiety. The most common diagnosis (52% of cases) was a MELAS mutation. Other genetic mitochondrial diagnoses included polymerase gamma mutations, Kearns-Sayre syndrome, mitochondrial DNA deletions, point mutations, twinkle mutations, and novel mutations. CONCLUSIONS Patients with mitochondrial disorders can present with primary psychiatric symptomatology, including mood disorder, cognitive impairment, psychosis, and anxiety. Psychiatrists need to be aware of the clinical features that are indicative of a mitochondrial disorder, investigate patients with suggestive presentations, and be knowledgeable about the treatment implications of the diagnosis.

A wellness class for inpatients with psychotic disorders.

OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.

Evaluation of a mental health outreach service for homeless families.

AIMS To describe the characteristics of homeless children and families seen by the mental health outreach service (MHOS), to evaluate the impact of this service on the short term psychosocial functioning of children and parents, and to establish perceptions of, and satisfaction with, the service. METHODS Twenty seven children from 23 families who were in receipt of the MHOS and 27 children from 23 families residing in other hostels where no such service was available were studied. The MHOS was delivered by a clinical nurse specialist with expertise in child mental health, who offered the following interventions: assessment and brief treatment of mental health disorders in children; liaison with agencies; and training of homeless centre staff. RESULTS Children in the experimental group had a significantly higher decrease in Strengths and Difficulties Questionnaire (SDQ) total scores. Having received the intervention was the strongest predictor of improvement in SDQ total scores. There was no significant impact on parental mental health (General Health Questionnaire) scores. Homeless families and staff expressed high satisfaction with the MHOS. CONCLUSION This MHOS for homeless families is an innovative intervention which meets the complex and multiple needs of a vulnerable population unable to access mainstream mental health services. The primary objective of the service was to improve child mental health problems; however, the service developed in a responsive way by meeting social and practical needs of families in addition to its clinical role.

Do Antidepressants Cure or Create Abnormal Brain States?

The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [ 1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms. In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms ( Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term. Table 1    Main Assumptions of Two Models of Psychotropic Drug Action The disease-centred model in psychiatry leads researchers to infer antidepressant effects from patients' scores on symptom rating scales presumed to assess the manifestations of the disease. The drug-centred model, on the other hand, suggests that physiological and subjective effects of drugs should be examined in their own right. These effects include various forms of sedation, stimulation, and a plethora of biopsychological states. Depending on individual inclination and context (including a person's emotional state upon drug ingestion), intoxication with some drugs produces euphoria or mood elevation. Because tolerance develops, however, euphoriant effects do not persist with long-term use. If antidepressants or any other psychotropic drugs could be shown to have mood-elevating effects that were long-term and not diminished by being in a depressed emotional state, this would distinguish them from psychotropic drugs that cause euphoria and might prove uniquely useful in depressed patients (see Sidebar).

Obesity as a medical problem.

Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Obesity is defined by a body-mass index (weight divided by square of the height) of 30 kg m(-2) or greater, but this does not take into account the morbidity and mortality associated with more modest degrees of overweight, nor the detrimental effect of intra-abdominal fat. The global epidemic of obesity results from a combination of genetic susceptibility, increased availability of high-energy foods and decreased requirement for physical activity in modern society. Obesity should no longer be regarded simply as a cosmetic problem affecting certain individuals, but an epidemic that threatens global well being.

Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.

CONTEXT Little is known about the extent or severity of untreated mental disorders, especially in less-developed countries. OBJECTIVE To estimate prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders in 14 countries (6 less developed, 8 developed) in the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative. DESIGN, SETTING, AND PARTICIPANTS Face-to-face household surveys of 60 463 community adults conducted from 2001-2003 in 14 countries in the Americas, Europe, the Middle East, Africa, and Asia. MAIN OUTCOME MEASURES The DSM-IV disorders, severity, and treatment were assessed with the WMH version of the WHO Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay-administered psychiatric diagnostic interview. RESULTS The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%. Between 33.1% (Colombia) and 80.9% (Nigeria) of 12-month cases were mild (IQR, 40.2%-53.3%). Serious disorders were associated with substantial role disability. Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview. Due to the high prevalence of mild and subthreshold cases, the number of those who received treatment far exceeds the number of untreated serious cases in every country. CONCLUSIONS Reallocation of treatment resources could substantially decrease the problem of unmet need for treatment of mental disorders among serious cases. Structural barriers exist to this reallocation. Careful consideration needs to be given to the value of treating some mild cases, especially those at risk for progressing to more serious disorders.

New Roles for Pharmacists in Community Mental Health Care: A Narrative Review

Medicines are a major treatment modality for many mental illnesses, and with the growing burden of mental disorders worldwide pharmacists are ideally positioned to play a greater role in supporting people with a mental illness. This narrative review aims to describe the evidence for pharmacist-delivered services in mental health care and address the barriers and facilitators to increasing the uptake of pharmacist services as part of the broader mental health care team. This narrative review is divided into three main sections: (1) the role of the pharmacist in mental health care in multidisciplinary teams and in supporting early detection of mental illness; (2) the pharmacists' role in supporting quality use of medicines in medication review, strategies to improve medication adherence and antipsychotic polypharmacy, and shared decision making; and (3) barriers and facilitators to the implementation of mental health pharmacy services with a focus on organizational culture and mental health stigma. In the first section, the review presents new roles for pharmacists within multidisciplinary teams, such as in case conferencing or collaborative drug therapy management; and new roles that would benefit from increased pharmacist involvement, such as the early detection of mental health conditions, development of care plans and follow up of people with mental health problems. The second section describes the impact of medication review services and other pharmacist-led interventions designed to reduce inappropriate use of psychotropic medicines and improve medication adherence. Other new potential roles discussed include the management of antipsychotic polypharmacy and involvement in patient-centered care. Finally, barriers related to pharmacists' attitudes, stigma and skills in the care of patients with mental health problems and barriers affecting pharmacist-physician collaboration are described, along with strategies to reduce mental health stigma.

β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat.

Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.

'Zero is not good for me': implications of infertility in Ghana.

BACKGROUND Given the high value placed on children in sub-Saharan Africa, previous research suggests that infertility increases the risk of psychological distress and marital conflict, encourages risky sexual behavior and deprives infertile individuals and couples of an important source of economic and social capital. This paper explores the implications of infertility for women in Ghana, West Africa. METHODS Semi-structured interview data collected from 107 women (aged 21-48 years, mean 33 years) seeking treatment in gynecological and obstetric clinics in Accra, Ghana, are analyzed. Based on iterative open coding of the interviews, the focus of the analysis is on mental health, marital instability, social interaction and gendered experiences. RESULTS Infertile women report facing severe social stigma, marital strain and a range of mental health difficulties. Many women feel that they shoulder a disproportionate share of the blame for infertility and, by extension, face greater social consequences than male partners for difficulties conceiving. Women who do not self-identify as infertile corroborate these findings, asserting that the social consequences of infertility are severe, particularly for women. CONCLUSIONS Infertility in Ghana has important consequences for social interactions, marital stability and mental health. These consequences are not perceived to be shared equally by Ghanaian men.

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial.

CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. RESULTS Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group. CONCLUSIONS Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. TRIAL REGISTRATION actr.org Identifier: ACTRN012605000159651.

Body mass index and magnetic resonance markers of brain integrity in adults.

OBJECTIVE Obesity and being overweight during adulthood have been consistently linked to increased risk for development of dementia later in life, especially Alzheimer's disease. They have also been associated with cognitive dysfunction and brain structural alterations in otherwise healthy adults. Although proton magnetic resonance spectroscopy may distinguish between neuronal and glial components of the brain and may point to neurobiological mechanisms underlying brain atrophy and cognitive changes, no spectroscopic studies have yet assessed the relationships between adiposity and brain metabolites. METHODS We have utilized magnetic resonance imaging and proton magnetic resonance spectroscopic imaging data from 50 healthy middle-aged participants (mean age, 41.7 +/- 8.5 years; 17 women), who were scanned as control subjects for another study. RESULTS After adjustment for age and sex, greater body mass indices (BMIs) correlated with: (1) lower concentrations of N-acetylaspartate (spectroscopic marker of neuronal viability) in frontal (p = 0.001), parietal (p = 0.006), and temporal (p = 0.008) white matter; (2) lower N-acetylaspartate in frontal gray matter (p = 0.01); and (3) lower concentrations of choline-containing metabolites (associated with membrane metabolism) in frontal white matter (p = 0.05). INTERPRETATION These results suggest that increased BMI at midlife is associated with neuronal and/or myelin abnormalities, primarily in the frontal lobe. Because white matter in the frontal lobes is more prone to the effects of aging than in other lobes, our results may reflect accelerated aging in individuals with high levels of adiposity. Thus, greater BMI may increase the odds of developing an age-related disease, such as Alzheimer's disease.

Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study.

OBJECTIVE The purpose of our study was to investigate alterations of white matter integrity in adults with major depressive disorder (MDD) using magnetic resonance imaging (MRI). METHODS We performed diffusion tensor imaging with a 3T MRI scanner on 45 patients with major depression and 45 healthy controls matched for age, sex and education. Using a voxel-based analysis, we measured the fractional anisotropy (FA), and we investigated the differences between the patient and control groups. We examined the correlations between the microstructure abnormalities of white matter and symptom severity, age of illness onset and cumulative illness duration, respectively. RESULTS We found a significant decrease in FA in the left hemisphere, including the anterior limb of the internal capsule and the inferior parietal portion of the superior longitudinal fasciculus, in patients with MDD compared with healthy controls. Diffusion tensor imaging measures in the left anterior limb of the internal capsule were negatively related to the severity of depressive symptoms, even after we controlled for age and sex. CONCLUSION Our findings provide new evidence of microstructural changes of white matter in non-late-onset adult depression. Our results complement those observed in late-life depression and support the hypothesis that the disruption of cortical- subcortical circuit integrity may be involved in the etiology of major depressive disorder.

Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes.

OBJECTIVE To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache. BACKGROUND There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache. METHODS We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders. RESULTS Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P =.02). Both depressive and anxiety disorders were significantly more frequent in women. CONCLUSION Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.

Mental health in prison populations. A review--with special emphasis on a study of Danish prisoners on remand.

OBJECTIVE To review the literature on mental health and psychiatric morbidity in prison populations and relate findings to a Danish study on remand prisoners. METHOD The literature is reviewed and subdivided in the following section: validity of psychometrics in prison populations, prevalence of psychiatric disorders prior to imprisonment, incidence of psychiatric disorders during imprisonment, psychopathy related to psychiatric comorbidity, dependence syndromes with special emphasis on different administrations of heroin use (smoke vs. injection). The results are compared with a longitudinal Danish study on remand prisoners in either solitary confinement (SC) or non-SC. RESULTS Many factors must be taken into consideration when dealing with prisoners and mental health, e.g. international differences, the prison setting, demographics and methodological issues. The prison populations in general are increasing worldwide. Psychometrics may perform differently in prison populations compared with general populations with the General Health Questionnaire-28 having a low validity in remand prisoners. Psychiatric morbidity including schizophrenia is higher and perhaps increasing in prison populations compared with general populations with dependence syndromes being the most frequent disorders. The early phase of imprisonment is a vulnerable period with a moderately high incidence of adjustment disorders and twice the incidence in SC compared with non-SC. Prevalence of psychopathy is lower in European than North American prisons. Medium to high scores of psychopathy is related to higher psychiatric comorbidity. Opioid dependence is the most frequent drug disorder with subjects using injection representing a more dysfunctional group than subjects using smoke administration. Many mentally ill prisoners remain undetected and undertreated. CONCLUSION There is a growing population of mentally ill prisoners being insufficiently detected and treated.

Mental health difficulties across childhood and mental health service use: findings from a longitudinal population-based study.

BACKGROUND Over the past 20 years the prevalence of child and adolescent mental disorders in high-income countries has not changed despite increased investment in mental health services. Insufficient contact with mental health services may be a contributing factor; however, it is not known what proportion of children have sufficient contact with health professionals to allow delivery of treatment meeting minimal clinical practice guidelines, or how long children experience symptoms prior to receiving treatment. AimsTo investigate the level of mental healthcare received by Australian children from age 4 years to 14 years. METHOD Trajectories of mental health symptoms were mapped using the Strengths and Difficulties Questionnaire. Health professional attendances and psychotropic medications dispensed were identified from linked national Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme records. RESULTS Four trajectories of mental health symptoms were identified (low, high-decreasing, moderate-increasing and high-increasing). Most children with mental health symptoms had few MBS mental health attendances, and only a minority received care meeting study criteria for minimally adequate treatment. Children in the high-increasing and moderate-increasing trajectories were more likely to access care, yet there was no evidence of improvement in symptoms. CONCLUSIONS It is important that children and adolescents with mental health problems receive treatment that meets minimal practice guidelines. Further research is needed to identify the quality of care currently provided to children with mental health difficulties and how clinicians can be best funded and supported to provide care meeting minimal practice guidelines. Declaration of interestsNone.

Behavioral treatment of obesity in patients encountered in primary care settings: a systematic review.

IMPORTANCE In 2011, the Centers for Medicare & Medicaid Services (CMS) approved intensive behavioral weight loss counseling for approximately 14 face-to-face, 10- to 15-minute sessions over 6 months for obese beneficiaries in primary care settings, when delivered by physicians and other CMS-defined primary care practitioners. OBJECTIVE To conduct a systematic review of behavioral counseling for overweight and obese patients recruited from primary care, as delivered by primary care practitioners working alone or with trained interventionists (eg, medical assistants, registered dietitians), or by trained interventionists working independently. EVIDENCE REVIEW We searched PubMed, CINAHL, and EMBASE for randomized controlled trials published between January 1980 and June 2014 that recruited overweight and obese patients from primary care; provided behavioral counseling (ie, diet, exercise, and behavioral therapy) for at least 3 months, with at least 6 months of postrandomization follow-up; included at least 15 participants per treatment group and objectively measured weights; and had a comparator, an intention-to-treat analysis, and attrition of less than 30% at 1 year or less than 40% at longer follow-up. FINDINGS Review of 3304 abstracts yielded 12 trials, involving 3893 participants, that met inclusion-exclusion criteria and prespecified quality ratings. No studies were found in which primary care practitioners delivered counseling that followed the CMS guidelines. Mean 6-month weight changes from baseline in the intervention groups ranged from a loss of 0.3 kg to 6.6 kg. In the control group, mean change ranged from a gain of 0.9 kg to a loss of 2.0 kg. Weight loss in both groups generally declined with longer follow-up (12-24 months). Interventions that prescribed both reduced energy intake (eg, ≥ 500 kcal/d) and increased physical activity (eg, ≥150 minutes a week of walking), with traditional behavioral therapy, generally produced larger weight loss than interventions without all 3 specific components. In the former trials, more treatment sessions, delivered in person or by telephone by trained interventionists, were associated with greater mean weight loss and likelihood of patients losing 5% or more of baseline weight. CONCLUSIONS AND RELEVANCE Intensive behavioral counseling can induce clinically meaningful weight loss, but there is little research on primary care practitioners providing such care. The present findings suggest that a range of trained interventionists, who deliver counseling in person or by telephone, could be considered for treating overweight or obesity in patients encountered in primary care settings.

Prevalence of late-life depression and gap in mental health service use across European regions.

Background We aimed to determine the prevalence and gap in use of mental health services for late-life depression in four European regions (Western Europe, Scandinavia, Southern Europe and Central and Eastern Europe) and explore socio-demographic, social and health-related factors associated with it. Methods We conducted a cross-sectional study based on data from the Survey on Health, Ageing and Retirement in Europe. Participants were a population-based sample of 28 796 persons (53% women, mean age 74 years old) residing in Europe. Mental health service use was estimated using information about the diagnosis or treatment for depression. Results The prevalence of late-life depression was 29% in the whole sample and was highest in Southern Europe (35%), followed by Central and Eastern Europe (32%), Western Europe (26%) and lowest in Scandinavia (17%). Factors that had the strongest association with depression were total number of chronic diseases, pain, limitations in instrumental activities of daily living, grip strength and cognitive impairment. The gap in mental health service use was 79%. Conclusions We suggest that interventions to decrease the burden of late-life depression should be targeted at individuals that are affected by chronic somatic comorbidities and are limited in mental and physical functioning. Promotion of help-seeking of older adults, de-stigmatization of mental illness and education of general practitioners could help decrease the gap in mental health service utilization.

Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter.

OBJECTIVE The purpose of this study was to determine whether microstructural abnormalities in the white matter of the dorsolateral prefrontal cortex are associated with late-life depression. METHOD Seventeen elderly depressed subjects were compared with 16 elderly subjects who were not depressed. Diffusion tensor imaging was used to measure the fractional anisotropy of the white matter in the dorsolateral prefrontal cortex's superior and middle frontal gyri bilaterally and in the left occipital lobe as a control region. The authors compared results between groups while controlling for age, sex, and comorbid medical disorders. RESULTS Even after controlling for age, sex, hypertension, and heart disease, the authors found significantly lower fractional anisotropy values in the right superior frontal gyrus white matter of depressed patients than comparison subjects. CONCLUSIONS Microstructural changes in the white matter of the right superior frontal gyrus are associated with late-life depression. Further work is needed to determine how these changes contribute to depression outcomes.

Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intraaxial tumors: a prospective trial of 200 cases.

OBJECT Awake craniotomy was performed as the standard surgical approach to supratentorial intraaxial tumors, regardless of the involvement of eloquent cortex, in a prospective trial of 200 patients surgically treated by the same surgeon at a single institution. METHODS Patient presentations, comorbid conditions, tumor locations, and the histological characteristics of lesions were recorded. Brain mapping was possible in 195 (97.5%) of 200 patients. The total number of patients sustaining complications was 33 for an overall complication rate of 16.5%. There were two deaths in this series, for a mortality rate of 1%. New postoperative neurological deficits were seen in 13% of the patients, but these were permanent in only 4.5% of them. Complication rates were higher in patients who had gliomas or preoperative neurological deficits and in those who had undergone prior radiation therapy or surgery. No patient who entered the operating room neurologically intact sustained a permanent neurological deficit postoperatively. Of the most recent 50 patients treated, three (6%) required a stay in the intensive care unit, and the median total hospital stay was 1 day. CONCLUSIONS Use of awake craniotomy can result in a considerable reduction in resource utilization without compromising patient care by minimizing intensive care time and total hospital stay. Awake craniotomy is a practical and effective standard surgical approach to supratentorial tumors with a low complication rate, and provides an excellent alternative to craniotomy performed with the patient in the state of general anesthesia because it allows the opportunity for brain mapping and avoids general anesthesia.

Evaluating the impact of pharmacists in mental health: a systematic review.

Efforts to improve the outcomes of patients with mental illness often have involved incorporating the skills of a variety of health care professionals into collaborative care models. For over 30 years, clinical pharmacists have contributed to these care models in capacities ranging from educator to consultant to provider. This systematic review evaluates the quantity and quality of medical literature examining the impact of pharmacists in mental health from 1972-2003. Although we identified approximately 35 publications describing the roles of clinical pharmacists in this regard, only 16 were of sufficient scientific rigor to permit evaluation and comparison. The 16 studies were divided equally between inpatient and outpatient settings and were conducted in a variety of health care organizations (e.g., Veterans Administration, health maintenance organizations, community mental health clinics, and nursing homes). Nine of the studies examined the role of pharmacists in providing treatment recommendations and patient education, five featured pharmacists as providers (with prescriptive authority), and the remaining two described the impact pharmacists have in delivering education to the psychiatric staff. Six of the 16 studies were prospective, but only three of these incorporated a randomization procedure for patients or facilities. Collectively, the results of the 16 studies were positive, demonstrating improvements in outcomes, prescribing practices, patient satisfaction, and resource use. Unfortunately, most of the investigations were small, and significant limitations in study design limited further comparison. Given the long history and anecdotal success of pharmacists in mental health care settings, additional multicenter cost-effectiveness trials are warranted to further support the role of the psychiatric pharmacist.

Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis.

Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are regarded as the most important clinical consideration in patients undergoing anti-MDR-TB treatment. To evaluate the frequency and type of treatment-related ADEs owing to MDR-TB therapy. The Cochrane Library, MEDLINE, and EMBASE were searched from inception through October 1, 2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studies with available ADEs were selected if MDR-TB patients were treated with regimen including second-line drugs. Pooled estimations of incidence for each specific type of ADEs were calculated with 95% confidence intervals using random-effects model. Of the 5346 patients included, 2602 (57.3%) experienced at least 1 kind of ADE. The 3 most common side effects were gastrointestinal disorders (32.1%), ototoxicity (14.6%), and psychiatric disorders (13.2%). Subgroup analyses based on each characteristic (study population, previous tuberculosis treated, human immunodeficiency virus prevalence, and length of treatment) did not show any significant difference between groups. Additionally, among 1519 patients who developed ADEs with available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB treatment. Adverse events were common among MDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change of anti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressively for side effects during therapy, especially for ototoxicity and psychiatric disorders.

Maternal and child undernutrition: consequences for adult health and human capital

In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.

Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Regulate Feeding and Reward.

UNLABELLED The overconsumption of calorically dense, highly palatable foods is thought to be a major contributor to the worldwide obesity epidemic; however, the precise neural circuits that directly regulate hedonic feeding remain elusive. Here, we show that lateral hypothalamic area (LHA) glutamatergic neurons, and their projections to the lateral habenula (LHb), negatively regulate the consumption of palatable food. Genetic ablation of LHA glutamatergic neurons increased daily caloric intake and produced weight gain in mice that had access to a high-fat diet, while not altering general locomotor activity. Anterior LHA glutamatergic neurons send a functional glutamatergic projection to the LHb, a brain region involved in processing aversive stimuli and negative reward prediction outcomes. Pathway-specific, optogenetic stimulation of glutamatergic LHA-LHb circuit resulted in detectable glutamate-mediated EPSCs as well as GABA-mediated IPSCs, although the net effect of neurotransmitter release was to increase the firing of most LHb neurons. In vivo optogenetic inhibition of LHA-LHb glutamatergic fibers produced a real-time place preference, whereas optogenetic stimulation of LHA-LHb glutamatergic fibers had the opposite effect. Furthermore, optogenetic inhibition of LHA-LHb glutamatergic fibers acutely increased the consumption of a palatable liquid caloric reward. Collectively, these results demonstrate that LHA glutamatergic neurons are well situated to bidirectionally regulate feeding and potentially other behavioral states via their functional circuit connectivity with the LHb and potentially other brain regions. SIGNIFICANCE STATEMENT In this study, we show that the genetic ablation of LHA glutamatergic neurons enhances caloric intake. Some of these LHA glutamatergic neurons project to the lateral habenula, a brain area important for generating behavioral avoidance. Optogenetic stimulation of this circuit has net excitatory effects on postsynaptic LHb neurons. This is the first study to characterize the functional connectivity and behavioral relevance of this circuit within the context of feeding and reward-related behavior.

Anti-obesity drugs: past, present and future

The ideal anti-obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built-in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti-obesity drug. However, GLP-1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body-weight-lowering effects in humans, will perhaps also pave the way for other anti-obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it seems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical trials, although recent regulatory experience suggests that large challenges lie ahead. In future, this polytherapeutic strategy could possibly rival surgery in terms of efficacy, safety and sustainability of weight loss.

Patient preferences and expectations for care: determinants in patients with lumbar intervertebral disc herniation.

STUDY DESIGN Prospective observational cohort. OBJECTIVE To describe the baseline characteristics of patients with a diagnosis of intervertebral disc herniation who had different treatment preferences and the relationship of specific expectations with those preferences. SUMMARY OF BACKGROUND DATA Data were gathered from the observational cohort of the Spine Patient Outcomes Research Trial (SPORT). Patients in the observational cohort met eligibility requirements identical to those of the randomized cohort, but declined randomization, receiving instead the treatment of their choice. METHODS Baseline preference and expectation data were acquired at the time of enrollment of the patient, before exposure to the informed consent process. Univariate analyses were performed using a t test for continuous variables and chi for categorical variables. Multivariate analyses were also performed with ANCOVA for continuous variables and logistic regression for categorical variables. Multiple logistic regression models were developed in a forward stepwise fashion using blocks of variables. RESULTS More patients preferred operative care: 67% preferred surgery, 28% preferred nonoperative treatment, and 6% were unsure; 53% of those preferring surgery stated a definite preference, whereas only 18% of those preferring nonoperative care had a definite preference. Patients preferring surgery were younger, had lower levels of education, and higher levels of unemployment/disability. This group also reported higher pain, worse physical and mental functioning, more back pain related disability, a longer duration of symptoms, and more opiate use. Gender, race, comorbidities, and use of other therapies did not differ significantly across preference groups. Patients' expectations regarding improvement with nonoperative care was the strongest predictor of preference. CONCLUSION Patient expectations, particularly regarding the benefit of nonoperative treatment, are the primary determinant of surgery preference among patients with lumbar intervertebral disc herniation. Demographic, functional status, and prior treatment experience had significant associations with patients' expectations and preferences.

Self-reported health status and access to health services in a sample of prisoners in Italy

BACKGROUND Self-reported health status in underserved population of prisoners has not been extensively explored. The purposes of this cross-sectional study were to assess self-reported health, quality of life, and access to health services in a sample of male prisoners of Italy. METHODS A total of 908 prisoners received a self-administered anonymous questionnaire pertaining on demographic and detention characteristics, self-reported health status and quality of life, access to health services, lifestyles, and participation to preventive, social, and rehabilitation programs. A total of 650 prisoners agreed to participate in the study and returned the questionnaire. RESULTS Respectively, 31.6% and 43.5% of prisoners reported a poor perceived health status and a poor quality of life, and 60% admitted that their health was worsened or greatly worsened during the prison stay. Older age, lower education, psychiatric disorders, self-reported health problems on prison entry, and suicide attempts within prison were significantly associated with a perceived worse health status. At the time of the questionnaire delivery, 30% of the prisoners self-reported a health problem present on prison entry and 82% present at the time of the survey. Most frequently reported health problems included dental health problems, arthritis or joint pain, eye problems, gastrointestinal diseases, emotional problems, and high blood pressure. On average, prisoners encountered general practitioners six times during the previous year, and the frequency of medical encounters was significantly associated with older age, sentenced prisoners, psychiatric disorders, and self-reported health problems on prison entry. CONCLUSIONS The findings suggest that prisoners have a perceived poor health status, specific care needs and health promotion programs are seldom offered. Programs for correction of risk behaviour and prevention of long-term effects of incarceration on prisoners' health are strongly needed.

Potential Mechanisms of Action of Lithium in Bipolar Disorder

Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For instance, the effects of lithium on the adenyl cyclase and phospho-inositide pathways, as well as protein kinase C, may serve to dampen excessive excitatory neurotransmission. In addition to these many putative mechanisms, it has also been proposed that the neuroprotective effects of lithium are key to its therapeutic actions. In this regard, lithium has been shown to reduce the oxidative stress that occurs with multiple episodes of mania and depression. Further, it increases protective proteins such as brain-derived neurotrophic factor and B-cell lymphoma 2, and reduces apoptotic processes through inhibition of glycogen synthase kinase 3 and autophagy. Overall, it is clear that the processes which underpin the therapeutic actions of lithium are sophisticated and most likely inter-related.

Influence of antidepressant therapy on sick leave in primary care: ADAS, a comparative observational study

Background Compared to other European countries, Sweden's yearly sick leave expenditures are moderate. Common mental disorders (CMD) are important causes of sick leave, affecting 10-15% of the adult population. A Swedish register based study indicates that antidepressant therapy for patients on long-term sick leave for CMD leads to longer sick leave and higher frequency of non-time-limited sickness compensation as compared to psychotherapy, work oriented rehabilitation, and other therapies. Aim To verify if patients on antidepressant therapy and on long-term sick leave for depression, anxiety and stress-related mental disorders have a longer sick leave than patients treated with other therapies. Method Prospective, observational study at 28 primary health care centers in the Region Västra Götaland, Sweden, including 192 patients on sick leave for CMD. Outcome measures were gross and net sick leave days. Interpretation There were no significant differences in sick leave days (gross or net) due to CMD when comparing the patients treated and not treated with antidepressants during the 12 month observation period. The groups differed at baseline only concerning frequency of exhaustion disorder, with a higher frequency of exhaustion disorder in the group without antidepressants. Analysis of other possible factors associated with shorter or longer sick leave only showed associations with the patient's own perception of possibility of returning to work in near and distant future. An important factor associated with longer sick leave was the patient's own perception of possibility of return to present workplace. As CMD are important causes of sick leave and sick leave costs, this factor should be highlighted in future research on the rehabilitation process.

A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time?

CONTEXT Despite improvements in mental health services in recent decades, it is unclear whether the risk of mortality in schizophrenia has changed over time. OBJECTIVE To explore the distribution of standardized mortality ratios (SMRs) for people with schizophrenia. DATA SOURCES Broad search terms were used in MEDLINE, PsychINFO, Web of Science, and Google Scholar to identify all studies that investigated mortality in schizophrenia, published between January 1, 1980, and January 31, 2006. References were also identified from review articles, reference lists, and communication with authors. STUDY SELECTION Population-based studies that reported primary data on deaths in people with schizophrenia. DATA EXTRACTION Operationalized criteria were used to extract key study features and mortality data. DATA SYNTHESIS We examined the distribution of SMRs and pooled selected estimates using random-effects meta-analysis. We identified 37 articles drawn from 25 different nations. The median SMR for all persons for all-cause mortality was 2.58 (10%-90% quantile, 1.18-5.76), with a corresponding random-effects pooled SMR of 2.50 (95% confidence interval, 2.18-2.43). No sex difference was detected. Suicide was associated with the highest SMR (12.86); however, most of the major causes-of-death categories were found to be elevated in people with schizophrenia. The SMRs for all-cause mortality have increased during recent decades (P = .03). CONCLUSIONS With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention.

Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status. DESIGN Updated meta-analysis of randomised trials. DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer. RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders. CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.

DEVELOPMENT AND VALIDATION OF A MEASURE OF EMOTIONAL INTELLIGENCE

This series of studies describes the development of a measure of emotional intelligence based on the model of emotional intelligence developed by Salovey and Mayer [Salovey, P. & Mayer, J. D. (1990). Emotional intelligence. Imagination, Cognition and Personality, 9, 185–211.]. A pool of 62 items represented the different dimensions of the model. A factor analysis of the responses of 346 participants suggested the creation of a 33-item scale. Additional studies showed the 33-item measure to have good internal consistency and testretest reliability. Validation studies showed that scores on the 33-item measure  1. (a) correlated with eight of nine theoretically related constructs, including alexithymia, attention to feelings, clarity of feelings, mood repair, optimism and impulse control;    2.  (b) predicted first-year college grades;    3. (c) were significantly higher for therapists than for therapy clients or for prisoners;    4.  (d) were significantly higher for females than males, consistent with prior findings in studies of emotional skills;    5. (e) were not related to cognitive ability and    6. (f) were associated with the openness to experience trait of the big five personality dimensions.

Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive) during early life (including prenatal period) or adulthood, giving emphasis to the data on the changes of neurotrophic factors and neuroinflammatory indices in the brain. These parameters are closely related to behavioral depression-like symptoms and impairments of neuronal plasticity and are both gender- and genotype-dependent. Stress-related changes in expression of neurotrophins and cytokines in rodent brain are region-specific. Some contradictory data reported by different groups may be a consequence of differences of stress paradigms or their realization in different laboratories. Like all experimental models, stress-induced depression-like conditions are experimental simplification of clinical depression states; however, they are suitable for understanding the involvement of neurotrophic factors and cytokines in the pathogenesis of the disease-a goal unachievable in the clinical reality. These major regulatory systems may be important targets for therapeutic measures as well as for development of drugs for treatment of depression states.

DNA Methylation in Major Depressive Disorder.

Epigenetic mechanisms regulate gene expression, influencing protein levels and ultimately shaping phenotypes during life. However, both stochastic epigenetic variations and environmental reprogramming of the epigenome might influence neurodevelopment and ageing, and this may contribute to the origins of mental ill-health. Studying the role of epigenetic mechanisms is challenging, as genotype-, tissue- and cell type-dependent epigenetic changes have to be taken into account, while the nature of mental disorders also poses significant challenges for linking them with biological profiles. In this chapter, we summarise the current evidence suggesting the role of DNA methylation as a key epigenetic mechanism in major depressive disorder.

What's in the 'treatment gap'? Ethnographic perspectives on addiction and global mental health from China, Russia, and the United States.

Recent years have seen the emergence of a 'global mental health' agenda, focused on providing evidence-based interventions for mental illnesses in low- and middle-income countries. Anthropologists and cultural psychiatrists have engaged in vigorous debates about the appropriateness of this agenda. In this article, we reflect on these debates, drawing on ethnographic fieldwork on the management of substance use disorders in China, Russia, and the United States. We argue that the logic of 'treatment gaps,' which guides much research and intervention under the rubric of global mental health, partially obscures the complex assemblages of institutions, therapeutics, knowledges, and actors framing and managing addiction (as well as other mental health issues) in any particular setting.

Brief Internet-Based Intervention Reduces Posttraumatic Stress and Prolonged Grief in Parents after the Loss of a Child during Pregnancy: A Randomized Controlled Trial

Background: The loss of a child during pregnancy causes significant psychological distress for many women and their partners, and may lead to long-lasting psychiatric disorders. Internet-based interventions using exposure techniques and cognitive restructuring have proved effective for posttraumatic stress disorder (PTSD) and prolonged grief. This study compared the effects of an Internet-based intervention for parents after prenatal loss with a waiting list condition (WLC). Methods: The Impact of Event Scale - Revised assessed symptoms of PTSD; the Inventory of Complicated Grief and the Brief Symptom Inventory assessed depression, anxiety, and general mental health. The 228 participants (92% female) were randomly allocated to a treatment group (TG; n = 115) or a WLC group (n = 113). The TG received a 5-week cognitive behavioral intervention including (1) self-confrontation, (2) cognitive restructuring, and (3) social sharing. Results: The TG showed significantly reduced symptoms of posttraumatic stress, prolonged grief, depression, and anxiety relative to the WLC control group. Intention-to-treat analysis revealed treatment effects of between d = 0.84 and d = 1.02 for posttraumatic stress and prolonged grief from pre- to posttreatment time points. Further significant improvement in all symptoms of PTSD and prolonged grief was found from the posttreatment evaluation to the 12-month follow-up. The attrition rate of 14% was relatively low. Conclusions: The Internet-based intervention proved to be a feasible and cost-effective treatment, reducing symptoms of posttraumatic stress, grief, depression, anxiety, and general mental health after pregnancy loss. Low-threshold e-health interventions should be further evaluated and implemented routinely to improve psychological support after pregnancy loss.

Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial.

CONTEXT Anxiety about bias, lack of accountability, and poor quality of peer review has led to questions about the imbalance in anonymity between reviewers and authors. OBJECTIVE To evaluate the effect on the quality of peer review of blinding reviewers to the authors' identities and requiring reviewers to sign their reports. DESIGN Randomized controlled trial. SETTING A general medical journal. PARTICIPANTS A total of 420 reviewers from the journal's database. INTERVENTION We modified a paper accepted for publication introducing 8 areas of weakness. Reviewers were randomly allocated to 5 groups. Groups 1 and 2 received manuscripts from which the authors' names and affiliations had been removed, while groups 3 and 4 were aware of the authors' identities. Groups 1 and 3 were asked to sign their reports, while groups 2 and 4 were asked to return their reports unsigned. The fifth group was sent the paper in the usual manner of the journal, with authors' identities revealed and a request to comment anonymously. Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study. MAIN OUTCOME MEASURE The number of weaknesses in the paper that were commented on by the reviewers. RESULTS Reports were received from 221 reviewers (53%). The mean number of weaknesses commented on was 2 (1.7, 2.1, 1.8, and 1.9 for groups 1, 2, 3, and 4 and 5 combined, respectively). There were no statistically significant differences between groups in their performance. Reviewers who were blinded to authors' dentities were less likely to recommend rejection than those who were aware of the authors' identities (odds ratio, 0.5; 95% confidence interval, 0.3-1.0). CONCLUSIONS Neither blinding reviewers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors. Such measures are unlikely to improve the quality of peer review reports.

Chronic daily headache. A clinical and psychological profile before and after treatment.

To assess the clinical and personality characteristics of patients with chronic daily headache before and after treatment, 20 patients were examined and the Minnesota Multiphasic Personality Inventory (MMPI [Italian 356-item abbreviated version]) and the Strait and Trait Anxiety Index 1,2 (STAI) administered. There were two groups: group 1 (n = 6), with a "conversion V" configuration (with elevation of hypochondria and hysteria scales, the depression scale being somewhat lower); and group 2 (n = 13) with elevation of depression and of other MMPI scales. One patient had no scale elevation. STAI 1,2 scores were high in both groups. Several psychosomatic symptoms and some migraine features were present in almost all patients. Occurrence, severity, and duration of headache were recorded regularly and the MMPI and the STAI administered again after treatment. Improvement of headaches and a decrease of several MMPI and STAI 2 scores were observed. However, 12 of 20 patients showed a conversion V configuration after treatment. It is concluded that chronic daily headache was transformed migraine in most cases and was accompanied by anxiety levels in all patients and hysteric traits in some. With time, these patients may develop a depressive disorder. After treatment, hysterical traits are still present at a lower level in those showing these traits before treatment and may be unmasked in those that had depression.

Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives.

Fibroblast growth factor 21 (FGF21), a metabolic hormone predominantly produced by the liver, is also expressed in adipocytes and the pancreas. It regulates glucose and lipid metabolism through pleiotropic actions in these tissues and the brain. In mice, fasting leads to increased PPAR-α mediated expression of FGF21 in the liver where it stimulates gluconeogenesis, fatty acid oxidation, and ketogenesis, as an adaptive response to fasting and starvation. In the fed state, FGF21 acts as an autocrine factor in adipocytes, regulating the activity of PPAR-γ through a feed-forward loop mechanism. Administration of recombinant FGF21 has been shown to confer multiple metabolic benefits on insulin sensitivity, blood glucose, lipid profile and body weight in obese mice and diabetic monkeys, without mitogenic or other side effects. Such findings highlight the potential role of FGF21 as a therapeutic agent for obesity-related medical conditions. However, in human studies, high circulating FGF21 levels are found in obesity and its related cardiometabolic disorders including the metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease and coronary artery disease. These findings may indicate the presence of FGF21 resistance or compensatory responses to the underlying metabolic stress, and imply the need for supraphysiological doses of FGF21 to achieve therapeutic efficacy. On the other hand, serum FGF21 has been implicated as a potential biomarker for the early detection of these cardiometabolic disorders. This review summarizes recent developments in the understanding of FGF21, from physiological and clinical perspectives.

The impact of homelessness on children.

This article reviews and critiques community-based research on the effects of homelessness on children. Homeless children confront serious threats to their ability to succeed and their future well-being. Of particular concern are health problems, hunger, poor nutrition, developmental delays, anxiety, depression, behavioral problems, and educational underachievement. Factors that may mediate the observed outcomes include inadequate shelter conditions, instability in residences and shelters, inadequate services, and barriers to accessing services that are available. Public policy initiatives are needed to meet the needs of homeless children.

Breast cancer and obesity: an update.

Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk. In both premenopausal and postmenopausal breast cancer, the mechanisms by which body weight and obesity affect risk have been related to estrogenic activity. Obesity has also been related to advanced disease at diagnosis and with a poor prognosis in both premenopausal and postmenopausal breast cancer. Breast cancer in African-American women, considering its relationship to obesity, exhibits some important differences from those described in white women, although the high prevalence of obesity in African-American women may contribute to the relatively poor prognosis compared with white American women. Despite the emphasis on estrogens to explain the effects of obesity on breast cancer, other factors may prove to be equally or more important, particularly as they relate to expression of an aggressive tumor phenotype. Among these, this review serves to stress insulin, insulin-like growth factor-I, and leptin, and their relationship to angiogenesis, and transcriptional factors.

Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress

During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of different cell types. The impact of the SNS on the immune modulation of social defeat has not been examined. The following studies were designed to determine whether SNS activation during social disruption stress (SDR) influences anxiety-like behavior as well as the activation, priming, and glucocorticoid resistance of splenocytes after social stress. CD-1 mice were exposed to one, three, or six cycles of SDR and HPLC analysis of the plasma and spleen revealed an increase in catecholamines. After six cycles of SDR the open field test was used to measure behaviors characteristic of anxiety and indicated that the social defeat induced increase in anxiety-like behavior was blocked by pre-treatment with the β-adrenergic antagonist propranolol. Pre-treatment with the β-adrenergic antagonist propranolol did not significantly alter corticosterone levels indicating no difference in activation of the hypothalamic-pituitary-adrenal axis. In addition to anxiety-like behavior the SDR induced splenomegaly and increase in plasma IL-6, TNFα, and MCP-1 were each reversed by pre-treatment with propranolol. Furthermore, flow cytometric analysis of cells from propranolol pretreated mice reduced the SDR-induced increase in the percentage of CD11b(+) splenic macrophages and significantly decreased the expression of TLR2, TLR4, and CD86 on the surface of these cells. In addition, supernatants from 18h LPS-stimulated ex vivo cultures of splenocytes from propranolol-treated SDR mice contained less IL-6. Likewise propranolol pre-treatment abrogated the glucocorticoid insensitivity of CD11b(+) cells ex vivo when compared to splenocytes from SDR vehicle-treated mice. Together, this study demonstrates that the immune activation and priming effects of SDR result, in part, as a consequence of SNS activation.

Unmet need for mental health care among U.S. children: variation by ethnicity and insurance status.

OBJECTIVE Policy discussions regarding the mental health needs of children and adolescents emphasize a lack of use of mental health services among youth, but few national estimates are available. The authors use three national data sets and examine ethnic disparities in unmet need (defined as having a need for mental health evaluation but not using any services in a 1-year period) to provide such estimates. METHOD The authors conducted secondary data analyses in three nationally representative household surveys fielded in 1996-1998: the National Health Interview Survey, the National Survey of American Families, and the Community Tracking Survey. They determined rates of mental health service use by children and adolescents 3-17 years of age and differences by ethnicity and insurance status. Among the children defined as in need of mental health services, defined by an estimator of mental health problems (selected items from the Child Behavior Checklist), they examined the association of unmet need with ethnicity and insurance status. RESULTS In a 12-month period, 2%-3% of children 3-5 years old and 6%-9% of children and adolescents 6-17 years old used mental health services. Of children and adolescents 6-17 years old who were defined as needing mental health services, nearly 80% did not receive mental health care. Controlling for other factors, the authors determined that the rate of unmet need was greater among Latino than white children and among uninsured than publicly insured children. CONCLUSIONS These findings reveal that most children who need a mental health evaluation do not receive services and that Latinos and the uninsured have especially high rates of unmet need relative to other children. Rates of use of mental health services are extremely low among preschool children. Research clarifying the reasons for high rates of unmet need in specific groups can help inform policy and clinical programs.

Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder.

The mood stabilizers lithium and valproic acid (VPA) are traditionally used to treat bipolar disorder (BD), a severe mental illness arising from complex interactions between genes and environment that drive deficits in cellular plasticity and resiliency. The therapeutic potential of these drugs in other central nervous system diseases is also gaining support. This article reviews the various mechanisms of action of lithium and VPA gleaned from cellular and animal models of neurologic, neurodegenerative, and neuropsychiatric disorders. Clinical evidence is included when available to provide a comprehensive perspective of the field and to acknowledge some of the limitations of these treatments. First, the review describes how action at these drugs' primary targets--glycogen synthase kinase-3 for lithium and histone deacetylases for VPA--induces the transcription and expression of neurotrophic, angiogenic, and neuroprotective proteins. Cell survival signaling cascades, oxidative stress pathways, and protein quality control mechanisms may further underlie lithium and VPA's beneficial actions. The ability of cotreatment to augment neuroprotection and enhance stem cell homing and migration is also discussed, as are microRNAs as new therapeutic targets. Finally, preclinical findings have shown that the neuroprotective benefits of these agents facilitate anti-inflammation, angiogenesis, neurogenesis, blood-brain barrier integrity, and disease-specific neuroprotection. These mechanisms can be compared with dysregulated disease mechanisms to suggest core cellular and molecular disturbances identifiable by specific risk biomarkers. Future clinical endeavors are warranted to determine the therapeutic potential of lithium and VPA across the spectrum of central nervous system diseases, with particular emphasis on a personalized medicine approach toward treating these disorders.

A feasibility study for a randomised controlled trial of the Positive Reappraisal Coping Intervention, a novel supportive technique for recurrent miscarriage

INTRODUCTION Recurrent miscarriage (RM) is diagnosed when a woman has had three or more miscarriages. Increased levels of distress and anxiety are common during the waiting period of any subsequent pregnancies, posing a significant threat to psychological well-being. However, only limited support and therapy are available for these women, and many are left to cope alone. The Positive Reappraisal Coping Intervention (PRCI) is a novel self-administered supportive technique which has been shown to be effective in patients awaiting the outcome of in vitro fertilisation treatment. The primary objective of this study is to assess the feasibility and effectiveness of the PRCI in improving quality of life in the difficult waiting period which women with previous RM endure before an ongoing pregnancy can be confirmed. METHODS AND ANALYSIS A randomised controlled trial (RCT) feasibility study will establish the viability of conducting a multicentre RCT to definitively test the effects of the PRCI on the psychological well-being of women who have experienced RM during the initial waiting period of a subsequent pregnancy. A second component consists of a qualitative process evaluation exploring the initial experience of pregnancy following repeated miscarriages. Participants (n=50) will be randomised into one of two groups. The PRCI intervention group will receive the PRCI card and weekly questionnaires to assess their psychological well-being during the waiting period of their new pregnancy. The non-intervention group will be asked to complete the same weekly questionnaires. The qualitative process analysis will employ semistructured interviews (n=20) to address relevant aspects of the study objectives. ETHICS AND DISSEMINATION Ethics approval has been obtained from the National Research Ethics Service Committee South Central-Hampshire A. Participating centres have given National Health Service R&D approval. Study findings will be disseminated through peer reviewed journals, national and international conferences and lay user groups. TRIAL REGISTRATION NUMBER ISRCTN43571276. This study was registered with the ISRCTN 18/02/2014 following adoption onto the United Kingdom Clinical Research Network (UKCRN) portfolio. Recruitment of the first participant occurred 04/02/2014.

Transtheoretical model-based multiple behavior intervention for weight management: effectiveness on a population basis.

BACKGROUND The increasing prevalence of overweight and obesity underscores the need for evidence-based, easily disseminable interventions for weight management that can be delivered on a population basis. The Transtheoretical Model (TTM) offers a promising theoretical framework for multiple behavior weight management interventions. METHODS Overweight or obese adults (BMI 25-39.9; n=1277) were randomized to no-treatment control or home-based, stage-matched multiple behavior interventions for up to three behaviors related to weight management at 0, 3, 6, and 9 months. All participants were re-assessed at 6, 12, and 24 months. RESULTS Significant treatment effects were found for healthy eating (47.5% versus 34.3%), exercise (44.90% versus 38.10%), managing emotional distress (49.7% versus 30.30%), and untreated fruit and vegetable intake (48.5% versus 39.0%) progressing to Action/Maintenance at 24 months. The groups differed on weight lost at 24 months. Co-variation of behavior change occurred and was much more pronounced in the treatment group, where individuals progressing to Action/Maintenance for a single behavior were 2.5-5 times more likely to make progress on another behavior. The impact of the multiple behavior intervention was more than three times that of single behavior interventions. CONCLUSIONS This study demonstrates the ability of TTM-based tailored feedback to improve healthy eating, exercise, managing emotional distress, and weight on a population basis. The treatment produced a high level of population impact that future multiple behavior interventions can seek to surpass.

Platelet activation in type 2 diabetes mellitus.

The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population.

A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children.

Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO(2) max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain.

Intestinal methane production in obese individuals is associated with a higher body mass index.

BACKGROUND Obesity is an epidemic that affects 1 in 3 individuals in the United States, and recent evidence suggests that enteric microbiota may play a significant role in the development of obesity. This study evaluated the association between methanogenic archaea and obesity in human subjects. METHODS Subjects with a body mass index (BMI) of 30 kg/m² or higher were prospectively recruited from the weight loss program of a tertiary care medical center. Subjects who met the study's inclusion criteria were asked to complete a questionnaire that included a series of visual analogue scores for bowel symptom severities. Subjects then provided a single end-expiratory breath sample to quantitate methane levels. Bivariate and multivariate analyses were used to determine associations with BMI. RESULTS A total of 58 patients qualified for enrollment. Twenty percent of patients (n = 12) had breath test results that were positive for methane (>3 parts per million [ppm]), with a mean breath methane concentration of 12.2±3.1 ppm. BMI was significantly higher in methane-positive subjects (45.2±2.3 kg/m²) than in methane-negative subjects (38.5±0.8 kg/m²; P=.001). Methane-positive subjects also had a greater severity of constipation than methane-negative subjects (21.3±6.4 vs 9.5±2.4; P=.043). Multiple regression analysis illustrated a significant association between BMI and methane, constipation, and antidepressant use. However, methane remained an independent predictor of elevated BMI when controlling for antidepressant use (P<.001) and when controlling for both constipation and antidepressant use (6.55 kg/m² greater BMI; P=.003). CONCLUSION This is the first human study to demonstrate that a higher concentration of methane detected by breath testing is a predictor of significantly greater obesity in overweight subjects.

A role for interleukin-1β in determining the lineage fate of embryonic rat hippocampal neural precursor cells.

Neurogenesis occurs in the hippocampus of the developing and adult brain due to the presence of multipotent stem cells and restricted precursor cells at different stages of differentiation. It has been proposed that they may be of potential benefit for use in cell transplantation approaches for neurodegenerative disorders and trauma. Prolonged release of interleukin-1β (IL-1β) from activated microglia has a deleterious effect on hippocampal neurons and is implicated in the impaired neurogenesis and cognitive dysfunction associated with aging, Alzheimer's disease and depression. This study assessed the effect of IL-1β on the proliferation and differentiation of embryonic rat hippocampal NPCs in vitro. We show that IL-1R1 is expressed on proliferating NPCs and that IL-1β treatment decreases cell proliferation and neurosphere growth. When NPCs were differentiated in the presence of IL-1β, a significant reduction in the percentages of newly-born neurons and post-mitotic neurons and a significant increase in the percentage of astrocytes was observed in these cultures. These effects were attenuated by IL-1 receptor antagonist. These data reveal that IL-1β exerts an anti-proliferative, anti-neurogenic and pro-gliogenic effect on embryonic hippocampal NPCs, which is mediated by IL-1R1. The present results emphasise the consequences of an inflammatory environment during NPC development, and indicate that strategies to inhibit IL-1β signalling may be necessary to facilitate effective cell transplantation approaches or in conditions where endogenous hippocampal neurogenesis is impaired.

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes.

Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.

Frailty Syndrome: A Transitional State in a Dynamic Process

Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.

Integrating nutrition security with treatment of people living with HIV: lessons from Kenya.

BACKGROUND The increased caloric requirements of HIV-positive individuals, undesirable side effects of treatment that may be worsened by malnutrition (but alleviated by nutritional support), and associated declines in adherence and possible increased drug resistance are all justifications for developing better interventions to strengthen the nutrition security of individuals receiving antiretroviral treatment. OBJECTIVE To highlight key benefits and challenges relating to interventions aimed at strengthening the nutrition security of people living with HIV who are receiving antiretroviral treatment. METHODS Qualitative research was undertaken on a short-term nutrition intervention linked to the provision of free antiretroviral treatment for people living with HIV in western Kenya in late 2005 and early 2006. RESULTS Patients enrolled in the food program while on treatment regimens self-reported greater adherence to their medication, fewer side effects, and a greater ability to satisfy increased appetite. Most clients self-reported weight gain, recovery of physical strength, and the resumption of labor activities while enrolled in dual (food supplementation and treatment) programs. Such improvements were seen to catalyze increased support from family and community. CONCLUSIONS These findings provide further empirical support to calls for a more holistic and comprehensive response to the coexistence of AIDS epidemics with chronic nutrition insecurity. Future work is needed to clarify ways of bridging the gap between short-term nutritional support to individuals and longer-term livelihood security programming for communities affected by AIDS. Such interdisciplinary research will need to be matched by intersectoral action on the part of the agriculture and health sectors in such environments.

Experimental and Theoretical Approaches to Conscious Processing

Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity. The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond nonconscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and nonconscious processing, point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronization at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network. We compare these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal, and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state, and schizophrenia are discussed.

Anorectic drugs and pulmonary hypertension from the bedside to the bench.

Anorectic drugs have been used for more than 30 years as an aid in weight reduction for obese persons. The use of aminorex, an amphetamine analog that increases norepinephrine levels in the central nervous system, led to an epidemic of primary pulmonary hypertension (PPH) in Europe in the late 1960s and early 1970s. The use of fenfluramine and later dexfenfluramine [drugs that inhibit 5-hydroxytryptamine (5-HT) release and reuptake and increases 5-HT and thus 5-HT secretion in the brain] was associated with a second epidemic of PPH. All of these drugs have been voluntarily withdrawn from the market. The pathogenesis of PPH in patients treated with these agents is uncertain, but recent evidence suggests that potassium channel abnormalities and vasoactive and proliferative properties of 5-HT may play a role. There is increasing experimental evidence suggesting that aminorex, fenfluramine and dexfenfluramine inhibit 4-aminopyridine-sensitive currents in potassium channels resulting in vasoconstriction in pulmonary resistance vessels and perhaps smooth muscle cell proliferation. 5-HT causes pulmonary artery vasoconstriction and smooth muscle cell proliferation. Its levels are known to be high in those with fenfluramine-induced PPH. However, a firm cause-and-effect relationship has not yet been established. One potentially beneficial effect of the epidemics of anorectic-related PPH is that it may have provided important insights into the causes of PPH unrelated to anorectic agents.

Defective regulation of adipose tissue autophagy in obesity

Objectives: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Subjects:Adipose tissue autophagy was evaluated in mice and humans. Results:First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Conclusion:Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.

A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction.

CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.

Epidemiology, health-related quality of life and economic burden of binge eating disorder: a systematic literature review

PURPOSE To perform a systematic review on the epidemiology, the health-related quality of life (HRQoL) and economic burden of binge eating disorder (BED). METHODS A systematic literature search of English-language articles was conducted using Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier and Cochrane Library. Literature search on epidemiology was limited to studies published between 2009 and 2013. Cost data were inflated and converted to 2012 US$ purchasing power parities. All of the included studies were assessed for quality. RESULTS Forty-nine articles were included. Data on epidemiology were reported in 31, HRQoL burden in 16, and economic burden in 7 studies. Diagnosis of BED was made using 4th Edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in 46 studies. Lifetime prevalence of BED was 1.1-1.9% in the general population (DSM-IV). BED was associated with significant impairment in aspects of HRQoL relating to both physical and mental health; the Short Form 36 Physical and Mental Component Summary mean scores varied between 31.1 to 47.3 and 32.0 to 49.8, respectively. Compared to individuals without eating disorder, BED was related to increased healthcare utilization and costs. Annual direct healthcare costs per BED patient ranged between $2,372 and $3,731. CONCLUSIONS BED is a serious eating disorder that impairs HRQoL and is related to increased healthcare utilization and healthcare costs. The limited literature warrants further research, especially to better understand the long-term HRQoL and economic burden of BED.

Short-term medical service trips: a systematic review of the evidence.

Short-term medical service trips (MSTs) aim to address unmet health care needs of low- and middle-income countries. The lack of critically reviewed empirical evidence of activities and outcomes is a concern. Developing evidence-based recommendations for health care delivery requires systematic research review. I focused on MST publications with empirical results. Searches in May 2013 identified 67 studies published since 1993, only 6% of the published articles on the topic in the past 20 years. Nearly 80% reported on surgical trips. Although the MST field is growing, its medical literature lags behind, with nearly all of the scholarly publications lacking significant data collection. By incorporating data collection into service trips, groups can validate practices and provide information about areas needing improvement.

Frontal stroke syndromes.

The frontal lobe is the largest lobe of the brain, and it is thus commonly involved in stroke. Moreover, almost one in five strokes is limited to the prerolandic areas. This high frequency of anatomical involvement is in sharp contrast with the apparent rarity of clinical frontal dysfunction in stroke. It is remarkable that frontal behavioral syndromes have been rather uncommonly reported in patients with stroke as compared to patients with other diseases, such as brain tumor. This fact is paradoxical, because an acute process (stroke) is expected to yield more clinical dysfunction than a more chronic disease (tumor). A volume effect may be the main factor leading to this phenomenon. Another interesting aspect of frontal strokes is the contribution of so-called 'silent' strokes, the recurrence of which may nevertheless lead to intellectual decline and compromise recovery from another stroke with more specific neurologic dysfunction. The contribution of stroke to understanding of frontal lobe dysfunction is important, because of the focal nature of this disease, and great opportunity for clinical-topographic classification correlations. One of the first modern attempts to develop a clinical-topographic classification of frontal lobe lesions came from the school of Luria, who tried to delineate three main types of frontal lobe syndromes (premotor syndrome, prefrontal syndrome, medial-frontal syndrome). Recent anatomic correlates using MRI make it possible to improve this classification. We suggest considering six main clinical-anatomic frontal stroke syndromes: (1) prefrontal; (2) premotor; (3) superior medial; (4) orbital-medial; (5) basal forebrain; (6) white matter. Finally, another fascinating topic relates to frontal lobe symptomatology due to stroke sparing the frontal cortex or white matter. This occurs mainly in three instances: lenticulo-capsular stroke, caudate stroke, and thalamic stroke. Studies using blood flow or metabolism measurements suggest that diaschisis (frontal lobe dysfunction from a remote lesion) may play a role. We believe that this is more likely to be related to dynamic interruption of complex circuitry than to static frontal lobe deactivation.

Leptin treatment ameliorates anxiety in ob/ob obese mice.

We investigated whether or not administered leptin influences anxiety-like behavior in ob/ob mice. Repeated intraperitoneal administrations of leptin were continued for 5 days. Anxiety was assessed in the standard elevated plus maze. Body weight was measured daily. Repeated administrations of leptin significantly increased the percentage of the total number of entries in the open arms and the number of total entries. The body weight was significantly reduced by 13.2% after treatment. Leptin treatment ameliorated not only obesity but also anxiety in ob/ob mice. Our results indicate that the treatment of obesity may lead to the solution of psychological problems.

Unmet needs and depressive symptoms among low--income older adults.

Previous studies have found that declining health, decreased social interaction, and inadequate financial resources were significant risk factors for late-life depression, and social support from families and friends and religiosity were significant protective factors. In this study, we examined if low-income older adults' perceived unmet need for home- and community-based services for many aging-associated problems would be independently associated with their depressive symptoms, controlling for these known risk and protective factors. We interviewed a total of 213 community-residing older adults to assess their depressive symptoms, using the Geriatric Depression Scale (GDS), and unmet needs in the areas of personal assistance, instrumental and environmental support, emotional support, and other facilitative/enabling services. We found that the number of unmet needs was significantly positively associated with these older adults' depressive symptoms, although it explained only a small proportion of the variance of the GDS scores. Future research and practice implications are discussed.

Effects of exercise intensity on cardiovascular fitness, total body composition, and visceral adiposity of obese adolescents.

BACKGROUND Little is known about how the intensity of exercise influences cardiovascular fitness and body composition, especially in obese adolescents. OBJECTIVE Our goal was to determine the effects of physical training intensity on the cardiovascular fitness, percentage of body fat (%BF), and visceral adipose tissue (VAT) of obese adolescents. DESIGN Obese 13-16-y-olds (n = 80) were assigned to 1) biweekly lifestyle education (LSE), 2) LSE + moderate-intensity physical training, or 3) LSE + high-intensity physical training. The intervention lasted 8 mo. Physical training was offered 5 d/wk, and the target energy expenditure for all subjects in physical training groups was 1047 kJ (250 kcal)/session. Cardiovascular fitness was measured with a multistage treadmill test, %BF with dual-energy X-ray absorptiometry, and VAT with magnetic resonance imaging. RESULTS The increase in cardiovascular fitness in the high-intensity physical training group, but not in the moderate-intensity group, was significantly greater than that in the LSE alone group (P = 0.009); no other comparisons of the 3 groups were significant. Compared with the LSE alone group, a group composed of subjects in both physical training groups combined who attended training sessions >or=2 d/wk showed favorable changes in cardiovascular fitness (P < 0.001), %BF (P = 0.001), and VAT (P = 0.029). We found no evidence that the high-intensity physical training was more effective than the moderate-intensity physical training in enhancing body composition. CONCLUSIONS The cardiovascular fitness of obese adolescents was significantly improved by physical training, especially high-intensity physical training. The physical training also reduced both visceral and total-body adiposity, but there was no clear effect of the intensity of physical training.

Psychological adaptation in children with idiopathic short stature treated with growth hormone or placebo.

The influence of short stature on psychological adaptation in childhood and adolescence is controversial. GH is currently used to treat children with idiopathic short stature (ISS, also known as non-GH-deficient short stature). This study represents the first double-blind, placebo-controlled trial of the effects of GH on the psychological adaptation of children and adolescents with ISS, treated with GH until adult height was attained. Sixty-eight children (53 males, 15 females), 9-16 yr old, with marked ISS (measured height or predicted adult height -2.5 sd or less) received either GH 0.074 mg/kg or placebo sc three times per week until height velocity decreased to less than 1.5 cm/yr. Parents completed the Child Behavior Checklist (CBCL) and children the Self-Perception Profile (SPP) and Silhouette Apperception Technique at baseline and annually thereafter. Baseline behavioral/emotional adjustment (CBCL) and self-concept (SPP) scores for children with ISS were within the normative range. The two study groups exhibited similar behavioral and self-concept profiles (CBCL) during the first 2 yr of the study. However, CBCL behavior problems (internalizing, externalizing, and total problems) appeared to decline, in yr 3 and 4, in the GH-treated group relative to the placebo-treated group. Group differences in CBCL competency domains and the SPP were not observed at any point during the study. Short stature among children with ISS enrolled in this long-term, placebo-controlled study was not associated with problems in psychological adaptation or self-concept with the psychological instruments employed. GH treatment was associated with a trend toward improvement in problem behaviors, as measured by questionnaires (CBCL) completed by study participants' parents. It remains to be determined whether GH treatment significantly impacts adaptation, psychosocial function, or quality of life in children with ISS.

Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients.

The delineation of dopamine dysfunction in the mentally ill has been a long-standing quest of biological psychiatry. The present study focuses on a recently recognized group of dopamine receptor-interacting proteins as possible novel sites of dysfunction in schizophrenic and bipolar patients. We demonstrate that the dorsolateral prefrontal cortex in schizophrenia and bipolar cases from the Stanley Foundation Neuropathology Consortium display significantly elevated levels of the D2 dopamine receptor desensitization regulatory protein, neuronal calcium sensor-1. These levels of neuronal calcium sensor-1 were not influenced by age, gender, hemisphere, cause of death, postmortem period, alcohol consumption, or antipsychotic and mood stabilizing medications. The present study supports the hypothesis that schizophrenia and bipolar disorder may be associated with abnormalities in dopamine receptor-interacting proteins.

Screening for concomitant diseases in peripheral vascular patients. Results of a systematic approach.

BACKGROUND Patients considered for arterial surgery, have been shown to have a high incidence of coexistent cardiac, vascular and other diseases, affecting operative risk and survival. We developed a systematic workup strategy for detecting these coexistent diseases in our vascular surgical patients, mainly based on non-invasive diagnostic techniques. METHODS We evaluated 200 consecutive patients, admitted to the department of vascular surgery in an academic teaching hospital, in order to establish the total incidence of relevant concomitant disorders, the extent to which this screening yielded previously unknown diagnostic information, and the impact on short-term (one year) survival. RESULTS Coronary artery disease was present in 46% of the patients; 22% had active ischaemia, newly diagnosed in 5.5%. Impaired cardiac function was found in 37%: severely impaired in 12%, newly diagnosed in 27%. Carotid artery disease was present in 32%: critical stenoses were found in 9%; new diagnoses in 29.9%. Aortic aneurysms were present in 7%, newly diagnosed in 5%. Severe renal artery stenosis was present in 5%, newly diagnosed in 3.5%. Sixteen % of the patients had chronic obstructive pulmonary disease, newly diagnosed in 3.5%, and 4.5% had unexpected disorders, which were all new diagnoses. Overall, new diagnoses were reached in 64.5% of the population, affecting therapeutic strategy immediately in 21% of the patients. The presence of coronary artery disease and of cardiac failure were clearly related to one year survival. CONCLUSIONS We conclude that a systematic screening strategy, mainly based on noninvasive techniques, can detect the presence of concomitant diseases in the vascular surgical patient. Most important seem the newly diagnosed diseases altering surgical management in one out of every five patients; they also have important implications for patient prognosis.

Breast cancer risk factors in relation to breast density (United States)

Evaluate known breast cancer risk factors in relation to breast density. We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.

Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications.

Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, such as brain-derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression's development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed.

A mental health intervention for schoolchildren exposed to violence: a randomized controlled trial.

CONTEXT No randomized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder (PTSD) that has resulted from personally witnessing or being personally exposed to violence. OBJECTIVE To evaluate the effectiveness of a collaboratively designed school-based intervention for reducing children's symptoms of PTSD and depression that has resulted from exposure to violence. DESIGN A randomized controlled trial conducted during the 2001-2002 academic year. SETTING AND PARTICIPANTS Sixth-grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD. INTERVENTION Students were randomly assigned to a 10-session standardized cognitive-behavioral therapy (the Cognitive-Behavioral Intervention for Trauma in Schools) early intervention group (n = 61) or to a wait-list delayed intervention comparison group (n = 65) conducted by trained school mental health clinicians. MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD (Child PTSD Symptom Scale; range, 0-51 points) and depression (Child Depression Inventory; range, 0-52 points), parent-reported psychosocial dysfunction (Pediatric Symptom Checklist; range, 0-70 points), and teacher-reported classroom problems using the Teacher-Child Rating Scale (acting out, shyness/anxiousness, and learning problems; range of subscales, 6-30 points). RESULTS Compared with the wait-list delayed intervention group (no intervention), after 3 months of intervention students who were randomly assigned to the early intervention group had significantly lower scores on symptoms of PTSD (8.9 vs 15.5, adjusted mean difference, - 7.0; 95% confidence interval [CI], - 10.8 to - 3.2), depression (9.4 vs 12.7, adjusted mean difference, - 3.4; 95% CI, - 6.5 to - 0.4), and psychosocial dysfunction (12.5 vs 16.5, adjusted mean difference, - 6.4; 95% CI, -10.4 to -2.3). Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out (-1.0; 95% CI, -2.5 to 0.5), shyness/anxiousness (0.1; 95% CI, -1.5 to 1.7), and learning (-1.1, 95% CI, -2.9 to 0.8). At 6 months, after both groups had received the intervention, the differences between the 2 groups were not significantly different for symptoms of PTSD and depression; showed similar ratings for psychosocial function; and teachers did not report significant differences in classroom behaviors. CONCLUSION A standardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians.

The behaviour change wheel: A new method for characterising and designing behaviour change interventions

BACKGROUND Improving the design and implementation of evidence-based practice depends on successful behaviour change interventions. This requires an appropriate method for characterising interventions and linking them to an analysis of the targeted behaviour. There exists a plethora of frameworks of behaviour change interventions, but it is not clear how well they serve this purpose. This paper evaluates these frameworks, and develops and evaluates a new framework aimed at overcoming their limitations. METHODS A systematic search of electronic databases and consultation with behaviour change experts were used to identify frameworks of behaviour change interventions. These were evaluated according to three criteria: comprehensiveness, coherence, and a clear link to an overarching model of behaviour. A new framework was developed to meet these criteria. The reliability with which it could be applied was examined in two domains of behaviour change: tobacco control and obesity. RESULTS Nineteen frameworks were identified covering nine intervention functions and seven policy categories that could enable those interventions. None of the frameworks reviewed covered the full range of intervention functions or policies, and only a minority met the criteria of coherence or linkage to a model of behaviour. At the centre of a proposed new framework is a 'behaviour system' involving three essential conditions: capability, opportunity, and motivation (what we term the 'COM-B system'). This forms the hub of a 'behaviour change wheel' (BCW) around which are positioned the nine intervention functions aimed at addressing deficits in one or more of these conditions; around this are placed seven categories of policy that could enable those interventions to occur. The BCW was used reliably to characterise interventions within the English Department of Health's 2010 tobacco control strategy and the National Institute of Health and Clinical Excellence's guidance on reducing obesity. CONCLUSIONS Interventions and policies to change behaviour can be usefully characterised by means of a BCW comprising: a 'behaviour system' at the hub, encircled by intervention functions and then by policy categories. Research is needed to establish how far the BCW can lead to more efficient design of effective interventions.

Disclosure of APOE genotype for risk of Alzheimer's disease.

BACKGROUND The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. METHODS We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. RESULTS There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons). CONCLUSIONS The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

A review of psychosocial needs of breast-cancer patients and their relatives.

AIM To identify the psychosocial needs of breast-cancer patients and their relatives along with factors affecting these needs and to develop a tentative model to guide further research and need assessments in clinical practice. BACKGROUND Women experiencing breast cancer must deal with the diagnosis of a life-threatening illness. Treatment and the recovery process can be demanding for patients and their relatives. Need assessment may help clinicians focus on providing appropriate help. DESIGN Literature review. METHOD Undertaken using electronic databases and specific research terms; 20 articles were identified and analysed. RESULTS The needs identified by patients involve (1) treatment-related physical and social impairment like fatigue, menopausal symptoms and a changed body image and (2) emotional distress like fear of recurrence, anxiety and depression. Partners need help to protect themselves and the patient from different threats. Women need information to maintain control and manage their illness. Partners want information concerning the patient's condition and both of them about the prognosis and perspectives. There is a lack of knowledge of relatives' needs. Mutual familial support, women's and partners' health and emotional distress may affect the interaction between the patients and their partners. CONCLUSIONS A tentative family-based model to guide further research and clinical support is proposed. Further research is needed to determine precisely which psychosocial factors may influence fulfilment of the patients' and relatives' needs. RELEVANCE TO CLINICAL PRACTICE The proposed model may provide a framework for healthcare professionals to evaluate the patients' and relatives' met and unmet needs and the real demand for help, to guide care planning, counselling and education.

Preventing obesity in children and adolescents.

In this review, we address the natural history of obesity in children, the most promising family- and school-based approaches to the prevention of obesity, and the barriers and opportunities associated with secondary prevention. In childhood, the most important periods of risk appear to be the periods of adiposity rebound and adolescence. Caution regarding the period of adiposity rebound is still warranted, because it is not yet clear that early rebound is attributable to changes in body fat. Families and schools represent the most important foci for preventive efforts in children and adolescents. One productive approach is to proceed from an examination of factors that affect energy balance to the identification of more proximal influences on those factors. This approach may help to narrow the strategies necessary to prevent or treat childhood obesity. For example, television viewing affects both energy intake and energy expenditure, and therefore represents a logical target for interventions. Anticipatory guidance by pediatricians may offer an effective mechanism by which to change parental attitudes and practices regarding television viewing. A similar process is used to emphasize the potential influence of school-based interventions directed at changes in food choices and sedentary behavior.

Comorbidity between ADHD and obesity: exploring shared mechanisms and clinical implications.

Recent studies suggest an association between attention-deficit/hyperactivity disorder (ADHD) and obesity. In this article, we systematically review and critically discuss evidence on the prevalence of ADHD in obese patients as well as the weight status of individuals with ADHD. Relevant articles were searched in PubMed, PsychInfo, and ISI Web of Science (January 1980 to June 2010). We found that current evidence indicates a high prevalence of ADHD in clinical samples of patients seeking treatment for their obesity. Moreover, available studies show that individuals with ADHD have higher-than-average body mass index z scores and/or a significantly higher prevalence of obesity compared with subjects without ADHD. Three mechanisms underlying the association between ADHD and obesity have been proposed: 1) it is possible that obesity and/or factors associated with it (such as sleep-disordered breathing) manifest as ADHD-like symptoms; 2) ADHD and obesity share common biological dysfunctions; and 3) ADHD contributes to obesity. With regards to the possible clinical implications, our findings suggest that it is noteworthy to screen for ADHD in patients with obesity and to look for abnormal eating behaviors as possible contributing factors of obesity in patients with ADHD. Based on preliminary findings, appropriate treatment of ADHD may improve the weight status of individuals with both obesity and ADHD.

Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury.

The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups at 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score of less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.

Homelessness and health.

Homelessness affects tens of thousands of canadians and has important health implications. Homeless people are at increased risk of dying prematurely and suffer from a wide range of health problems, including seizures, chronic obstructive pulmonary disease, musculoskeletal disorders, tuberculosis, and skin and foot problems. Homeless people also face significant barriers that impair their access to health care. More research is needed to identify better ways to deliver care to this population.

Pleiotropic effects of statins.

Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

A diffusion tensor magnetic resonance imaging study of corpus callosum from adult patients with migraine complicated with depressive/anxious disorder.

OBJECTIVE The aim of this study was to investigate the possible microstructural abnormalities of the corpus callosum (CC) in adult patients with migraine without aura complicated with depressive/anxious disorder. BACKGROUND Emotional disorders, especially depression and anxiety, are with relatively higher incidence in migraine population. However, the mechanism of migraine complicated with depressive/anxious disorder remains unclear. METHODS Diffusion tensor magnetic resonance imaging was carried out in 12 adult patients with simple migraine (without aura and without depressive/anxious disorder) (S-M group), 12 adult patients with complicated migraine (without aura but complicated with depressive/anxious disorder) (Co-M group), and 12 age- and sex-matched healthy subjects (Control group). Fractional anisotropy (FA) and apparent diffusion coefficient were measured at genu, body, and splenium of the CC, respectively. RESULTS There were significant differences in FA values at all locations of the CC among the 3 groups. The FA values from both the SM and Co-M groups were significantly lower than the control (P < .05 and P < .01, respectively). The FA values from Co-M group were significantly lower than the SM group (P < .01). The apparent diffusion coefficient values of the above regions had no significant differences among these groups (P > .05). There were negative correlations between FA value of genu of the CC and disease course as well as FA value of genu and body of the CC and headache frequency (P < .05). Negative correlations were also found between FA values at all locations of the CC and Hamilton anxiety and Hamilton depression scores (both P < .05). CONCLUSIONS There might be an integrity change of neurofibrotic microstructures existing as a possible neuroanatomical basis in the CC of migraine patients complicated with depressive/anxious disorder.

MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.

Key features of diabetic nephropathy (DN) include the accumulation of extracellular matrix proteins such as collagen 1-alpha 1 and -2 (Col1a1 and -2). Transforming growth factor beta1 (TGF-beta), a key regulator of these extracellular matrix genes, is increased in mesangial cells (MC) in DN. By microarray profiling, we noted that TGF-beta increased Col1a2 mRNA in mouse MC (MMC) but also decreased mRNA levels of an E-box repressor, deltaEF1. TGF-beta treatment or short hairpin RNAs targeting deltaEF1 increased enhancer activity of upstream E-box elements in the Col1a2 gene. TGF-beta also decreased the expression of Smad-interacting protein 1 (SIP1), another E-box repressor similar to deltaEF1. Interestingly, we noted that SIP1 is a target of microRNA-192 (miR-192), a key miR highly expressed in the kidney. miR-192 levels also were increased by TGF-beta in MMC. TGF-beta treatment or transfection with miR-192 decreased endogenous SIP1 expression as well as reporter activity of a SIP1 3' UTR-containing luciferase construct in MMC. Conversely, a miR-192 inhibitor enhanced the luciferase activity, confirming SIP1 to be a miR-192 target. Furthermore, miR-192 synergized with deltaEF1 short hairpin RNAs to increase Col1a2 E-box-luc activity. Importantly, the in vivo relevance was noted by the observation that miR-192 levels were enhanced significantly in glomeruli isolated from streptozotocin-injected diabetic mice as well as diabetic db/db mice relative to corresponding nondiabetic controls, in parallel with increased TGF-beta and Col1a2 levels. These results uncover a role for miRs in the kidney and DN in controlling TGF-beta-induced Col1a2 expression by down-regulating E-box repressors.

Arteriolar function in visceral adipose tissue is impaired in human obesity.

OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.

Psychiatric comorbidity in chronic daily headache.

Clinical evidence suggests that chronic daily headache (CDH) occurs in association with psychopathologies: previous studies have focused particularly on migraine. To evaluate this association, we studied, using the DSM-IIIR criteria, a population of 88 patients (18M, 70F) affected by CDH (mean duration 7.4 +/- 8.7 years). We documented the presence of a psychiatric disorder in 90% of this population. The most frequent diagnosis was a comorbidity of anxiety and mood disorders. The comorbidity of psychiatric disorders and headache has important implications as far as treatment is concerned.

Pain catastrophizing and general health status in a large Dutch community sample.

The aim of the present study was to examine the association between pain catastrophizing and general health status in a Dutch adult community sample, including various subgroups of people with musculoskeletal pain in the analyses. For exploratory reasons this study partly replicated previous studies of the factor structure, reliability, and validity of the Pain Catastrophizing Scale (PCS). Results demonstrated that across different pain subgroups, catastrophizing uniquely contributed variance to the prediction of the various aspects of general health status beyond the variance explained by pain intensity, age, gender, and chronicity. Across subgroups strongest associations were found between catastrophizing and mental health, general health perception, social functioning, and vitality. Furthermore, the association between catastrophizing and the various aspects of general health status was not moderated by the chronicity of the pain. Results of the confirmatory factor analysis statistically confirmed a three-factor model of the PCS, which was invariant across different subgroups of people with musculoskeletal pain. Inter-factor correlations were high, and the incremental explanatory power of the three-factor model over that of a one-factor model was only marginal. This implies that a one-factor model might be justifiable as well, at least in the general community. Across various pain subgroups the reliability of the PCS total and subscales was adequate. Additional evidence for the concurrent validity of the PCS was found as well.

Vegetarian vs. conventional diabetic diet – A 1-year follow-up

Abstract Objective Our previous 6-month, randomized study demonstrated the beneficial effect of a vegetarian (V) compared to a conventional diet (C) with similar caloric restriction on cardiovascular risk factors for patients with type 2 diabetes (T2D), namely increased insulin sensitivity, reduced body weight, reduced volume of visceral and subcutaneous fat, decreased LDL-cholesterol and improved oxidative stress markers and chosen adipokines. We conducted post-trial monitoring to determine whether the improved outcomes persisted 1 year after the end of the study. Methods 62 subjects with T2D who completed the study were asked to come for a 1-year follow-up to measure weight, waist circumference, HbA1c and blood lipids. No attempts were made to maintain their previously assigned diets. Results 44 patients (71%) attended the post-trial monitoring. Hypoglycemic agents were increased by 14% in V and by 26% in C; insulin therapy was introduced in 5% in V and in 13% in C one year after the end of the intervention. Neither weight nor waist circumference changed significantly in either group. HbA1c increased ( p  ≤ 0.05) similarly in both groups (+0.49 ± 1.04% in V vs. +0.42 ± 0.8% in C). Blood lipids did not change in either group. Conclusion One year after the end of the intervention, the positive effects of a vegetarian diet on cardiovascular risk factors compared to a conventional diet were partially maintained.

Early gastric cancer and dysplasia.

Since the concept of early gastric cancer was first described in Japan in 1962, its treatment has evolved from curative surgical resection to endoscopic resection, initially with polypectomy to more recently with endoscopic submucosal dissection. As worldwide experience with these endoscopic techniques evolve and gain acceptance, studies have confirmed its comparable effectiveness with historical surgical outcomes in carefully selected patients. The criteria for endoscopic resection have expanded to offer more patients improved quality of life, avoiding the morbidity and mortality associated with surgery. This article summarizes the evolutional role of endoscopic and surgical therapy in early gastric cancer.

Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development.

Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.

Immune dysregulation in major depression: a critical review of existing evidence.

It is now well established that depression is associated with immune dysregulation. It is not, however, known whether this immune dysregulation plays a role in the pathophysiology of major depression or whether it increases the susceptibility of the depressed patient to immune-related disorders. This article presents a critical review of existing evidence for immune dysregulation in major depression, including changes in leucocyte trafficking, lymphocyte function, and markers of immune activation. Possible mediators of immune dysregulation in major depression are briefly discussed. Finally, the relationship between major depression and several medical conditions such as infection, allergy and autoimmune disorders, cardiovascular diseases, cancer and AIDS is critically reviewed.

Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia

OBJECTIVES To investigate the effects of a high-intensity functional exercise program on independence in activities of daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types. DESIGN Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study. SETTING Residential care facilities, Umeå, Sweden. PARTICIPANTS Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N=186). INTERVENTION Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity. MEASUREMENTS Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months. RESULTS Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=-1.6-4.3; BI=0.6, 95% CI=-0.2-1.4) or 7 (FIM=0.8, 95% CI=-2.2-3.8; BI=0.6, 95% CI=-0.3-1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8-6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months. CONCLUSION In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia.

Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.

Quality of life in patients with advanced heart failure.

Although evaluation of the treatment of congestive heart failure is usually based on objective clinical outcomes, patient self-assessment is increasingly recognized as an important component of evaluation. A study was designed to measure the quality of life of 134 patients with symptoms of advanced heart failure who were being evaluated for possible heart transplantation. The patients' quality of life was assessed using a mix of subjective and objective measures, including functional status, physical symptoms, emotional state, and psychosocial adaptation. There was no significant relationship between patients' cardiac ejection fraction and any quality-of-life measures; however, the results of a 6-minute walking test, New York Heart Association classification, and self-reported functional status were all significantly correlated with psychosocial adjustment. Self-reported functional status, depression, and hostility accounted for 43% of the variance in total psychosocial adjustment to illness. These findings support the inclusion of quality of life as an outcome measure in any evaluation of treatment efficacy and suggest that interventions to improve the quality of life of patients with advanced heart failure need to be targeted at reducing depression and hostility and increasing daily activity levels.