***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Using longitudinal and prospect i ve measures of trauma during childhood , the authors assessed the risk of developing psychotic symptoms associated with maltreatment , bullying , and accidents in a nationally representative U.K. cohort of young twins . METHOD Data were from the Environmental Risk Longitudinal Twin Study , which follows 2,232 twin children and their families . Mothers were interviewed during home visits when children were ages 5 , 7 , 10 , and 12 on whether the children had experienced maltreatment by an adult , bullying by peers  , or involvement in an accident . At age 12 , children were asked about bullying experiences and psychotic symptoms . Children 's reports of psychotic symptoms were verified by clinicians . RESULTS Children who experienced mal-treatment by an adult ( relative risk=3.16 , 95 % CI=1.92 - 5.19 ) or bullying by peers ( relative risk=2.47 , 95 % CI=1.74 - 3.52 ) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events . The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood . The risk associated with childhood trauma remained significant in analyses controlling for children 's gender , socioeconomic deprivation , and IQ ; for children 's early symptoms of internalizing or externalizing problems ; and for children 's genetic liability to developing psychosis . In contrast , the risk associated with accidents was small ( relative risk=1.47 , 95 % CI=1.02 - 2.13 ) and inconsistent across ages . CONCLUSIONS Trauma characterized by intention to harm is associated with children 's reports of psychotic symptoms . Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying BACKGROUND Victims of bullying are at risk for psychotic experiences in early adolescence . It is unclear if this elevated risk extends into late adolescence . The aim of this study was to test whether bullying perpetration and victimization in elementary school predict psychotic experiences in late adolescence . METHOD The current study is based on the Avon Longitudinal Study of Parents and Children ( ALSPAC ) , a prospect i ve community-based study . A total of 4720 subjects with bullying perpetration and victimization were repeatedly assessed between the ages of 8 and 11 years by child and mother reports . Suspected or definite psychotic experiences were assessed with the Psychosis-Like Symptoms  semi-structured interview at age 18 years . RESULTS Controlling for child 's gender , intelligence quotient at age 8 years , childhood behavioural and emotional problems , and also depression symptoms and psychotic experiences in early adolescence , victims [ child report at 10 years : odds ratio ( OR ) 2.4 , 95 % confidence interval ( CI ) 1.6 - 3.4 ; mother report : OR 1.6 , 95 % CI 1.1 - 2.3 ] , bully/victims ( child report at 10 years : OR 3.1 , 95 % CI 1.7 - 5.8 ; mother : OR 2.9 , 95 % CI 1.7 - 5.0 ) and bullies ( child report at 10 years : OR 4.9 , 95 % CI 1.3 - 17.7 ; mother : OR 1.2 , 95 % CI 0.46 - 3.1 , n.s . ) had a higher prevalence of psychotic experiences at age 18 years . Path analysis revealed that the association between peer victimization in childhood and psychotic experiences at age 18 years was only partially mediated by psychotic or depression symptoms in early adolescence . CONCLUSIONS Involvement in bullying , whether as victim , bully/victim or bully , may increase the risk of developing psychotic experiences in adolescence . Health professionals should ask routinely during consultations with children about their bullying of and by peers Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase ( COMT Val158Met ) gene moderate the psychosis-inducing effect of cannabis . To replicate and extend this finding , a double-blind , placebo-controlled cross-over design was used in which patients with a psychotic disorder ( n=30 ) , relatives of patients with a psychotic disorder ( n=12 ) , and healthy controls ( n=32 ) were exposed to Δ-9-tetrahydrocannabinol ( Δ-9-THC , the principal component of cannabis ) or placebo , followed by cognitive assessment and assessment of current psychotic experiences . Previous expression of psychometric psychosis liability was also assessed . Models of current psychotic experiences and cognition were examined with multilevel r and om regression analyses to assess ( i ) main effects of genotype and condition , ( ii ) interactions between condition and genotype , and ( iii ) three-way interactions between condition , genotype , and psychometric psychosis liability . Carriers of the Val allele were most sensitive to Δ-9-THC-induced psychotic experiences , but this was conditional on prior evidence of psychometric psychosis liability . Δ-9-THC impacted negatively on cognitive measures . Carriers of the Val allele were also more sensitive to Δ-9-THC-induced memory and attention impairments compared to carriers of the Met allele . Experimental effects of Δ-9-THC on cognition and psychosis are moderated by COMT Val158Met genotype , but the effects may in part be conditional on the additional presence of pre-existing psychosis liability . The association between cannabis and psychosis may represent higher order gene – environment and gene – gene interactions Positive and negative schizotypy exhibit differential patterns of impairment in social relations , affect , and functioning in daily life . However , studies have not examined the association of schizotypy with real-world expression of psychotic-like , paranoid , and negative symptoms . The present study employed experience-sampling methodology ( ESM ) to assess positive and negative schizotypy in daily life in a non clinical sample of 206 Spanish young adults . Participants were prompted r and omly 8 times daily for 1 week to complete assessment s of their current symptoms and experiences . Positive schizotypy was associated with psychotic-like and paranoid symptoms in daily life . Negative schizotypy was associated with a subset of these symptoms and with negative symptoms in daily life . Momentary stress was associated with psychotic-like and paranoid symptoms , but only for those high in positive schizotypy . Social stress predicted momentary psychotic-like symptoms in both positive and negative schizotypy . Time-lagged analyses indicated that stress at the preceding signal predicted psychotic-like symptoms at the current assessment , but only for individuals high in positive schizotypy . The results are consistent with models linking stress sensitivity with the experience of psychotic symptoms . The findings provide cross-cultural support for the multidimensional model of schizotypy and schizophrenia . Furthermore , the findings demonstrate that ESM is an effective method for predicting the experience of psychotic-like symptoms , as well as their precursors , in daily life OBJECTIVE Many studies have implicated prenatal infection in the etiology of schizophrenia . Cytokines , a family of soluble polypeptides , are critically important in the immune response to infection and in other inflammatory processes . The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 ( IL-8 ) , interleukin-1beta ( IL-1beta ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects . METHOD The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort , born 1959 - 1967 . Cases ( N=59 ) were subjects diagnosed with schizophrenia spectrum disorders ( mostly schizophrenia and schizoaffective disorder ) who had available second-trimester maternal serum sample s. Comparison subjects ( N=105 ) were members of the birth cohort , had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder , and were matched to subjects with schizophrenia for date of birth , gender , length of time in the cohort , and availability of maternal sera . Maternal second-trimester serum levels of IL-8 , IL-1beta , IL-6 , and TNF-alpha were determined by s and wich enzyme-linked immunosorbent assay . RESULTS The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects . There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta , IL-6 , or TNF-alpha . CONCLUSIONS Using prospect ively collected prenatal sera in a large and well-characterized birth cohort , the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring . These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia . Moreover , these results may have important implication s for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies ( DIGS ) , a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions . The DIGS , which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health ( NIMH ) Genetics Initiative , has the following additional features : ( 1 ) polydiagnostic capacity ; ( 2 ) a detailed assessment of the course of the illness , chronology of psychotic and mood syndromes , and comorbidity ; ( 3 ) additional phenomenologic assessment s of symptoms ; and ( 4 ) algorithmic scoring capability . The DIGS is design ed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings . A two-phase test-retest ( within-site , between-site ) reliability study was carried out for DSM-III-R criteria -based major depression , bipolar disorder , schizophrenia , and schizoaffective disorder .  Reliabilities using algorithms were excellent ( 0.73 to 0.95 ) , except for schizoaffective disorder , for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability . A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions . The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders , schizophrenia , and related conditions Aim The present study employed Experience Sampling Methodology to examine whether the interaction between  childhood bullying  and FKBP5 variability ( i ) is associated with the expression of psychotic-like experiences , paranoia , and negative affect , and ( ii ) moderates psychotic-like , paranoid , and affective reactivity to different forms of momentary stress ( situational and social ) in daily life . Methods A total of 206 non clinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted r and omly eight times daily for one week to complete assessment s of their current experiences , affect , and stress appraisal s. Participants were genotyped for three FKBP5 single nucleotide polymorphisms ( SNPs ) ( rs3800373 , rs9296158 , and rs1360780 ) that have been linked to hypothalamus-pituitary-adrenal axis reactivity . Multilevel analyses were conducted to examine the effect of the interaction between childhood bullying and the FKBP5 haplotype derived from these three SNPs . Results The interaction between bullying and the FKBP5 haplotype was associated with positive , but not negative , psychotic-like experiences , paranoia , and negative affect . The bullying x FKBP5 interaction also moderated the association of a social stress appraisal ( specifically , being alone because people do not want to be with you ) with psychotic-like experiences and negative affect in daily life . Simple slopes analyses indicated that , in all cases , the associations were significantly increased by exposure to bullying in participants with the risk haplotype , but not for those with the non-risk haplotype . Discussion The present study provides the first evidence of the interplay between childhood bullying and FKBP5 variability in the real-world expression of psychosis proneness and social stress reactivity . The findings underscore the importance of investigating how gene-environment interactions are involved in mechanistic pathways to the extended psychosis phenotype and lend further support to the increasing relevance given to socially defeating appraisal s in the experience of reality distortion The Clinical Global Impressions Scale ( CGI ) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder . Criticisms of the original CGI were addressed by correcting inconsistencies in scaling , identifying time frames for comparison , clarifying definitions of illness severity and change , and separating out assessment of treatment side effects from illness improvement during treatment . A Detailed User 's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version ( CGI-BP ) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness . The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania , depression , and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis . Interrater reliability of the scale was demonstrated 
    Output:
    
Almost consistently , these studies revealed that polymorphisms in COMT , BDNF , and FKBP5 genes might interact with early life stress and cannabis abuse or dependence , influencing various outcomes of schizophrenia spectrum disorders and BD .