***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 This study aim ed to evaluate the efficacy and safety of N-acetylcysteine , a glutamate-modulating agent , in patients with treatment-refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake inhibitor treatment . METHODS Forty-eight patients ( 36 women ; mean ± SD age , 30.93 ± 4.99 ) with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment  were r and omized to a 12-week intervention period of N-acetylcysteine ( up to 2400 mg/d ) or placebo . Primary outcome measures were the change in Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) score from baseline to end point and the rate of full response in each group at the end of trial . Full response was defined as 35 % or greater reduction in Y-BOCS score from baseline . RESULTS Changes of Y-BOCS score were different over time ( P < 0.001 ) and between groups ( P < 0.001 ) . N-acetylcysteine-assigned patients showed significantly improved mean Y-BOCS score ( P = 0.003 ) and Clinical Global Impression-Severity of Illness scale score ( P = 0.01 ) but not Clinical Global Impression-Improvement scale score at study end point . Of the patients in the N-acetylcysteine group , 52.6 % were full responders at the end of the study , which was significantly higher than 15 % of the patients in the placebo group ( P = 0.013 ) . CONCLUSION This trial suggests that N-acetylcysteine may be a safe and effective option to augment st and ard treatment in patients with refractory obsessive-compulsive disorder Early life trauma ( ELT ) may increase the risk towards bipolar disorder ( BD ) and major depression ( MDD ) , disorders associated with activated neuro-oxidative and neuro-nitrosative stress ( O&NS ) pathways . It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with distinct affective disorder phenotypes . This case-control study examined patients with BD ( n = 68 ) and MDD ( n = 37 ) and healthy controls ( n = 66 ) . The Child Trauma Question naire ( CTQ ) was used to assess specific ELT . We measured malondialdehyde ( MDA ) , lipid hydroperoxides ( LOOH ) , superoxide dismutase ( SOD ) , catalase , advanced oxidation protein products ( AOPP ) ; NO metabolites ( NOx ) , paraoxonase 1 activity , zinc , albumin , high density lipoprotein cholesterol and -SH groups and computed z-unit weighted composite scores . Physical neglect significantly predicts higher z-unit weighted composite scores of LOOH+SOD , LOOH+SOD+NOx , LOOH+SOD+NOx + MDA and LOOH+SOD+NOx + AOPP . Sexual abuse was associated with a significantly lower composite score of zinc+albumin+SH . Emotional abuse was associated with severity of depression and anxiety , number of depressive and manic episodes , alcohol and hypnotics use , lifetime suicidal behavior and lowered quality of life . Sexual abuse was associated with an increased risk towards BD , but not MDD . ELT , especially physical neglect , may drive increased (nitro-)oxidative stress coupled with lipid and protein oxidation , which - together with emotional abuse - may play a role in severity of illness , lowered quality of life and MDD . ELTs are also associated with the onset of BD , but this link did not appear to be related to activated O&NS pathways . These novel findings deserve confirmation in prospect i ve studies Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections ( P AND AS ) originated from the observational work of Swedo and collaborators , who formalized their definition in 1998 in a set of operational criteria . The application of these criteria , which focuses on tics and obsessive-compulsive symptoms as core symptoms , has encountered difficulties , eventually leading to a high rate of misdiagnosis . In particular , the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies . Exploratory studies aim ing to identify clinical or cognitive features that could discriminate P AND AS from other pediatric obsessive-compulsive and tic disorders present method ological limitations , and therefore are not conclusive . Other behavioral features , in addition to obsessive-compulsive symptoms and tics , have been included in pediatric acute-onset neuropsychiatric syndromes ( PANS ) and childhood acute neuropsychiatric syndromes ( CANS ) , two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities . Given the uncertainties on the clinical definition of P AND AS , it is not surprising that evidence in support of a post-infectious , immune-mediated pathophysiology is also insufficient . Anti-dopamine receptor antibodies might be relevant to both Sydenham ’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder— and some rare forms of encephalitis targeting the basal ganglia specifically , but studies exploring their association with children fulfilling Swedo ’s criteria for P AND AS have been inconclusive . Moreover , we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy  in patients fulfilling Swedo ’s criteria for P AND AS , whereas a response to immune-mediated treatments like  intravenous immunoglobulins has been documented by one study , but needs replication in larger trials . Overall , the available evidence does not convincingly support the concept that P AND AS are a well-defined , isolated clinical entity subdued by definite pathophysiological mechanisms ; larger , prospect i ve studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC . Research is also under way to shed further light on a possible relationship between streptococcal infections , other biological and psychosocial stressors , and the complex pathobiology of chronic tic disorders Treatment with N-acetylcysteine ( NAC ) normalizes glutamate ( Glu ) homeostasis and prevents relapse in drug-dependent animals . However , the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated . Proton magnetic resonance spectroscopy ( 1H MRS ) was used to investigate Glu changes in the dorsal anterior cingulate cortex ( dACC ) after a single dose of NAC in cocaine-dependent patients and normal controls . In an open-label , r and omized , crossover study , 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions : one group receiving no compound and the other following a single administration of 2400 mg NAC . The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity . In the medication-free condition , Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls . After administration of NAC , Glu levels were reduced in the cocaine-dependent group , whereas NAC had no effect in healthy controls . Higher baseline Glu levels were associated with higher impulsivity , and both were predictive of greater NAC-induced Glu reduction . The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients . These findings may have important implication s for treatment , because abnormal Glu levels are related to relapse , and treatment with NAC prevented relapse in animal studies . Furthermore , clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients , and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established . N-acetyl cysteine ( NAC ) is a glutamate modulator with promising therapeutic effect . This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders . A further objective was to detail the methodology of current clinical trials being conducted in the area . Methods PubMed , Web of Science and Cochrane Library Data base were search ed for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder ( OCD ) or obsessive compulsive related disorders . Research ers with known involvement in NAC studies were contacted for any unpublished data . Results Four clinical trials and five case reports/series were identified . Study duration s were commonly 12-weeks , using 2,400–3,000 mg/day of NAC . Overall , NAC demonstrates activity in reducing the severity of symptoms , with a good tolerability profile and minimal adverse effects . Currently there are three ongoing r and omized controlled trials using NAC for OCD ( two adults and one pediatric ) , and one for excoriation . Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted . These results are detailed , in addition to a discussion of future potential research BACKGROUND Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders , including bipolar disorder . This dysregulation may be amenable to therapeutic intervention . Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain , and the most generic of all endogenous antioxidants in terms of action . N-acetylcysteine ( NAC ) is a glutathione precursor that effectively replenishes brain glutathione . Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy , and the limited efficacy of mood stabilisers in the depressive phase of the disorder , this is a major unmet need . METHOD This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a r and omised  placebo controlled clinical trial of the efficacy of 1 g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder . RESULTS In this trial , the estimated mean baseline Bipolar Depression Rating Scale ( BDRS ) score was 19.7 ( SE=0.8 ) , and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 ( SE=0.8 ) . This reduction was statistically significant ( p<0.001 ) . Improvements in functioning and quality of life were similarly evident . CONCLUSION These open label data demonstrate a robust decrement in depression scores with NAC treatment . Large placebo controlled trials of acute bipolar depression are warranted OBJECTIVE To examine whether  adverse perinatal experiences of  children  are associated with obsessive compulsive disorder ( OCD ) in youth . METHODS Subjects were 130 children and adolescents with OCD recruited from a family genetic study of pediatric OCD and 49 matched controls from a contemporaneous family case-control study of attention-deficit/hyperactivity disorder ( ADHD ) . Subjects were comprehensively assessed in multiple domains of function . A systematic history of pregnancy , delivery , and infancy complications was obtained . RESULTS Compared to normal controls , children with OCD had mothers with significantly higher rates of illness during pregnancy requiring medical care ( chi(2 ) + /- 8.61 , p + /- 0.003 ) and more birth difficulties ( induced labor , forceps delivery , nuchal cord , or prolonged labor ) ( chi(2 ) + /- 7.51 , p + /- 0.006 ) . Among the OCD-affected children , we found several significant associations between adverse perinatal experiences and earlier age at onset , increased OCD severity , and increased risk for comorbid ADHD , chronic tic disorder , anxiety disorder , and major depressive disorder . CONCLUSION Although exploratory , our analyses found that children with OCD had higher rates of several adverse perinatal experiences compared with controls . Among OCD-affected children , comorbid psychopathology was predicted by specific perinatal risk factors . Prospect i ve studies of perinatal adverse events that minimize potential recall bias and type I errors are needed BACKGROUND Although a large body of evidence indicates the efficacy of pharmacotherapy in the treatment of obsessive-compulsive disorder ( OCD ) , a considerable percentage of these patients do not respond . Very few studies focus on factors related to treatment response of OCD . The purpose of this study was to investigate which clinical factors are related to drug treatment response in OCD . METHOD We examined 53 OCD patients treated with either clomipramine or fluoxetine for a period of 6 months , dividing the sample into " responders " and " nonresponders " to treatment . At admission , patients were evaluated using a semistructured clinical interview , the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) , the Hamilton Rating Scale for Depression , and the Hamilton Rating Scale for Anxiety . We then compared acute-phase patient characteristics and response to drug treatment . Response was defined as a decrease of at least 40 % in the Y-BOCS total score and a rating of " improved " or " very improved " on the Clinical Global Impressions scale within 16 weeks of treatment and maintained over three consecutive evaluations . RESULTS By the sixth month of treatment , 31 patients ( 58.5 % ) responded to either clomipramine or fluox 
    Output:
    
We found that , in OCD patients , the oxidant markers 8-hydroxydeoxyguanosine and malondialdehyde , and the antioxidants glutathione peroxidase and superoxide dismutase , were significantly increased while total antioxidant status , vitamin C , and vitamin E were significantly decreased , when comparing with controls .
CONCLUSIONS Our meta- analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system .