***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: BACKGROUND Childhood trauma is associated with higher risk for mental disorders , including psychosis . Heightened sensitivity to social stress may be a mechanism . This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress , in interaction with psychosis liability and level of social stress exposure . METHOD Seventy-five individuals with higher psychosis liability ( 55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis ) and 95 individuals with lower psychosis liability ( 42 siblings and 53 controls ) were exposed to a virtual café in five experiments with 0 - 3 social stressors ( crowded , other ethnicity and hostility ) . Paranoid ideation was measured after each experiment . Subjective distress was self-rated before and after experiments . Multilevel r and om regression analyses were used to test main effects of childhood trauma and interaction effects . RESULTS Childhood trauma was more prevalent in individuals with higher psychosis liability , and was associated with higher level of ( sub clinical ) psychotic and affective symptoms . Individuals with a history of childhood trauma responded with more subjective distress to virtual social stress exposures . The effects of childhood trauma on paranoia and subjective distress were significantly stronger when the number of virtual environmental stressors increased . Higher psychosis liability increased the effect of childhood trauma on peak subjective distress and stress reactivity during experiments . CONCLUSIONS Childhood trauma is associated with heightened social stress sensitivity and may contribute to psychotic and affective dysregulation later in life , through a sensitized paranoid and stress response to social stressors The aim of this study was to look into the balance of pro-inflammatory ( TNF-α , IL-6 ) and anti-inflammatory ( TGF-β ) cytokines and their association with stress , alterations in HPA axis activity and the disease severity in acute psychosis . Socio-demographic and clinical details were collected from 41 in- patients with a diagnosis of Acute and Transient Psychotic Disorder .  Holmes and Rahe Stress Scale for stress in the preceding year , and Brief Psychiatric Rating Scale at baseline and follow up ( 4 - 12 weeks ) for psychopathology were applied .  IL-6 , TNF-α ( pro-inflammatory ) , TGF-β ( anti-inflammatory ) and Cortisol ( morning and afternoon values ) were measured at baseline and follow up . A total of 30 out of 41 cases recruited had follow up data available . The levels of IL-6 ( p<0.001 ) , TNF-α ( p<0.001 ) and TGF-β ( p<0.001 ) at baseline were all found to be significantly elevated compared to 42 age and gender matched healthy controls . There was a significant increase in the levels of TNF-α ( p=0.020 ) and morning levels of cortisol ( p=0.009 ) and a significant decrease in the levels of TGF-β ( p=0.004 ) and afternoon levels of cortisol ( p=0.043 ) from baseline to follow up . This study showed that there was an increased level of both pro and anti-inflammatory cytokines at baseline and a prolonged pro - inflammatory compared to anti - inflammatory response which warrants larger prospect i ve studies and comparative studies to patients with schizophrenia and bipolar disorders 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 IMPORTANCE Longitudinal studies have linked the systemic inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) with the risk of developing heart disease and diabetes mellitus , which are common comorbidities for depression and psychosis . Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression , first-episode psychosis , and acute psychotic relapse ; however , the direction of the association has been unclear . OBJECTIVE To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis  . DESIGN , SETTING , AND PARTICIPANTS The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospect i ve general population birth cohort study based in Avon County , Engl and . We have studied a sub sample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessment s.  MEASUREMENT OF EXPOSURE Levels of IL-6 and CRP were measured in nonfasting blood sample s obtained in participants at age 9 years . MAIN OUTCOMES AND MEASURES  Participants were assessed at age 18 years . Depression was measured using the Clinical Interview Schedule-Revised ( CIS-R ) and Mood and Feelings Question naire ( MFQ ) , thus allowing internal replication ; psychotic experiences ( PEs ) and psychotic disorder were measured by a semistructured interview . RESULTS After adjusting for sex , age , body mass index , ethnicity , social class , past psychological and behavioral problems , and maternal postpartum depression , participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed ( CIS-R ) at age 18 years ( adjusted odds ratio [ OR ] , 1.55 ; 95 % CI , 1.13 - 2.14 ) . Results using the MFQ were similar . Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline ( adjusted OR , 1.81 ; 95 % CI , 1.01 - 3.28 ; and adjusted OR , 2.40 ; 95 % CI , 0.88 - 6.22 , respectively ) . Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner . CONCLUSIONS AND RELEVANCE Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood . Inflammatory pathways may provide important new intervention and prevention targets for these disorders . Inflammation might explain the high comorbidity between heart disease , diabetes mellitus , depression , and schizophrenia Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia , suggesting defects in phospholipid metabolism and cell signaling in schizophrenia . The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids ( PUFAs ) were associated with an increased secretion of proinflammatory cytokines . Thus , we measured interleukin 6 ( IL-6 ) and interleukin 10 ( IL-10 ) in cerebrospinal fluid ( CSF ) of patients with chronic schizophrenia as well as PUFAs of red blood cell ( RBC ) membranes from the same individuals . A significant and inverse correlation was found between CSF IL-6 ( not IL-10 ) and RBC membrane PUFAs levels in both  haloperidol-treated and medication-free patients with schizophrenia . Specifically , such an association was found in the n-6 ( 18:2 , 20:4 , and 22:4 ) and , to a lesser extent , the n-3 fatty acids . Taken together , the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia , possibly result ing from an increased phospholipase A2 activity mediated through the proinflammatory cytokines An overactivation of the Th1 activity in schizophrenia had been described . Interleukin-12 ( IL-12 ) , a proinflammatory cytokine , plays a key role in the regulation of the Th1 response . The aims of this study were to investigate the effect of first and second generation antipsychotic drugs on IL-12 production during the acute phase of the illness and its association with clinical features . Participants comprised 56 drug-naïve first episode psychotic patients and 28 healthy volunteers . Patients were initially r and omly assigned to risperidone ( n=16 ) , olanzapine ( n=20 ) or haloperidol ( n=20 ) ; subject were maintained on the same medication throughout the study . Clinical assessment s were conducted at baseline and at 6 weeks . IL-12 plasma levels were assessed at baseline and after 6 weeks of antipsychotic treatment . IL-12 haplotypes were also analysed . Patients showed higher IL-12 plasma levels at baseline compared with controls , and had a significant increase in IL-12 plasma level after 6 weeks of antipsychotic treatment . No significant differences in IL-12 level increase were found among the three antipsychotic treatments . IL-12 plasma levels at week 6 were not significantly associated with the severity of psychopathology at week 6 . Thus , patients with a first episode of psychosis have inflammatory-like immunological function during early phases of the illness that it is independent of the antipsychotic treatment used An increasing body of evidence suggests a role for the immune system in the pathogenesis of schizophrenia . The information concerning the effects of antipsychotics on cytokine profiles are limited and often controversial in particular regarding novel antipsychotics . The authors first investigated the production of various cytokines [ interleukin (IL)-2 , IL-4 , IL-10 , interferon (INF)-gamma ] in drug-free ( n = 12 ) and drug-naive ( n = 3 ) schizophrenic patients and in healthy controls ( n = 33 ) and then the modifications of cytokines values during a 3-month period of treatment with risperidone . In the baseline condition , the production of IL-2 and INF-gamma was significantly higher ( P = .023 and .026 , respectively ) in patients than in controls . In the same patients , the use of risperidone was associated with augmented IL-10 ( a suppressor of Type I cytokines ) and decreased INF-gamma production . This modification suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in not currently treated schizophrenic patients BACKGROUND Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients . Thus far , the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor ( sIL-2R ) associated with clozapine treatment . Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine , but its immunomodulatory effects have not been investigated in schizophrenia yet . The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology . METHODS Participants were 29 schizophrenia-spectrum disorder patients ( DSM-IV criteria ) , and 28 healthy controls . Patients had a comorbid substance use disorder ( cannabis > alcohol > cocaine ) , since quetiapine is increasingly used in this population of dual diagnosis . No participant suffered from infection or overt inflammatory diseases . On baseline , patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial . Five patients were drop-outs . Mean dose of quetiapine for trial completers ( n=24 ) was 466.6mg±227.3 . Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calg 
    Output:
    
This systematic review confirms the existence of cytokines abnormalities in schizophrenia disease .
Immune imbalances such as increased levels of some cytokines ( either at protein level or at mRNA expression ) , cytokine mRNAs , as well as cytokine gene polymorphisms have been reported with a large support in schizophrenia .
These findings provide a strong evidence of a concomitant process of inflammatory activity in schizophrenia illness course