***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 Polyunsaturated fatty acid ( PUFA ) metabolism abnormalities have been long implicated in the etiology of schizophrenia . Although several r and omized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in population s of chronic patients with schizophrenia , only a few concern first-episode schizophrenia . The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid ( ethyl-EPA ) , however , with conflicting results . An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far . No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses . Methods A r and omized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention , composed of either 1320 mg/day of EPA and 880 mg/day of DHA , or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients . Eighty-two patients ( aged 16–35 ) will be recruited for the study . Eligible patients will be r and omly allocated to one of two intervention arms : an active arm or a placebo arm ( olive oil ) . The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale ( PANSS ) . Other outcomes include depressive symptoms , patient functioning and the level of insight . Correlates of change measured during the study will include structural brain changes , oxidative stress and defense , as well as neuroplasticity indicators . Metabolic syndrome components will also be assessed throughout the study . Discussion By comparing 26-week administration of EPA + DHA or ( placebo ) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia , it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change , and contribute to the improvement of mental health care for individuals suffering from schizophrenia . Trial registration This study has been registered at Clinical Trials.gov with the following number : NCT02210962 BACKGROUND Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients . Recently , we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients . We report now a concomitant increase in plasma lipid peroxides . METHODS The plasma lipid peroxides [ thiobarbituric acid reactive substances ( TBARS ) ] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic ( N = 17 ) or schizophreniform psychosis ( N = 9 ) and 16 normal control subjects . The patients had a duration of 4.5 days ( SD 2.8 ) of psychosis at the time of the study . RESULTS Plasma TBARS levels were significantly higher in the patients than in normal controls ( P < .002 ) . TBARS levels were above the normal range in 16 of the 26 patients .  Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase . CONCLUSIONS The findings indicate ongoing oxidative injury at the very onset of psychosis . If valid , this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses . This might prevent a deteriorating course and development of the deficit syndrome OBJECTIVE Diverse electrophysiological abnormalities have been associated with schizophrenia , but the underlying causes remain elusive . We tested whether the altered oxidative stress in schizophrenia contributes to the electrophysiological abnormalities . METHODS We used an auditory oddball task to measure  mismatch negativity ( MMN ) and gamma b and response on 29 schizophrenia patients and 25 normal controls . Oxidative stress was assessed by monomeric glutathione ( GSH , reduced form ) and glutathione disulfide ( GSSG , oxidized form ) . RESULTS Patients had reduced MMN ( p=0.015 ) and reduced power of gamma b and responses at 21 - 40 Hz and 41 - 85 Hz ( all p<0.001 ) . GSH was significantly lower ( p<0.001 ) while % GSSG was higher ( p=0.023 ) in patients compared with controls . MMN was correlated with GSH in controls ; while 21 - 40 Hz responses were correlated with GSH in patients . Lower GSH and higher GSSG levels were associated with low community functioning ( p=0.018 ) . Multivariate mediation modeling showed that gamma b and at 21 - 40 Hz was a significant mediator for GSH effect on community functions . CONCLUSIONS High beta/low gamma range ( 21 - 40 Hz ) responses may be an intermediate biomarker indexing oxidative stress and its effect on clinical functions . SIGNIFICANCE Electrophysiological abnormalities and associated clinical functional changes may in part be associated with heightened oxidative stress in schizophrenia AIM Mood disorders are associated with low levels of the long-chain omega-3 ( LCn-3 ) fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker . METHOD Erythrocyte fatty acid composition was determined in healthy adolescents ( n = 28 , HC ) , asymptomatic adolescents with a biological parent with bipolar I disorder ( n = 30 ; ' high risk ' , HR ) , adolescents with a biological parent with bipolar I disorder and major depressive disorder , or depressive disorder not otherwise specified ( n = 36 ; ' ultra-high risk ' , UHR ) , and first-episode adolescent bipolar manic patients ( n = 35 , BP ) . RESULTS Group differences were observed for DHA ( P ≤ 0.0001 ) and EPA ( P = 0.03 ) . Compared with HC , erythrocyte EPA + DHA ( ' omega-3 index ' ) was significantly lower in BP ( -24 % , P ≤ 0.0001 ) and UHR ( -19 % , P = 0.0006 ) groups , and there was a trend in the HR group ( -11 % , P = 0.06 ) . Compared with HC ( 61 % ) , a greater percentage of HR ( 77 % , P = 0.02 ) , UHR ( 80 % , P = 0.005 ) and BP ( 97 % , P = 0.001 ) subjects exhibited EPA + DHA levels of ≤4.0 % . Among all subjects ( n = 130 ) , EPA + DHA was inversely correlated with manic ( r = -0.29 , P = 0.0008 ) and depressive ( r = -0.28 , P = 0.003 ) symptom severity . The AA/EPA + DHA ratio was significantly greater in BP ( + 22 % , P = 0.0002 ) and UHR ( + 16 % , P = 0.001 ) groups . CONCLUSIONS Low EPA + DHA levels coincide with the initial onset of mania , and increasing risk for developing bipolar disorder is associated with grade d erythrocyte EPA + DHA deficits . Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospect i ve studies 
    Output:
    
A review of these studies revealed several potential metabolite signatures of schizophrenia including reduced levels of essential polyunsaturated fatty acids ( EPUFAs ) , vitamin E and creatinine ; and elevated levels of lipid peroxidation metabolites and glutamate .