Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia Oxidative–antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: Effects of short term antipsychotic treatment Cognitive effects of adjunctive N-acetyl cysteine in psychosis. AZD8529, a positive allosteric modulator at the mGluR2 receptor, does not improve symptoms in schizophrenia: A proof of principle study The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers. Cognition, functioning and quality of life in schizophrenia treatment: Results of a one-year randomized controlled trial of olanzapine and quetiapine Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study Raloxifene as an Adjunctive Treatment for Postmenopausal Women With Schizophrenia: A 24-Week Double-Blind, Randomized, Parallel, Placebo-Controlled Trial. Adjunctive Pregnenolone Ameliorates the Cognitive Deficits in Recent-Onset Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Effect of therapeutic hypothermia on oxidative stress and outcome in term neonates with perinatal asphyxia: a randomized controlled trial. Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial Adjunctive Intranasal Oxytocin Reduces Symptoms in Schizophrenia Patients Coronary Heart Disease in Smokers: Vitamin C Restores Coronary Microcirculatory Function Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: Results from a randomized double blind placebo controlled pilot study Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people. Adjunctive Lisdexamfetamine Dimesylate Therapy in Adult Outpatients With Predominant Negative Symptoms of Schizophrenia: Open-Label and Randomized-Withdrawal Phases
Rationale Several investigators implicated role of free radical-mediated pathology in schizophrenia . No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia . Objective The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde ( MDA ) , plasma ascorbic acid levels , and brief psychiatric rating scale ( BPRS ) score in schizophrenic patients . Method Forty schizophrenic patients participated in a prospect i ve , double-blind , placebo-controlled , noncrossover , 8-week study . The patients with schizophrenia were divided r and omly into placebo and vitamin C group of 20 each . Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye , respectively . Result Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients . These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics .  BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo . Conclusion Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels , reduces oxidative stress , and improves BPRS score , hence both the drugs in combination can be used in the treatment of schizophrenia Oxidative stress may be a contributing factor in the etiopathophysiology of schizophrenia , which may be exacerbated by the treatment with antipsychotics with pro-oxidant properties . Increased levels of S100 B are associated with neurodegenerative disorders , including schizophrenia . The aim of the present study was to investigate the role of oxidative cell damage in the pathogenesis of schizophrenia . Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study .  Serum S100 B level was determined to investigate brain damage . Plasma malondialdehyde ( MDA ) levels and susceptibility of red blood cell ( RBC ) to oxidation were determined to investigate the oxidative status and plasma vitamin E , vitamin C , serum total carotenoid levels and total antioxidant capacity and RBC superoxide dismutase ( SOD ) and whole blood glutathione peroxidase activities were measured to investigate the antioxidative defence before and after 6 weeks of antipsychotic treatment .  Plasma MDA and serum S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia group than those of the control group . Treatment did not modify any of the oxidative-antioxidative system parameters or serum S100 B levels . S100 B level was significantly higher in patients with negative symptoms than the patients with positive symptoms and the control subjects . S100 B levels were significantly reduced after 6 weeks of treatment in patients with negative symptoms . The results of the present study might support the oxidative cell injury hypothesis of the schizophrenia . Furthermore , the underlying mechanisms of the subgroups of schizophrenia might be different as suggested by the increased S100 B levels and its decrement after treatment in patients with negative symptoms BACKGROUND Cognitive deficits are predictors of functional outcome in patients with psychosis . While conventional antipsychotics are relatively effective on positive symptoms , their impact on negative and cognitive symptoms is limited . Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis . N-acetylcysteine ( NAC ) , a glutathione precursor with glutamatergic properties , has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder , respectively . However , there are few evidence -based approaches for managing cognitive impairment in psychosis . The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder . METHOD A sample of 58 participants were r and omized in a double fashion to receive 2 g/day of NAC ( n = 27 ) or placebo ( n = 31 ) for 24 weeks . Attention , working memory and executive function domains were assessed . Differences between cognitive performance at baseline and end point were examined using Wilcoxon 's test . The Mann-Whitney test was used to examine the differences between the NAC and placebo groups at the end point . RESULTS Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo ( U = 98.5 , p = 0.027 ) . CONCLUSIONS NAC may have an impact on cognitive performance in psychosis , as a significant improvement in working memory was observed in the NAC-treated group compared with placebo ; however , these preliminary data require replication . Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis INTRODUCTION Activation of metabotropic glutamate ( mGluR2/3 ) receptors has been proposed as an alternative mechanism to dopaminergic-based antipsychotics to correct glutamatergic deficits hypothesized to underlie schizophrenia symptoms . This study investigates the efficacy and safety of AZD8529 , a selective positive allosteric modulator ( PAM ) at the mGlu2 receptor , in symptomatic patients with schizophrenia . METHODS Patients were r and omized to receive AZD8529 40 mg , risperidone 4  mg , or placebo as monotherapy . Treatment lasted for 28 days , and clinical efficacy was assessed using Positive and Negative Syndrome Scale ( PANSS ) and Clinical Global Impression ( CGI ) scores . RESULTS There were no significant differences between patients treated with AZD8529 versus placebo in change from baseline to endpoint in PANSS total , negative and positive symptom subscale , or CGI-S scores . In contrast , risperidone demonstrated significant efficacy relative to placebo . CONCLUSION These results do not support a role for the mGluR-2 PAM AZD8529 as an antipsychotic and indicate that positive modulation of mGluR type 2 receptors alone is not sufficient for antipsychotic effects in acutely ill schizophrenia patients Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain . Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia . Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia . Thus we decided to assess the impact of combining omega-3 fatty acids , vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol .  Ongoing  haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids ( 180 mg EPA+120 mg DHA ) bid , vitamin E 400 IU bid and vitamin C 1000 mg/day . Patients were assessed with Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Negative Symptoms ( SANS ) , Simpson Angus Scale ( SAS ) and Barnes Akathisia Rating Scale ( BARS ) over a 4 month period . Gluthatione peroxidase , superoxide dismutase , malondialdehyde , vitamin E and C levels were also evaluated at baseline and at the end of study . BPRS , SANS , SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline . Superoxide dismutase level was significantly lower at the end of study . No significant differences were detected in other laboratory parameters . Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol . The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies BACKGROUND Recent research on schizophrenia indicates that cognitive deficits in this illness are important predictors of functional outcome , highlighting the need for treatments that have a positive impact on cognitive function . Here we explore the hypothesis that acute administration of d-amphetamine can improve cognitive function in individuals with schizophrenia who are well-treated with typical antipsychotics , as well as in healthy controls performing under dual task conditions design ed to elicit performance deficits analogous to those found in schizophrenia . METHODS Ten individuals with schizophrenia taking haldol or prolixin and 22 healthy controls performed spatial working memory , language production , and Stroop tasks under both placebo and 0.25 mg/kg of D-amphetamine . RESULTS D-Amphetamine improved reactions times on the spatial working memory and Stroop tasks for both individuals with schizophrenia and controls , and improved working memory accuracy in schizophrenia . In addition , D-amphetamine improved language production for both individuals with schizophrenia and controls . CONCLUSIONS These results provide support for the hypothesis that the adjunctive administration of dopamine agonist can improve cognitive in individuals with schizophrenia taking typical antipsychotics . The results are discussed in terms of their implication s for underst and ing the nature of working memory deficits in schizophrenia , and potential future avenues for cognitive enhancement in this illness BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia : negative symptoms and cognitive deficits .  Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders . Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia . These findings may be linked to the effect of minocycline on the glutamatergic system , through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity . Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation . OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia . METHOD A longitudinal double-blind , r and omized , placebo-controlled design was used , and patients were followed for 6 months from August 2003 to March 2007 . Seventy early-phase schizophrenia patients ( according to DSM-IV ) were recruited and 54 were r and omly allocated in a 2:1 ratio to minocycline 200 mg/d  . All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry ( risperidone , olanzapine , quetiapine , or clozapine ; 200 - 600 mg/d  chlorpromazine-equivalent  doses ) . Clinical , cognitive , and functional assessment s were conducted , with the Scale for the Assessment of Negative Symptoms ( SANS ) as the primary outcome measure . RESULTS Minocycline was well tolerated , with few adverse events . It showed a beneficial effect on negative symptoms and general outcome ( evident in SANS , Clinical Global Impressions scale ) . A similar pattern was found for cognitive functioning , mainly in executive functions ( working memory , cognitive shifting , and cognitive planning ) . CONCLUSIONS Minocycline treatment was associated with improvement in negative symptoms and executive functioning , both related to frontal-lobe activity . Overall , the findings support the beneficial effect of minocycline add-on therapy in early-phase schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00733057 Background The Mental Health Biomarker Project ( 2010–2014 ) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance . Within a case – control discovery design with exclusion criteria design ed to produce a highly characterised sample , results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital , clinic and community catchment area . Participants underwent protocol -based diagnostic-checking , functional-rating , biological sample - collection for thirty c and i date markers and sensory-processing assessment . Results Fifteen biomarkers were identified on ROC analysis . Using these biomarkers , odds ratios , adjusted for a case – control design , indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder , delayed visual processing , low visual span , delayed auditory speed of processing , low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines . Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress , vitamin D , B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio . When individual biomarkers were ranked by odds ratio and correlated with clinical severity , five functional domains of visual processing , auditory processing , oxidative stress , catecholamines and nutritional-biochemical variables were formed . When the strengths of their inter-domain relationships were predicted by Lowess ( non-parametric ) regression , predominant bidirectional relationships were found between visual processing and catecholamine domains . At a cellular level , the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains . Conclusions The findings of this biomarker research point towards a much-required advance in Psychiatry : quantification of some theoretically-underst and able , translationally-informative , treatment-relevant underpinnings of serious mental illness . This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner , as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical setting s. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance , relapse-prevention , cost burden and social stigma in these conditions . If replicated and vali date d in prospect i ve trials , such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder BACKGROUND Fruit and vegetables contain both nutritive and nonnutritive factors that might contribute to redox ( antioxidant and prooxidant ) actions . OBJECTIVE We investigated the relative influence of nutritive and nonnutritive factors in fruit and vegetables on oxidative damage and enzymatic defense . DESIGN A 25-d intervention study with complete control of dietary intake was performed in 43 healthy male and female nonsmokers who were r and omly assigned to 1 of 3 groups . In addition to a basic diet devoid of fruit and vegetables , the fruit and vegetables ( Fruveg ) group received 600 g fruit and vegetables/d ; the placebo group received a placebo pill , and the supplement group received a vitamin pill design ed to contain vitamins and minerals corresponding to those in 600 g fruit and vegetables . Biomarkers of oxidative damage to protein and lipids and of antioxidant nutrients and defense enzymes were determined before and during intervention . RESULTS Plasma lipid oxidation lag times increased during intervention in the Fruveg and supplement groups , and the increase was significantly higher in the former . Plasma protein carbonyl formation at lysine residues also increased in both of these groups . Glutathione peroxidase activity increased in the Fruveg group only . Other markers of oxidative damage , oxidative capacity , or antioxidant defense were largely unaffected by the intervention . CONCLUSIONS Fruit and vegetables increase erythrocyte glutathione peroxidase activity and resistance of plasma lipoproteins to oxidation more efficiently than do the vitamins and minerals that fruit and vegetables are known to contain . Plasma protein carbonyl formation at lysine residues increases because of the vitamins and minerals in fruit and vegetables BACKGROUND Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia ; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure . OBJECTIVES The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia . METHODS In a prospect i ve , rater-blinded study , 86 participants were r and omized to receive either olanzapine or quetiapine , and assessed at baseline and after 3 , 6 , 9 and 12 months . Outcome measures included , besides symptoms and side effects rating scales , the subjective scale to investigate cognition in schizophrenia ( SSTICS ) , a computer-assisted cognitive test battery ( COGLAB ) , the sickness impact profile ( SIP ) , the global assessment of functioning ( GAF ) scale , and the drug attitude inventory ( DAI ) . RESULTS Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects . Quetiapine was significantly better tolerated ( p=0.002 ) , improved self-rated cognitive dysfunction ( p=0.002 ) and subjects ' performance on selected neurocognitive tasks ( p=0.01 ) . Olanzapine use was associated with greater symptom stability , fewer drop outs ( p=0.01 ) and frequent metabolic aberrations ( p=0.001 ) . The accrued benefits of drug therapy , however , were not reflected as significant gains in daily functioning and quality of life . CONCLUSIONS Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration . The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to , and fast dissociation from the dopamine receptors . Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities OBJECTIVE Selective serotonin reuptake inhibitor ( SSRI ) medication does not appear to be effective in ill , malnourished anorexia nervosa ( AN ) patients . However , it may be effective in preventing relapse after weight restoration . The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects . METHOD Twenty-six subjects with AN participated in a trial of fluoxetine . In a double-blind , placebo-controlled manner , subjects received either nutritional supplements or a nutritional placebo . The nutritional supplement included tryptophan ( the precursor of serotonin ) , vitamins , minerals , and essential fatty acids believed to influence serotonin pathway function . RESULTS There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo . Moreover , there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms . DISCUSSION The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects Objectives Despite the burden of negative symptoms on quality of life in schizophrenic patients , no completely effective treatment has been developed to address such symptoms yet . Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia , and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia . N-Acetylcysteine ( NAC ) is a potent antioxidant with neuroprotective properties . This study aim ed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia . Material s and Methods In this r and omized , double-blind , placebo-controlled , parallel-group study , 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale ( PANSS ) were enrolled in the active phase of their illness . The participants were equally r and omized to receive NAC ( up to 2 g/d ) or placebo , in addition to risperidone ( up to 6 mg/d ) for 8 weeks . The participants were rated using PANSS every 2 weeks , and the decrease of PANSS negative subscale score was considered as our primary outcome . Results By the study end point , NAC-treated patients showed significantly greater improvement in the PANSS total ( P = 0.006 ) and negative subscale ( P < 0.001 ) scores than that in the placebo group , but this difference was not significant for positive and general psychopathology subscales . There was no significant difference between the 2 groups in the frequency of adverse effects .  Conclusions NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia UNLABELLED The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized . Raloxifene , a selective estrogen receptor modulator , appears to act similarly to estrogens on dopamine and serotonin brain systems . One previous trial by our team found that raloxifene was useful to improve negative , positive , and general psychopathological symptoms , without having the negative side effects of estrogens . In this study , we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms . This was a 24-week , r and omized , parallel , double-blind , placebo-controlled study . Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu , Hospital Universitari Institut Pere Mata , and Corporació Sanitària Parc Taulí . Seventy postmenopausal women with schizophrenia ( DSM-IV ) were r and omized to either adjunctive raloxifene ( 38 women ) or adjunctive placebo ( 32 women ) . Psychopathological symptoms were assessed at baseline and at weeks 4 , 12 , and 24 with the Positive and Negative Syndrome Scale ( PANSS ) and the Scale for the Assessment of Negative Symptoms ( SANS ) . The addition of raloxifene ( 60 mg/d ) to regular antipsychotic treatment significantly reduced negative ( P = .027 ) , general ( P = .003 ) , and total symptomatology ( P = .005 ) measured with the PANSS during the 24-week trial , as compared to women receiving placebo . Also Alogia SANSS subscale improved more in the raloxifene ( P = .048 ) than the placebo group . In conclusion , raloxifene  improved negative and general psychopathological symptoms , compared with antipsychotic medication alone , in postmenopausal women with schizophrenia . These data replicate our previous results with a larger sample and a longer follow-up . TRIAL REGISTRATION NCT01573637 PURPOSE This study aim ed to examine the effect of add-on treatment with the neurosteroid pregnenolone ( PREG ) on neurocognitive dysfunctions of patients with recent-onset schizophrenia ( SZ ) and schizoaffective disorder ( SA ) . METHOD Sixty out- and in patients that met DSM-IV criteria for SZ/SA were r and omized to an 8-week , double-blind , r and omized , placebo-controlled , 2-center trial . Participants received either pregnenolone ( 50 mg/d ) or placebo added on to antipsychotic medications .  Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment . ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time . RESULTS Compared to placebo , adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task ( p=0.002 ) , with moderate effect sizes ( d=0.42 ) . In addition , a significant improvement was observed from baseline to end-of- study with respect to the visual ( p=0.008 ) and sustained attention ( Rapid Visual Information Processing , p=0.038 ) deficits , and executive functions ( Stockings of Cambridge , p=0.049 ; Spatial Working Memory , p<0.001 ) among patients receiving PREG but not among those receiving placebo ( all p's>0.05 ) . This beneficial effect of PREG was independent of the type of antipsychotic agents , gender , age , education , and illness duration . CONCLUSIONS Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA . Long-term , large-scale studies are required to obtain greater statistical significance and more confident clinical generalization OBJECTIVES To evaluate in term babies with perinatal asphyxia , the effect of therapeutic hypothermia ( TH ) on oxidative stress and neurological outcome at discharge . METHODS Babies who satisfied inclusion criteria were r and omized to TH  , with cooling gel packs to a target temperature of 33 - 34 ° C for 72 h or normothermia . Blood sample was collected before and after TH for oxidative stress assessment : total antioxidant status ( TAS ) and malondialdehyde ( MDA ) . RESULTS Of 116 babies r and omized , there was no statistically significant difference in the baseline TAS and MDA . After 72 h of TH , TAS was significantly higher ( p = < 0.001 ) ( 761.69 ± 114.01 vs. 684.16 ± 88.86 ) and MDA was significantly lower ( p = < 0.001 ) in TH group ( 1.73 ± 0.66 vs. 5.2 ± 1.06 ) . Risk of developing deficit was lower ( p < 0.001 ) in TH group with relative risk of 0.49 and 95 % confidence interval : 0.29 - 0.68 . CONCLUSION TH reduces oxidative stress and improves neurological outcome in perinatal asphyxia . TRIAL REGISTRATION NUMBER CTRI/2011/12/002196 Background —Hyperlipidemia is associated with endothelial dysfunction , an early event in atherosclerosis and predictor of risk for future coronary artery disease . Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease . The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children . Methods and Results —In a r and omized , double-blind , placebo-controlled trial , the effects of antioxidant vitamins C ( 500 mg/d ) and E ( 400 IU/d ) for 6 weeks and the National Cholesterol Education Program Step II ( NCEP-II ) diet for 6 months on endothelium-dependent flow-mediated dilation ( FMD ) of the brachial artery were examined in 15 children with familial hypercholesterolemia ( FH ) or the phenotype of familial combined hyperlipidemia ( FCH ) .  Antioxidant vitamin therapy  improved FMD of the brachial artery compared with baseline ( P < 0.001 ) without an effect on biomarkers for oxidative stress ( autoantibodies to epitopes of oxidized LDL , F2-isoprostanes , 8-hydroxy-2′-deoxyguanosine ) , inflammation ( C-reactive protein ) , or levels of asymmetric dimethylarginine , an endogenous inhibitor of nitric oxide . Conclusions —Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children . Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis BACKGROUND Both human and animal studies suggest oxytocin may have antipsychotic properties . Therefore , we conducted a clinical trial to directly test this notion . METHODS Nineteen schizophrenia patients with residual symptoms despite being on a stable dose of at least one antipsychotic were enrolled in a r and omized , double-blind , crossover study . They received 3 weeks of daily intranasal oxytocin ( titrated to 40 IU twice a day ) and placebo adjunctive to their antipsychotics . Order of intranasal treatment was r and omly assigned and there was a 1-week washout between treatments . RESULTS Analysis of the 15 subjects who completed all the study visits revealed that oxytocin significantly reduced scores on the Positive and Negative Symptom Scale ( p < .001 ) and Clinical Global Impression-Improvement Scale ( p < .001 ) compared with placebo at the 3-week end point . No benefit was seen at the early time points . Oxytocin was well tolerated and produced no adverse effects based upon patient reports or laboratory analysis . CONCLUSIONS The results support the hypothesis that oxytocin has antipsychotic properties and is well tolerated . Higher doses and longer duration of treatment may produce larger benefits and should be evaluated in future studies Background Coronary endothelial function and vasomotion are impaired in smokers without coronary disease , and this is thought to be due to increased oxidative stress . Methods and Results We used positron emission tomography to measure the coronary flow reserve , an integrated measure of coronary flow , through both the large epicardial coronary arteries and the microcirculation in 11 smokers and 8 control subjects before and after administration of the antioxidant vitamin C. At baseline , coronary flow reserve was reduced by 21 % in smokers compared with control subjects ( P < 0.05 ) but was normalized after vitamin C , whereas the drug had no effect in control subjects . Conclusions The present study is the first to demonstrate that the noxious prooxidant effects of smoking extend beyond the epicardial arteries to the coronary microcirculation and affect the regulation of myocardial blood flow .  Vitamin C restores coronary microcirculatory responsiveness and impaired coronary flow reserve in smokers , which provides evidence that the damaging effect of smoking is at least in part accounted for by an increased oxidative stress BACKGROUND Although increased mortality is one of the most consistent and accepted epidemiological findings in schizophrenia , a high rate of suicide appears unable to account fully for this burden which remains poorly understood . METHOD A cohort of 88 in- patients was followed prospect ively over a 10-year period and predictors of survival sought among demographic , clinical and treatment variables . RESULTS Over the decade , 39 of the 88 patients ( 44 % ) died , with no instances of suicide . Reduced survival was predicted by increasing age , male gender , edentulousness and time since pre-terminal withdrawal of antipsychotics ; additionally , two indices of polypharmacy predicted reduced survival : maximum number of antipsychotics given concurrently ( relative risk 2.46 , 95 % CI 1.10 - 5.47 ; P = 0.03 ) and absence of co-treatment with an anticholinergic ( relative risk 3.33 , 95 % CI 0.99 - 11.11 ; P = 0.05 ) . CONCLUSIONS Receiving more than one antipsychotic concurrently was associated with reduced survival , in the face of little or no systematic evidence to justify the widespread use of antipsychotic polypharmacy . Conversely , over-cautious attitudes to the use of adjunctive anticholinergics may require re-evaluation OBJECTIVE This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia . METHOD Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) project . In phase 1 , patients were r and omly assigned to receive olanzapine , perphenazine , quetiapine , risperidone , or ziprasidone for up to 18 months . Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy ; all other patients received another second-generation antipsychotic .  Psychosocial functioning was assessed using the Quality of Life Scale . RESULTS Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months ( average effect size 0.19 SD units ) . Although for several of the drugs individually there were significant changes from baseline , overall there were no significant differences between the different agents . Results were similar at 6 and 18 months . There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6 , 12 , or 18 months . Patients treated with clozapine in the efficacy pathway made comparable gains . Early treatment discontinuations , especially among patients most impaired at baseline , limited the ability to achieve more substantial functional gains . CONCLUSIONS All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning . There were no differences among them after 6 , 12 , or 18 months . More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions BACKGROUND Deficits in olfactory identification have been widely reported in patients with schizophrenia ( SZ ) and are associated with negative symptomatology . Adjunctive oxytocin delivered intranasally has been shown to improve some aspects of social cognition as well as positive and negative symptoms in patients with schizophrenia . Given the intranasal delivery route of oxytocin to olfactory pathways and that olfactory abnormalities are a potential endophenotype in SZ , we investigated the effect of intranasal oxytocin on olfactory identification as well as positive and negative symptoms in people with schizophrenia . METHODS Individuals with schizophrenia or schizoaffective disorder ( n=28 ; 16 out patients , 12 in patients ) were r and omized to receive adjunctive intranasal oxytocin 20 IU BID or placebo for 3 weeks . RESULTS All 28 participants completed the clinical trial .  Odor identification performance significantly improved on the University of Pennsylvania Smell Identification Test ( UPSIT ) total score and subscore for pleasant smells . UPSIT score ( F=5.20 , df=1,23 , p=0.032 ) and subscore for pleasant smells ( F=4.56 , df=1,23 , p=0.044 ) , in patients treated with oxytocin were compared to placebo from baseline to endpoint . Global symptomatology as well as positive and negative symptoms were not improved by intranasal oxytocin . In fact , global symptoms , not positive or negative symptoms , improved in the placebo group . Secondary analysis shows that intranasal oxytocin improved negative symptoms in the small group of in patients . Intranasal oxytocin was well tolerated during the three week trial . CONCLUSION Adjunctive intranasal oxytocin may improve olfactory identification , particularly in items of positive valence . Larger studies are needed to determine the effects of oxytocin on negative symptoms in SZ . ( NCT00884897 ; http://www . clinical trials.gov ) OBJECTIVES To assess the impact of a personalized diet , with or without addition of VSL#3 preparation , on biomarkers of inflammation , nutrition , oxidative stress and intestinal microbiota in 62 healthy persons aged 65 - 85 years . DESIGN Open label , r and omized , multicenter study . PRIMARY ENDPOINT High-sensitivity C-reactive protein . SETTING Community . INTERVENTIONS Eight week web-based dietary advice ( RISTOMED platform ) alone or with supplementation of VSL#3 ( 2 capsules per day ) . The RISTOMED diet was optimized to reduce inflammation and oxidative stress . MEASUREMENTS Blood and stool sample s were collected on days 1 and 56 . RESULTS Diet alone reduced ESR ( p = 0.02 ) , plasma levels of cholesterol ( p < 0.01 ) and glucose ( p = 0.03 ) . Addition of VSL#3  reduced ESR ( p = 0.05 ) and improved folate ( p = 0.007 ) , vitamin B12 ( p = 0.001 ) and homocysteine ( p < 0.001 ) plasma levels . Neither intervention demonstrated any further effects on inflammation . Subgroup analysis showed 40 participants without signs of low- grade inflammation ( hsCRP<3 mg/l , subgroup 1 ) and 21 participants with low- grade inflammation at baseline ( hsCRP≥3 mg/l , subgroup 2 ) . In subgroup 2 addition of VSL#3  increased bifidobacteria ( p = 0.005 ) in more participants and improved both folate ( p = 0.015 ) and vitamin B12 ( p = 0.035 ) levels compared with subgroup 1 . The increases were positively correlated to the change in the bifidobacteria concentration for folate ( p = 0.023 ) and vitamin B12 ( p = 0.001 ) . As expected change in homocysteine correlated negatively to change in folate ( r = -0.629 , p = 0.002 ) and vitamin B12 ( r = -0.482 , p = 0.026 ) . CONCLUSIONS Addition of VSL#3  increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low- grade inflammation . Decrease in homocysteine with VSL#3 was clinical ly relevant . suggesting protective potentials for aging-associated conditions , e.g. cardiovascular or neurological diseases . Clinical Trials.gov : NCT01069445-NCT01179789 Negative symptoms of schizophrenia ( NSS ) , related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex , are predictive of poor outcomes and have no effective treatment . Use of dopamine-enhancing drugs ( eg , psychostimulants ) has been limited by potential adverse effects . This multicenter study examined lisdexamfetamine dimesylate ( LDX ) , a d-amphetamine prodrug , as adjunctive therapy to antipsychotics in adults with clinical ly stable schizophrenia and predominant NSS . Out patients with stable schizophrenia , predominant NSS , limited positive symptoms , and maintained on stable atypical antipsychotic therapy underwent a 3-week screening , 10-week open-label adjunctive LDX ( 20–70 mg/day ) , and 4-week , double-blind , r and omized , placebo-controlled withdrawal . Efficacy measures included a modified Scale for the Assessment of Negative Symptoms ( SANS-18 ) and Positive and Negative Syndrome Scale ( PANSS ) total and subscale scores . Ninety-two participants received open-label LDX ; 69 received double-blind therapy with placebo ( n=35 ) or LDX  ( n=34 ) . At week 10 ( last observation carried forward ; last open-label visit ) , mean ( 95 % confidence interval ) change in SANS-18 scores was −12.9 ( −15.0 , −10.8 ; P<0.0001 ) . At week 10 , 52.9 % of participants demonstrated a minimum of 20 % reduction from baseline in SANS-18 score . Open-label LDX was also associated with significant improvement in PANSS total and subscale scores . During the double-blind/r and omized-withdrawal phase , no significant differences ( change from r and omization baseline ) were found between placebo and LDX in SANS-18 or PANSS subscale scores . In adults with clinical ly stable schizophrenia , open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening .  Abrupt LDX discontinuation was not associated with positive or negative symptom worsening . Confirmation with larger controlled trials is warranted
There were no overall effects from antioxidant vitamins , inositol or dietary minerals on psychiatric symptoms .
There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia .
BACKGROUND When used as an adjunctive with antipsychotics , certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia , by restoring nutritional deficits , reducing oxidative stress , or modulating neurological pathways .