The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Range adaptive value representations in schizophrenia and major depression.

Anhedonia and amotivation are core symptoms of schizophrenia (SCZ) and major depressive disorder (MDD). Reward processing involves constructing and contrasting the representations for expected value (EV) and outcome value (OV) of a given stimulus, a phenomenon termed range adaptation. Impaired range adaptation can lead to anhedonia and amotivation. This study aimed to examine range adaptation in SCZ patients and MDD patients. Fifty SCZ, 46 MDD patients and 56 controls completed the Effort-based Pleasure Experience Task to measure EV and OV adaptation. SCZ and MDD patients showed altered range adaptation, albeit in different patterns. SCZ patients exhibited over-adaptation to OV and reduced adaptation to EV. By contrast, MDD patients exhibited diminished OV adaptation but intact EV adaptation. Both OV and EV adaptation were correlated with anhedonia and amotivation in SCZ and MDD. Taken together, our findings suggest that range adaptation is altered in both SCZ and MDD patients. Associations of OV and EV adaptation with anhedonia and amotivation were consistently found in SCZ and MDD patients. Impaired range adaptation in SCZ and MDD patients may be putative neural mechanisms and potential intervention targets for anhedonia and amotivation.

Sex differences in subjective cognitive impairment and clinical correlates in Chinese patients with subthreshold depression.

OBJECTIVE: Subthreshold depression (SD) is a global mental health problem given its high prevalence, comorbidity, functional impairment, and its association with increased service utilization. However, currently little is known about sex differences of SD in cognitive impairment with clinical correlates. This study aims to explore sex differences in subjective cognitive impairment and clinically associated risk factors in Chinese patients with subthreshold depression (SD). METHODS: A total of 126 patients with SD, 40 males and 86 females, aged 18-45 years, were included in this cross-sectional observational study. Their general information, psychological assessments, and psychiatric symptom assessments were collected online. The Patient Health Questionnaire depression-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Deficits Questionnaire-Depression (PDQ-D), and Toronto Alexithymia Scale (TAS-20) with 3 subdomains were used. The obtained scores were analyzed with partial correlation and multiple linear regression analysis models. RESULTS: Our results showed that females had significantly higher PDQ-D-20 total score than males. However, the differences in TAS-20 and subdomain score according to sex were not significant. Notably, TAS-20 and DDF (difficulty describing feelings) subdomain contributed to cognitive impairment in males, whereas both PHQ-9 total score and TAS-20 or DDF subdomain contributed to cognitive impairment in females. CONCLUSION: These findings revealed significant sex differences in cognitive impairment and clinical correlates in SD, which should be further followed-up in the future.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. METHODS: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. RESULTS: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. CONCLUSION: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

Revisiting the latent structure of negative symptoms in schizophrenia: Evidence from two second-generation clinical assessments.

BACKGROUND: Negative symptoms are core symptom of schizophrenia, and many previous research studied the latent structure of negative symptoms based on a single measurement scale. Applying two second-generation negative symptom scales to the same sample can address measurement-invariance of latent structure. METHODS: Three-hundred-and-five schizophrenia patients were assessed using the CAINS and the BNSS. Confirmatory Factor Analysis (CFA) tested four competing factor-models: (1) a 1-factor model; (2) a 2-factor model comprising the motivation and pleasure (MAP) domain and the diminished expression (EXP) domain; (3) a 5-factor model comprising anhedonia, avolition, asociality, blunted affect and alogia; (4) a hierarchical model comprising the "first-order" 5-domain factors and the "second-order" MAP & EXP factors. RESULTS: The CFA results for the data of the CAINS showed that the 2-factor model had the best data fit over the other competing models. The CFA using the BNSS data in the same sample also supported the superiority of the 2-factor model. Lastly, after combining the items of the BNSS and CAINS together in the same sample for CFA, the 2-factor model prevailed over the other competing models. CONCLUSIONS: The 2-factor model appears to be measurement-invariant latent structure of negative symptoms. The novel method of combining the items of the CAINS and BNSS might have circumvented the possible imperfect construct of a single scale. Our findings support the MAP and EXP factors as the latent structure for negative symptoms.

Emotion Context Insensitivity is generalized in individuals with major depressive disorder but not in those with subclinical depression.

BACKGROUND: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression. METHODS: Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (ControlMDD, N = 50), Subclinical Depression Group (SD, N = 56), and Control Group for SD (ControlSD, N = 56). The Hamilton Depression Rating Scale and the Beck Depression Inventory were used to assess the severity of depression and anhedonia symptoms. The Monetary Incentive Delay Task evaluated participants' affective responses towards monetary stimuli. RESULTS: The MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect. LIMITATIONS: Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards. CONCLUSION: The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression.

Reduced learning bias towards the reward context in medication-naive first-episode schizophrenia patients.

BACKGROUND: Reinforcement learning has been proposed to contribute to the development of amotivation in individuals with schizophrenia (SZ). Accumulating evidence suggests dysfunctional learning in individuals with SZ in Go/NoGo learning and expected value representation. However, previous findings might have been confounded by the effects of antipsychotic exposure. Moreover, reinforcement learning also rely on the learning context. Few studies have examined the learning performance in reward and loss-avoidance context separately in medication-naïve individuals with first-episode SZ. This study aimed to explore the behaviour profile of reinforcement learning performance in medication-naïve individuals with first-episode SZ, including the contextual performance, the Go/NoGo learning and the expected value representation performance. METHODS: Twenty-nine medication-naïve individuals with first-episode SZ and 40 healthy controls (HCs) who have no significant difference in age and gender, completed the Gain and Loss Avoidance Task, a reinforcement learning task involving stimulus pairs presented in both the reward and loss-avoidance context. We assessed the group difference in accuracy in the reward and loss-avoidance context, the Go/NoGo learning and the expected value representation. The correlations between learning performance and the negative symptom severity were examined. RESULTS: Individuals with SZ showed significantly lower accuracy when learning under the reward than the loss-avoidance context as compared to HCs. The accuracies under the reward context (90%win- 10%win) in the Acquisition phase was significantly and negatively correlated with the Scale for the Assessment of Negative Symptoms (SANS) avolition scores in individuals with SZ. On the other hand, individuals with SZ showed spared ability of Go/NoGo learning and expected value representation. CONCLUSIONS: Despite our small sample size and relatively modest findings, our results suggest possible reduced learning bias towards reward context among medication-naïve individuals with first-episode SZ. The reward learning performance was correlated with amotivation symptoms. This finding may facilitate our understanding of the underlying mechanism of negative symptoms. Reinforcement learning performance under the reward context may be important to better predict and prevent the development of schizophrenia patients' negative symptom, especially amotivation.

Negative belief-updating bias for positive daily life events in individuals with schizophrenia and social anhedonia.

INTRODUCTION: Low-pleasure beliefs are found in both patients with schizophrenia (SZ) and individuals with high social anhedonia (SocAnh), and are associated with anhedonia. However, little is known about the development and maintenance of these low-pleasure beliefs in the clinical and subclinical populations. We investigated whether patients with SZ and individuals with high SocAnh have deficits in updating their beliefs, which may contribute to the understanding of the formation and maintenance of low-pleasure beliefs. METHODS: The Modified Belief Updating Task was administered to assess belief-updating patterns in a clinical sample (36 SZ patients and 30 matched controls) and a subclinical sample (27 individuals with high SocAnh and 30 matched controls). RESULTS: We found that compared with controls, SZ patients updated their beliefs to a greater extent and more frequently when receiving bad news for positive life events, but not for negative life events. Moreover, individuals with high SocAnh also exhibited similar patterns in updating their beliefs for positive life events after controlling depressive symptoms. CONCLUSIONS: Our findings suggest that negative belief-updating patterns for positive events may play an important role in the formation and maintenance of low-pleasure beliefs in patients with SZ and individuals with high SocAnh.

Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia.

BACKGROUND: Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. METHODS: A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. RESULTS: A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, pBonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, pBonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = - 0.07, p = 0.02). CONCLUSION: Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

MicroRNA-195 predicts olanzapine response in drug-free patients with schizophrenia: A prospective cohort study.

BACKGROUND: Disturbances of microRNA-195 have been implicated in the pathogenesis of schizophrenia. However, microRNA-195 levels in schizophrenia are controversial. AIMS: To the best of our knowledge, this is the first study to examine microRNA-195 levels in untreated schizophrenia patients and their relationship to olanzapine response. METHODS: We recruited 81 untreated schizophrenia patients and 96 healthy controls. The patients received 2 months olanzapine treatment. MicroRNA-195 levels in peripheral blood mononuclear cells were measured using quantitative real-time polymerase chain reaction testing. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale. RESULTS: No significant differences in microRNA-195 levels were found between patients and healthy controls (p > 0.05). Olanzapine significantly reduced microRNA-195 levels after 2 months treatment (p = 0.003). Interestingly, microRNA-195 levels decreased significantly in responders (p = 0.010), but not in non-responders (p > 0.05). Both baseline microRNA-195 levels (p = 0.027, p = 0.030) and the reduction rate of microRNA-195 levels (p = 0.034, p = 0.044) were positively associated with the reduction rate of Positive and Negative Syndrome Scale total score and general psychopathological subscale score. Multiple stepwise regression analysis revealed that baseline microRNA-195 level was an independent contributor to the reduction in Positive and Negative Syndrome Scale total score and the general psychopathological subscale score (p = 0.018, p = 0.030). Finally, logistic regression analysis suggested that baseline microRNA-195 level can serve as a biomarker for response to olanzapine (p = 0.037). CONCLUSIONS: Our data indicate that microRNA-195 level may predict symptomatic improvement and olanzapine response in schizophrenia patients, suggesting that microRNA-195 should be considered as a potential therapeutic target for antipsychotics.

Sex difference in cognitive impairment in drug-free schizophrenia: Association with miR-195 levels.

OBJECTIVE: There is evidence that microRNA-195 (miR-195) is associated with schizophrenia (SZ) and cognition, but the relationship between miR-195 and cognitive impairment in SZ is still unknown. Sex differences in both microRNA (miRNA) expression and cognition were found in SZ. We aim to investigate whether sex moderates the relationship between miR-195 levels and cognition in SZ. METHODS: We recruited 121 drug-free SZ patients and 129 healthy controls. miR-195 expression levels in peripheral blood mononuclear cells (PBMCs) were measured using qRT-PCR. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. MANCOVA, ANCOVA, correlation analysis and hierarchical linear regression analysis were used to test the effect of sex on the aforementioned variables. RESULTS: All RBANS scores significantly decreased in patients compared to healthy controls (all p < 0.001); ANCOVA analysis demonstrated female SZ patients had lower delayed memory score (F = 15.36, p < 0.001) and total score (F = 5.26, p = 0.024) than male patients. There was no diagnosis, sex or sex by diagnosis interaction effect on miR-195 levels (all p > 0.05). Interestingly, correlation analysis showed significant negative association between miR-195 and attention score (r = -0.389, p = 0.019), delayed memory score (r= -0.351, p = 0.036), and total score (r = -0.386, p = 0.020) only in female patients. Hierarchical regression analysis showed sex by miR-195 interaction was a significant predictor of the RBANS total score (ΔR2 = 0.042, F(1, 67) = 4.71, p = 0.033). CONCLUSION: Our data indicate that miR-195 is associated with cognitive impairment in female SZ patients, and it may be involved in the underlying mechanism of sex differences in cognitive impairment in SZ.

Interaction between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia.

There has been evidence that the disturbances of TNF-α and the oxidative stress (OxS) status are involved in the mechanism of schizophrenia. However, the results of their levels in schizophrenia are still controversial, and their interactions have not yet been examined, especially in first-episode drug-naïve (FEDN) patients. We therefore applied Enzyme-linked immunosorbent assays (ELISAs) method to compare peripheral blood serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) levels in 119 FEDN patients with schizophrenia and 135 healthy controls. We found that TNF-α and MDA were higher, whereas GSH-Px was lower, in FEDN patients with schizophrenia compared to healthy controls (TNF-α, 2.21 ± 0.33 vs. 2.11 ± 0.36, Bonferroni p = 0.04; MDA, 2.95 ± 0.87 vs. 2.68 ± 0.76, Bonferroni p = 0.04, GSH-Px, 177.33 ± 28.84 vs. 188.32 ± 29.34, Bonferroni p = 0.03). Furthermore, TNF-α levels had an independent positive association with negative symptoms (r = 0.37, Bonferroni p < 0.001). Finally, GSH-Px levels were negatively associated with the presence of schizophrenia (B =-0.014, Wald statistic = 9.22, p = 0.002, 95 %CI = 0.97-0.99), while the interaction of TNF-α with MDA was a risk factor for schizophrenia (B = 0.22, Wald statistic = 10.06, p = 0.002, 95 %CI = 1.09-1.43). Our results suggest that TNF-α and disturbance of oxidative stress status as well as their interaction may be involved in the pathophysiology of schizophrenia.

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients. METHODS: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted. RESULTS: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05). CONCLUSIONS: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Revisiting anticipatory hedonic processing in patients with schizophrenia: An examination between representation activation and maintenance.

BACKGROUND: Anticipatory anhedonia is one of the key deficits found in patients with schizophrenia (SCZ). However, the underlying mechanism of this deficit remains unclear. The present study examined whether representation activation and maintenance capacity influenced anticipatory experiences in SCZ patients. METHODS: We recruited 46 SCZ patients (26 males) and 45 matched healthy controls (24 males). The Reward Representation Activation and Maintenance (RRAM) Task was administrated to assess anticipatory experience and representation activation and maintenance capacity. RESULTS: SCZ patients exhibited lower subjective arousal than controls in anticipation of rewards with high probability when representation activation and maintenance were difficult to accomplish. SCZ patients also tended to reduce their button presses more than HC when they were required to maintain reward representation. CONCLUSIONS: Our findings suggest that representation activation and maintenance may partially account for anticipatory anhedonia observed in SCZ patients.

The remediation effects of working memory training in schizophrenia patients with prominent negative symptoms.

Introduction: Negative symptoms, particularly amotivation and anhedonia, are important predictors of poor functional outcome in patients with schizophrenia. There has been interest in the efficacy and mechanism of non-pharmacological interventions to alleviate these symptoms. The present study aimed to examine the remediation effect of working memory (WM) training in patients with schizophrenia with prominent negative symptoms.Methods: Thirty-one schizophrenia patients with prominent negative symptoms were recruited and assigned to either a WM training group or a treatment-as-usual (TAU) control group. The WM training group underwent 20 sessions of training using the dual n-back task over one month. A functional neuroimaging paradigm of the Affective Incentive Delay (AID) task was administered before and after the training intervention to evaluate the remediation effect of the intervention.Results: Our results showed that the WM training group demonstrated significant improvement in the WM training task and inattention symptoms. Compared with the TAU group, increased brain activations were observed at the right insula and the right frontal sub-gyral after WM training in the training group.Conclusions: These findings support the efficacy of WM training in ameliorating hedonic dysfunction in schizophrenia patients with prominent negative symptoms.

Predicting individual responses to lithium with oxidative stress markers in drug-free bipolar disorder.

Objectives: This is the first study to investigate the oxidative stress (OxS) levels in drug-free bipolar disorder (BD) patients and their association with lithium response.Methods: A total of 61 drug-free BD patients and 49 controls were included. Patients treated with lithium were followed-up for 6 weeks. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) were measured at baseline and at the end of the sixth week.Results: Compared to controls, the SOD levels were lower, whereas the MDA were higher in the BD-depression (BD-D) group (both P < 0.001). GSH-Px levels were higher in both the BD-D and the BD-mania (BD-M) group (both P < 0.001). Both GSH-Px and MDA levels in the BD (P = 0.009, P < 0.001) and the BD-D subgroup (P = 0.006, P = 0.001) decreased significantly after the 6-week treatment with lithium. Interestingly, both GSH-Px and MDA levels decreased in responders (P = 0.03, P = 0.002) but not in the non-responders of BD-D (both p > 0.05). Moreover, the reduction in the MDA levels were associated with lithium response (B = 1.47, Wald statistic = 5.94, P = 0.015, odds ratio = 4.35, 95% confidence interval 1.33-14.20).Conclusions: Our study demonstrates an imbalance of OxS in drug-free BD, especially BD-D. Lithium reduces the GSH-Px and MDA levels in BD patients. The reduction in MDA levels may predict individual responsiveness to lithium.

Genetic Association of Olanzapine Treatment Response in Han Chinese Schizophrenia Patients.

Olanzapine, a second-generation antipsychotic medication, plays a critical role in current treatment of schizophrenia (SCZ). It has been observed that the olanzapine responses in schizophrenia treatment are different across individuals. However, prediction of this individual-specific olanzapine response requires in-depth knowledge of biomarkers of drug response. Here, we performed an integrative investigation on 238 Han Chinese SCZ patients to identify predictive biomarkers that were associated with the efficacy of olanzapine treatment. This study applied HaloPlex technology to sequence 143 genes from 79 Han Chinese SCZ patients. Our result suggested that there were 12 single nucleotide polymorphisms (SNPs) had significant association with olanzapine response in Han Chinese SCZ patients. Using MassARRAY platform, we tested that if these 12 SNPs were also statistically significant in 159 other SCZ patients (independent cohort) and the combined 238 SCZ patients (composed of two tested cohorts). The result of this analysis showed that 2 SNPs were significantly associated with the olanzapine response in both independent cohorts (rs324026, P = 0.023; rs12610827, P = 0.043) and combined SCZ patient population (rs324026, adjust P = 0.014; rs12610827, adjust P = 0.012). Our study provides systematic analyses of genetic variants associated with olanzapine responses of Han Chinese SCZ patients. The discovery of these novel biomarkers of olanzapine-response will facilitate to advance future olanzapine treatment specific for Han Chinese SCZ patients.