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Background Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. Method Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. Results The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = −3.161, p = 0.007] and 16 (LS mean difference = −3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. Conclusions Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.

Na Zhu,1,&ast; WeiHua Zhang,2,&ast; Jia Huang,3 Yousong Su,3 JingFang Lu,3 Lu Yang,3 YiFan Shi,3 ShaoHua Hu,4,&ast; Jun Chen,3,5,&ast; Yiru Fang3,5,6,&ast; 1Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tong Ji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 3Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 6State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ShaoHua Hu; Jun Chen, Email dorhushaohua@zju.edu.cn; doctorcj2010@gmail.comBackground: Cognitive impairment is one of the core features of bipolar depression. A unified, reliable, and valid assessment tool is key to screening and assessing cognitive impairment. The THINC-Integrated Tool (THINC-it) is a simple and quick battery for screening cognitive impairment in patients with major depressive disorder. However, the use of the tool has not been validated in patients with bipolar depression.Methods: The cognitive functions of 120 patients with bipolar depression and 100 healthy controls were evaluated using the THINC-it tool including Spotter, Symbol Check, Codebreaker, Trials, and the only one subjective test (PDQ-5-D) and five corresponding standard tests. A psychometric analysis of the THINC-it tool was performed.Results: The overall Cronbach’s alpha coefficient of the THINC-it tool was 0.815. The intra-group correlation coefficient (ICC) of retest reliability ranged from 0.571 to 0.854 (P< 0.001), while the correlation r of parallel validity ranged from 0.291 to 0.921 (P< 0.001). There were significant differences in the two groups Z-scores of THINC-it total score, Spotter, Codebreaker, Trails, and PDQ-5-D (P< 0.05). Construct validity was analyzed using exploratory factor analysis (EFA). The Kaiser-Meyer-Olkin (KMO) value was 0.749. Using Bartlett’s Sphericity test, the χ2 (10) value was 198.257 (P< 0.001). The factor loading coefficients of Spotter, Symbol Check, Codebreaker, and Trails on the common factor 1 were − 0.724, 0.748, 0.824, and − 0.717, respectively, and the factor loading coefficient of PDQ-5-D on the common factor 2 was 0.957. Results revealed that the correlation coefficient of the two common factors was 0.125.Conclusion: The THINC-it tool has good reliability and validity in assessing patients with bipolar depression.Keywords: bipolar disorder, cognitive impairment, reliability, THINC-it tool, validity

Background: Antipsychotics are known to be associated with metabolic syndromes (MetS). Chlorpromazine (CPZ) and Clozapine (CLZ) are currently the most commonly used antipsychotics in low-income districts of China. However, potential differences in the long-term effects of CPZ and CLZ on MetS in schizophrenia inpatients are not well understood. Here, we aimed to identify any MetS profile differences between long-term schizophrenia patients who were prescribed either CPZ or CLZ at a primary psychiatric hospital. Methods: We recruited a total of 204 male schizophrenia patients who received either CPZ or CLZ. We measured their weight, height, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP), as well as their biochemical indicators, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). Results: The MetS prevalence in the CPZ and CLZ groups was 31% and 37.5%, respectively. The CLZ group had significantly higher DBP levels and a higher incidence of dyslipidemia (HDL-c) but lower HDL-c and TC levels than the CPZ group. We also determined that smoking history, BMI, and duration of hospitalisation were risk factors for the development of MetS. Moreover, we found that CPZ and CLZ were correlated with the same risk for developing MetS and that BMI was a vital risk factor of MetS for both the CPZ and CLZ groups. Conclusion: Long-term CPZ and CLZ prescriptions were associated with similar profiles for developing MetS of schizophrenia patients.

Effective and targeted interventions for improving quality of life (QOL) in addition to achieving 'clinical remission' are imperatives for patients with major depressive disorder (MDD). This study aimed to examine potential predictors and moderators of QOL in depression. Data were obtained from the Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD) study, a multisite, randomized controlled trial composed of 980 depressed patients. Mixed Model Repeated Measures (MMRM) analyses were conducted to identify baseline characteristics associated with QOL overall (predictors) and their interaction effects (moderators). Severe core depressive, anxiety and pain symptoms were found to be independently associated with poor QOL over the 12-week acute phase treatment. Severe depression, severe anxiety or pain symptoms, or severe suicidal ideation predicted a larger improvement of QOL during acute phase treatment, whereas males showed less improvement. None of the putative moderators were identified except for the educational level. Patients with lower educational level showed a larger improvement of QOL in the AGT started with escitalopram (AGT-E) group and AGT started with mirtazapine (AGT-M) group compared to the treatment as usual (TAU) group. These findings may help to instruct informed decision-making for heterogeneous patients with MDD in the view of full recovery.

Little is known how often depressive episodes are accompanied by gastrointestinal symptoms in major depressive disorders (MDD). The authors sought to determine the frequency and clinical correlates of gastrointestinal symptoms during episodes of depressive disorder.3,256 MDD patients from the National Survey on Symptomatology of Depression (NSSD), which was designed to investigate the magnitude of symptoms of current major depressive episodes in China, were enrolled and assessed for gastrointestinal symptoms in this study. Illness characteristics were compared in patients with a different frequency of gastrointestinal symptoms. Pearson correlation analysis and multiple linear regression analysis were employed to investigate the associations between gastrointestinal symptoms and psychological characteristics in the patients.More than 70% of the subjects with depressive episodes had concomitant gastrointestinal symptoms. A higher frequency of gastrointestinal symptoms was associated with an increased risk of suicide ideation, suicide attempts, anxious mood, depressed mood, insomnia, feeling a failure, poor concentration, body pain, hopelessness, anger, and irritability. Pearson correlation analysis indicated moderate but significant associations between gastrointestinal symptoms and psychological characteristics (p0.001). Multiple linear regression analysis showed that suicide ideation (β=0.161, p0.001), anxiety mood (β=0.166, p = 0.006), insomnia (β =0.262, p0.001), anger (β=0.144, p0.001), feeling a failure (β =0.365, p0.001), and body pain (β=0.581 p0.001) were independently associated with gastrointestinal symptoms in MDD patients.Gastrointestinal symptoms were one of the most prevalent clinical presentations of MDD. The associations between gastrointestinal symptoms and psychological characteristics may prove useful in expanding our understanding of how gastrointestinal symptoms contributes to MDD.

Background The co-occurrence of insomnia and hypersomnia symptoms in patients with major depressive disorder (MDD) is associated with suicidal ideation and functional impairment. The relationship between sleep disturbances and clinical features and outcomes may not be adequately studied. In this study, we measured the functional impairments and clinical features of co-occurring insomnia and hypersomnia symptoms in Chinese patients with MDD. Methods A post-hoc analysis was performed on data from the National Survey on Symptomatology of Depression (NSSD), which assessed the MDD patients in 32 hospitals by a clinician-rating questionnaire. The clinical features and outcomes were compared among the following four groups: insomnia symptom only, hypersomnia symptom only, both insomnia and hypersomnia symptoms, no sleep disturbance, respectively. Results Totally, 234 (7.15%) of 3275 participants with MDD co-occurred insomnia and hypersomnia symptoms. They had more depressive symptoms (27.41 ± 9.123), higher rate of suicide ideation (39.7%), more severe impairment in physical (58.1%), economic (32.9%), work (55.1%), and relationship with families (29.5%). Patients with both sleep disturbances were more likely to excessive worry about sleep, have suicidal ideation, the distress of social disharmony, more somatic symptoms, lack of energy, hyperphagia, loss of mood reactivity, and diurnal change, whereas less likely to have anxious mood. Limitations Sleep disorders were not diagnosed by current standard diagnostic criteria. Conclusions Patients co-occurring with both sleep disturbances are associated with a higher rate of suicide risk and poorer social function. Our study could provide implications for suicidal risk evaluation and the development of therapeutic strategies for depression.

Background: Hyodeoxycholic acid (HDCA) is a natural secondary bile acid with enormous pharmacological effects, such as modulating inflammation in neuron. However, whether HDCA could suppress microglial inflammation has not been elucidated yet. Aims: To determine the anti-microglial inflammatory effect of HDCA in lipopolysaccharide (LPS) models and its mechanisms. Methods: The effect of HDCA was evaluated in LPS-stimulated BV2 microglial cells in vitro and the cortex of LPS-treated mice in vivo. Immunohistochemistry and immunofluorescence were used to visualize the localization of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and ionized calcium-binding adaptor protein-1 (Iba-1), respectively. The mRNA expression of inflammatory cytokines was measured by RT-qPCR. The protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), takeda G-coupled protein receptor 5 (TGR5), and the phosphorylation of protein kinase B (AKT), NF-κB, and inhibitor of NF-κB protein α (IκBα) was examined by Western blot. Results: HDCA inhibited the inflammatory responses in LPS-treated BV2 cells and in the cortex of LPS-treated mice, evidenced by decreased production of inflammatory mediators such as iNOS, COX-2, tumor necrosis factor (TNF-α), interleukin (IL)-6, and IL-1β. Further study demonstrated that HDCA repressed the phosphorylation, nuclear translocation, and transcriptional activity of NF-κB and inhibited the activation of AKT in BV-2 cells induced by LPS. Meanwhile, addition of TGR5 inhibitor, triamterene, abolished the effects of HDCA on TGR5, AKT, and NF-κB. Conclusion: The present study demonstrated that HDCA prevents LPS-induced microglial inflammation in vitro and in vivo, the action of which is via regulating TGR5/AKT/NF-κB signaling pathway.

Tao Yang,1,2 Raymond W Lam,2 Jia Huang,1 Yousong Su,1 Jing Liu,2 Xiaorui Yang,1 Lu Yang,1 Na Zhu,3 Guoqing Zhao,4 Ruizhi Mao,1 Rubai Zhou,1 Weiping Xia,5 Hongmei Liu,1 Zuowei Wang,6 Jun Chen,1 Yiru Fang1,7,8 1Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; 3Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychology, Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 5Department of Medical Psychology, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China; 6Division of Mood Disorders, Shanghai Hongkou District Mental Health Center, Shanghai, People’s Republic of China; 7CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China; 8Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of ChinaCorrespondence: Yiru FangClinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Room B2409, Building 2, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaTel +86 139 0199 7089Email yirufang@aliyun.comJun ChenClinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Room B2411, Building 2, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaTel +86 180 1731 1373Email doctorcj2010@gmail.comBackground: Patients with bipolar disorder (BD) and patients with major depressive disorder (MDD) have relatively specific temperament and structural abnormalities of brain regions related to emotion and cognition. However, the effects of temperament factors on the structure of frontal and temporal cortex is still unclear. The aims of this study were to explore the differences and relationships between temperament characteristics and the gray matter volume of frontal and temporal cortex in patients with BD or MDD.Methods: T1-weighted magnetic resonance imaging (MRI) data, demographic and clinical information were obtained from 279 depressed patients (90 patients with BD, 189 patients with MDD) and 162 healthy controls (HC). Temperament was assessed with the Chinese short version of Temperament Evaluation of Memphis, Pisa and San Diego – Auto questionnaire (TEMPS-A). The Desikan-Killiany atlas was used for yielding gray matter volume by FreeSurfer 6.0 software suite. A total of 22 frontal and temporal regions were chosen as regions of interest (ROIs).Results: Compared with patients with MDD, patients with BD had higher TEMPS-A total scores and scores on cyclothymic, irritable and hyperthymic subscales. The gray matter volume in bilateral rostral middle frontal gyrus (RMFG), left temporal pole and right superior frontal gyrus were reduced in patients with BD. Patients with MDD only had lower gray matter volume in bilateral temporal pole. In the pooled patients, there were negative associations between hyperthymia and gray matter volume in right RMFG.Conclusion: Patients with BD and MDD had different temperament characteristics. The prominent temperament subscales in patients with BD were cyclothymia, irritable and hyperthymia. Patients with greater hyperthymia had lower gray matter volume in right frontal gyrus. Temperament may reflect an endophenotype in patients with mood disorders, especially in BD.Keywords: bipolar disorder, major depressive disorder, temperament, gray matter volume

Background This study aims to explore the changes in functional neuroimaging in bipolar depression patients with anxiety symptoms (BDP-A). Methods Forty-five BDP-A patients, 22 bipolar depression patients without anxiety symptoms (BDP-NA), and 48 healthy controls (HC) were finally involved. The low-frequency oscillation characteristics, functional connectivity (FC), and network properties among the three groups of participants were analyzed. Results Compared with the BDP-NA group, BDP-A patients exhibited significantly decreased amplitude of low-frequency fluctuation (ALFF) in the left middle frontal gyrus (MFG), superior occipital gyrus, and inferior parietal, but supramarginal and angular gyri (IPL). Enhanced FC from left IPL to middle temporal gyrus, from left precentral gyrus (PreCG) to bilateral angular gyri, medial superior frontal gyrus, and left superior frontal gyrus (SFG)/MFG were also revealed. Compared with HC, the BDP-A group showed remarkably increased ALFF in the left MFG/PreCG, right superior parietal gyrus, while decreased ALFF in the left inferior frontal gyrus, opercular part, and SFG. In addition, higher regional homogeneity in the left MFG/PreCG was found. Limitations The limitations are as follows: (1) relatively small sample size; (2) not all the patients were drug-naive; (3) lack of pure anxiety disorder patients as a controlled group; (4) mental health conditions of HC were not systemic evaluated. Conclusions BDP-A patients showed significant differences in resting-state fMRI properties when compared with BDP-NA or HC group. These results may infer the dysfunction of the dorsal attention network, the default network, and the fronto-limbic system as well as disrupted brain network efficiency in BDP-A patients.

Nutritional supplementations have been widely used as adjunctive treatments for schizophrenia. However, among these supplementations, of which the most beneficial is currently unknown. This study aimed to compare and rank the effectiveness of nutritional supplementations in the adjunctive treatments of schizophrenia. The four nutritional supplementations evaluated were: 1) folate acid or vitamin B12; 2) vitamin D; 3) N-acetyl cysteine (NAC); 4) Omega-3 polyunsaturated fatty acid, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). 17 eligible RCTs with 1165 participants were included in this network meta-analysis based on study criteria. NAC supplementation was significantly more efficacious than folic acid or vitamin B12 [MD (95% CI): -6.6 (-10.8, -2.4)] and omega-3 polyunsaturated fatty acid [MD (95% CI): -5.1(-9.9, -0.8)] supplementation in the term of PANSS score changes. There were no significant differences in the PANSS score changes between NAC and vitamin D [MD (95% CI): -5.2 (-10.9, 0.5)] supplementations. The estimated ranking probabilities of treatments showed that NAC might be the most effective adjunctive intervention over all nutritional supplementations. These results indicate that NAC could improve PANSS score and it may be among the most effective nutritional supplementations in schizophrenia patients.

Background: Most patients with the major depressive disorder (MDD) have varying degrees of impaired social functioning, and functional improvement often lags behind symptomatic improvement. However, it is still unclear if certain neurobiological factors underlie the deficits of social function in MDD. The aim of this study was to investigate the biomarkers of social function in MDD using structural magnetic resonance imaging (MRI). Methods: 3T anatomical MRI was obtained from 272 subjects including 46 high-functioning (high-SF, Sheehan Disability Scale (SDS) rating < 18) and 63 low-functioning (low-SF, SDS score ≥ 18) patients with MDD and 163 healthy controls (HC). Voxel-based morphometry (VBM) was employed to locate brain regions with grey matter (GM) volume differences in relation to social function in MDD. Regions showing GM differences in relation to social function at baseline were followed up longitudinally in a subset of 38 patients scanned after 12-week treatment. Results: Volume of right parahippocampal gyrus (rPHG) was significantly reduced in low-SF patients with MDD when compared to high-SF ones (FDR-corrected p < 0.05). Over 12 weeks of follow-up, though SF improved overall, the high and low-SF subgroups continued to differ in their SF, but had no progressive changes in PHG volume. Limitations: Limited functional assessment, high drop-out rate and median-based grouping method. Conclusions: Greater GM volume (GMV) of the rPHG may mark better social function in patients with MDD.

Background In spite of numerous options, the most efficacious treatment for major depressive disorder (MDD) remains elusive. Algorithm-guided treatments (AGTs) are proposed to address inadequate remission and optimize treatment delivery. This study aimed to evaluate the clinical benefit of AGTs for MDD, and to explore specific moderators of treatment outcomes for individual patients. Methods The study recruited 987 patients with MDD across eight hospitals who were randomly assigned to AGT with escitalopram (AGT-E), AGT with mirtazapine (AGT-M), or treatment-as-usual (TAU). The outcomes were symptom remission, response rate, early improvement rate, subsymptom clusters improvement over time, the mean time to first remission, relapse rate at 6-months posttreatment follow-up, quality of life (QOL), and adverse events. Resutls No significant differences were observed across groups in outcome, except that TAU showed significantly poorer QOL, higher relapse rates at 6-months posttreatment follow-up, and marginally significantly worse maximal burden of adverse events than the AGT groups. After 6 weeks of treatment initiation, remission rate did not significantly increase with extended treatment. AGT-M outperformed the TAU and AGT-E in treating sleep symptoms. AGT-E was less effective than AGT-M and TAU in patients with severe depression and somatic symptoms (DSSS). The superiority of TAU over AGTs was observed in recurrent MDD patients. Conclusion Although the superiority of AGTs over TAU was limited by failure of alternative subsequent treatment, AGTs outperformed in QOL and relapse rate. Types of disease episode and DSSS were regarded as specific moderators in treatment of depression. These findings might contribute to future research on targeted antidepressant treatment.

BackgroundTwo-thirds of major depressive disorder (MDD) patients initially present with somatic symptoms, yet no study has used approaches based on somatic symptoms to subtype MDD. This study aimed to classify MDD via somatic symptoms and tracked the prognosis of each subtype.MethodsData were obtained from the study of Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD). We recruited 395 subjects who received monotherapy of mirtazapine or escitalopram and conducted 2-, 4-, 6-, 8-, and 12-week follow-up assessments (n = 311, 278, 251, 199, and 178, respectively). Latent profile analysis (LPA) was performed on somatic symptom items of the depression and somatic symptoms scale (DSSS). Generalized linear mixed models (GLMM) were used to study the longitudinal prognosis of the subtypes classed by LPA. Primary outcome measures were the Hamilton Depression Rating Scale (HAMD), HAMD score reduction rate, as well as somatic and depressive items of DSSS.ResultsThree subtypes of MDD were found, namely, depression with mild somatic symptoms (68.9%), depression with moderate somatic symptoms (19.2%), and depression with severe somatic symptoms (11.9%). Scores of HAMD (F = 3.175, p = 0.001), somatic (F = 23.594, p < 0.001), and depressive (F = 4.163, p < 0.001) DSSS items throughout the 12-week follow-up showed statistical difference among the three subtypes. The moderate group displayed a higher HAMD-17 score and a lower reduction rate at the 6th week, and more severe depressive symptoms both at the 4th and 6th weeks.ConclusionThe results indicate that somatic symptoms should be emphasized in patients with MDD, and more attention is needed for those with moderate somatic symptoms, which may be relevant to a worse prognosis.

Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroanatomical features. Brain structural data were obtained at 3 T from a sample of 90 patients with BD, 189 patients with MDD, and 162 healthy individuals. We applied sparse partial least squares discriminant analysis (s-PLS-DA) to identify clinical and brain structural features that may discriminate between the two clinical groups, and heterogeneity through discriminative analysis (HYDRA) to detect patient subgroups with reference to healthy individuals. Two clinical dimensions differentiated BD from MDD (area under the curve: 0.76, P

Background Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. Objective This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. Methods We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. Results Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. Conclusions The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.

Aims Nonadherence is one of the leading challenges to treatment of the major depressive disorder (MDD). Few studies have systematically analyzed the relationship between clinical characteristics, especially symptoms of depressive patients and their therapeutic nonadherence over a relatively large sample. This study aimed to investigate factors of nonadherence in a nationwide survey in China. Methods Participants with MDD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) were recruited from 32 sites throughout China. Patients were all over 16 years old. A doctor-rating questionnaire with 64 symptoms based on DSM-IV was constructed to evaluate depression-related feeling and behavior. Single-factor logistic regression was utilized to screen variables, and multifactor logistic regressive analysis was used to identify which factors were risk or protective for nonadherence. We included 882 patients of poor adherence and 857 patients of good adherence. Results Recurrence, untreated first episode, tricyclic antidepressant (TCA)-treated first episode, antidepressant-only-treated current episode, decrease or loss of interest, more somatic symptoms, and "atypical" symptoms were risk factors for nonadherence, whereas selective noradrenaline reuptake inhibitor (SNRI)-treated first episode was a protecting factor. Conclusion Clinical characteristics may play an important role in predicting nonadherence. Doctors may have to pay much attention on patients with these factors and should keep on discussing them with patients.

Olanzapine (OLZ) is efficacious whereas leads to adverse metabolic effects thus lead to higher risk of cardiovascular diseases (CVD) on schizophrenia. Cytokines have been found associated with metabolic disorders. Therefore, pretreatment prediction of OLZ-induced adverse metabolic effects is urgently needed. To investigate if baseline cytokine levels could become biomarkers for pathogenesis of schizophrenia or prediction for OLZ-induced adverse metabolic effects, we recruited 75 participants, including 23 schizophrenia inpatients, who were antipsychotic-free over the past 6 months or first episode and drug-naive and 52 matched health controls, in our prospective cohort study and cross-sectional study. We simultaneously examined 7 serum cytokine levels (IFN-γ, IL-1ra, IL-1β, IL-8, TNF-α, MCP-1, VEGF) before OLZ treatment by using liquid suspension array technique and obtained clinical correlates at 4-week intervals in total 8 weeks. The psychopathology was assessed with the Positive and Negative Symptom Scale (PANSS). The metabolic parameters were BMI, TG, total cholesterol, LDL, HDL, ApoA1, ApoB, lipoprotein a, fasting glucose, HbA1c, insulin, and leptin. At baseline, IL-1ra and MCP-1 levels in schizophrenia were significantly higher than health controls (t = 4.55, P = 0.0001, t = 3.08 P = 0.003). BMI, fasting insulin, cholesterol, triglyceride, LDL, ApoB and leptin were significantly increased in patients with schizophrenia after 8 weeks of olanzapine treatment. Correlation analysis showed that the baseline IL-1ra level were significantly correlated with the increased levels of cholesterol (P = 0.004), LDL (P = 0.005), ApoB (P = 0.018) and leptin (P = 0.010), but not with the increased BMI, insulin or triglycerides. Further stepwise multiple linear regression analysis indicated that IL-1ra levels prior to treatment remained significantly associated with increased levels of cholesterol, LDL, ApoB and leptin. Above all, higher IL-1ra and MCP-1 levels may be biomarkers indicating pathogenesis of schizophrenia. Higher serum levels of IL-1ra may predict subsequent higher possibility of hypercholesterolemia and hyperleptinemia following OLZ treatment in schizophrenia patients.

The relationship between thyroid function and depression has long been recognized, but little is known about the effect of thyroid function on the risk of readmission after hospitalization for major depressive disorder (MDD). This retrospective cohort study was aimed to explore the effect of thyroid function on psychiatric readmission after hospitalization for MDD. Data was derived from electronic medical records (EMR) of the Shanghai Mental Health Center (SMHC), Shanghai, China. Univariate and multivariate logistic regression analyses were conducted in subjects aged ≥ 18 years who had been hospitalized for MDD between January 1, 2007, and May 31, 2019. Of the 1803 eligible patients, 85 and 132 patients experienced psychiatric readmission within 90 days and 180 days after discharge respectively. Multivariate analyses showed that serum FT3 level (aOR=1.271; 95%CI=1.051-1.537) and comorbidity of thyroid disease (aOR=2,179; 95%CI=1.136-4.179) was independently associated with the risk of 90-day and 180-day readmission respectively. These findings indicated that high serum FT3 levels and comorbidity of thyroid disease could increase the risk of readmission after hospitalization for MDD. It is warranted to provide routine assessment and intervention of the thyroid function during the treatment of depression so as to prevent re-hospitalization.

Many studies have indicated that immune dysfunction might be involved in the physiopathology of schizophrenia and aggression. This study aimed to investigate the correlation between high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-10 and clinical characteristics, especially aggression, and to explore the potential role of hsCRP and IL-10 as plasma biomarkers of schizophrenia.Forty-one patients with schizophrenia and forty healthy individuals were enrolled. Psychopathological severity and aggression were assessed using the Positive and Negative Syndrome Scale (PANSS) and Modified Overt Aggression Scale (MOAS). Plasma concentrations of hsCRP and IL-10 were assessed by enzyme-linked immunosorbent assay (ELISA).(1) Higher levels of hsCRP (p0.001), lower levels of logIL-10 (p0.001) and higher ratio of hsCRP to IL-10 (p0.001) were observed in the plasma of patients with schizophrenia, compared to healthy controls; (2) ROC (receiver operating characteristic) curve analysis revealed that ratio of hsCRP/IL-10 (predictive value: 0.783, p0.01; sensitivity: 85.4%; specificity: 67.5%) was more applicable as a biomarker to distinguish patients with schizophrenia from the control group than hsCRP and IL-10 alone (predictive value: 0.718, p0.01; 0.275, p0.001, respectively); (3) we found positive correlations between hsCRP and the total score and verbal aggression score of MOAS (r=0.654, p0.01; r=0.678, p0.05), and between hsCRP/IL-10 and the total score of MOAS (r=0.636, p0.01).Our results suggest the possible function of hsCRP and IL-10 in the pathogenesis of schizophrenia and the possible value of hsCRP/IL-10 as a potential peripheral biomarker of schizophrenia. This finding also suggests a relationship between hsCRP, IL-10 and their ratio with aggression in patients with schizophrenia.

Increasing evidence indicates that immune inflammatory processes, especially autoimmune reaction, should be considered in the pathophysiology of schizophrenia and aggressive behavior. The present study aimed to explore the correlation between immune factors (C3 and Th17-related cytokines) and aggressive behavior in schizophrenia patients. Forty schizophrenia patients and forty age- and gender-matched healthy controls participated in the study. Blood samples were assessed by ELISA upon enrollment. Positive and negative syndrome scale (PANSS) and modified overt aggression scale (MOAS) were used to estimate the severity and aggressive symptoms of schizophrenia patients. Plasma levels of IL-17, IL-23, and TGF-β1 in schizophrenia patients were significantly higher than those in healthy controls [(37.63±17.82) vs. (29.34±10.38)pg/ml, p=0.02; (101.40±135.26) vs. (13.09±5.94) pg/ml, p=0.01; (2864.57±2163.61) vs. (1839.69±1797.73)pg/ml, p=0.04], whereas C3 levels were significantly lower in schizophrenia patients [( 120,479.67± 65,612.50) vs. ( 208,060.21± 217,008.21)ng/ml, p=0.02]. IL-17, IL-23, and TGF-β1 levels were positively related to total scores of MOAS (p=0.02, p=0.02 and p=0.03, respectively) and PANSS (p=0.04, p=0.04 and p=0.02, respectively), whereas C3 levels were negatively related to total PANSS scores (p=0.03). IL-17 and IL-23 levels were positively correlated with PANSS excited component scores (p=0.04 and p=0.01, respectively). Our findings suggested that the Th17-related cytokine levels were positively related to the severity of schizophrenia and aggressive behavior, whereas C3 levels were negatively related to the severity of schizophrenia. This study demonstrated that elevated levels of Th17-related cytokines and decreased levels of C3 could be potential biomarkers for schizophrenia and aggressive behavior.

Background Measurement-based care (MBC) is a popular strategy of clinical management for patients with major depressive disorder (MDD). The consistency of self-report and clinical measurements is of importance, but whether individual symptom severity is in agreement for both self-report and clinician rating in MDD has not been comprehensively tested. This study aimed to test whether individual symptom severity of MDD was in agreement between self-report and clinician rating, and to explore factors affecting the agreement. Methods In the National Survey on Symptomatology of Depression (NSSD) of China, 3275 patients with a major depressive episode were evaluated by both self-report and a clinician-rated version of 62 questions. Results On average, 59% of all patients reached absolute agreement with their research clinicians. Among all questions, 73% returned with moderate positive strength of correlation, followed by 27% with low positive correlation. In 77% of the total questions, there was a tendency to rate higher in the self-report version compared with the clinician-rated version. After classifying the symptoms by six major domains, it was found that patients and clinicians showed more consistent answers in history and somatic questions (81% and 65% reached agreement), and that there were more differences in mood, energy, and anxiety questions (up to 56% in full agreement). “Outpatient”, “high financial status”, “poor working condition”, and “high education level” were found to be significant positive predictors for patients rating higher than clinicians or patients and clinicians reaching agreement as opposed to clinicians rating higher than patients. Limitations The cross-sectional nature of our study undermines the interpretation of the results across the MDD treatment course. Conclusions It is sufficient to use the self-report version of a questionnaire to screen, monitor, and detect remission for MDD symptoms. Complete assessment of depression severity should take both clinician-rated scales and self-reported measures into consideration. Factors other than source of admission, financial status, working condition, and education level should be further investigated for the discrepancy between self-report and clinician rating.

Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center. Voxel-based morphometry (VBM) followed by graph theory based structural covariance analysis was applied to locate diagnosis x genotype interactions. Irrespective of diagnosis, individuals with the high-risk genotype (T-carriers) had reduced volume in left angular gyrus (main effect of genotype). Diagnosis x genotype interaction was exclusively localized to the visual cortex (right superior occipital gyrus). The same region also showed reduced volume in patients with MDD than HC (main effect of diagnosis), with this effect being most pronounced in patients carrying the high-risk genotype. However, neither global nor regional network of structural covariance was found to have group difference. In conclusion, a genetic variation which can increase TNF-α expression selectively affects the anatomy of the visual cortex among the depressed subjects, with no effect on the topographical organization of multiple cortical regions. This supports the notion that anatomical changes in depression are in part influenced by the genetic determinants of inflammatory activity.

Although previous studies showed the reduced risk of cancer in patients with schizophrenia, whether patients with schizophrenia possess genetic factors that also contribute to tumor suppressor is still unknown. In the present study, based on our previous microarray data, we focused on the tumor suppressor genes TXNIP and AF1q, which differentially expressed in patients with schizophrenia. A total of 413 patients and 578 healthy controls were recruited. We found no significant differences in genotype, allele, or haplotype frequencies at the selected five single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene; rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with schizophrenia and controls. However, we found the association between the interaction of TXNIP and AF1q with schizophrenia by using the MDR method followed by traditional statistical analysis. The best gene-gene interaction model identified was a three-locus model TXNIP (rs2236566, rs7211)-AF1q (rs2140709). After traditional statistical analysis, we found the high-risk genotype combination was rs2236566 (GG)-rs7211(CC)-rs2140709(CC) (OR = 1.35 [1.03-1.76]). The low-risk genotype combination was rs2236566 (GT)-rs7211(CC)-rs2140709(CC) (OR = 0.67 [0.49-0.91]). Our finding suggested statistically significant role of interaction of TXNIP and AF1q polymorphisms (TXNIP-rs2236566, TXNIP-rs7211, and AF1q-rs2769605) in schizophrenia susceptibility.

The aims of this study were to investigate the differences in executive function and the relationship with clinical factors between drug-naïve patients with bipolar depression (BDD) and unipolar depression (UPD).Drug-naïve patients with BDD, UPD and healthy controls (HC) were recruited (30 cases in each group). All patients were assessed with Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression-17 (HAM-D), and Young Mania Rating Scale (YMRS). Executive function was evaluated by Stroop color-word test (CWT) and Wisconsin Card Sorting Test (WCST).In the BDD group, only the CWT number of missing was higher than HCs (P = 0.047). In the UDP group, CWT number of correct was lower, CWT number of missing was higher, and the WCST indices were worse than the HC group (P 0.05). The WCST percentage of errors (PE) and percentage of conceptual level responses (PCLR) in the UPD group were worse than the BDD group (P 0.05). In the BDD group, no correlations between CWT and WCST indices and clinical features were detected after correcting for multiple comparisons (P 0.05). In the UDP group, the WCST PE, PCLR, number of categories completed (CC), and the percentage of perseverative responses (PPR) were correlated to the number of mood episodes (P 0.01).This was a small-sample cross-sectional study. The possibility of UPD transforming to bipolar disorder (BD) in future could not be ruled out.Our results suggested only small differences in executive function between drug-naïve patients with BDD and UPD, but in this sample only the UPD group showed differences with HCs. The executive function of drug-naïve BDD patients may be associated with duration of current depressive episode, while for UDP patients executive function indices were significantly correlated with number of mood episodes.

Background Immune system dysregulation is critical in the physiopathology of major depressive disorder (MDD) and bipolar disorder (BD). However, it is unclear whether both diseases present the same inflammatory patterns during depressive episodes. We explored the differences in pro- and anti-inflammatory cytokines between unipolar and bipolar depression (BDD) and the trajectory of these cytokines after acute-phase treatment. Methods Sixty-four MDD patients, 61 BDD patients, and 62 healthy controls (HCs) were enrolled. We assessed the clinical features and cytokines plasma levels at baseline and week 12. The pro-inflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokines (IL-4, IL-13) of all subjects were assessed by multiplexed sandwich ELISA-based quantitative arrays. Results Before acute-phase treatment, the initial levels of TNF-α and IL-13 were significantly lower in the BDD patients than in the MDD patients. The results demonstrated that there was no relationship between each cytokine level and clinical features of unipolar and bipolar depressions. After 12 weeks, TNF-α, IL-4, and IL-13 levels became lower in MDD patients than in the other two groups regardless of the patients’ response to treatment while the levels of TNF-α and IL-4 increased only in the BDD responders. Limitations The effects of different drugs on inflammatory cytokines in MDD or BDD could not be explored further due to the relatively small sample size. Conclusion Even within the same depressive states, MDD and BDD patients present different inflammatory features, particularly in regard to pro-inflammatory TNF-α and anti-inflammatory IL-13. In addition, the fluctuations of cytokines induced by medication may provide a hint regarding the prediction of treatment response.

Atypical antipsychotics are highly effective antischizophrenic medications but their clinical utility is limited by adverse metabolic sequelae. We investigated whether upregulation of macrophage migration inhibitory factor (MIF) underlies the insulin resistance that develops during treatment with the most commonly prescribed atypical antipsychotic, olanzapine. Olanzapine monotherapy increased BMI and circulating insulin, triglyceride, and MIF concentrations in drug-naive schizophrenic patients with normal MIF expression, but not in genotypic low MIF expressers. Olanzapine administration to mice increased their food intake and hypothalamic MIF expression, which led to activation of the appetite-related AMP-activated protein kinase and Agouti-related protein pathway. Olanzapine also upregulated MIF expression in adipose tissue, which reduced lipolysis and increased lipogenic pathways. Increased plasma lipid concentrations were associated with abnormal fat deposition in liver and skeletal muscle, which are important determinants of insulin resistance. Global MIF-gene deletion protected mice from olanzapine-induced insulin resistance, as did intracerebroventricular injection of neutralizing anti-MIF antibody, supporting the role of increased hypothalamic MIF expression in metabolic dysfunction. These findings uphold the potential pharmacogenomic value of MIF genotype determination and suggest that MIF may be a tractable target for reducing the metabolic side effects of atypical antipsychotic therapy.

BackgroundEarly identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode.AimsTo explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode.MethodA total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode.ResultsAt baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (PP = 0.02 respectively) and plasma levels (P = 0.002 and P = 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree).ConclusionsOur findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.

Although lines of evidence demonstrated that cytokines play an important role in the pathogenesis of major depressive disorder (MDD), none of the them have been established as reliable biomarkers. We use our previous whole-genome cRNA microarray data to identify epithelial cell-derived neutrophil-activating peptide 78 (ENA78), the most differentially expressed cytokine in peripheral blood between MDD patients and healthy controls; and then we confirmed the result by the quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) for mRNA and protein level, respectively, in an independent drug-naive first-episode sample set. In addition, to replicate the role of plasma ENA 78 in MDD, and determine the role of ENA78 on the venlafaxine efficiency, we further detected the plasma ENA78 in another independent 8- week follow-up sample set. We found that both of mRNA and plasma of ENA78 decreased in MDD patients, and displayed much lower after venlafaxine treatment. We also found that venlafaxine non-responders had lower level of peripheral plasma ENA78 prior to treatment than responders. Our findings for the first time provided strong evidence that the ENA78 may play a key role of mediator in pathogenesis of MDD and in the mechanism of vinlafaxine effects on MDD indicating that reduced ENA78 may be a potential biomarker for diagnosing of MDD and predicting of response to venlafaxine.

BackgroundDepressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.ObjectiveAimsTo assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.MethodsCross-sectional studies were applied to (1) compare the levels of plasma leptin between schizophrenia (n=74) and healthy controls (n=50); and (2) investigate the relationship between plasma leptin levels and depressive subscores.Results(1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls. (2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale (PANSS). (3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.ConclusionLeptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.

Accurate and efficient segmentation of medical serial images is of paramount importance for a wide range of clinical applications. A novel method for serial image segmentation is proposed in this paper. In the proposed framework, an adaptive external force is designed based on Laplacian of Gaussian to correctly attract the evolving curve from either side of object boundary, which makes the automatic segmentation of serial images become possible. The Tukey's bi-weight function is also introduced to match the evolving curve with object boundary, so the moving contour will stop evolution at object boundary accurately even if the blurry image is processed. Experiments on both single and serial images demonstrate the advantages of our method in terms of accuracy and robustness.

Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = −0.161), plasma levels of inflammatory regulation factors (including TGF-β1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R2 = 0.897, p

The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.

To study the involvement of the N-acylsphingosine amidohydrolase 1 gene (ASAH1) in the susceptibility to schizophrenia in the Han Chinese population.We performed cDNA microarray analysis to exam the gene expression profile in six schizophrenic patients and six healthy controls. We evaluated the ASAH1 expression levels in 30 subjects with chronic schizophrenia and 30 healthy controls by using real-time polymerase chain reaction (PCR). A total of 254 unrelated probands with schizophrenia and their biological parents were also genotyped at three single nucleotide polymorphisms (SNPs: rs3753118, rs3753116, and rs7830490) of the ASAH1 gene for association analysis.In the microarray analysis, the ASAH1 gene was down-regulated in all schizophrenic patients compared with healthy controls. In real-time PCR, the ASAH1 expression levels for schizophrenic patients with positive family history were significantly decreased (P = 0.020). In the association analyses, two SNPs (rs7830490 and rs3753118) and one haplotype (rs7830490 (A)-rs3753116 (G)) of ASAH1 showed significant evidence of nominal associations with schizophrenia (P = 0.026; P = 0.046; P = 0.007, respectively). The haplotype remained statistically significant (empirical P = 0.045) after correction for multiple testing.This study supports that the ASAH1 gene may be a potential candidate gene for schizophrenia in Han Chinese subjects.