Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.

BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R2 for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R2 = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R2 = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder.

BACKGROUND: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. METHODS: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. RESULTS: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. CONCLUSIONS: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .

Transcriptomic analyses of humans and mice provide insights into depression.

Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder (MDD). In particular, transcriptomic analyses in brain regions engaged in cognitive and emotional processes, e.g., the dorsolateral prefrontal cortex (DLPFC), have provided essential insights. Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls, we performed differential expression analyses using two alternative approaches for cross-validation. We also conducted transcriptomic analyses in mice undergoing chronic variable stress (CVS) and chronic social defeat stress (CSDS). We identified 12 differentially expressed genes (DEGs) through both analytical methods in MDD patients, the majority of which were also dysregulated in stressed mice. Notably, the mRNA level of the immediate early gene FOS ( Fos proto-oncogene) was significantly decreased in both MDD patients and CVS-exposed mice, and CSDS-susceptible mice exhibited a greater reduction in Fos expression compared to resilient mice. These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure. Altered transcriptomes in the DLPFC of MDD patients might be, at least partially, the result of stress exposure, supporting that stress is a primary risk factor for MDD.

Effect of glucomannan on functional constipation in children: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND OBJECTIVES: Constipation, a common complaint in children, considerably affects the quality of life. This systematic review assessed the treatment effects of glucomannan on children with constipation by summarising evidence from previous randomised controlled trials (RCTs). METHODS AND STUDY DESIGN: A comprehensive electronic literature search was conducted for identifying eligible RCTs that evaluated the effectiveness of glucomannan. The results were reported as mean differences (MDs), standardised mean differences (SMDs), and risk ratios (RRs) with 95% confidence intervals (CIs). The primary outcome was the defecation frequency per week; the secondary outcomes were stool consistency and the rate of successful treatment. A metaanalysis was conducted using the random effects model. RESULTS: Three RCTs evaluating 122 participants were identified. Glucomannan use was associated with an increased frequency of defecation (3 trials; MD=1.40; 95% CI: 0.36-2.44, p=0.008); however, there were no significant differences in the outcomes of stool consistency (3 trials; SMD=0.48; 95% CI: -0.44 to 1.40, p=0.300) or the rate of successful treatment (2 trials; RR=1.36; 95% CI: 0.48-3.81, p=0.110). CONCLUSIONS: Glucomannan moderately increases the defecation frequency of children with constipation but is not associated with a reduction in stool consistency or overall improvement in the rate of successful treatment. However, these results should be cautiously interpreted because of the small sample size and the risk of products containing glucomannan need to be considered. Additional large-scale and well-designed RCTs are necessary to evaluate the efficacy and long-term safety of glucomannan.

Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study.

It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis.

Effect of chronic social defeat stress on behaviors and dopamine receptor in adult mice.

Victims of bullying often undergo depression, low self-esteem, high anxiety and post-traumatic stress disorder symptoms. The social defeat model has become widely accepted for studying experimental animal behavior changes associated with bullying; however, differences in the effects in susceptible and unsusceptible individuals have not been well studied. The present study investigated the effects of social defeat stress on behavior and the expression of dopamine receptors D1 and D2 in the brains of adult mice. Adult mice were divided into susceptible and unsusceptible groups after 10days of social defeat stress. Behavioral tests were conducted, and protein levels in the brains were assessed by Western blotting. The results indicate that all mice undergo decreased locomotion and increased anxiety behavior. However, decreased social interaction and impaired memory performance were only observed in susceptible mice. A significantly decreased expression of D1 was observed in the prefrontal cortex and amygdala of susceptible mice only. No significant differences in D2 expression were shown between control and defeated mice in any area studied. These data indicate that depression-like behavior and cognition impairment caused by social defeat stress in susceptible mice may be related to changes in the dopamine receptor D1.

Antidepressant-like and anti-oxidative efficacy of Campsis grandiflora flower.

OBJECTIVES: Our study aimed to investigate the antidepressant-like effect of ethyl acetate extract of the flowers of Campsis grandiflora (EFCG) in a mice model of chronic unpredictable mild stress (CUMS). METHODS: HPLC-Q-TOF-MS was used to identify the chemical constituents of EFCG. The DPPH assay and ABTS radical-scavenging assay were performed to measure the antioxidant properties. The protective properties of EFCG against H2 O2 -induced oxidative damage were analysed in PC12 cells. The changes of behaviour profiles were investigated by using open-field test, sucrose preference test, forced swimming test (FST) and tail suspension test (TST). Brain tissue samples of mice were collected, and antioxidative measure levels were measured. KEY FINDINGS: The result showed that EFCG had the most active anti-oxidative effect and the protective effect against H2 O2 oxidative injury in PC12 cells. Treatment with the EFCG significantly reduced the depressant-like severity and immobility period as compared with untreated CUMS mice in FST and TST. Moreover, EFCG significantly elevated the contents of superoxide dismutase, Glutathione Peroxidase and decreased the contents of Malonaldehyde (MDA) in mice brain. CONCLUSIONS: Our study found first the antidepressant activity of the EFCG. The results suggested the therapeutic potential of EFCG for depressive disorder.

Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of schizophrenia patients.

Alterations in microRNAs (miRNAs) have been considered to have diagnostic implications in most diseases, but few studies have reported dysregulated miRNAs in schizophrenia (SCZ). In order to observe an association between miRNAs and SCZ, this study was designed to investigate expression profiling of miRNAs in peripheral blood mononuclear cells (PBMCs). miRNA microarray technology was employed to compare the expression of miRNAs in PBMCs from SCZ patients (n=105) and normal controls (n=130), and real-time quantitative polymerase chain reaction (QPCR) was used to analyze the results. Several important miRNA levels were examined before and after antipsychotic treatment in first-onset SCZ patients. In addition, an SCZ-like rat model was established using dizocilpine (MK-801), and miR-132 expression in PBMCs and whole-brain tissue from SCZ-like rats was studied using QPCR. In humans, dysregulated miRNAs were observed before treatment and QPCR verified that miR-132, miR-134, miR-1271, miR-664(⁎), miR-200c and miR-432 levels were significantly decreased (P<0.01 for all) in PBMCs of SCZ patients compared with healthy controls. After antipsychotic treatment there was a marked increase in miR-132 (P<0.01), miR-664(⁎) (P<0.05) and miR-1271 (P<0.05) levels in SCZ patients compared with the levels before treatment. In the animal assays, miR-132 levels declined in PBMCs and whole-brain tissues (both P<0.05) of the SCZ-like rats compared to controls. For the first time, our results suggest that miR-132 is a potential and superior biomarker in peripheral blood that will allow discrimination of SCZ patients from healthy controls.

The interaction between the oxytocin and pain modulation in headache patients.

Oxytocin (OXT), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of OXT to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that OXT in the central nervous system rather than the blood circulation plays an important role in rat pain modulation. The communication tried to investigate the interaction between the OXT and pain modulation in Chinese patients with headache to understand the OXT effect on human pain modulation. The results showed that (1) intranasal OXT could relieve the human headache in a dose-dependent manner; (2) OXT concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients in relation with the pain level; and (3) there was a positive relationship between plasma and CSF OXT concentration in headache patients. The data suggested that intranasal OXT, which was delivered to the central nervous system through olfactory region, could treat human headache and OXT might be a potential drug of headache relief by intranasal administration.

[Expressional changes of neuregulin-1 gene mRNA in peripheral blood from schizophrenia patients].

OBJECTIVE: To explore the effect of anti-psychotic treatment on the expression of Neuregulin-1 (NRG1) mRNA in the peripheral blood lymphocytes of schizophrenia patients. METHODS: The NRG1 mRNA in peripheral blood lymphocytes was measured using semi-quantitative reverse transcription (RT)-PCR in 80 first-onset schizophrenia patients, 37 sibling controls and 83 non-related controls. The patients were treated with risperdone and quetiapine for 4 weeks. Positive and negative symptom scale (PANSS) was used to evaluate the severity and clinical efficacy. RESULTS: Prior to the treatment, the expression of NRG1 mRNA expression was significantly lower in patients than other two groups (F=73.004, P=0.000). From the second week on, the level of NRG1 mRNA expression in patients became significantly higher than before and gradually increased, whilst no significant difference between sib and non-sib controls. Prior to the treatment, there was significant correlation (r=-0.232, P=0.038) between the level of NRG1 mRNA and PANSS scores. Four weeks after the treatment, a significant correlation between the reduction rate of PANSS and the change of NRG1 mRNA (r=0.27, P=0.016). CONCLUSION: The expression of NRG1 gene mRNA is associated with schizophrenia. Decreased expression of NRG1 may play a role in the development of schizophrenia, which can be improved by anti-psychotic drugs.

Roux-en-Y gastric bypass promotes expression of PDX-1 and regeneration of beta-cells in Goto-Kakizaki rats.

AIM: To study the effects of Roux-en-Y gastric bypass (RYGB) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and pancreatic beta-cell regeneration/neogenesis, and their possible mechanisms in diabetics. METHODS: Three groups of randomly selected non-obese diabetic Goto-Kakizaki (GK) rats were subjected to RYGB, sham-RYGB and sham-operation (sham-op) surgery, respectively. The rats were euthanized at post-operative 1, 2, 4 and 12 wk. Their pancreases were resected and analyzed using reverse transcription polymerase chain reaction to detect the mRNA of PDX-1. Anti-PDX-1 immunohistochemical (IHC) staining and Western blotting were used to detect the protein of PDX-1. Double IHC staining of anti-Brdu and -insulin was performed to detect regenerated beta-cells. The index of double Brdu and insulin positive cells was calculated. RESULTS: In comparison with sham-RYGB and sham-op groups, a significant increase in the expressions of PDX-1 mRNA in RYGB group was observed at all experimental time points (1 wk: 0.378 +/- 0.013 vs 0.120 +/- 0.010, 0.100 +/- 0.010, F = 727.717, P < 0.001; 2 wk: 0.318 +/- 0.013 vs 0.110 +/- 0.010, 0.143 +/- 0.015, F = 301.509, P < 0.001; 4 wk: 0.172 +/- 0.011 vs 0.107 +/- 0.012, 0.090 +/- 0.010, F = 64.297, P < 0.001; 12 wk: 0.140 +/- 0.007 vs 0.120 +/- 0.010, 0.097 +/- 0.015, F = 16.392, P < 0.001); PDX-1 protein in RYGB group was also increased significantly (1 wk: 0.61 +/- 0.01 vs 0.21 +/- 0.01, 0.15 +/- 0.01, F = 3031.127, P < 0.001; 2 wk: 0.55 +/- 0.00 vs 0.15 +/- 0.01, 0.17 +/- 0.01, F = 3426.455, P < 0.001; 4 wk: 0.39 +/- 0.01 vs 0.18 +/- 0.01, 0.22 +/- 0.01, F = 882.909, P < 0.001; 12 wk: 0.41 +/- 0.01 vs 0.20 +/- 0.01, 0.18 +/- 0.01, F = 515.833, P < 0.001). PDX-1 mRNA and PDX-1 protein production showed no statistical significance between the two sham groups. Many PDX-1 positive cells could be found in the pancreatic islets of the rats in RYGB group at all time points. In addition, the percentage of Brdu-insulin double staining positive cells was higher in RYGB group than in the other two groups (1 wk: 0.22 +/- 0.13 vs 0.03 +/- 0.06, 0.03 +/- 0.06, P < 0.05; 2 wk: 0.28 +/- 0.08 vs 0.00 +/- 0.00, 0.03 +/- 0.06, P < 0.05; 4 wk: 0.24 +/- 0.11 vs 0.07 +/- 0.06, 0.00 +/- 0.00, P < 0.001; 12 wk: 0.20 +/- 0.07 vs 0.03 +/- 0.06, 0.00 +/- 0.00, P < 0.05). CONCLUSION: RYGB can increase the expression of pancreatic PDX-1 and induce the regeneration of beta-cells in GK rats. The associated regeneration of islet cells may be a possible mechanism that how RYGB could improve type 2 diabetes mellitus.

[Association analysis of neuregulin 1 gene polymorphism with schizophrenia in Chinese Han population].

OBJECTIVE: To investigate the association of the Neuregulin 1(NRG1) gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent-proband trios. METHODS: Quantitative real-time PCR was used to check the genotypes of four SNPs-rs221533(C/T), rs7820838(C/T), 433E1006(A/G) and rs3924999(C/T), located at the 5o terminus of the Nrg1 gene, in 258 Chinese Han schizophrenic parent-proband trios. The transmission disequilibrium test (TDT) program (Genehunter software 2.0) was used to evaluate the association of the NRG1 gene with schizophrenia. RESULTS: For all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parent-proband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively (rs221533: chi-square was 27.45, P was 0.000; 433E1006: chi-square was 56.08, P was 0.000; rs3924999: chi-square was 10.53, P was 0.001). Haplotype was analyzed at frequency exceeding 1%. In three-marker-haplotype, C/C/G and C/C/A (marker order: rs221533, rs7820838, 433E1006) transmitted predominantly(C/C/G: chi-square was 5.26, P was 45.08; C/C/A: chi-square was 0.026, P was 0.000). In four-marker-haplotype (marker order: rs221533, rs7820838, 433E1006, rs3924999), C/C/G/T, C/C/A/C and C/C/A/T showed transmission disequilibrium (C/C/G/T: chi-square was 10.71, P was 0.001; C/C/A/C: chi-square was 8.83, P was 0.006, C/C/A/T: chi-square was 27.00, P was 0.000). In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed. CONCLUSION: The NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.

The interaction of nuclear factor-kappa B and cytokines is associated with schizophrenia.

BACKGROUND: Many reports suggest that schizophrenia is associated with the inflammatory response mediated by cytokines, and nuclear factor-kappa B (NF-kappaB) regulates the expression of cytokines. However, it remains unclear whether the interaction between NF-kappaB and cytokines is implicated in schizophrenia and whether the effect of neuroleptics treatment for 4 weeks is associated with the alteration of cytokines. METHODS: Sixty-five healthy subjects and 83 first-episode schizophrenic patients who met DSM-IV criteria and who were never treated with neuroleptics previously were included. Serum levels of cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were examined by using sandwich enzyme immunoassay (EIA). Peripheral blood mononuclear cell (PBMC) mRNA expressions of cytokines (IL-1beta, TNF-alpha) and NF-kappaB were detected by using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). NF-kappaB activation was examined by using transcription factor assay kits. RESULTS: Schizophrenic patients showed significantly higher serum levels and PBMC mRNA expressions of IL-1beta and TNF-alpha compared with healthy subjects. However, treatment with the neuroleptic risperidone for 4 weeks significantly decreased serum levels and PBMC mRNA expressions of IL-1beta in schizophrenic patients. NF-kappaB activation and PBMC mRNA expression in patients were significantly higher than those in healthy subjects. Furthermore, PBMC mRNA expressions of IL-1beta and TNF-alpha were positively correlated to NF-kappaB activation in both schizophrenic patients and healthy control subjects. CONCLUSIONS: Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappaB activation may play a pivotal role in schizophrenia through interaction with cytokines.

Explorative study on the expression of neuregulin-1 gene in peripheral blood of schizophrenia.

Neuregulin-1 (Nrg-1)(1) gene has been considered as a schizophrenia susceptibility gene. In order to observe the association of Nrg-1 gene with schizophrenia, the study was designed to investigate the effect of anti-psychotic treatment on the Nrg-1 mRNA expression in peripheral blood lymphocytes of the patients with a diagnosis of schizophrenia. The Nrg-1 mRNA expression in peripheral blood lymphocytes (PBLs) was measured by using semi-quantitative RT-PCR in 31 first-onset schizophrenia patients, 16 sibling controls and 31 no-sibship controls. Results showed that Nrg-1 mRNA expression in PBLs of patients was lower than that in other two control groups (F=6.722, P=0.002). However, as follow-up time extended, from the second week, Nrg-1 mRNA expression of PBLs in antipsychotic treated patients gradually increased and has obvious statistical significance compared the efficacy of taking anti-psychotic before and after therapy. These results demonstrated that Nrg-1 gene has association with schizophrenia. It is possible to select Nrg-1 mRNA expression of PBLs in schizophrenia patients as a potential therapeutic marker.

[Association study of the polymorphisms of monoamine oxidase A genes with schizophrenia].

OBJECTIVE: To investigate the relationship between monoamine oxidase A (MAOA) gene polymorphisms and schizophrenia in a Chinese Han population. METHODS: Two hundred and twelve schizophrenic patients and 168 healthy controls were recruited according to CCMD-3. The polymorphisms of MAOA gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The case-control association analysis was adopted to analyze the frequencies of genotype and allele in schizophrenic patients and controls. RESULTS: (1) The genotypes of MAOA gene were consistent with Hardy-Weinberg equilibrium in patient group and control group (chi2 = 0.618, df= 2, P> 0.05; chi2 = 3.173, df= 2, P> 0.05). (2) The distributions of genotypes or alleles of MAOA genes had no significant difference between patient group and control group (P> 0.05). (3)Divided by sex, the frequency of CT genotype in male patients was higher than that in male controls (chi2 = 7.654, P= 0.022). (4) There were no significant differences of genotypic and allelic distribution in MAOA genes between schizophrenic patients with positive family history and schizophrenic patients with negative family history and among different clinical subtypes in schizophrenic patients (P> 0.05). CONCLUSION: No association between MAOA gene and schizophrenia is found in Chinese Han population, but CT genotype is likely to be a susceptible factor of male schizophrenia.