Polymorphism of rs12294045 in EAAT2 gene is potentially associated with schizophrenia in Chinese Han population.

BACKGROUND: Recent studies have shown that the excitatory amino acid transporters (EAATs) are associated with schizophrenia. The aim of this study was to investigate the relationship between the polymorphism of EAAT1 and EAAT2 genes and schizophrenia in Chinese Han population. METHODS: A total of 233 patients with schizophrenia and 342 healthy controls were enrolled. Two SNPs in EAAT1 gene (rs2269272, rs2731880) and four SNPs in EAAT2 gene (rs12360706, rs3088168, rs12294045, rs10836387) were genotyped by SNaPshot. Clinical features were collected using a self-made questionnaire. Psychotic symptoms of patients were measured by the Positive and Negative Syndrome Scale (PANSS), and patients' cognitive function was assessed by Matrics Consensus Cognitive Battery (MCCB). RESULTS: Significant difference in allelic distributions between cases and controls was confirmed at locus rs12294045 (Ρ = 0.004) of EAAT2 gene. Different genotypes of rs12294045 were associated with family history (P = 0.046), in which patients with CT genotype had higher proportion of family history of psychosis. The polymorphism of rs12294045 was related to working operational memory (LNS: P = 0.016) and verbal learning function (HVLT-R: P = 0.042) in patients in which CT genotype had lower scores. However, these differences were no longer significant after Bonferroni correction. CONCLUSIONS: Our study showed that the polymorphism of rs12294045 in EAAT2 gene may be associated with schizophrenia in Chinese Han population. CT genotype may be one of the risk factors for family history and cognitive deficits of patients.

Evidence for an Interaction Between NEDD4 and Childhood Trauma on Clinical Characters of Schizophrenia With Family History of Psychosis.

Background: Neural precursor cell-expressed developmentally downregulated 4 (NEDD4) polymorphisms and childhood trauma (CT) are associated with schizophrenia. However, whether NEDD4 interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene-environment interaction effect. Methods: We recruited 289 schizophrenia patients and 487 controls and genotyped rs2303579, rs3088077, rs7162435, rs11550869, and rs62043855 in their NEDD4 gene. Results: We found significant differences in the rs2303579 and rs3088077 between the two groups. Patients with the rs2303579 CC genotype had higher scores compared with other genotype (P = 0.026) in the test of positive schizophrenia syndrome scores, whereas patients with the rs3088077 TT (P = 0.037) and rs7162435 CC genotypes (P = 0.009) had higher scores compared with the other genotypes in the test of excitement factor. Patients with a family history of psychosis (FH+) reported higher negative scores (P = 0.012) than those without. Patients exposed to physical abuse (PA) reported a lower language learning and memory score (P = 0.017) and working memory score (P = 0.047) than those not. Patients exposed to sexual abuse (SA) reported a lower reasoning and problem-solving skills score (P = 0.025); those exposed to emotional neglect (EN) reported a lower social cognition score (P = 0.044); and those exposed to physical neglect reported a lower social cognition score (P = 0.036) but higher visual learning and memory score (P = 0.032). Rs3088077 could interact with EN to increase risk for schizophrenia. Optimal model rs62043855 × EA, rs3088077 × rs7162435 × rs11550869 × SA × EN and rs2303579 × rs7162435 × rs11550869 × rs62043855 × EA × PA could explain positive symptom, excitement symptom and working memory, respectively, in FH+ group. Conclusion: The study highlighted that the combined interaction of NEDD4 and CT may be associated with symptoms of schizophrenia especially for those with FH+.

Dynamic MRI Reconstruction via Weighted Tensor Nuclear Norm Regularizer.

In this paper, we propose a novel multi-dimensional reconstruction method based on the low-rank plus sparse tensor (L+S) decomposition model to reconstruct dynamic magnetic resonance imaging (dMRI). The multi-dimensional reconstruction method is formulated using a non-convex alternating direction method of multipliers (ADMM), where the weighted tensor nuclear norm (WTNN) and l1-norm are used to enforce the low-rank in L and the sparsity in S, respectively. In particular, the weights used in the WTNN are sorted in a non-descending order, and we obtain a closed-form optimal solution of the WTNN minimization problem. The theoretical properties provided guarantee the weak convergence of our reconstruction method. In addition, a fast inexact reconstruction method is proposed to increase imaging speed and efficiency. Experimental results demonstrate that both of our reconstruction methods can achieve higher reconstruction quality than the state-of-the-art reconstruction methods.

Epigenetic Alterations of the Promoter Region of the POMC Gene in Adolescent Depressive Disorder Patients with Nonsuicidal Self-injury Behaviors.

PURPOSE: The incidence of nonsuicidal self-injury (NSSI) behavior among adolescents increases year by year. Patients with a history of both depression and NSSI behaviors tend to have greater risk of suicide. At present, the mechanism of adolescent depressive disorder patients with NSSI behaviors is not clear, epigenetic mechanism may be involved. Proopiomelanocortin (POMC) gene may be associated with depressive disorder. The purpose of this study was to investigate DNA methylation of POMC gene promoter region of adolescent depressive disorder patients with NSSI behaviors. METHODS: Bisulfite Sequencing PCR (BSP) was used to test the methylation level of POMC promoter of 15 adolescent depressive disorder patients with NSSI behaviors and 15 healthy controls (HC). Self-made questionnaires were used to collect clinical data of the case group and control group. Hamilton depression scale-24 (HAMD-24), Hamilton anxiety scale (HAMA), Symptom Checklist-90 (SCL-90) were used to evaluate the characteristics and severity of depressive, anxiety and psychotic symptoms. Adolescent self-injury questionnaire was used to assess NSSI behaviors and its severity. RESULTS: BSP analysis found that the POMC methylation level of cytosine-guanine dinucleotide 1 (CpG1) site was higher in the case group than that of HC (P<0.05). The significance in POMC methylation at CpG1 between case group and HC was gender-independent, and CpG1 methylation level was higher in both male (P<0.05) and female (P<0.05) patients than that in HC. The CpG1 methylation level had a little correlation trends with family history of psychosis (P=0.05). We also found that POMC methylation level at CpG17 in female patients was significantly higher than that of the female HC (P<0.05). CONCLUSION: There was abnormal methylation in the POMC promoter region of adolescent depressive disorder patients with NSSI behaviors, the methylation of CpG1 may act as epigenetic markers for those adolescents.

Association between polymorphism of the NEDD4 gene and cognitive dysfunction of schizophrenia patients in Chinese Han population.

BACKGROUND: Schizophrenia is a complex psychiatric disorder with unknown etiology. A number of recent studies have shown that the polymorphism of the neural precursor cell expressed developmentally down-regulated 4 (NEDD4) gene is associated with a variety of neuropsychiatric disorders, such as schizophrenia, and may also be associated with cognitive dysfunction in these diseases. METHODS: A case-control study was carried out, the alleles and genotypes distributions of five loci (rs3088077, rs2303579, rs7162435, rs11550869, rs62043855) of the NEDD4 gene from 296 schizophrenia patients and 320 healthy controls were detected by using Taqman single-nucleotide polymorphism (SNP) genotyping technology. The clinical data of case and control group members were collected by self-made questionnaire and the psychotic symptoms of case group members were assessed by the Positive and Negative Syndrome Scale (PANSS). The Matrics Consensus Cognitive Battery (MCCB) was used to test the cognitive function of case group members. RESULTS: The alleles and genotypes frequency of two loci (rs3088077, rs2303579) between case and control group showed significant differences (P <  0.05). There was no significant difference in MCCB scores of patients with different genotypes at rs3088077, rs11550869 and rs7162435 loci in case group. The study of rs2303579 locus showed that, patients' scores with CT genotype were significantly lower than those with CC and TT genotypes (P <  0.05) in the test of Wechsler Memory Scale-Third Edition (WMS-III): Spatial Span, the scores of patients with TT genotype were significantly higher than those with CT genotype (P < 0.05) in the test of Hopkins Verbal Learning Test-Revised (HVLT-R). The study of rs62043855 locus showed that patients with TG genotype had significantly lower scores than those with GG genotype (P < 0.05) in the test of Neuropsychological Assessment Battery (NAB): Mazes. CONCLUSIONS: Our study showed that in schizophrenia patients of Chinese Han population, the polymorphisms of rs3088077 and rs2303579 loci were related to the pathogenesis of schizophrenia, while the polymorphisms of rs2303579 and rs62043855 loci were associated with cognitive dysfunction.

Prevalence, clinical correlates and IQ of suicidal ideation in drug naïve Chinese Han patients with major depressive disorder.

BACKGROUND: Suicidal ideation (SI) is a common and serious clinical concern in people with major depressive disorder (MDD). Inconsistent evidence suggests that individuals with SI may have a lower measured intelligence quotient (IQ) than those without SI. The aims of this study were to examine SI prevalence and its associations with demographic, clinical variables and IQ in Chinese drug-naïve MDD patients. METHODS: 488 drug-naïve Chinese Han patients (male: 203, 41.6%) meeting a DSM-IV diagnosis of MDD were enrolled in a cross-sectional study involving seven hospitals. All participants were asked to complete a series of questionnaires, which include information on socio-demographic and clinical variables. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Brief Psychiatric Rating Scale (BPRS) were also administered. Verbal IQ (VIQ), performance IQ (PIQ) and full-scale IQ (FIQ) scores were measured using the Chinese version of the Wechsler Adult Intelligence Scale-Ⅲ (WAIS-Ⅲ). We categorized patients with SI based on a cut-off score of ≥3 on HAMD item 3. RESULTS: An estimated prevalence 32.8% (160/488) of drug-naïve MDD patients experienced SI during the current episode of illness. Patients with SI were more likely to be divorced (x2 = 6.93, p = 0.031), male (x2 = 6.04, p = 0.014), had higher severity of depression and anxiety symptoms (t = -8.14, p < 0.001, t = -3.28, p < 0.001, respectively), comorbid psychotic features (t = -5.71, p < 0.001), and lower FIQ levels (t = -4.21, p < 0.001), when compared to patients without SI. Using logistic regression analysis and adjusting for confounding variables, the following variables were independently associated with SI: divorced marital status compared to married (OR=4.674, 95% CI: 1.676~13.036), severity of depression symptoms (OR=1.312, 95% CI: 1.196~1.440), psychotic features (OR=1.044; 1.012~1.077), and FIQ /PIQ levels which expressed in OR per SD increase in IQ score (OR=0.740, 95% CI: 0.561~0.977; OR=0.744, 95% CI: 0.557~0.994, respectively). LIMITATIONS: A cross-sectional study which did not assess the influence of severity of SI. CONCLUSIONS: The prevalence of SI in drug-naive Chinese patients with MDD is high, and associated with marital status, severity of depression, psychotic features and measured IQ. Further research is needed to further explore these and other potentially relevant risk factors which might affect clinical outcomes.

Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms.

The gene - environment (G × E) interaction effect is involved in severe mental disorders. However, whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism participates in the childhood-abuse influenced schizophrenic symptoms remains unclear. We examined the interaction between BDNF Val66Met, and childhood trauma (ChT) on psychotic symptoms in a Chinese Han population.To estimate the G × E interaction, psychiatric interviews, self-report questionnaires for ChT, and genotyping for BDNF Val66Met were carried out on 201 schizophrenic patients. G × E interactions were analyzed by generalized multifactor dimensionality reduction (GMDR).Among all patients, 11.9%, 19.4%, 23.4%, 26.4%, and 73.6% reported emotional abuses, physical abuses (PA), sexual abuses (SA), emotional neglects (EN), and physical neglects (PN), respectively. Significant negative correlations were observed between anxiety/depression factors, and ChT total scores. Patients with 3 different BDNF genotypes showed significant differences in anxiety/depression scores. Significant 2-way interactions were found for Val66Met × PN, 3-way interactions were found for Val66Met × PN × PA, and four-way interactions were found for Val66Met × PN × PA × EN with regard to the excitement scores.Our findings suggested an involvement of BDNF Val66Met polymorphism after ChT in terms of risk for schizophrenia symptoms.

[Association of NEDD4 gene polymorphisms with schizophrenia and its clinical characteristics in Chinese Han population].

OBJECTIVE: To assess the association of neural precursor cell expressed developmentally down-regulated 4 (NEDD4) with schizophrenia. METHODS: Five single nucleotide polymorphisms (SNPs) of the NEDD4 gene were genotyped by TaqMan SNP genotyping assay in an independent sample of 464 individuals with schizophrenia and 487 healthy controls from eastern Han Chinese population. Clinical data were collected with a general information questionnaire and Positive and Negative Syndrome Scale (PANSS). RESULTS: Frequencies of rs3088077 (allelic: χ2=18.024, P=0.000; genotypic: χ2=16.634, P=0.000), rs7162435 (allelic: χ2=6.771, P=0.009; genotypic: χ2=7.352, P=0.025) and rs2303579 (allelic: χ2=11.253, P=0.001; genotypic: χ2=12.248, P=0.002) were found to be significant different between the two groups. Moreover, TT of rs7162435 was significantly correlated with scores of factors of excitement and hostility (14.53±3.925, F=3.551, P=0.029). CONCLUSION: rs3088077, rs7162435 and rs2303579 of the NEDD4 gene may be associated with schizophrenia. Moreover, the TT genotype of rs7162435 may increase the severity of excitement and hostility. Our results may provide a clue for delineating the connection between the glutamate hypothesis of schizophrenia and ubiquitination.

The interaction of polymorphisms of IL10 and DBH was associated with general symptoms of PANSS with TD in Chinese Han schizophrenic patients.

OBJECTIVE: Tardive dyskinesia (TD) is a human hyperkinetic movement disorder as a result of potentially irreversible long-term chronic first-generation antipsychotic medications. Unfortunately, mechanisms involved in the development of TD have been poorly understood. Previous studies have indicated that some genetic polymorphisms of immune system and dopamine beta-hydroxylase (DBH) genes may be involved in the pathogenesis of TD. Rs1800872 and rs72393728 are located on the promoter of interleukin-10 (IL10) and DBH gene, respectively. The genetic association between the rs1800872 and TD is unclear. Previous studies have indicated that genetic variations of IL 10 and DBH are implicated in the positive and negative symptoms in schizophrenia. However, the interaction of two variations with severity of TD and symptoms of schizophrenic patients with TD has not been reported. The present study investigated whether these variations and their interaction were associated with clinical phenotypes of TD with schizophrenia in a genetically homogeneous northern Chinese Han population. METHODS: Rs1800872 and rs72393728 were genotyped in schizophrenic patients with TD (n = 372) and without TD (NTD; n = 412). The Abnormal Involuntary Movement Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were applied to assess the severity of TD and psychopathology of schizophrenia, respectively. RESULTS: The allele and genotype frequencies of rs1800872 and rs72393728 did not significantly differ between TD and NTD patients (p>0.05). No significant difference was found in the AIMS total score among the genotypes of two loci (p>0.05). Interestingly, the interaction of rs1800872 and rs72393728 showed a significant association with the PANSS general score (p = 0.011), and a trend toward to the PANSS total score (p = 0.055). CONCLUSION: These findings suggest that the interaction of rs1800872 and rs72393728 variants may play a role in psychopathology of the general symptoms on PANSS in schizophrenic patients with TD in a northern Chinese Han population.

BDNF Val66Met polymorphism and anxiety/depression symptoms in schizophrenia in a Chinese Han population.

BACKGROUND: Although several lines of evidences suggest that the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be involved in the pathophysiology of schizophrenia, this association remains controversial. Here, we aim to investigate the genetic association between the BDNF Val66Met polymorphism and schizophrenia and to explore whether this polymorphism could influence the severity of clinical symptoms in schizophrenic patients in a Chinese Han population. PATIENTS AND METHODS: Genotyping of the BDNF Val66Met polymorphism was carried out in 456 schizophrenic patients and 483 controls using the fluorescence resonance energy transfer method. The patients' psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. The general clinical data of schizophrenic patients were analyzed. RESULTS: There were significant differences in the genotype distribution and allelic frequencies of the BDNF Val66Met polymorphism between the schizophrenia group and the controls. Multiple linear regression analysis showed that the BDNF Val66Met polymorphism explained ~16% of the variance in anxiety/depression symptoms in schizophrenic patients. CONCLUSION: Our data provide evidence that the BDNF Val66Met polymorphism may be involved in the etiology of schizophrenia in a Chinese Han population. Furthermore, the BDNF Val66Met polymorphism is a significant factor influencing the severity of anxiety/depression symptoms in schizophrenic patients.

[Association study of brain-derived neurotrophic factor Val66Met polymorphism and clinical characteristics of first episode schizophrenia].

OBJECTIVE: To assess the association between brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism and clinical characteristics of first episode schizophrenia in a Chinese Han population. METHODS: Genotyping of BDNF Val66Met polymorphism was carried out for 135 schizophrenic patients and 483 healthy controls with TaqMan probe technology. The patients' psychotic symptoms were assessed using the positive and negative syndrome scale (PANSS). RESULTS: A significant difference was found in genotype distribution and allelic frequency of the Val66Met polymorphism between the two groups (P< 0.01). In patients, Met homozygotes had a significantly higher score in anxiety/depression factor, cognitive factor and total score of PANSS than Val carriers. CONCLUSION: BDNF gene Val66Met polymorphism is associated with the pathogenesis of schizophrenia. The Met/Met genotype of BDNF Val66Met variant may be a risk factor for symptoms in first episode schizophrenia patients.