Interaction of CEND1 gene and life events in susceptibility to depressive symptoms in Chinese Han college students.

BACKGROUND: . The development of depressive symptoms (DSs) is a complex process caused by both genetic and environmental factors. CEND1 gene coordinates cell division, differentiation and maturation of neural precursor cells, which affects brain structure and function. Our study investigated whether CEND1 was a genetic factor for DSs, particularly under negative life events. METHODS: . 272 freshmen with DSs and 467 healthy controls were recruited via the Center for Epidemiologic Studies Depression Scale (CES-D). The adolescent Self-rating Life Event Checklist (ASLEC) was adopted to assess stressful life events during the past 12 months. Two SNPs (rs7946354, rs6597982) within the CEND1 gene were genotyped using Agena MassARRAY iPLEX technology. We combined generalized multifactor dimensionality reduction (GMDR) with RStudio programming to assess the direct association and gene-environment interaction (G × E). RESULTS: . Rs7946354 was associated with DSs in an overdominant model (GT vs. GG+TT). In addition, both rs7946354 and rs6597982 had considerable impacts on negative life events. GMDR showed a statistical G × E that the AG genotype of rs6597982 and GT genotype of rs7946354 contribute to the maximum risk of DSs under high negative life events. LIMITATIONS: . Only two single nucleotide polymorphisms (SNPs) were examined. Verification studies with bigger sample size and more varied demographic background information could be adopted to further support the generalization of these findings. CONCLUSIONS: .CEND1 can potentially cause high sensitivity to life events and affect DSs especially in the presence of negative life events, which contribute to the field of depression prevention and treatment.

Influence and interaction of genetic, cognitive, neuroendocrine and personalistic markers to antidepressant response in Chinese patients with major depression.

OBJECTIVE: Despite there is a wide range of antidepressants available, with various mechanisms of actions, the efficacy of current therapeutic options is yet satisfactory. Previous shreds of evidence have indicated that genetics, cognitive, neuroendocrine, as well as personality factors, are all intrinsically linked and contribute to the diversity of treatment outcomes. We, therefore, sought to investigate this hypothesis in this study. METHOD: Based on 610 samples treated with a selection of serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) or tricyclic antidepressant (TCA), we compared the therapeutic effects of these four classes of drugs by survival analyses. Pharmacogenomic and survival analyses were carried out to explore the hereditary factors for curative effect and the accumulation of genetic factors was further discussed through pathway analysis and the global test. We built a machine learning-based prediction model that integrates genetic and non-genetic factors (including cognition, endocrinology, personality intelligence) to distinguish drug efficacy in single class drug situations. The values of the non-genetic makers after 6 weeks' treatment were collected to evaluate the efficacy of the model. RESULTS: Our results from the 6-week antidepressant therapeutic study indicated that SSRI and SNRI are better treatments than those of TCA and NaSSA in the Chinese population. Among all possible paired single-agent survival analyses, citalopram and venlafaxine were more effective than mirtazapine. Allele C carriers at rs6354 (SLC6A4) and allele G carriers at rs12150214 (SLC6A4) were significantly prone to poorer treatment response to fluoxetine. Besides, the combination of three loci (rs929377-rs6191-rs32897) located in HPA pathway was significantly associated with the treatment outcome of fluoxetine. In female MDD patients, the minor allele of rs6323 and rs1137070 on the MAOA gene likely lead to a worse response to venlafaxine. Furthermore, genetic variants linked to drug efficacy tended to concentrate on the neurotrophin pathway in depressed patients comorbid with anxiety. From multivariate models, more severe cognitive deficits, psychopathic personality and lower levels of operational intelligence, and higher levels of cortisol predicted worse response status with SSRI or SNRI after 6-week treatment. Notably, genetic factors in the multi-dimensional prediction model for both classes of drugs include loci in HTR2A and CRHBP genes. CONCLUSION: SSRI and SNRI are more suitable for the treatment of Chinese people with depression. SLC6A4 genetic variants, as well as HPA pathway, play an important role in the fluoxetine antidepressant therapeutic response while the polymorphism of MAOA gene involved in the pharmacological action of venlafaxine among female MDD patients. The presence of anxiety in MDD patients was related to the neurotrophin pathway. Genetic, cognitive, neuroendocrine, and personality intelligence factors combined have an ensemble impact on the medication effect of patients with major depression, leading to more precise and personalized medicine for specific groups of people.

Role of rs454214 in Personality mediated Depression and Subjective Well-being.

Happiness and depression are interlinked and both heritable, while personality, as an important predictor of them, shares the genetic basis with them. We conjecture that genetic factors of depression can affect both depressive symptoms (DS) and subjective well-being (SWB), while personality traits play important roles in mediating this process. In this study, 878 Han Chinese college freshmen and 384 Han Chinese patients with the major depressive disorder (MDD) were included. SNPs were genotyped using AGENA MassARRAY iPLEX technology and we investigated an important MDD variant rs454214. Correlation, association and mediation analysis were employed, aiming to decipher the complex relationship between SWB, DS, personality traits and the genetic variant. Association study indicated that rs454214 was not only associated with both SWB and DS (P < 0.05), but also possibly linked to MDD. Mediational analysis showed that rs454214 had no direct effect on SWB and DS, but had a significant indirect effect through personality traits, i.e., Extraversion, Neuroticism, Agreeableness and Openness to Experience or SWB, Extraversion, Neuroticism and Agreeableness for DS. This study found a shared genetic basis for happiness and depression; the causal process could be better explained if personality traits are taken as mediating factors.

A novel NR3C2 polymorphism and the increased thyroid-stimulating hormone concentration are associated with venlafaxine treatment outcome in Chinese Han MDD patients.

OBJECTIVE: We aimed to study the association among venlafaxine antidepressive outcome, NR3C2 gene polymorphisms and the change of two neuroendocrine hormones during treatment. METHODS: 195 Chinese Han major depressive disorder (MDD) patients were recruited and received a 6-week venlafaxine treatment in this study. Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) levels were measured at the beginning and at the end of treatment. Six single-nucleotide polymorphisms (SNPs) (NR3C2: rs1512325, rs1512342, rs2070951; NR3C1: rs6191, rs6196, rs10482614) were selected for high-throughput SNP genotyping. Allele and genotype frequencies of them were compared between remission and non-remission groups. RESULTS: We found that genotype frequency of the rs1512325 located in the NR3C2 gene was significantly different between remission and non-remission groups respectively (p < 0.05). Meanwhile, the frequency of the rs1512325 C-allele was significantly lower (p < 0.05) in remission group. The TSH concentration significantly increased after venlafaxine treatment in remission group (p < 0.05). CONCLUSION: The rs1512325 in NR3C2 gene and TSH concentration may be related to venlafaxine treatment outcome in Chinese Han MDD patients.

Prediction of adolescent subjective well-being: A machine learning approach.

BACKGROUND: Subjective well-being (SWB), also known as happiness, plays an important role in evaluating both mental and physical health. Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood. AIM: The present paper aims to predict undergraduate students' SWB by machine learning method. METHODS: Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10 518 Chinese adolescents. The online survey included 298 factors such as depression and personality. Quality control procedure was used to minimise biases due to online survey reports. We applied feature selection to achieve the balance between optimal prediction and result interpretation. RESULTS: The top 20 happiness risks and protective factors were finally brought into the predicting model. Approximately 90% individuals' SWB can be predicted correctly, and the sensitivity and specificity were about 92% and 90%, respectively. CONCLUSIONS: This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.

Metabolomic profiling on rat brain of prenatal malnutrition: implicated for oxidative stress and schizophrenia.

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring. All these abnormalities are highly consistent with the pathophysiology of schizophrenia. We developed a prenatal famine rat model by restricting daily diet of the pregnant rat to 50% of low protein diet. A metabolomics study of prefrontal cortex was performed to integrate GC-TOFMS and UPLC-QTOFMS. Thirteen controls and thirteen famine offspring were used to differentiate in PLS-DA (partial least squares-discriminate analysis) model. Furthermore, metabolic pathways and diseases were enriched via KEGG and HMDB databases, respectively. A total of 67 important metabolites were screened out according to the multivariate analysis. Schizophrenia was the most statistical significant disease (P = 0.0016) in our famine model. These metabolites were enriched in key metabolic pathways related to energy metabolism and glutamate metabolism. Based on these important metabolites, further discussion speculated famine group was characterized by higher level of oxidized damage compared to control group. We proposed that oxidative stress might be the pathogenesis of prenatal undernutrition which is induced schizophrenia.

A Case-Control Study of ABCB1, ABCB6, and ABCG1 Polymorphisms and Schizophrenia in a Han Chinese Population.

BACKGROUND: Schizophrenia (SCZ) is a complex, heritable, and devastating psychiatric disorder. Mutations in the members of ABC transporters have been associated with psychiatric illnesses. AIMS: In this study, we investigated whether 9 SNPs in ABCB1 (rs6946119, rs28401781, rs4148739, and rs3747802), ABCB6 (rs1109866, rs1109867, rs3731885, and rs3755047), and ABCG1 (rs182694) contribute to the risk of SCZ in a Han Chinese population. METHODS: We conducted a case-control study in a Han Chinese population, involving 1,034 SCZ patients and 1,034 unrelated healthy controls to genotype 9 SNPs. RESULTS: The analysis demonstrated that rs182694 of ABCG1 was significantly different between SCZ patients and controls as to allele (rs182694: p = 0.0070, χ2 = 7.27) and genotype frequencies (rs182694: p = 0.0013, χ2 = 13.35). CONCLUSIONS: Our findings support an association between ABCG1 polymorphism and SCZ in a Han Chinese population.

GRIK4 and GRM7 gene may be potential indicator of venlafaxine treatment reponses in Chinese of Han ethnicity.

Venlafaxine is one of commonly prescribed antidepressants for major depressive disorder (MDD). Accumulated evidence implicates the involvement of glutamatergic receptors in the pathophysiology of MDD and antidepressant treatment.By using 193 MDD patients who have been taking venlafaxine for 6 weeks, we investigated whether single nucleotide polymorphisms (SNPs) in glutamate ionotropic receptor kainate type subunit 4 (GRIK4), glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) and glutamate metabotropic receptor 7 (GRM7) were associated with treatment response. 14 SNPs were selected randomly depended on association studies. Efficacy of treatment was determined by 17-item of Hamilton Rating Scale. Allele and genotype frequencies were compared between responders and non-responders.After adjusting by the false discovery rate (FDR), rs6589847 and rs56275759 in GRIK4 and rs9870680 in GRM7 showed associating with venlafaxine treatment response at week 6. (FDR: P = .018, P = .042, and P = .040, respectively).Our results indicated that genetic variants in the GRIK4 and GRM7 may associate with the treatment response in MDD patients treated by venlafaxine.

GSK-3ß and BDNF genes may not be associated with venlafaxine treatment response in Chinese of Han ethnicity.

PURPOSE: Venlafaxine is one of the commonly prescribed antidepressants for major depressive disorder (MDD). Accumulated evidence revealed the involvement of glutamatergic system in the pathophysiology of MDD and antidepressant treatment. METHODS: We recruited 193 MDD patients who have been taking venlafaxine for 6 weeks, and investigated whether single nucleotide polymorphisms (SNPs) in GSK-3ß and BDNF were associated with treatment response. Nine SNPs were selected randomly depending on association studies. Efficacy of treatment was determined by 17-item Hamilton Rating Scale. Allele and genotype frequencies were compared between responders and nonresponders. RESULTS: After adjusting the false discovery rate, no significant difference was observed between response and nonresponse groups in allele or genotype distributions after venlafaxine treatment for 6 weeks. CONCLUSION: Our results indicated that genetic variants in the GSK-3ß and BDNF may not be associated with treatment response in MDD patients treated with venlafaxine.

Porcine reproductive and respiratory syndrome virus counteracts type I interferon-induced early antiviral state by interfering IRF7 activity.

Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease with a significant impact on the pig industry. It is caused by PRRS virus (PRRSV), which predominantly infects and replicates in porcine pulmonary alveolar macrophages (PAMs). We pretreated PAMs with porcine interferon (IFN)-α to induce an antiviral state within the cells and subsequently infected them with highly pathogenic PRRSV. Changes in global gene expression in IFN-α-pretreated PAMs in response to PRRSV infection were determined by RNA-sequence analysis and confirmed by real-time PCR. We found that IRF7 and other antiviral interferon stimulating genes (ISG)s were suppressed by PRRSV infection. Further studies demonstrated that PRRSV could down-regulate the expression of IRF7 by the non-structure protein 7 (nsp7). In conclusion, PRRSV infection had a strong immunosuppressive effect of IFN. PRRSV nsp7 inhibits the expression of IRF7, thereby down-regulating the expression of IFN and downstream ISGs and facilitated the virus to replicate.

No association of BRD1 and ZBED4 polymorphisms with schizophrenia in the Chinese Han population.

The distal long arm of chromosome 22 (22q13.3) may harbor genes implicated in schizophrenia. This is evidenced by various genetic mapping studies. BRD1 and its neighboring gene ZBED4, both located within this region, have repeatedly been found to be associated with schizophrenia in the Caucasian population. In this study, we chose seven SNPs (two BRD1 SNPs, five ZBED4 SNPs) to carry out an association study between these two genes and schizophrenia in the Chinese population. However, no significant result was obtained, which was consistent with the Japanese population. Taken together, we could conclude that BRD1 and ZBED4 might be population specific in schizophrenia and may not account for a substantial proportion of genetic risk for schizophrenia in the Asian population.