Dataset Information

The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.

ABSTRACT: Psychiatric disorders (such as bipolar disorder, depression, and schizophrenia) affect the lives of millions of individuals worldwide. Despite the tremendous efforts devoted to various types of psychiatric studies and rapidly accumulating genetic information, the molecular mechanisms underlying psychiatric disorder development remain elusive. Among the genes that have been implicated in schizophrenia and other mental disorders, disrupted in schizophrenia 1 (DISC1) and glycogen synthase kinase 3 (GSK3) have been intensively investigated. DISC1 binds directly to GSK3 and modulates many cellular functions by negatively inhibiting GSK3 activity. The human DISC1 gene is located on chromosome 1 and is highly associated with schizophrenia and other mental disorders. A recent study demonstrated that a neighboring gene of DISC1, translin-associated factor X (TRAX), binds to the DISC1/GSK3? complex and at least partly mediates the actions of the DISC1/GSK3? complex. Previous studies also demonstrate that TRAX and most of its interacting proteins that have been identified so far are risk genes and/or markers of mental disorders. In the present review, we will focus on the emerging roles of TRAX and its interacting proteins (including DISC1 and GSK3?) in psychiatric disorders and the potential implications for developing therapeutic interventions.

SUBMITTER: Weng YT

PROVIDER: S-EPMC6171312 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.

Weng Yu-Ting YT Chien Ting T Kuan I-I II Chern Yijuang Y

Journal of biomedical science 20181004 1

Psychiatric disorders (such as bipolar disorder, depression, and schizophrenia) affect the lives of millions of individuals worldwide. Despite the tremendous efforts devoted to various types of psychiatric studies and rapidly accumulating genetic information, the molecular mechanisms underlying psychiatric disorder development remain elusive. Among the genes that have been implicated in schizophrenia and other mental disorders, disrupted in schizophrenia 1 (DISC1) and glycogen synthase kinase 3 ...[more]

PMID: 30285728

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Project description:BACKGROUND:It is presumed that pharmacological and non-pharmacological treatment of prenatal common mental disorders can mitigate associated adverse effects in offspring, yet strong evidence for the prophylactic benefits of treatment is lacking. We therefore examined the effect of prenatal treatments for common mental disorders on offspring outcomes. METHODS:For this meta-analysis, articles published up to August 31, 2017, were obtained from PubMed, PsycInfo, Embase, and Cochrane databases. Included studies needed to be randomized controlled trials (RCTs) on the effect of treatment of prenatal common mental disorders comparing an intervention to a control condition, including offspring outcome(s). Random effects models were used to calculate Hedges' g in the program Comprehensive Meta-Analysis© (version 3.0). RESULTS:Sixteen randomized controlled trials among 2778 pregnant women compared offspring outcomes between prenatal interventions and control groups. There were zero pharmacological, 13 psychological, and three other interventions (homeopathy, relaxation interventions, and short psycho-education). Birth weight (mean difference 42.88 g, g?=?0.08, 95% CI -0.06 to 0.22, p?=?0.27, n?=?11), Apgar scores (g?=?0.13, 95% CI -0.28 to 0.54, p?=?0.53, n?=?4), and gestational age (g?=?0.03, 95% CI -0.06 to 0.54, p?=?0.49, n?=?10) were not significantly affected. Other offspring outcomes could not be meta-analyzed due to the inconsistent reporting of offspring outcomes and an insufficient number of studies. CONCLUSIONS:Non-pharmacological interventions had no significant effect on birth outcomes, although this outcome should be considered with caution due to the risk of biases. No randomized controlled trial examined the effects of prenatal pharmacological treatments as compared to treatment as usual for common mental disorders on offspring outcomes. Present clinical guidelines may require more research evidence on offspring outcomes, including child development, in order to warrant the current recommendation to routinely screen and subsequently treat prenatal common mental disorders. TRIAL REGISTRATION:PROSPERO CRD42016047190.

Dataset Information

The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.

Publications

The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.

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