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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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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.

Project description:BackgroundDigital mental health interventions offer unique advantages, and research indicates that these interventions are effective for a range of mental health concerns. Although these interventions are less established for individuals with serious mental illnesses, they demonstrate significant promise. A central consideration in traditional face-to-face therapies is the therapeutic alliance, whereas the nature of a digital therapeutic alliance and its relationship with outcomes requires further attention, particularly for individuals with serious mental illnesses.ObjectiveThis narrative review aims to encourage further consideration and critical evaluation of the therapeutic alliance in digital mental health, specifically for individuals with serious mental illnesses.MethodsA narrative review was conducted by combining 3 main areas of the literature: the first examining the evidence for digital mental health interventions for serious mental illnesses, the second illuminating the nature and role of the therapeutic alliance in digital interventions, and the third surrounding practical considerations to enhance a digital therapeutic alliance.ResultsResults indicated that a therapeutic alliance can be cultivated in digital interventions for those with serious mental illnesses, but that it may have unique, yet-to-be-confirmed characteristics in digital contexts. In addition, a therapeutic alliance appears to be less directly associated with outcomes in digital interventions than with those in face-to-face therapies. One possibility is that the digital therapeutic alliance is associated with increased engagement and adherence to digital interventions, through which it appears to influence outcomes. A number of design and implementation considerations may enhance the digital therapeutic alliance, including human support and technological features.ConclusionsMore research is required to further understand the nature and specific role of a therapeutic alliance in digital interventions for serious mental illnesses, particularly in informing their design. This review revealed several key research priorities to advance the therapeutic alliance in digital interventions.

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

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