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Serotonin, genetic variability, behaviour, and psychiatric disorders--a review.

ABSTRACT: Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development.

SUBMITTER: Nordquist N

PROVIDER: S-EPMC2853349 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Serotonin, genetic variability, behaviour, and psychiatric disorders--a review.

Nordquist Niklas N Oreland Lars L

Upsala journal of medical sciences 20100201 1

Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of ...[more]

PMID: 20187845

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Project description:IntroductionThe bioethics literature reflects significant interest in and concern with the use of genetic and genomic information in various settings. Because psychiatric treatment and research raises unique ethical, legal, and social issues, we conducted a scoping review of the biomedical, bioethics, and psychology literature regarding the application of genetic and genomic tools to psychiatric disorders (as listed in the DSM-5) and two associated behaviors or symptoms to provide a more detailed overview of the state of the field.ObjectivesThe primary objective was to examine the available bioethics, biomedical, and psychology literature on applying genetic and genomic tools to psychiatric disorders (other than neurodevelopmental disorders) and two behaviors or symptoms sometimes associated with them (aggression or violence and suicidality) to identify the disorders to which these tools have been applied, the contexts in or purposes for which they have been applied, the ethical, legal, or social concerns associated with those uses, and proposed recommendations for mitigating those concerns.MethodsWe used Arksey and O'Malley's scoping review framework: (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarize, and report results (2005). We relied on Levac et al. to inform our application of the framework (2010). The PRISMA extension for scoping reviews checklist informed our reporting (2018). We searched three electronic databases MEDLINE (PubMed), Embase, and PsycInfo (EbscoHost) for peer-reviewed journal articles in English to identify relevant literature. One author screened the initial results and additional screening was done in consultation with other authors. A data extraction form using DSM-5 diagnostic categories (excluding neurodevelopmental disorders) was developed and two authors independently each reviewed approximately half of the articles. Inter-rater reliability was ensured by double-coding approximately 10% of the papers. An additional author independently coded 10% of the articles to audit the data.ResultsIn 365 coded publications, we identified 15 DSM-5 diagnostic categories in addition to the two pre-selected behaviors or symptoms (aggression or violence and suicidality) to which genetic or genomic tools have been applied. We identified 11 settings in or purposes for which these tools were applied. Twenty-two types of ethical, legal, or social concerns associated with the application of genetic or genomic tools to these disorders or behaviors/symptoms were identified along with 13 practices or policies that could mitigate these concerns.ConclusionGenetic and genomic tools have been applied to a wide range of psychiatric disorders. These raise a range of ethical, legal, and social concerns. Additional research is warranted to better understand the concerns and effective ways to address them. Advancing the literature to identify relevant ethical, legal, or social concerns and solutions to those problems likely requires greater attention to specific applications of genetic or genomic tools to particular psychiatric disorders and associated behaviors/symptoms as well as broad stakeholder engagement.

Project description:Background: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour is explained by shared genetic aetiology. Methods: We identified nine genome-wide association statistics of suicidal behaviour (sample sizes, n, ranging from 62,648 to 125,844), ten psychiatric traits [n up to 386,533] and collectively, nine summary datasets of anthropometric, behavioural and socioeconomic-related traits [n ranging from 58,610 to 941,280]. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling, identified shared biological processes and pathways between suicidal behaviour and psychiatric disorders and evaluated potential causal associations using Mendelian randomisation. Results: Among populations of European ancestry, we observed strong positive genetic correlations between suicide ideation, attempt and self-harm (rg range, 0.71-1.09) and moderate to strong genetic correlations between suicidal behaviour traits and a range of psychiatric disorders, most notably, major depression disorder (rg = 0.86, p = 1.62 × 10-36). Multivariate analysis revealed a common factor structure for suicidal behaviour traits, major depression, attention deficit hyperactivity disorder (ADHD) and alcohol use disorder. The derived common factor explained 38.7% of the shared variance across the traits. We identified 2,951 genes and 98 sub-network hub genes associated with the common factor, including pathways associated with developmental biology, signal transduction and RNA degradation. We found suggestive evidence for the protective effects of higher household income level on suicide attempt [OR = 0.55 (0.44-0.70), p = 1.29 × 10-5] and while further investigation is needed, a nominal significant effect of smoking on suicide attempt [OR = 1.24 (1.04-1.44), p = 0.026]. Conclusion: Our findings provide evidence of shared aetiology between suicidal behaviour and psychiatric disorders and indicate potential common molecular mechanisms contributing to the overlapping pathophysiology. These findings provide a better understanding of the complex genetic architecture of suicidal behaviour and have implications for the prevention and treatment of suicidal behaviour.

Project description:IntroductionDialectical behaviour therapy (DBT) is a well-known intervention for treating borderline personality disorder, and has been increasingly adapted for other disorders. Standard DBT consists of four treatment modes, delivered over a year. Adaptations to DBT include changes to modes of delivery, treatment length, and skills modules taught to clients, or incorporating interventions from other evidence-based therapies. There is a need to synthesise existing evidence on DBT so that stakeholders-clinicians, researchers and policymakers-can understand how it has been provided for various psychiatric conditions, and whether it has been effective.Methods and analysisThis study proposes a scoping review conducted according to Arksey and O'Malley's (2005) procedures, to map and summarise the literature on DBT interventions for treating a range of psychiatric concerns. Electronic databases (ie, the Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, SCOPUS, EBSCOhost and ProQuest Dissertations and Theses), conference proceedings and the US National Institutes of Health Ongoing Trial Register will be searched for intervention studies that involve a control or comparison group, and that report quantitative data on pre/post-measures for psychiatric symptom severity. The initial search was conducted on 18 September 2020, and data charting has not commenced. An update will be performed in September 2022, pending this protocol's publication. Data charting will collect individual studies' characteristics, methodology and reported findings. Outcomes will be reported by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for Scoping Reviews.Ethics and disseminationNo ethical approval is required for this study. The goal of dissemination is to keep DBT stakeholders abreast on latest updates in clinical applications of DBT. Findings from this research are intended to inform a more specific topic of study (eg, a meta-analysis), to further aid in the development of DBT interventions for psychiatric populations.Registration detailsThe study protocol was pre-registered with the Open Science Framework on 24 August 2021 (https://osf.io/vx6gw).

Project description:There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

Dataset Information

Serotonin, genetic variability, behaviour, and psychiatric disorders--a review.

Publications

Serotonin, genetic variability, behaviour, and psychiatric disorders--a review.

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