Courtet P, Gottesman II, Jollant F, Gould TD. The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies? Transl Psychiatry 1: 1-7

Department of Emergency Psychiatry, CHRU Montpellier, Inserm U1061, University of Montpellier I, Montpellier, France.
Translational Psychiatry (Impact Factor: 5.62). 05/2011; 1(5):e7. DOI: 10.1038/tp.2011.6
Source: PubMed


Vulnerability to suicidal behavior (SB) is likely mediated by an underlying genetic predisposition interacting with environmental and probable epigenetic factors throughout the lifespan to modify the function of neuronal circuits, thus rendering an individual more likely to engage in a suicidal act. Improving our understanding of the neuroscience underlying SBs, both attempts and completions, at all developmental stages is crucial for more effective preventive treatments and for better identification of vulnerable individuals. Recent studies have characterized SB using an endophenotype strategy, which aims to identify quantitative measures that reflect genetically influenced stable changes in brain function. In addition to aiding in the functional characterization of susceptibility genes, endophenotypic research strategies may have a wider impact in determining vulnerability to SB, as well as the translation of human findings to animal models, and vice versa. Endophenotypes associated with vulnerability to SB include impulsive/aggressive personality traits and disadvantageous decision making. Deficits in realistic risk evaluation represent key processes in vulnerability to SB. Serotonin dysfunction, indicated by neuroendocrine responses and neuroimaging, is also strongly implicated as a potential endophenotype and is linked with impulsive aggression and disadvantageous decision making. Specific endophenotypes may represent heritable markers for the identification of vulnerable patients and may be relevant targets for successful suicide prevention and treatments.

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Available from: Irving Gottesman, Oct 05, 2015
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    • "They may be of neurophysiological, biochemical , endocrinological, neuroanatomical, cognitive, or neuropsychological nature. The most commonly accepted criteria for a genetically influenced endophenotype include trait identification in an objective and quantitative manner in patients before onset of the disorder and/or periods of remission ; they should also run in families and be associated with an increased risk of clinical illness (Courtet et al., 2011). Endophenotypes thus provide critical evidence on the mechanistic pathways associated with genetic susceptibility. "
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    ABSTRACT: Objective: Genetically at-risk yet healthy relatives of patients with schizophrenia, sharing an important part of the genetic susceptibility to the disease, allow the study of neuroimaging endophenotypes. The aim of our study was to perform a meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies that compared adult healthy relatives of patients with schizophrenia and controls. Methods: Twenty-one whole-brain fMRI studies were included (17 using cognitive tasks and four using emotional tasks), published between 2003 and 2013. These studies included 467 healthy relatives of patients with schizophrenia and 768 controls. To conduct the statistical analysis, we used the effect-size signed differential mapping software, a voxel-based meta-analytic approach. Results: In healthy relatives of patients with schizophrenia, we observed a general pattern of overactivation across the 21 fMRI studies in right-sided frontal, parietal and temporal regions compared to controls. This pattern was accompanied by an underactivation in the cingulate gyrus. Our analyses showed a very similar pattern during purely cognitive tasks; during emotional tasks, healthy relatives additionally overactivated the left parahippocampal gyrus. Conclusions: This fMRI pattern of prefrontal overactivation and hypoactivation of the cingulate gyrus may represent a candidate endophenotype for schizophrenia.
    Australian and New Zealand Journal of Psychiatry 06/2014; 48(10). DOI:10.1177/0004867414540753 · 3.41 Impact Factor
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    • "Indeed, Conrad et al. (2009) has reported that different character dimensions are associated with attempters vs ideators (low 'self-directedness'). Other studies clearly suggest that there may be a neurobiological difference (Courtet et al., 2011). In our study we collapsed plans and attempts into the one category, on the basis that suicide planning is an initial step towards an intentional motor behaviour, which we regard more as a behaviour than a thought. "
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    ABSTRACT: The Interpersonal-Psychological Theory of Suicide (IPTS) has been supported by recent research. However, the nature of the models׳ three major constructs - perceived burdensomeness, thwarted belongingness and acquired capability - requires further investigation. In this paper, we test a number of hypotheses about the predictors and correlates of the IPTS constructs. Participants aged 32-38 from an Australian population-based longitudinal cohort study (n=1167) were assessed. IPTS constructs were measured by items from the Interpersonal Needs Questionnaire (INQ) and Acquired Capability for Suicide Scale (ACSS), alongside demographic and additional measures, measured concurrently or approximately 8 years earlier. Cross-sectional analyses evaluating the IPTS supported earlier work. Mental health was significantly related to all three IPTS constructs, but depression and anxiety caseness were associated only with perceived burdensomeness. Various social support measures were differentially associated with the three constructs. Stressful events and lifetime traumas had robust independent associations with acquired capability for suicide only. The IPTS model provides a useful framework for conceptualising suicide risk. The findings highlight the importance of perceived social support in suicide risk, identify the importance of personality and other factors as new avenues of research, and provide some validation for the independence of the constructs.
    Psychiatry Research 05/2014; 219(2). DOI:10.1016/j.psychres.2014.05.029 · 2.47 Impact Factor
    • "This results in personality developments, such as aggression and/or impulsivity traits, which can lead to suicidal behavior, especially under the influence of acute stressors or psychopathological states. This figure is a suggestive conceptual model but far from definitive: many more genes, gene–gene interactions, are involved, not mentioned here due to the specific focus of the review (for genes beyond the serotonergic system, see Rujescu and Giegling (2010); many neurobiological, cognitive and personality changes are also involved, for extensive reviews on such endophenotypes of suicide, see Courtet et al. (2011) and Mann et al. (2009) "
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    ABSTRACT: Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly heritable. Neurobiological evidence implicates serotonergic dysfunction in suicidality, stimulating genetic research to focus on genes related to the serotonergic system. In this paper, we review evidence from studies examining the association between various serotonergic genes (Tryptophan Hydroxylase genes: TPH1; TPH2, Serotonin Transporter gene: 5-HTTLPR in SLC6A4, Serotonin Receptor genes: HTR1A, HTR2A, HTR1B, HTR2C and Monoamine Oxidase A gene: MAOA) and suicidal behavior. The data show associations between variation on the TPH1 gene and 5-HTTLPR gene and violent suicidal behavior in Caucasian populations, with the least inconsistencies. Results are mixed for the TPH2 gene and serotonin receptor genes, but for some genes, studies that include haplotypic analyses or that examine a larger coding region of the genes tend to provide more reliable results. Findings on endophenotypes of suicidality, such as aggression and impulsivity traits, show positive associations for the TPH1, HTR2A, and MAOA genes, but need further replication, since negative associations are also occasionally reported. Since genes can only partially explain suicidal risk, several studies during the past decade have tried to incorporate environmental factors in the susceptibility model. Studies to date show that variation on the 5-HTTLPR, MAOA and HTR2A gene can interact with stressful life events to increase risk for suicidal behavior. Limitations of case-control studies are discussed and future considerations are put forward with regard to endophenotypic measurements and gene-environment interactions.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2013; 23(10). DOI:10.1016/j.euroneuro.2013.03.013 · 4.37 Impact Factor
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