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.


Available from: Irving Gottesman
    • "social negative events like marital conflict or job loss, depression or alcohol abuse (Mann, 2003a). This lower ability to respond adequately to stress is also highlighted by numerous studies showing deficient cognitive functioning, notably disadvantageous decision-making (Richard-Devantoy et al., 2013b; Courtet et al., 2011a) or reduced cognitive inhibition (Richard-Devantoy et al., 2012a). Decision-making impairment and deficient cognitive control were viewed to contribute to suicidal behavior synergistically, yet independently (Richard-Devantoy et al., 2013c). "
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    ABSTRACT: Objective: Disadvantageous decision-making (mainly measured by the Iowa Gambling Task) has been demonstrated in patients with suicidal behavior compared to controls. We, therefore, aimed at clarifying the qualitative and quantitative relationship between decision-making and the risk of suicidal behavior in unipolar and bipolar disorders respectively, as well as establishing the strength of this relationship. Methods: (1) We conducted a cross-sectional study comparing IGT performances between 141 unipolar suicide attempters and 57 bipolar suicide attempters. (2) We conducted a systematic review and a meta-analysis of studies comparing IGT performances in patients with vs. without a history of suicidal acts in bipolar and unipolar disorder, together and separately. Results: (1) Among suicide attempters, bipolar and unipolar groups performed similarly (t(195)=-0.7; p=0.48). Unipolar non-attempters performed better IGT than unipolar suicide attempters (t(221)=3.1; p=0.002), only in female gender, whereas performances were similar in bipolar patients whatever the history of suicide attempt (t(77)=-0.3; p=0.7). (2) A meta-analysis of 10 studies confirmed significantly impaired decision-making with a moderate effect-size (-0.38 (95% CI[-0.61--0.16]; z=-3.3; p=0.001) in unipolar disorder and (g=-0.4 (95% CI[-0.75 to -0.05]; z=-2.2; p<0.026) in bipolar disorder suicide attempters compared to unipolar and bipolar non-attempters, respectively. Limitations: It was not possible to analyse according to the level of lethality attempt. Conclusion: Overall, a strong significant association was found between decision-making and the risk of suicidal behavior in unipolar disorder and bipolar disorder. However, further neuropsychological studies need to analyse separately unipolar and bipolar disorder and to study gender differences.
    Journal of Affective Disorders 10/2015; 190:128-136. DOI:10.1016/j.jad.2015.10.001 · 3.38 Impact Factor
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    • "Thus, suicidal vulnerability may involve long-term difficulties in the ability to perceive and respond to social environment. Great hopes have been put on the ability of neuroscientific research to uncover the intimate pathophysiological mechanisms of suicidal vulnerability, to reveal biomarkers that may help to detect patients at risk of suicide, and to identify targets of interventions and markers of response (Courtet et al., 2011) Preliminary neroimaging findings have pointed toward several brain regions associated with suicidal vulnerability that are related to comorbid mental disorders like depression (Jollant et al., 2011). However, a major issue is the frequent lack of replication of biological findings in psychiatry (Kapur et al., 2012). "
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    ABSTRACT: Suicidal vulnerability has been related to impaired value-based decision-making and increased sensitivity to social threat, mediated by the prefrontal cortex. Using functional magnetic resonance imaging, we aimed at replicating these previous findings by measuring brain activation during the Iowa Gambling Task and an emotional faces viewing task. Participants comprised 15 euthymic suicide attempters (history of depression and suicidal behavior) who were compared with 23 euthymic patient controls (history of depression without suicidal history) and 35 healthy controls. The following five model-based regions of interest were investigated: the orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (VLPFC), anterior cingulate cortex (ACC), medial (MPFC) and dorsal prefrontal cortex (DPFC). Suicide attempters relative to patient controls showed (1) increased response to angry vs. neutral faces in the left OFC and the VLPFC, as previously reported; (2) increased response to wins vs. losses in the right OFC, DPFC and ACC; (3) decreased response to risky vs. safe choices in the left DPFC; and (4) decreased response to sad vs. neutral faces in the right ACC. This study links impaired valuation processing (here for signals of social threat, sadness and reward) to prefrontal cortex dysfunction in suicide attempters. These long-term deficits may underlie the impaired decision-making and social difficulties found in suicide attempters.
    Psychiatry Research: Neuroimaging 10/2015; DOI:10.1016/j.pscychresns.2015.09.020 · 2.42 Impact Factor
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    • "Of considerable clinical interest, therefore , is the hypothesis that decision-making deficits may be involved in the pathophysiology and/or the chronicity of psychiatric disorders (Goschke, 2014). Impaired decision-making may also be a heritable marker for the identification of vulnerable patients (Courtet et al. 2011) and, should this be so, it would be a relevant target for prevention and treatment. Although many tasks simulate the various aspects of decision-making (such as uncertainty, risk-taking and temporal discounting ), the most widely used is the Iowa gambling task (IGT), which measures the preference for risky and disadvantageous choices in a context of uncertainty (the participant is unable to assess the long-term risk associated with each option). "
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    ABSTRACT: Background: Impaired decision-making is a potential neurocognitive phenotype of eating disorders. It is therefore important to disentangle the decision-making deficits associated with the eating disorder subtypes and determine whether this putative impairment is a state or trait marker of the disease or more related to starvation. We systematically reviewed the literature on decision-making in eating disorders and conducted a meta-analysis to explore its role in anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). Method: A search of the Medline and EMBASE databases and article references was performed. A total of 23 studies (2044 participants) met the selection criteria. When the Iowa gambling task (IGT) was used in at least three of the studies, a meta-analysis was run. Results: IGT performance was significantly worse in patients with an eating disorder diagnosis (AN, BN or BED) compared with healthy controls, indicating that eating disorders have a negative effect on decision-making. Hedges' g effect sizes were moderate to large (-0.72 in AN, -0.62 in BN, and -1.26 in BED). Recovered AN patients had IGT scores similar to those of healthy controls. Restrictive AN patients had significantly lower IGT net scores than purging AN patients, and both AN subtypes had worse performances than healthy controls. Age and body mass index did not explain results. Conclusions: Decision-making was significantly altered in patients with eating disorders. Poor decision-making was more pronounced during the acute phase than in the recovered state of AN. Nutritional status during the acute phase of the disease did not seem to influence decision-making skills.
    Psychological Medicine 09/2015; 45(16):1-15. DOI:10.1017/S003329171500152X · 5.94 Impact Factor
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