Suicidal behaviors remain mysterious acts. Fifty years of research have largely focused on a few socio-demographic and clinical risk factors that dramatically lack predictive power. Understanding these complex acts, in order to develop novel and individualized preventative strategies, will necessitate the use of alternative investigation tools and explicative models.
Over the last two decades, neuroimaging and neuropsychology have shed new lights on determinants of suicide vulnerability. Our group and others have notably identified risky decision-making as a major mechanism in suicidal behavior, notably in the transition from suicidal ideas to acts. Neuroimaging studies have mainly linked decision-making deficits to specific brain regions, especially the ventral and dorsal prefrontal cortices and the striatum (a set of deep subcortical brain structures).
Deficits in decision-making have been found to be more marked in suicide attempters who used a violent suicidal means (VSA), broadly defined as any suicidal act other than drug overdose and superficial cutting. Use of a violent suicidal means is associated with an increased risk of current or future death. Studies notably revealed a particular clinical and biological profile associated with VSA, including more impulsive-aggression traits and serotonergic deficits. Recently, the two groups applying to this grant reported that, while there was no overall group difference in local brain volumes between suicide attempters and patient controls, VSA differed from non-VSA in striatum volumes. In light of the heterogeneity of suicidal behavior, investigating specific subgroups of individuals with similar characteristics, such as VSA, may be a profitable strategy to elucidate more consistent alteration patterns in suicide behavior.
The general aim of the projected study will be to use cognitive neuroscience to investigate the cognitive and brain basis of violent suicidal behavior. Based on recent findings and models of decision-making, we hypothesize that VSA in comparison to non-VSA are characterized by a series of dysfunctional cognitive and physiological processes facilitating the suicidal transition. This includes high expected outcomes, high pain tolerance, low loss aversion, and low inhibition in an aversive context, in relation to structural and functional alterations in prefrontal-striatal networks.
To this aim, we will recruit from two European sites and compare 40 patients with a history of violent suicidal act, 40 patients with a personal history of only non-violent suicidal act, 40 patients with no personal or family history of suicidal behavior, and 40 healthy controls. Participants will be 25 to 60 year old males and females. They will be investigated at the clinical and neuropsychological levels, then will be scanned with 3T MRI scans using a combination of high-definition structural and functional sequences. These acquisitions will allow investigating alterations in structural and functional connectivity in the prefrontal-striatal networks. Analyses (computational modeling) will be applied to functional data to extract specific abnormal processes in VSA. Secondary analyses will link these brain alterations to selected peripheral measures of the serotonergic system. Finally, we will apply current classification approaches to identify that set of assessed multimodal measures, which best differentiate between attempters from non-attempters in general and VSA from non-VSA in particular.
Future research direction will comprise the use of these findings to develop targeted cognitive treatments.
