Frontal-Limbic Abnormalities and Early Life Stress in Susceptibility and Resilience to Suicide

Why do some individuals die by suicide while others who have a similar background and experiences do not? Our goal is to identify neurobiological and environmental risk factors (and their interplay) that can help determine who goes on to develop suicidal attempts and ideation (susceptibility) versus who does not (resilience). Previous work using both animal and human post-mortem studies from our collaborators shows a key role for the hippocampus, a key region of the frontal-limbic neural circuit, in susceptibility and resilience to depression and suicide after early life stress. This proposal builds on these studies and combines my background in hippocampal neuroscience research with psychiatric epidemiology to translate these findings to clinical populations.

The study will test these questions in a unique three-generation longitudinal family study of depression that contains a battery of neuroimaging and early childhood data. The clustering of suicidal attempts and ideation within families in the study sample allows us to study the role of hippocampus and other frontal-limbic biomarkers as well as early life adversity across groups of (1) individuals at high familial risk with a personal history of suicide attempts and ideations (susceptible); (2) individuals at high familial risk without a personal history of suicide attempts and ideations (resilience); (3) individuals without a personal or family history of suicide attempts and ideations (controls).

The broad aims of the study are to (1) identify frontal-limbic markers of susceptibility and resilience in individuals at high family risk for suicide; (2) identify early life adversity markers that predispose to subsequent suicide attempts and ideations and to test whether these are mediated by the frontal-limbic circuitry.

The predicted contribution of the study is to provide a better understanding of frontal-limbic mechanisms through which early life adversity increases suicide susceptibility and resilience in individuals at high familial risk for suicide.