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Research / Funded grants

2020 Young Investigator

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

1 research finding from this AFSP-funded study.

Research finding · January 2025

A family history of depression is often associated with an elevated risk for suicidal ideation

Depression runs in families across generations, contributing to elevated risks for various psychiatric disorders in offspring, including anxiety, ADHD, and suicidal ideation. The intergenerational transmission of depression involves complex genetic and environmental pathways, with children from families affected by depression experiencing higher rates of mental health challenges at younger ages. Understanding the genetic mechanisms underlying this transmission is essential for advancing prevention and intervention strategies, especially as genetic tools like polygenic scores become available. Polygenic risk scores are numerical values that reflect the potential cumulative effect genetics for a specific trait or disease.

With her AFSP grant, Dr. Milenna van Dijk analyzed data from over 8,000 children in the Adolescent Brain Cognitive Development (ABCD) study to investigate the role of polygenic scores (PGSs) in mediating the association between family history of depression and psychopathology among offspring. Dr. van Dijk found that children with two generations of familial depression had significantly higher PGSs for depression, which contributed to their increased risk for psychiatric outcomes, including anxiety, suicidal ideation, and other psychiatric disorders. These findings underscore the genetic basis of depression and highlight the value gained by combining genetic and family history assessments.

Citation: Cha, J., Lee, E., van Dijk, M., Kim, B., Kim, G., Murphy, E., Talati, A., Joo, Y., & Weissman, M. (2024). Polygenic scores for psychiatric traits mediate the impact of multigenerational history for depression on offspring psychopathology. Research square, rs.3.rs-4264742. https://doi.org/10.21203/rs.3.rs-4264742/v1

This finding comes from an AFSP-funded study — see the grant below ↓

The grant behind this work · 2020 Young Investigator

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

Milenna van Dijk, PhD

Milenna van Dijk, Ph.D.

New York State Psychiatric Institute

Mentor: Myrna Weissman, Ph.D., MSW

Amount awarded
$89,996 Focus area
Neurobiological, Psychosocial

Inside the Research

Some individuals with a family history of suicide die by suicide while others do not. Researchers will use brain imaging and childhood adversity data to investigate the neurobiological and environmental factors which influence whether individuals with a family history of suicide experience suicidal ideation or attempt suicide (i.e. susceptibility) or do not (i.e. resilience). The goal is to identify characteristics specific to susceptibility and resilience among individuals with high familial risk for suicide.

Full scientific abstract

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.

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