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Investigating Genetic and Epigenetic Changes in the HPA Axis in Suicidal Behavior

2013 Postdoctoral Fellowship
Amount Awarded: $104,000
Focus Areas: Neurobiological Studies, Genetic Studies

Marie Breen, Ph.D.
University of Iowa

Mentor: Virginia Willour, Ph.D., University of Iowa

Inside the Research

Bio: Dr. Breen received her doctorate at Queen's University in Belfast, U.K. in 2012. She is currently a Postdoctoral Research Fellowship Researcher in the Department of Psychiatry at the University of Iowa.

Research Categories: Neurobiology, Genetics

Abstract:Our response to stress is managed, in part, by the genetics of our hypothalamic-pituitary-adrenal (HPA) axis, or stress response system. Environmental factors such as early childhood physical and sexual abuse can alter one’s HPA axis, potentially increasing the risk for suicide.  Using two state-of-the-art approaches to genetics, this series of studies will examine the genetics of the HPA axis and stress in relation to suicide.

Previously, the investigators found that suicidal behavior was linked to specific genes associated with the HPA axis.  However, a fuller picture of suicide will only emerge as genetic susceptibility is considered in combination with other factors, such as environmental risk factors and epigenetic changes (the way genes communicate). The investigators will put their efforts towards understanding how HPA axis genes and early trauma influence the risk for suicidal behavior in participants with major depression disorder (MDD). They will study 22 genes involved in the HPA axis. Genetic information will be provided by two federally funded studies, the Genetics of Recurrent Early-onset Depression (GenRED) and the Psychiatric Genomics Consortium. This Gene-by-environment (GxE) approach may shed light on this complicated process.

In addition, the researchers will study gene expression in the prefrontal cortex of samples from post-mortem brains of depressed subjects who died by suicide, depressed people who died of other causes, and psychiatrically healthy controls. The prefrontal cortex is the part of the brain that organizes and controls behavior and functioning in this area of the brain has been found to relate to suicidal behavior.  Again, the 22 HPA axis genes will be the focus and the most significant genes will be validated and screened for differential expression. The availability of the data from the federally funded studies allows the investigators to take the most promising findings from one sample and validate their findings in a second sample.

Impact:  The identification of possible genes and the process of gene expression will provide important new insights into the biological basis of suicidal behavior and new therapeutic targets.