Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Hilary P. Blumberg

Subject Area(s)

Neurosciences, Mental health

Abstract

Suicide is one of the leading causes of death in the adolescent and young adult population. Furthermore, it is estimated that for every completed suicide there are many more attempters. The majority of suicide attempters have a mood disorder and neuroimaging research on the neural circuitry of suicidal behavior has primarily focused on these individuals. However, few studies have been designed to compare suicidal behavior across diagnoses. We used diffusion tensor imaging (DTI) to investigate white matter (WM) integrity in Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in adolescents and young adults with a history of suicide attempt. Participants included 21 BD attempters, 18 MDD attempters, 25 BD non-attempters, 17 MDD non-attempters and 43 healthy control (HC) subjects. Analyses were performed to identify similarities and differences in fractional anisotropy (FA) between attempters as compared to non-attempters and HCs. Correlations between FA values and several clinical variables were explored including childhood maltreatment, a risk factor for mood disorders and suicidal behavior. Across all attempters, there was decreased FA in WM in regions of the left and right dorsomedial prefrontal cortex (dmPFC), bilateral ventral anterior commissure/uncinate fasciculus (AC/UF), right anterior cingulate cortex (ACC), and a region within the right putamen. BD attempters showed distinct decreases in WM FA, compared to BD non-attempters, in bilateral uncinate fasciculus (UF), and the right orbitofrontal cortex (OFC). MDD attempters showed decreases in FA in WM within the dorsolateral prefrontal cortex (dlPFC). Across all BD and MDD subjects, suicidal ideation was negatively correlated with FA values in the left dmPFC, right dmPFC bilateral AC/UF, and right ACC. In addition, across all attempters, physical abuse was positively correlated with values in the left dlPFC These results provide evidence for commonalites in suicide attempters across BD and MDD as well as differences within diagnoses. Commonalities within this age group may provide evidence for shared mechanisms of development of suicidal behavior. Further investigation of the differences may be useful for diagnosis-specific suicide prevention and treatment studies.

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