Suicidality in Bipolar and Major Depression Disorders

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The rate of mortality by suicide is approximately twenty times higher in psychiatric disorders as compared to the general population. Among psychiatric disorders, bipolar disorder (BD) has the highest rate of attempts (~40%), which is 2-3 times higher than in major depressive disorder (MDD). While neural circuits underlying suicidal behavior have been proposed, these have emerged largely based on studies of MDD and exclude the cerebellum. Work from our group and others have implicated the cerebellum in suicidal behavior, impulsivity, and bipolar disorder suggesting that it may play a key role in suicidal behavior. In this study, we propose to study a putative suicide risk circuit (SRC) that includes the cerebellum to prospectively evaluate the connectome of this neural circuit and metabolism in the nodes of the proposed SRC. To assess the SRC, brain imaging coupled with measurements of suicidal behavior, psychiatric symptoms, and personality traits will be acquired in a sample of 300 subjects with a psychiatric disorder (BD I and MDD) with 75 having a prior suicide attempt and 75 without a prior attempt for each psychiatric diagnosis. Seventy-five matched controls will also be acquired. Brain imaging will include multi-modal MR imaging to study anatomy (T1, T2), functional (task based fMRI), connectome (resting state fMRI and diffusion imaging) and metabolism (MRS and T1ρ). This data will be used to answer the following aims: Aim 1) Does the SRC differentiate suicide attempter from non- attempter in BD? and Aim 2) Does the SRC differentiate suicide attempter / non-attempter in MDD in the same way as BD? This work will increase our understanding of the brain circuits implicated in suicidal behavior, how the cerebellum may be involved in these circuits, and what metabolic differences are associated with suicidal behavior. In addition, the study will reveal if the same neural circuit (i.e. the SRC) plays a significant role in suicidal behavior across disorders or if there are different neural circuits involved across disorders. The goal of this project is to better undertand the neurobiology of suicidality to help identify those at risk for a future suicide attempt. We anticipate that this study will reveal new targets for treating subjects at risk for suicidal behavior. .