Over the past decade an important approach to describing and treating psychiatric disorders has been the application of cognitive neuroscience techniques to understanding the neural mechanisms underlying clinical dysfunction. For example, relative to healthy volunteers, individuals with major depressive disorder (MDD) may show hypoactivation of brain systems implicated in cognitive control (e.g. dorsal and ventrolateral prefrontal cortex, dIPFC and vIPFC) and hyperactivation of systems implicated in triggering emotional responses (e.g. the amygdala). Of particular interest is the extent to which such patterns may be related not just to MDD, but to suicide risk associated with depressive episodes. Although to date little functional imaging data have addressed this question, PET and postmortem work from Conte Center labs has shown that ventrolateral PFC and anterior cingulate hypofunction, as well as lower serotonin transporter binding in the amygdala and ventral/orbital PFC, may contribute to the risk of suicide or nonfatal suicide attempts. This proposal seeks to clarify these links, building on an emerging model of the cognitive control of emotion in healthy adults to examine the neural bases of a specific cognitive strategy for emotion regulation - known as reappraisal - in individuals with major depressive disorder who have attempted suicide (MDD-Atts), who have never attempted suicide (MDD-Non-Atts), healthy volunteers (HVs) and currently non-depressed adult offspring of MDD-Atts who may be at higher risk for suicide (HRs).
In Aims 1 -3, we will compare the neural correlates of reappraisal performance of MDD-Atts, MDD-NonAtts, and HVs to determine whether depressed individuals in general, and those who attempt suicide in particular (Aim 1) generate stronger negative emotions or have greater trouble down-regulating them, (Aim 2) generate weaker positive emotions or have greater trouble up-regulating them, or show patterns of regulation-related activity under Aims 1 and 2 that (Exploratory Aim 3) are related to abnormalities in 5-HT function (see P3), childhood adversity, stress responsiveness and/or aggression (see CEC). In Exploratory Aim 4 we ask whether HRs show response patterns under Aims 1-3 that resemble Atts, thereby suggesting a diathesis towards suicide.
; This proposal examines a level of analysis - that of functional neural systems involved in emotion regulation - intermediate to the lower levels examined in PET Project 3, Postmortem Project 1 and Animal Project 2, and the higher level examined in the Clinical Evaluation Core and Project 5 (i.e., clinical diagnoses). It therefore is positioned to bridge the gap between them, enabling the Conte Center as a whole to provide a multi-leveled description of the factors influencing suicide risk in major depressive disorder.
|Haghighi, Fatemeh; Xin, Yurong; Chanrion, Benjamin et al. (2014) Increased DNA methylation in the suicide brain. Dialogues Clin Neurosci 16:430-8|
|Schnieder, Tatiana P; Trencevska, Iskra; Rosoklija, Gorazd et al. (2014) Microglia of prefrontal white matter in suicide. J Neuropathol Exp Neurol 73:880-90|
|Oquendo, Maria A; Miller, Jeffrey M; Sublette, M Elizabeth (2013) Neuroanatomical correlates of childhood sexual abuse: identifying biological substrates for environmental effects on clinical phenotypes. Am J Psychiatry 170:574-7|
|Moreno, Carmen; Hasin, Deborah S; Arango, Celso et al. (2013) The bipolar-depressive continuum in the National Epidemiologic Survey on Alcohol and Related Conditions. Bipolar Disord 15:112-3|
|Sher, Leo; Mann, J John; Oquendo, Maria A (2013) Sleep, psychiatric disorders and suicide. J Psychiatr Res 47:135|