Patients meeting clinical criteria for major depressive disorder (MOD) can present with varied clinical symptomatology including, but not limited to dysphoria, anhedonia, feelings of guilt/worthlessness, sleep disturbance, abnormal appetite, motor slowing, loss of energy, restlessness, and agitation. This heterogeneity within the current psychiatric nosological classification system interferes with the research and clinical treatment of MOD. Translational research, utilizing behavioral, electrophysiological, hemodynamic, and self-report methodology, offers the possibility to examine the correlation between the cortical regions hypothesized to be critical for distinct cognitive processes and variations in depressive symptomatology. As this research progresses the knowledge gained can be applied towards the implementation of targeted pharmacological treatments incorporating information pertaining to the involved neural regions of individual patients, and/or the tailoring of psychological therapies to address a specific pattern of dysfunction. The eventual result of this translational research would be the drastic improvement of treatment efficacy. Recently, advances in neuroimaging techniques have uncovered reliable structural and functional cortical abnormalities in patients with MOD. Specifically, evidence suggests that depression is associated with executive dysfunction, particularly in situations requiring adaptive behavioral adjustments in response to negative feedback or perceived failure. These deficits can be particularly debilitating, and are often associated with decreased functioning and increased hospitalization rates. When this literature is combined with findings implicating certain neural networks as critical subcomponents of adaptive behavioral responses clear patterns emerge. The project described herein proposes two studies to examine the neural underpinnings of this specific aspect of depressive symptomatology. In each study participants will perform a Stroop task coupled with a feedback manipulation. During the study sessions event-related potentials (ERP; study 1) and functional magnetic resonance imaging (fMRI; study 2) data will be collected. This research will assess the temporal and spatial nature of the cortical processes associated with the commission of errors and the receipt of task-relevant feedback in patients with MOD and healthy control participants. Isolating specific components of MOD and the associated underlying neural networks will encourage the development of individually tailored therapies and pharmacological interventions with the eventual goal of improving diagnoses and treatment. ? ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F12B-J (20))
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Rubio, Mercedes
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Harvard University
Schools of Arts and Sciences
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Holmes, Avram J; Bogdan, Ryan; Pizzagalli, Diego A (2010) Serotonin transporter genotype and action monitoring dysfunction: a possible substrate underlying increased vulnerability to depression. Neuropsychopharmacology 35:1186-97
Holmes, Avram J; Pizzagalli, Diego A (2010) Effects of task-relevant incentives on the electrophysiological correlates of error processing in major depressive disorder. Cogn Affect Behav Neurosci 10:119-28
Chiu, Pearl H; Holmes, Avram J; Pizzagalli, Diego A (2008) Dissociable recruitment of rostral anterior cingulate and inferior frontal cortex in emotional response inhibition. Neuroimage 42:988-97
Holmes, Avram J; Pizzagalli, Diego A (2008) Response conflict and frontocingulate dysfunction in unmedicated participants with major depression. Neuropsychologia 46:2904-13
Holmes, Avram J; Pizzagalli, Diego A (2008) Spatiotemporal dynamics of error processing dysfunctions in major depressive disorder. Arch Gen Psychiatry 65:179-88