This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K23) titled """"""""Physiologic Studies of Anger in Depressed Patients"""""""". It allows the candidate, who has experience with clinical psychopharmacology and positron emission tomography (PET) activation studies, to gain expertise in psychophysiology and in vivo neuroreceptor imaging techniques in the study of affective dysregulation in major depressive disorder (MDD). Numerous PET studies have demonstrated abnormal metabolic patterns in anterior paralimbic structures in patients with MDD. Numerous PET studies following negative emotion induction paradigms in healthy controls have demonstrated that anterior paralimbic structures are involved in the processing of negative emotions such as sadness and disgust. Few studies have utilized these paradigms to study emotional processing in subjects with MDD, a disorder characterized by profound disturbances of affect regulation. Patients with a well-characterized subtype of MDD, MDD with anger attacks, present with sudden uncharacteristic spells of anger accompanied by autonomic activation. This subtype of MDD provides an opportunity to characterize affect dysregulation of a specific type (anger) in a well-defined clinical population, ultimately helping to elucidate the pathophysiology of MDD. We propose to study three populations: MDD with anger attacks, MDD without anger attacks, and healthy control subjects. We will utilize narrative scripts to induce emotional states (angry, sad, and neutral states) and assess physiologic responses in the study populations utilizing psychophysiologic measures, PET activation studies, and PET in vivo neuroreceptor imaging techniques. By this proposal, the candidate seeks training in (1) clinical studies of MDD, (2) affective neuroscience, (3) statistics relevant to functional neuroimaging, and (4) neuroreceptor imaging with PET. This rigorous training plan, integrating strong didactics and multidisciplinary expertise, will teach the candidate how to synthesize information from diverse fields in studying affect dysregulation in MDD. This integrated program of training and research will advance our knowledge of the pathophysiology of MDD, yield new tools for studying emotional processing, and give the candidate the skills needed to achieve independence in a highly complex field.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Wynne, Debra K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Marci, Carl D; Glick, Debra M; Loh, Rebecca et al. (2007) Autonomic and prefrontal cortex responses to autobiographical recall of emotions. Cogn Affect Behav Neurosci 7:243-50
Dougherty, Darin D; Bonab, Ali A; Ottowitz, William E et al. (2006) Decreased striatal D1 binding as measured using PET and [11C]SCH 23,390 in patients with major depression with anger attacks. Depress Anxiety 23:175-7
Ottowitz, William E; Dougherty, Darin D; Sirota, Alan et al. (2004) Neural and endocrine correlates of sadness in women: implications for neural network regulation of HPA activity. J Neuropsychiatry Clin Neurosci 16:446-55
Dougherty, Darin D; Rauch, Scott L; Deckersbach, Thilo et al. (2004) Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks. Arch Gen Psychiatry 61:795-804