Diego A. Pizzagalli

Director, Center for Depression, Anxiety and Stress Research
Director, McLean Imaging Center 
Director, Laboratory for Affective and Translational Neuroscience
Professor, Department of Psychiatry, Harvard Medical School

McLean Hospital/Harvard Medical School
de Marneffe Building, Room 233C

CDASR Office: 617-855-4230 (Room 233C, de Marneffe Building)
MIC Office: 617-855-2797 (Room 130, McLean Imaging Center)   
Fax: 617-855-4231

E-mail:  This email address is being protected from spambots. You need JavaScript enabled to view it.

To schedule an appointment: Dr. Pizzagalli's Calendar

Curriculum Vitae - Link

Research Interests

Depression is a major public health problem, but our understanding of this debilitating disorder remains incomplete. This reflects the fact that depression is clinically, etiologically, and pathophysiologically heterogeneous. The aim of Dr. Pizzagalli’s research is to advance our understanding of the psychological, environmental, and neurobiological factors implicated in depression and related disorders (e.g., anxiety). The ultimate goal of this work is to identify novel targets for prevention and treatment.

Dr. Pizzagalli takes a multidisciplinary approach to investigating the causes, consequences, and pathophysiology of depression. For example, studies in his laboratory use:

  • Functional and structural magnetic resonance imaging (MRI), high-density electroencephalography (EEG), and positron emission tomography (PET) to identify neural and neurochemical substrates of core depressive symptoms and vulnerabilities, including anhedonia (loss of pleasure), emotion dysregulation, increased stress sensitivity, and executive dysfunction;
  • Molecular genetics to investigate the role of particular genes in the emergence of depressive phenotypes (e.g., anhedonia, stress sensitivity) and vulnerability to depression;
  • Comprehensive, contextual stress interviews to investigate the role of stress and early adversity in the etiology and maintenance of depression;
  • Pharmacological challenges to probe the role of particular neurotransmitters in depression;
  • Neurobiologically realistic computational models to investigate the influence of specific neuromodulators on normal and abnormal behavior (in collaboration with Peter Dayan and Quentin Huys, University College London and Michael Frank, Brown University);
  • Animal models to more directly test hypotheses about the role of stressors on the emergence of anhedonic behavior (in collaboration with Athina Markou, UCSD).

Anhedonia, the loss of interest in previously pleasurable activities, is a major focus of Dr. Pizzagalli’s work. Several studies from his laboratory have made important conceptual and methodological contributions to the study of anhedonia. For example, in a series of behavioral and neuroimaging studies, depression was characterized by (1) reduced ability to modulate behavior as a function of reward and (2) dysfunction in striatal regions implicated in hedonic coding and reinforcement learning. Similar abnormalities emerged in currently asymptomatic individuals with a history of depression, psychiatrically healthy individuals carrying genetic variants previously linked to depression (particularly when exposed to laboratory or naturalistic stressors), and young adults exposed to childhood adversities two decades earlier. Altogether, these and other findings emerging from Dr. Pizzagalli’s laboratory indicate that anhedonia is an important endophenotype of depression. Furthermore, they suggest that hedonic deficits, including dysfunction in reward-related striatal dopaminergic pathways, constitute a promising candidate mechanism linking stress to depression.

To facilitate tests of his hypotheses and increase translational impact, Dr. Pizzagalli has developed behavioral tests that can objectively assess core symptoms of depression. In particular, Dr. Pizzagalli developed a brief computer task that can be used to measure a key form of hedonic behavior—namely, participants’ ability to modify their choices as a function of differential rewards. More than 65 research groups worldwide are currently using this task to probe reward processing dysfunction across Axis I and II disorders.

In a second line of work, Dr. Pizzagalli is investigating executive dysfunction in depression, especially abnormal reactions to errors and negative feedback. It is clear from several studies that depressed individuals show a catastrophic response to errors, evident in a rapid downward spiral in performance following error commission. Studies from Dr. Pizzagalli’s laboratory were among the first to show that these behavioral impairments are linked to an exaggerated, automatic neural response to errors, along with weak recruitment of brain regions that implement cognitive control. Ongoing studies in the laboratory are testing the hypothesis that these dysfunctions foster the emergence and maintenance of negative processing biases, and thus increase vulnerability to subsequent episodes of depression.

Finally, Dr. Pizzagalli’s laboratory was the first to show that pre-treatment resting EEG activity in the rostral anterior cingulate cortex predicted therapeutic improvement 4-6 months later in depressed individuals. To follow up on this key finding, his laboratory is currently exploring novel behavioral and EEG markers that could be used to examine treatment response prospectively, ultimately leading to improvements in treatment selection. Given that a substantial percentage of depressed individuals do not respond to standard antidepressant treatments, establishing predictors of treatment response could greatly facilitate treatment selection, thus reducing the personal suffering and socio-economic burden associated with the current trial-and-error approach to treatment.

Education and Awards

Dr. Pizzagalli received his M.A. (1995) and Ph.D. (1998) from the University of Zurich, Switzerland and did post-doctoral work at University of Wisconsin, Madison. From 2002-2010 he was a faculty member in the Department of Psychology at Harvard University, where he served as the John and Ruth Hazel Associate Professor of the Social Sciences. In 2010, he was recruited to McLean Hospital to serve as the Director of the newly established Center for Depression, Anxiety and Stress Research, as well as the Director of the McLean Imaging Center. Dr. Pizzagalli has published over 130 papers and chapters and serves on the editorial board of 10 journals. Among several awards, he received the Distinguished Scientific Award for an Early Career Contribution to Psychophysiology from the Society for Psychophysiological Research (2006), the Early Career Award from the EEG and Clinical Neuroscience Society (2007), and the Anne M. Cataldo Excellence in Mentoring Award from McLean Hospital (2015). He is currently a Professor of Psychiatry at Harvard Medical School.

Selected Publications

Neurobiology of anhedonia

Admon, R., Pizzagalli, D.A. (in press). Cortico-striatal pathways contribute to the natural time course of positive mood. Nature Communications.

Der-Avakian, A., D’Souza, M.S., Pizzagalli, D.A.*, Markou, A.* (2013). Assessment of reward responsiveness in the Response Bias Probabilistic Reward Task in rats: Implications for cross-species translational research. Translational Psychiatry 3, e297; doi:10.1038/tp.2013.74 

Pechtel, P., Pizzagalli, D.A. (2013). Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: A high-density event-related potential study. JAMA Psychiatry, 70, 499-507.

Pizzagalli, D.A., Holmes, A.J., Dillon, D.G., Goetz, E.L., Birk, J.L., Bogdan, R., Dougherty, D.D., Iosifescu, D.V., Rauch, S.L., Fava, M. (2009). Reduced caudate and nucleus accumbens response to rewards in unmedicated subjects with Major Depressive Disorder. American Journal of Psychiatry, 166, 702-710.

Pizzagalli, D.A. (2014). Depression, stress, and anhedonia: Toward a synthesis and integrated model. Annual Review of Clinical Psychology, 10, 393-423.

Functional neuroanatomy of depression

Admon, R., Holsen, L.M., Aizley, H., Remington, A., Whitfield-Gabrieli, S., Goldstein, J.M., Pizzagalli, D.A. (2015). Striatal hyper-sensitivity during stress in remitted individuals with recurrent depression. Biological Psychiatry, 78, 67-76.

Kaiser, R.H., Andrews-Hanna, J.R., Wager, T.D., Pizzagalli, D.A. (2015). Large-scale network dysfunction in Major Depressive Disorder: Meta-analysis of resting-state functional connectivity. JAMA Psychiatry, 72, 603-611.

Treadway, M.T., Waskom, M.L., Dillon, D.G., Holmes, A.J., Park, M.T.M., Chakravarty, M.M., Dutra, S.J., Polli, F.E., Iosifescu, D.V., Fava, M., Gabrieli, J.D.E., Pizzagalli, D.A. (2015). Illness progression, recent stress and morphometry of hippocampal subfields and medial prefrontal cortex in Major Depression. Biological Psychiatry, 77, 285-294.

Webb, C.A., Dillon, D.G., Pechtel, P., Goer, F., Murray, L., Huys, Q.J.M., Fava, M., McGrath, P.J., Weissman, M., Parsey, R., Kurian, B., Adams, P., Weyandt, S., Trombello, J., Grannemann, B., Cooper, C., Deldin, P., Tenke, C., Trivedi, M., Bruder, G., Pizzagalli, D.A. (in press). Neural correlates of three promising endophenotypes of depression: Evidence from the EMBARC study. Neuropsychopharmacology. 2015 Jun 12. doi: 10.1038/npp.2015.165. [Epub ahead of print]

Whitton, A.E., Kakani, P., Foti, D., Van’t Veer, A., Haile, A., Crowley, D.J., Pizzagalli, D.A. (in press). Blunted neural responses to reward in remitted major depression: A high-density event-related potential study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

 

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