McLean Hospital 115 Mill Street Belmont, MA 02478
Diego A. Pizzagalli, PhD, is founding director of the Center for Depression, Anxiety and Stress Research, director of the McLean Imaging Center, and director of the Laboratory for Translational and Affective Neuroscience at McLean Hospital, and is a professor of psychiatry at Harvard Medical School. He is an internationally known expert on the neurobiology of depression, and has made major contributions toward the identification of biomarkers of depression and treatment response.
The main goals of Dr. Pizzagalli’s research are to improve our understanding of the psychological, environmental, and neurobiological factors associated with mood disorders, in particular major depression. To this end, he integrates behavioral, electrophysiological, neuroimaging, and, more recently, molecular genetics approaches to investigate three important (endo)phenotypes of depression: anhedonia (loss of pleasure), increased stress sensitivity, and negative processing biases.
As director of the Center for Depression, Anxiety and Stress Research (CDASR), director of the Laboratory for Translational and Affective Neuroscience (part of the CDASR), and co-director of the McLean Imaging Center, Dr. Pizzagalli is a leading expert in depression and anxiety research.
Depression, anxiety, and related disorders affect one in five Americans over their lifetimes. Recent breakthroughs in genetics, neuroscience, and cognitive science are revolutionizing the understanding of these conditions. The ultimate goal of Dr. Pizzagalli’s research is to identify the biological, environmental, and psychological factors that contribute to depression and anxiety and translate those findings into new treatments.
The scientists in Dr. Pizzagalli’s Laboratory for Translational and Affective Neuroscience focus on the brain mechanisms involved in anhedonia (a core symptom of depression); functional, structural, and neurochemical brain abnormalities in depression; neurobiological predictors of treatment response in depression; and neurobiological predictors of depression onset and relapse.
Anhedonia—the loss of pleasure or lack of reactivity to reward—is one of the core symptoms of and a potential vulnerability marker for depression. Surprisingly, few studies have utilized laboratory-based measures to objectively characterize anhedonia. The goal of this research is to employ a variety of techniques, including electroencephalography (EEG), event-related potentials, functional magnetic resonance imaging (fMRI), positron emission tomography (PET), molecular genetics, as well as stress and pharmacological manipulations, to advance the understanding of anhedonia.
One of the lab’s goals is to improve the understanding of functional, structural, and neurochemical brain abnormalities in depression. This information will be critical for developing better treatments and for identifying individuals at increased risk for depression. Dr. Pizzagalli’s research has shown that specific patterns of brain activation correspond to individual differences in treatment response and particular phenotypes of depression.
Dr. Pizzagalli and his staff are interested in investigating executive dysfunction in depression, especially abnormal reactions to errors and negative feedback. Depressed individuals show a catastrophic response to errors, evident in a rapid downward spiral in performance. Studies from Dr. Pizzagalli’s laboratory were among the first to show that these impairments are linked to an exaggerated, automatic neural response to errors, along with weak recruitment of brain regions that implement cognitive control. These dysfunctions might raise vulnerability to subsequent episodes of depression.
In an investigation of predictors of treatment response in depression, Dr. Pizzagalli’s laboratory was the first to show that pretreatment resting EEG activity in the rostral anterior cingulate cortex predicted therapeutic improvement 4-6 months later in depressed individuals. The group is currently exploring novel behavioral and EEG markers that could be used to examine treatment response prospectively, ultimately leading to improvements in treatment selection and reducing the personal and socioeconomic burden associated with the current trial and error approach.
Pizzagalli DA. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annual Review of Clinical Psychology 2014;10:393-423.
Treadway MT, Waskom ML, Dillon DG, Holmes AJ, Park MTM, Chakravarty MM, Dutra SJ, Polli FE, Iosifescu DV, Fava M, Gabrieli JDE, Pizzagalli DA. Illness progression, recent stress and morphometry of hippocampal subfields and medial prefrontal cortex in major depression. Biological Psychiatry 2015;77(3):285-94.
Kaiser RH, Andrews-Hanna JR, Wager TD, Pizzagalli DA. Large-scale network dysfunction in major depressive disorder: a meta-analysis of resting-state functional connectivity. JAMA Psychiatry 2015;72:603-11.
Belmont campus - de Marneffe Building, Room 233C