The overarching aim of our research is to advance our understanding of the neurobiology of depression and related disorders (e.g., bipolar disorders, anxiety). The ultimate goal of this work is to identify novel targets for prevention and treatment. We take a multidisciplinary approach to the study of depression. For example, studies in Dr. Pizzagalli’s 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 and vulnerability to depression;

* Pharmacological challenges to probe the role of particular neurotransmitters in depression.

Anhedonia is a major focus of our work. In a series of behavioral and neuroimaging studies, we have found that depression is 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, and young adults exposed to childhood adversities two decades earlier. Altogether, these and other findings 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.