Developing a dopamine and neural systems model of anhedonia

    More than 60 million people in the United States currently suffer from a serious mental illness, and the associated financial, productivity and human suffering costs are only projected to rise in the near future. Patients who suffer from serious mental disorders, such as depression, schizophrenia and substance abuse, frequently experience anhedonia, the loss of the normal experience of pleasure or positive emotion. Anhedonia is itself a significant predictor of poor health outcomes, disability, and low quality of life and one of the most difficult to treat psychiatric complaints. Currently, our ability to optimize existing treatments or develop better therapies for anhedonia is limited because we do not yet understand sufficiently how the brain’s reward system and the neural circuits involved interact to produce it.

    The current research plan aims to address this gap in knowledge and use the new information to improve treatment effectiveness. We are asking the following questions: a) how does evidence on reward network dysfunction in animals translate to human patients, b) does the reward system in anhedonic patients respond differently to treatments of different modalities and c) how can we use this knowledge to guide treatment selection? To answer these questions we will: a) formulate and test direct hypotheses on the relationship between neurotransmitter function, reward network function and anhedonia in humans based on animal findings, b) study anhedonia as a distinct process common across mental disorders, and c) we will investigate how pharmacological and magnetic neural stimulation affect the activity and connectivity of neural circuits that mediate reward.

    Study participants will undergo clinical assessments, behavioral tests, and MRI scans to visualize the function and communication of specific brain regions before and after eight weeks of each treatment. We predict that the treatments will have overlapping but also distinct effects on reward network reactivity and connectivity in treatment responders. Comparing the effects of a drug that alters neurotransmitter levels in the brain versus a treatment that provides magnetic stimulation to neurons, together with understanding the core dysfunctions present in anhedonic patients before treatment will help us understand the mechanisms that produce and alleviate anhedonia symptoms. These insights will likely help to improve outcomes for people suffering from anhedonia by personalizing treatments according to each person’s specific network dysfunctions.  

Project Details

Funding Type:

Interdisciplinary Postdoctoral Scholar Award

Award Year:


Lead Researcher(s):

Team Members:

Leanne M Williams (Sponsor, Psychiatry & Behavioral Sciences)
Robert C Malenka (Sponsor, Psychiatry & Behavioral Sciences)