Gabriel Dichter, PhD, associate professor of psychiatry in the UNC School of Medicine and adjunct associate professor of psychology and neuroscience in the UNC College of Arts and Sciences, is the principal investigator of a 5-year $2.5-million award as part of the Experimental Therapeutics Initiative of the National Institute of Mental Health (NIMH). This new grant will use ultra-high field 7-tesla functional neuroimaging to develop and evaluate a new form of psychotherapy to treat anhedonia – a condition marked by a decreased capacity to experience motivation and pleasure. It is a core feature of a number of psychiatric disorders, including mood and anxiety disorders, substance-use disorders, schizophrenia, and attention-deficit/hyperactivity disorder.
“Anhedonia is one of the most difficult psychiatric symptoms to treat and represents a critical vulnerability factor for a range of psychiatric disorders,” said Dichter, who is also an investigator at the Carolina Institute for Developmental Disabilities at UNC. “We need better treatments, and we hope this project will establish a first-of-its-kind intervention for anhedonia.”
NIMH’s Experimental Therapeutics Initiative, which was launched in 2014, marked a major shift in the types of clinical trials funded through NIMH. Traditionally, clinical trials in mental health fields involved solely a focus on symptom reductions. Such trials, whether positive or negative, delivered little information about how an intervention might work or the underlying cause of the disorder, and therefore the trials provided little guidance for further treatment development.
The Experimental Therapeutics Initiative promotes research in which interventions are evaluated in stages. The first stage is to demonstrate that the intervention exerts an effect on a hypothesized “target” or mechanism of action. Targets may be molecular, cellular, behavioral, interpersonal, or neural circuitry. Once target engagement is demonstrated, the next stage of the trial evaluates relations between target engagement and symptom reductions.
These types of trials also focus on symptoms that cut across disorders, opposed to broad diagnostic categories in which not all participants share the same underlying disease process. In this way, a given trial will indicate not only whether a novel intervention works, but will provide information about the underlying etiology of both the disorder and the mechanisms of treatment response. In this way, future trials can build on the lessons learned from prior trials while increasing the understanding of the pathophysiology of the disorder.
Dr. Dichter’s new study, to be conducted with collaborator Moria Smoski, PhD, in the department of psychiatry at Duke University, will investigate the viability and efficacy of a new “transdiagnostic” psychotherapy for anhedonia called Behavioral Activation Therapy for Anhedonia. This intervention is designed to restore reward motivation and reward responsiveness in individuals with clinically impairing anhedonia. The 15-week course of individual psychotherapy includes patient education about anticipatory versus consummatory anhedonia, positive versus negative reinforcement, and how anhedonia can foster avoidance. The treatment focuses on increasing the frequency of the initiation of new pleasurable behaviors, exercises to increase present-moment savoring, and the reduction of avoidance behaviors.
The research team will first evaluate the impact of the new treatment on brain systems that process rewards using ultra-high field 7-tesla functional brain imaging at the UNC Biomedical Research Imaging Center (BRIC). This phase will also collect brain imaging data at multiple time points during psychotherapy to derive an optimal “dose” of the treatment (in other words, how many weeks of treatment are needed to derive the most benefit). After demonstrating that the treatment engages this reward processing brain target and deriving the optimal treatment dose, a formal clinical trial will evaluate the impact of the novel treatment on patient symptoms.
Co-investigators for this study include BRIC Director Weili Lin, PhD; Stacy Daughters, PhD, associate professor in UNC’s department of psychology and neuroscience; Susan Gaylord, PhD, associate professor in UNC’s department of physical medicine and rehabilitation and director of the department’s program on integrative medicine; biostatistician John Sideris, PhD, an advanced research scientist at UNC’s Frank Porter Graham Child Development Institute; and Erin Walsh, PhD, a postdoctoral fellow in the program on integrative medicine in UNC’s department of physical medicine and rehabilitation.