Decision value signals in the ventromedial prefrontal cortex and anhedonia across mood and psychotic disorders
Kang, M. S., Wolf, D. H., Kazinka, R., Lee, S., Ruparel, K., Elliott, M., Baldassano, C., Xu, A., Cieslak, M., Prettyman, G., Satterthwaite, T. D., Kable, J. W.
Importance: Anhedonia, or diminished ability to experience pleasure, is a prominent symptom in mood and psychotic disorders. More specifically, anticipatory pleasure is impaired in these psychiatric conditions, and this impairment may be reflected in blunted activity in the fronto-striatal circuitry during evaluation of future rewards.
Objective: To examine the neural correlates of anhedonia during decision-making across mood and psychotic disorders.
Design: A cross-sectional study was conducted from August 2, 2011 to October 4, 2013. Data analysis was conducted from January 31, 2019 to May 8, 2019.
Setting: University of Pennsylvania
Participants: Adults between the ages of 19 and 61 with major depressive disorder, bipolar disorder, schizophrenia, or no history of psychopathology completed the study.
Main Outcomes and Measures: Participants performed a delay discounting paradigm while functional imaging data were acquired at 3T. We examined the relationship between anhedonia and neural activity in two a priori regions of interest critical for valuation, the ventromedial prefrontal cortex (vmPFC) and ventral striatum. Anhedonia was measured using a dedicated semi-structured clinical interview; cognition, depression, and symptoms of psychosis were also evaluated.
Results: Analyses included data from 81 adults (mean [SD] age, 39.10 [11.24] years; 43 female [53%]), with major depression (n=17), bipolar disorder (in depressed state, n=21), schizophrenia (n=23), or no history of psychopathology (n=20). Discounting behavior did not differ as function of primary diagnosis or level of anhedonia (F(3,77) = 0.28, p = 0.84; r = 0.03, p = 0.78). Value-related activity in the vmPFC was blunted in association with anhedonia (b = -0.27; 95% CI, -0.48 to -0.06; p = 0.01). This relationship remained significant while controlling for psychiatric diagnosis, behavioral performance, cognitive functioning, smoking, depression severity, and both positive and negative symptoms of schizophrenia.
Conclusions and Relevance: Hypofunction in the vmPFC during decision-making about future rewards is specifically linked to anhedonia, rather than a general feature of psychopathology. These findings help elucidate the pathophysiological underpinnings of anhedonia across mood and psychotic disorders and inform the development of novel treatment approaches.