title: Trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and paralimbic reward pathways.
abstract: Anhedonia is the inability to experience pleasure from normally pleasant stimuli. Although anhedonia is a prominent feature of many psychiatric disorders, trait anhedonia is also observed dimensionally in healthy individuals. Currently, the neurobiological basis of anhedonia is poorly understood because it has been mainly investigated in patients with psychiatric disorders. Thus, previous studies have not been able to adequately disentangle the neural correlates of anhedonia from other clinical symptoms. In this study, trait anhedonia was assessed in well-characterized healthy participants with no history of Axis I psychiatric illness. Functional magnetic resonance imaging with musical stimuli was used to examine brain responses and effective connectivity in relation to individual differences in anhedonia. We found that trait anhedonia was negatively correlated with pleasantness ratings of music stimuli and with activation of key brain structures involved in reward processing, including nucleus accumbens (NAc), basal forebrain and hypothalamus which are linked by the medial forebrain bundle to the ventral tegmental area (VTA). Brain regions important for processing salient emotional stimuli, including anterior insula and orbitofrontal cortex were also negatively correlated with trait anhedonia. Furthermore, effective connectivity between NAc, VTA and paralimbic areas, that regulate emotional reactivity to hedonic stimuli, was negatively correlated with trait anhedonia. Our results indicate that trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and related limbic and paralimbic systems involved in reward processing. Critically, this association can be detected even in individuals without psychiatric illness. Our findings have important implications both for understanding the neurobiological basis of anhedonia and for the treatment of anhedonia in psychiatric disorders.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keller
authors.forename: Christina B
authors.initials: CB
authors.lastname: Young
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kelley
authors.forename: Katherine
authors.initials: K
authors.lastname: Prater
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Levitin
authors.forename: Vinod
authors.initials: V
authors.lastname: Menon
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D059445:Anhedonia; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009146:Music; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance; D011930:Reaction Time / Q000502:physiology; D012201:Reward; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Anhedonia; Insula; Mesolimbic reward system; Nucleus accumbens; Orbitofrontal cortex; Ventral tegmental area