The neural correlates of anhedonia in major depressive disorder.
BACKGROUND
Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia.


METHODS
Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia.


RESULTS
In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia.


CONCLUSIONS
These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.
Keedwell
Paul A
PA
Section of Neuroscience and Emotion, Department of Psychological Medicine, Institute of Psychiatry, Decrespigny Park, London, United Kingdom. p.keedwell@iop.kcl.ac.uk
Andrew
Chris
C
Williams
Steven C R
SC
Brammer
Mick J
MJ
Phillips
Mary L
ML
D000328:Adult; D000339:Affect / Q000502:physiology; D001007:Anxiety / Q000503:physiopathology; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000473:pathology / Q000523:psychology*; D017352:Echo-Planar Imaging; D005260:Female; D006240:Happiness; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D017072:Neostriatum / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D012201:Reward