Neural representation of reward in recovered depressed patients

Abstract

Introduction: Anhedonia, a loss of interest and pleasure in normally rewarding stimuli, is a key diagnostic criterion for major depression. It has been suggested that deficits in the processing of reward-relevant stimuli could represent an endophenotype for depression. We hypothesized that people at risk of depression by virtue of a personal history of the illness would show impaired neural responses to a primary rewarding stimulus.

Materials and methods: Using functional magnetic resonance imaging, we measured the neural response to the sight and flavor of chocolate, and their combination, in 13 unmedicated recovered patients with a history of major depression and 14 healthy controls matched for age and gender. We also examined a control aversive condition consisting of the sight of moldy strawberries and a corresponding unpleasant taste. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting."

Results and discussion: Despite no differences between the groups in stimulus ratings, patients showed decreased neural responses to the pleasant stimulus in the ventral striatum and increases in the caudate nucleus to the aversive stimulus. Furthermore, patients had a diminished neural supralinearity response (the potentiation produced by simultaneous presentation of the sight and flavor of the stimuli) in the prefrontal cortex for both aversive and pleasant conditions. Patients recovered from depression appear to have deficits in the neural basis of reward and may also have impairments in the cross-modal integration of sensory stimuli.

Conclusion: These findings support the view that abnormal neural responses to reward may be an endophenotype for depression and a potential target for intervention and prevention strategies.

Fig. 1

The effects of taste in the mouth, across all subjects for taste stimuli. a Axial, coronal, and sagittal images depicting activation in the primary taste cortex in the anterior insula. b The % BOLD signal change in the anterior insula for the recovered depressed and control groups, no significant group difference

Fig. 2

Chocolate in the mouth with the sight of chocolate condition: controls vs. recovered depressed. a Axial, coronal, and sagittal images depicting significantly decreased activations in the recovered depressed group in bilateral ventral striatum, caudate, pregenual, and anterior cingulate cortex. b The % BOLD signal change in the ventral striatum for the recovered depressed and control groups ([−8 8 −12], p < 0.03, fully corrected)

Fig. 3

Sight of moldy strawberries: recovered depressed vs. controls. a Axial, coronal, and sagittal images depicting significantly increased activations in the recovered depressed group in the bilateral caudate. b The % BOLD signal change in the caudate for the recovered depressed and control groups ([12 10 22], p < 0.004, small volume correction)

Fig. 4

Supralinearity condition for chocolate and strawberry conditions: controls vs. recovered depressed. a Axial, coronal, and sagittal images depicting significantly decreased activations in the recovered depressed group in the VMPFC/medial orbitofrontal cortex. b The % BOLD signal change for the chocolate picture plus chocolate taste condition minus the chocolate picture alone minus the chocolate taste alone in the VMPFC/medial orbitofrontal cortex ([8 56 −12], p = 0.03, small volume correction). c Axial, coronal, and sagittal images depicting significantly decreased activations in the recovered depressed group in the lateral orbitofrontal cortices. d The % BOLD signal change for the strawberry picture plus strawberry taste condition minus the strawberry picture alone minus the strawberry taste alone in the lateral orbitofrontal cortex ([20 22 −8], p = 0.01, small volume correction)