Lack of ventral striatal response to positive stimuli in depressed versus normal subjects.
OBJECTIVE
Most of the functional neuroimaging studies of depression have focused primarily on the resting state or responses to negatively valenced stimuli. However, depression consists not only of an accentuation of negative affective processing but of an inability to experience pleasure or positive motivation. The authors tested the hypothesis that depressed subjects would show less activation than healthy comparison subjects, in response to positive stimuli, in ventral striatal regions associated with processing of reward and positive stimuli.


METHODS
Positive, negative, and neutral words were presented to 10 unmedicated depressed patients and 12 healthy comparison subjects in the context of a 3T functional magnetic resonance imaging (MRI) paradigm. Image processing and analysis were performed using statistical parametric mapping with a mixed-effects model. Significant differences in neural responses were assessed, examining group, condition, and interaction effects of interest within the context of a general linear model.


RESULTS
Relative to comparison subjects, depressed patients demonstrated significantly less bilateral ventral striatal activation to positive stimuli, correlating with decreased interest/pleasure in and performance of activities. They also displayed decreased activation to positive stimuli in a dorsomedial frontal region associated with processing of self-related stimuli. Responses of depressed subjects to negative stimuli were consistent with the growing literature on frontolimbic dysfunction in depression.


CONCLUSIONS
This finding 1) supports a pathophysiological model of depression that includes reward/motivational pathway dysfunction, 2) suggests a contributing neural substrate of the inability to experience pleasure or engage in rewarding activities, 3) provides greater specification of abnormalities of basal ganglia function in depression, and 4) may help guide treatment approaches.
Epstein
Jane
J
Department of Psychiatry, Box 140, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021, USA. jae2001@med.cornell.edu
Pan
Hong
H
Kocsis
James H
JH
Yang
Yihong
Y
Butler
Tracy
T
Chusid
Jesse
J
Hochberg
Hilary
H
Murrough
James
J
Strohmayer
Erika
E
Stern
Emily
E
Silbersweig
David A
DA
D000328:Adult; D000339:Affect / Q000502:physiology*; D001479:Basal Ganglia / Q000502:physiology* / Q000503:physiopathology*; D001931:Brain Mapping; D003866:Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D005625:Frontal Lobe / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000502:physiology / Q000503:physiopathology; D020534:Parahippocampal Gyrus / Q000502:physiology / Q000503:physiopathology; D012054:Reinforcement, Psychology; D012201:Reward; D014705:Verbal Behavior / Q000502:physiology*