Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder.
BACKGROUND
Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB).


RESULTS
We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.


CONCLUSIONS
These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.
Depression Clinic and Research Program, Mood and Motor Control Laboratory, Addiction Research Program, Laboratory of Neuroimaging and Genetics, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Anne J
AJ
Blood
Dan V
DV
Iosifescu
Nikos
N
Makris
Roy H
RH
Perlis
David N
DN
Kennedy
Darin D
DD
Dougherty
Byoung Woo
BW
Kim
Myung Joo
MJ
Lee
Shirley
S
Wu
Sang
S
Lee
Jesse
J
Calhoun
Steven M
SM
Hodge
Maurizio
M
Fava
Bruce R
BR
Rosen
Jordan W
JW
Smoller
Gregory P
GP
Gasic
Hans C
HC
Breiter
D000328:Adult; D016880:Anisotropy; D001362:Avoidance Learning / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008474:Medial Forebrain Bundle / Q000503:physiopathology; D008875:Middle Aged; D012201:Reward; D013378:Substantia Nigra / Q000002:abnormalities / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000002:abnormalities / Q000503:physiopathology*; D055815:Young Adult