Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder |
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Authors: | Blood Anne J,Iosifescu Dan V,Makris Nikos,Perlis Roy H,Kennedy David N,Dougherty Darin D,Kim Byoung Woo,Lee Myung Joo,Wu Shirley,Lee Sang,Calhoun Jesse,Hodge Steven M,Fava Maurizio,Rosen Bruce R,Smoller Jordan W,Gasic Gregory P,Breiter Hans C Phenotype Genotype Project on Addiction Mood Disorders |
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Affiliation: | 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. |
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Abstract: | BackgroundPrevious 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).Methodology/Principal FindingsWe 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/SignificanceThese 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. |
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