Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder

• Published in: PloS one 2010-11, Vol.5 (11), p.e13945
• Main 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
• Format: Article
• Language: English
• Subjects: Abnormalities; Addictions; Adult; Anisotropy; Antidepressants; Anxiety; Aversion; Avoidance Learning - physiology; Bias; Brain; Brain Mapping - methods; Brain research; Circuits; Cohort Studies; Collaboration; Cortex (temporal); Depressive Disorder, Major - physiopathology; Dopamine; Female; Forebrain; Genetic research; Hedonic response; Humans; Hypotheses; Informatics; Laboratories; Magnetic resonance imaging; Major depressive disorder; Male; Medial forebrain bundle; Medial Forebrain Bundle - physiopathology; Medical imaging; Medical research; Medical schools; Mental depression; Mental Health/Anxiety Disorders; Mental Health/Mood Disorders; Mesencephalon; Microstructure; Middle Aged; Neurogenesis; Neuroimaging; Neurosciences; Physicians; Posture; Prefrontal cortex; Psychiatrists; Psychiatry; Radiology and Medical Imaging/Magnetic Resonance Imaging; Reinforcement; Reward; Subgroups; Substantia alba; Substantia nigra; Substantia Nigra - abnormalities; Substantia Nigra - physiopathology; Trends; Ventral Tegmental Area - abnormalities; Ventral Tegmental Area - physiopathology; Ventral tegmentum; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013945

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). 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. 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.