The hippocampus, amygdala, and ventral anterior cingulate are each implicated in the pathophysiology of mood disorders. The volume of the subiculum of the hippocampus is abnormally decreased in major depressive disorder (MDD) and bipolar disorder. Subtle decreases in hippocampal volume were previously reported by some MRI studies of mood disorders, although many other studies were unable to confirm this difference. Two studies of the hippocampus performed post mortem provided clues that the reduction in volume may be confined to discreet subregions of the hippocampus, namely the subiculum and the adjacent CA1 region. The subiculum plays major roles in guiding reward-directed behavior and in modulating endocrine responses to stress. It is also the portion of the hippocampus that shares the heaviest anatomical connections with other brain regions implicated in regulating emotional behavior. A method for imaging the human brain at a very high spatial resolution, developed in collaboration between NIMH and NINDS, permitted reliable volumetric measures of the subiculum and adjacent CA1 cortex. Application of this technique revealed a marked reduction in the volume of the subiculum exists in bipolar disorder, and demonstrated this abnormality can be noninvasively detected using MRI. Secondly, the amygdala has an abnormal reduction of glial cells in MDD. Glial cells were previously shown to be decreased in other brain regions of the prefrontal cortex which share extensive anatomical connections with the amygdala in both MDD and bipolar disorder. The glial cells play a variety of important roles in assisting the function of the neurons, the cells responsible for carrying signals from one brain region to another. Working in collaboration with researchers at Washington University, we were able to show that the abnormal reduction in glia in the amygdala specifically involves oligodendrocytes, which play major roles in maintaining the communication across connections between neurons. This abnormality could therefore interfere with the normal functioning of the amygdala, which plays major roles in the regulation of emotional behavior. The amygdala plays a major role in organizing and regulating the behavioral, autonomic and endocrine responses to threat or stress, and the emotional inferences that occur in response to sad or anxious facial expressions or statements. Using high resolution images obtained on high magnetic field strength magnets at the NIH, we were able to show that the amygdala is reduced in volume by about 20% in both currently depressed subjects with recurrent MDD and in currently remitted subjects with MDD. In contrast, the abnormal reduction in volume did not extend to patients with bipolar disorder, consistent with the post mortem data described above. During this past year, we used high resolution MRI images acquired on a high field strength magnet to investigate cerebral volumes in mood disorders. Images were obtained in an additional 32 currently depressed subjects with MDD, 14 currently remitted subjects with MDD, 27 subjects with bipolar disorder, and 43 healthy controls. Comparisons across groups showed that the volumes of the amygdala and infralimbic cortex are decreased in depressed samples who have developed a chronic or intermittent course (i.e., have undergone the disabling process of """"""""cycle acceleration"""""""", in which episodes become more frequent or chronic, less responsive to treatment, more severe, and do not completely remit in the intervals between illness exacerbations.) The regions implicated in these studies are involved in emotion regulation, and our findings imply that the preservation of volume in subjects who have developed MDD may enable them to recover from depressive symptoms and maintain recovery for extended periods between episodes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002790-04
Application #
7136362
Study Section
(MIB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Adams, Hieab H H (see original citation for additional authors) (2016) Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat Neurosci 19:1569-1582
Hasler, Gregor; van der Veen, Jan Willem; Geraci, Marilla et al. (2009) Prefrontal cortical gamma-aminobutyric Acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry 65:273-5
Salvadore, Giacomo; Nugent, Allison C; Chen, Guang et al. (2009) Bcl-2 polymorphism influences gray matter volume in the ventral striatum in healthy humans. Biol Psychiatry 66:804-7
Drevets, Wayne C; Savitz, Jonathan; Trimble, Michael (2008) The subgenual anterior cingulate cortex in mood disorders. CNS Spectr 13:663-81
Bonne, Omer; Vythilingam, Meena; Inagaki, Masatoshi et al. (2008) Reduced posterior hippocampal volume in posttraumatic stress disorder. J Clin Psychiatry 69:1087-91
Hasler, Gregor; van der Veen, Jan Willem; Tumonis, Toni et al. (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 64:193-200
Drevets, Wayne C (2007) Orbitofrontal cortex function and structure in depression. Ann N Y Acad Sci 1121:499-527
Hasler, Gregor; Drevets, Wayne C; Gould, Todd D et al. (2006) Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 60:93-105
Nugent, Allison C; Milham, Michael P; Bain, Earle E et al. (2006) Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 30:485-97
Milham, Michael P; Nugent, Allison C; Drevets, Wayne C et al. (2005) Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation. Biol Psychiatry 57:961-6

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