Tractography of the brainstem in major depressive disorder using diffusion tensor imaging.
BACKGROUND
The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA) axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD). However, the brainstem's role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI), we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls.


METHODS
MDD patients (n = 95) and age- and gender-matched controls (n = 34) were assessed using probabilistic tractography of DTI to delineate three distinct brainstem tracts: the nigrostriatal tract (connecting brainstem to striatum), solitary tract (connecting brainstem to amygdala) and corticospinal tract (connecting brainstem to precentral cortex). Fractional anisotropy (FA) was used to measure the white matter integrity of these tracts, and measures were compared between MDD and control participants.


RESULTS
MDD participants were characterized by a significant and specific decrease in white matter integrity of the right solitary tract (p<0.009 using independent t-test), which is a "bottom up" afferent pathway that connects the brainstem to the amygdala. This decrease was not related to symptom severity.


CONCLUSIONS
The results provide new evidence to suggest that structural connectivity between the brainstem and the amygdala is altered in MDD. These results are interesting in light of predominant theories regarding amygdala-mediated emotional reactivity observed in functional imaging studies of MDD. The characterization of altered white matter integrity in the solitary tract in MDD supports the possibility of dysfunctional brainstem-amygdala connectivity impacting vulnerable circuits in MDD.
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia ; Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
Yun Ju C
YJ
Song
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia ; Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
Mayuresh S
MS
Korgaonkar
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Lucy V
LV
Armstrong
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Sarah
S
Eagles
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia ; Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Westmead Hospital, Sydney, NSW, Australia ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America.
Leanne M
LM
Williams
The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
Stuart M
SM
Grieve
D000293:Adolescent; D000328:Adult; D000368:Aged; D000679:Amygdala / Q000473:pathology* / Q000503:physiopathology; D016880:Anisotropy; D001931:Brain Mapping / Q000379:methods; D001933:Brain Stem / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000473:pathology* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged