Tractography of the brainstem in major depressive disorder using diffusion tensor imaging

Yun Ju C Song; Mayuresh S Korgaonkar; Lucy V Armstrong; Sarah Eagles; Leanne M Williams; Stuart M Grieve

doi:10.1371/journal.pone.0084825

Tractography of the brainstem in major depressive disorder using diffusion tensor imaging

PLoS One. 2014 Jan 21;9(1):e84825. doi: 10.1371/journal.pone.0084825. eCollection 2014.

Authors

Yun Ju C Song¹, Mayuresh S Korgaonkar¹, Lucy V Armstrong², Sarah Eagles², Leanne M Williams³, Stuart M Grieve²

Affiliations

¹ 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.
² The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.
³ 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.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Amygdala / pathology*
Amygdala / physiopathology
Anisotropy
Brain Mapping / methods
Brain Stem / pathology*
Brain Stem / physiopathology
Case-Control Studies
Depressive Disorder, Major / pathology*
Depressive Disorder, Major / physiopathology
Diffusion Tensor Imaging
Female
Humans
Male
Middle Aged

Grant support

This study was sponsored by the Brain Resource Company Operations Pty Ltd. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.