Aberrant integrity of the cortico-limbic-striatal circuit in major depressive disorder with suicidal ideation

Jun Yang; Lena Palaniyappan; Chang Xi; Yixin Cheng; Zebin Fan; Chujun Chen; Manqi Zhang; Yunzhi Pan; Haojuan Tao; Xuan Ouyang; Jie Yang; Zhening Liu

doi:10.1016/j.jpsychires.2022.02.003

Aberrant integrity of the cortico-limbic-striatal circuit in major depressive disorder with suicidal ideation

J Psychiatr Res. 2022 Apr:148:277-285. doi: 10.1016/j.jpsychires.2022.02.003. Epub 2022 Feb 12.

Authors

Jun Yang¹, Lena Palaniyappan², Chang Xi¹, Yixin Cheng¹, Zebin Fan¹, Chujun Chen¹, Manqi Zhang³, Yunzhi Pan¹, Haojuan Tao¹, Xuan Ouyang¹, Jie Yang⁴, Zhening Liu¹

Affiliations

¹ Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.
² Department of Psychiatry, University of Western Ontario, London, ON, Canada; Robarts Research Institute, University of Western Ontario, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada.
³ Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China. Electronic address: yang0826@csu.edu.cn.

PMID: 35180634
DOI: 10.1016/j.jpsychires.2022.02.003

Abstract

Background: Suicidal ideation is a common symptom of major depressive disorder (MDD) that reflects a cognitive alteration in the background of intense emotional dysregulation. Amygdala is a critical emotion processing center that facilitates moving from emotional appraisal to action. However, whether MDD patients with suicidal ideation show dysconnectivity of the amygdala within a large-scale neurocognitive circuitry remains unknown.

Methods: Participants were 22 MDD patients without suicidal ideation (MDD-NSI), 59 MDD patients with suicidal ideation (MDD-SI), and 60 healthy controls (HCs). We compared the amygdala-based resting-state functional connectivity of four amygdala subregions across the three groups. We selected brain regions with significant between-group differences in amygdalar conectivity as the regions of interest (ROI) and performed ROI-to-ROI and graph-theoretical analyses to explore dysconnectivity patterns at various granularity levels.

Results: Brain regions showing omnibus differences across the three groups were distributed across a cortico-limbic-striatal circuitry. MDD-SI had unique dysconnectivity of the lateral amygdala with caudate, middle temporal gyrus, and postcentral gyrus compared with the other two groups. MDD-SI and MDD-NSI had shared dysconnectivity of the medial amygdala with medial superior frontal gyrus and middle temporal gyrus. Within the derived cortico-limbic-striatal circuitry, MDD-SI exhibited lower global connectivity, reduced sigma (small-worldness), but increased lambda (path-length) than HCs. Reduced sigma correlated with increased severity of suicidal ideation. We achieved high classification accuracy (84.09%, with AUC 0.82) in distinguishing MDD-SI from MDD-NSI.

Conclusions: Aberrant integrity of the cortico-limbic-striatal circuit centered on the amygdala provides a promising neural substrate for suicidal ideation that requires further investigation in MDD.

Keywords: Amygdala; Cortico-limbic-striatal circuit; Machine learning; Major depressive disorder; Resting-state functional connectivity; Suicidal ideation.

MeSH terms

Amygdala / diagnostic imaging
Corpus Striatum / diagnostic imaging
Depressive Disorder, Major*
Humans
Magnetic Resonance Imaging
Suicidal Ideation