Brain connectomic associations with traditional Chinese medicine diagnostic classification of major depressive disorder: a diffusion tensor imaging study

Lan-Ying Liu, Xiao-Pei Xu, Li-Yuan Luo, Chun-Qing Zhu, Ya-Ping Li, Pei-Rong Wang, Yuan-Yuan Zhang, Chun-Yu Yang, Hong-Tao Hou, Yu-Lin Cao, Gang Wang, Edward S Hui, Zhang-Jin Zhang, Lan-Ying Liu, Xiao-Pei Xu, Li-Yuan Luo, Chun-Qing Zhu, Ya-Ping Li, Pei-Rong Wang, Yuan-Yuan Zhang, Chun-Yu Yang, Hong-Tao Hou, Yu-Lin Cao, Gang Wang, Edward S Hui, Zhang-Jin Zhang

Abstract

Background: Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Further classification may help characterize its heterogeneity. We previously have shown differential metabolomic profiles of traditional Chinese medicine (TCM) diagnostic subtypes of MDD. We further determined brain connectomic associations with TCM subtypes of MDD.

Methods: In this naturalistic study, 44 medication-free patients with a recurrent depressive episode were classified into liver qi stagnation (LQS, n = 26) and Heart and Spleen Deficiency (HSD, n = 18) subtypes according to TCM diagnosis. Healthy subjects (n = 28) were included as controls. Whole-brain white matter connectivity was analyzed on diffusion tensor imaging.

Results: The LQS subtype showed significant differences in multiple network metrics of the angular gyrus, middle occipital gyrus, calcarine sulcus, and Heschl's gyrus compared to the other two groups. The HSD subtype had markedly greater regional connectivity of the insula, parahippocampal gyrus, and posterior cingulate gyrus than the other two groups, and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole. The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.

Conclusions: The LQS subtype is mainly characterized by aberrant connectivity of the audiovisual perception-related temporal-occipital network, whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbic-paralimbic network. Insular connectivity may serve a biomarker for TCM-based classification of depression.Trial registration Registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015.

Keywords: Classification; Connectome; Diffusion tensor imaging; Major depressive disorder; Traditional Chinese medicine.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Recruitment profile. LQS liver qi stagnation, HSD heart spleen deficiency
Fig. 2
Fig. 2
Diffusion tensor imaging based brain connectomic analysis. Liver qi stagnation (LQS) subtype versus healthy controls (HC) (a), Heart Spleen Deficiency (HSD) subtype versus HC (b), and HSD versus LQS (c). Red and blue filled circles indicate hyper- and hypo-connectivity, respectively, as compared with HC (a, b) or LQS (c)
Fig. 3
Fig. 3
Diffusion tensor imaging white matter microstructural analysis. Significant decreases in fractional anisotropy (FA) of the frontal medial orbital gyrus (ORBmed, a) and the middle temporal pole (TPOmid, b indicated with blue) and significant increase in mean diffusivity (MD) of the frontal medial orbital gyrus (ORBmed, c indicated with red) in HSD subtype compared to the other two groups
Fig. 4
Fig. 4
Insular betweenness centrality value is significantly inversely correlated with HAMD-24 score in a pool of liver qi stagnation (LQS) and heart spleen deficiency (HSD) subtypes (a). The two subtypes are well dichotomized at a cutoff value of 295 insular betweenness centrality with a sensitivity of 0.667 and a specificity of 0.769 (b)

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