Abstract
BackgroundMajor 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.MethodsIn 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.ResultsThe 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.ConclusionsThe 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
Highlights
Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations
Subjects were eligible for this study if they: (a) were aged 18–65 years; (b) were currently experiencing a recurrent, moderate or severe depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as evidenced by a score of at least 21 on the 24-item Hamilton Rating Scale for Depression (HAMD-24) [16]; (c) met the diagnostic criteria of the liver qi stagnation (LQS) or heart and spleen deficiency (HSD) subtype as defined in Table 1; (d) had received no treatment with antidepressants or other psychotropic drugs in the previous 3 months; and (e) were right-handed
Pairwise comparisons further showed that the LQS subtype had a markedly lower degree than healthy controls in the calcarine sulcus (P < 0.001), but a significantly higher degree in the angular gyrus than the HSD subtype (P < 0.001)
Summary
Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Various pharmacological and non-pharmacological therapies have been developed, the treatment outcomes are unsatisfactory [2]. This is largely because MDD is a complicated condition with multi-system etiopathogenesis and diverse clinical manifestations. It is thought that further classification could help characterize its symptomatic and pathological heterogeneity. Various classification approaches of MDD have been explored, there is still a dearth of compelling evidence for the existence of depressive symptom dimensions and symptomatic subtypes [4]. The development of a novel classification system that could improve clinical applicability and more precisely differentiate MDD subtypes is highly desired
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