Two functional connectivity based subtypes of MDD and related biological mechanisms

Motivation: There’s a large clinical heterogeneity presented in MDD and inconsistent MRI evidence on abnormal functional connectivity (FC) in MDD, let alone the unclear biological mechanisms underlying the neuroimaging alterations. Goal(s): To identify FC based subtypes of MDD and their genetic mechanisms and neurotransmission patterns. Approach: Consensus clustering of FC was applied to subtyping MDD. Correlation analyses were used to explore the underlying biological mechanisms of FC alterations in each subtype. Results: Two stable neurophysiological MDD subtypes were found. While the two subtypes were indistinguishable by clinical symptoms, FC alterations of each subtype had distinct spatial correlations with cognition, gene, and neurotransmission profiles. Impact: Our findings suggested the presence of two neuroimaging subtypes in MDD and the two subtypes can be characterized by different genetic mechanisms, neurotransmitter receptor/transporter profiles, and cognition types, providing new clues to understand the pathophysiology of MDD.