Structural-functional coupling subtypes of major depressive disorder and their associations with genetic and neurotransmitter profiles

Motivation: The neurobiological underpinning of heterogeneity in structural-functional coupling (SFC) remains unclear in major depressive disorder (MDD). Goal(s): This study aims to explore subtypes of MDD based on SFC alteration and investigate their differences in clinical symptoms and the molecular basis of SFC alterations. Approach: We calculated SFC derived from resting-state fMRI and T1-weighted images, identified MDD subtypes based on its alterations, and correlated SFC alterations with clinical assessments, genes and neurotransmitters. Results: Two MDD subtypes characterized by increased and decreased SFC were identified in present study, respectively. They demonstrated differences in depressive symptoms and exhibited different molecular basis for their SFC alterations. Impact: Our study identified two neurophysiological subtypes of MDD, characterized by unique SFC alteration patterns, along with specific associations with genetic and neurotransmitter profiles. These subtypes may offer promising implications for personalized diagnosis and targeted treatment of MDD.