Abstract—The Default Mode Network (DMN) is a large-scale brain system involved in self-referential processing, memory, mentalizing, and internally directed cognition. Increasing evidence suggests that abnormalities in the relationship between brain structure and function may contribute to psychiatric disorders, but the pattern of structure–function coupling within the DMN is not consistent across conditions. This review examines recent evidence on DMN-related Structural–Functional Connectivity (SC–FC) coupling in Major Depressive Disorder (MDD), schizophrenia, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Across these disorders, altered SC–FC coupling is observed at regional and network levels, but both increased and decreased coupling have been reported. MDD is characterized by increased coupling in several DMN-related regions, whereas schizophrenia shows a more heterogeneous pattern involving both increased and decreased coupling. ASD also shows multidirectional alterations between the DMN and other large-scale systems, while ADHD demonstrates regional, subtype-, and development-dependent differences in coupling. These findings suggest that psychiatric disorders are unlikely to be defined by a uniform abnormal direction of SC–FC coupling. Changes in the ratio of structural limitations to functional flexibility may instead be reflected in changing coupling. Since structure-function coupling changes throughout childhood and adolescence, development is crucial in understanding these anomalies. In order to differentiate disorder-related changes from normal developmental variation and to determine whether DMN SC–FC coupling can be a useful indicator of common and disorder-specific mechanisms across psychiatric conditions, future longitudinal and transdiagnostic research is therefore required.
 
Keywords—Default Mode Network (DMN), coupling, neurodevelopment, transdiagnostic research

Cite: Zhuoyun Xu, "Aberrant Coupling of the Default Mode Network in Psychiatric Disorders: From Structural–Functional Integration to Network Dysfunction," International Journal of Pharma Medicine and Biological Sciences, Vol. 15, No. 4, pp. 134-139, 2026.

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