Structural rather than functional brain alterations that characterize the differences between major depressive disorder and primary insomnia: a comparative meta-analysis

BMC Med. 2025 Nov 4;23(1):606. doi: 10.1186/s12916-025-04442-y.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) and primary insomnia (PI) share overlapping symptoms and neurobiological features, yet they represent distinct clinical entities. Thus, identifying both shared and disorder-specific structural and functional brain alterations is critical for enhancing our mechanistic understanding and improving diagnostic differentiation between these conditions.

METHODS: A comprehensive literature search was conducted in the PubMed, Web of Science, and Embase databases, covering publications up to April 2024. The seed-based d-mapping software was used to investigate common and distinct abnormalities of gray matter volume (GMV) and resting-state amplitude of low-frequency fluctuations (ALFF) between MDD and PI. Meta-regression analysis was employed to assess the effect of demographic and clinical features on the identified structural and functional characteristics. The study complied with the PRISMA reporting guideline, and the detailed checklist is included in Additional File 2.

RESULTS: Across 54 GMV and 25 ALFF studies, both MDD and PI showed increased ALFF in the left temporal pole, superior temporal gyrus (STG), and right amygdala relative to healthy controls. Compared to MDD, PI exhibited smaller GMV in the left striatum and median cingulate/paracingulate gyri (DCG), but greater GMV in the right STG, reflecting structural divergence. Functionally, PI showed lower ALFF values in the right cerebellum and parietal regions, but higher ALFF values in the right occipital and temporal areas than MDD. Subgroup analyses conducted in studies within homogenous and key methodological parameters confirmed the robustness of most findings. Meta-regression revealed that functional rather than structural alterations were more strongly associated with the severity of symptoms in both disorders.

CONCLUSIONS: Common increased resting-state activation in limbic and temporal circuits may underlie overlapping neurobiological mechanisms between MDD and PI and represent potential transdiagnostic phenotypes. Distinct patterns of structural changes in gray matter, especially in striatum, cingulate, and temporal regions, may represent potential biomarkers for differential diagnosis between these two disorders.

PMID:41188841 | DOI:10.1186/s12916-025-04442-y