Original Title: Structural rather than functional brain alterations that characterize the differences between major depressive disorder and primary insomnia: a comparative meta-analysis
Journal: BMC medicine
DOI: 10.1186/s12916-025-04442-y
Overview
Major depressive disorder (MDD) and primary insomnia (PI) share overlapping symptoms, complicating diagnosis. This study conducted a comparative meta-analysis to identify shared and distinct brain alterations in these conditions. Researchers synthesized data from 79 neuroimaging studies, including 54 on structural gray matter volume (GMV) and 25 on functional resting-state activity (ALFF). The analysis revealed common functional alterations, with both MDD and PI patients showing increased ALFF in the left temporal pole, superior temporal gyrus (STG), and right amygdala. However, no shared structural GMV abnormalities were found. A direct comparison indicated that PI patients had smaller GMV in the left striatum and median cingulate gyrus but larger GMV in the right STG compared to MDD patients. Furthermore, a meta-regression showed that symptom severity in both disorders correlated more strongly with functional (ALFF) alterations than with structural (GMV) changes.
Novelty
This study’s primary contribution is its direct, comparative meta-analysis of both structural and functional neuroimaging data for MDD and PI. By synthesizing a large body of literature, it moves beyond single-disorder studies to uncover distinguishing and overlapping neural signatures. The key finding is a dissociation between brain structure and function: shared functional hyperactivity in emotional and arousal circuits (amygdala, temporal lobe) may explain symptomatic overlap, while distinct structural differences in the striatum and cingulate gyrus differentiate the two disorders. This suggests that while moment-to-moment brain activity is similar, the underlying anatomical changes are not. The finding that symptom severity correlates with functional but not structural alterations provides evidence that functional measures may better reflect a patient's current clinical state, whereas structural changes may be more trait-like.
Potential Clinical / Research Applications
The results have clear implications for clinical work and research. Clinically, the distinct gray matter volume patterns in the striatum and cingulate gyrus could form the basis of biomarkers for differential diagnosis between MDD and PI. The shared functional hyperactivity in the amygdala and temporal regions suggests that transdiagnostic treatments targeting these circuits, such as specific neuromodulation techniques, could benefit patients with either condition.
For research, these findings justify longitudinal studies to test if functional alterations precede structural changes, clarifying the progression of these disorders. The specific brain regions identified also provide precise targets for future mechanistic studies and can serve as regions of interest in clinical trials to objectively measure treatment response.
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