Joint and distinct neural structure and function deficits in major depressive disorder with suicidality: a multimodal meta-analysis of MRI studies

J Psychiatry Neurosci. 2025 Apr 23;50(2):E126-E141. doi: 10.1503/jpn.240112. Print 2025 Mar-Apr.

ABSTRACT

BACKGROUND: Suicide risk is a major concern for patients with major depressive disorder (MDD). Neuroimaging studies have demonstrated that patients with MDD with suicidal ideation or suicide attempt (MDD-S) are accompanied by neurostructural or functional abnormalities, but there is no consensus of opinion on neural substrate alterations involved in MDD-S.

METHODS: We performed a whole-brain multimodal meta-analysis of existing magnetic resonance imaging (MRI) studies to identify conjoint and separate alterations of grey matter volume (GMV) and spontaneous brain activity characteristics (regional homogeneity and amplitude of low-frequency fluctuations) between patients with MDD-S and patients with MDD without suicidal ideation or suicidal attempt (MDD-NS) via the seed-based d mapping software. We excluded studies that used other modalities, had overlapping data, or had insufficient information.

RESULTS: Our systematic search identified 13 structural MRI studies (471 patients with MDD-S and 508 patients with MDD-NS) and 16 resting-state functional MRI studies (704 patients with MDD-S and 554 patients with MDD-NS) published up to Dec. 5, 2023. Compared with patients with MDD-NS, those with MDD-S showed increased GMV with hypoactivity in the left postcentral gyrus, decreased GMV with hypoactivity in the right inferior parietal gyri, decreased GMV with hyperactivity in the right insula, and separate GMV and functional changes within the bilateral parietal, occipital, and frontal lobes, and the left thalamus.

LIMITATIONS: We were unable to analyze the association between brain features and clinical detail because of a lack of data. Included studies showed considerable heterogeneity and publication bias.

CONCLUSION: These findings provide a comprehensive overview of brain morphological and spontaneous functional impairments linked to impulsivity, impaired positive reward modulation, emotional disturbances, abnormal emotional processing, and cognitive deficits in MDD-S. These results support an understanding of the relationship between neural substrates and clinical symptoms in MDD-S, and these alterations provide useful insight into pathophysiological mechanisms and intervention strategies to decrease suicide risk in MDD.

PMID:40268326 | DOI:10.1503/jpn.240112