Neuroimaging Findings in Major Depressive Disorder: An Integrative Narrative Review

Narrative review

Abstract

Objective: To critically evaluate the alterations in large-scale brain networks and corticolimbic connectivity associated with major depressive disorder (MDD), focusing on their consistency, clinical significance, and reproducibility across neuroimaging studies.

Methodology: We categorized the 35 author-supplied publications by evidence type, anatomical scale, clinical context, and neuroimaging approach. We distinguished empirical studies from reviews, methodological reports, and studies of related disorders.

Results: Default mode, control, salience-related, amygdala–hippocampal, and anterior cingulate circuits have repeatedly been implicated in MDD. However, no single abnormal connection or uniform direction of connectivity change has emerged. Nuclei-specific and dynamic techniques provide complementary information, although they introduce trade-offs involving measurement reliability and multiple testing. Large-scale datasets strengthen confidence in some small population-level associations while also revealing the limits of case–control findings and imaging-only prediction.

Conclusions: A distributed, clinically heterogeneous model that accounts for measurement scale is the most defensible account of MDD. Translating imaging findings into clinically useful biomarkers will require specific hypotheses, careful image-quality control, transparent statistical correction, longitudinal assessment, and genuinely independent cross-site replication.