Phenotypic characteristics of major depressive disorder and cerebral gray matter abnormalities according to voxel-based morphometry data

Abstract

Introduction: Although the neuroanatomy of major depressive disorder (MDD) as an entire entity is extensively studied, the neurological basis of MDD phenotypes is investigated much less. Objective: We aimed to analyze voxel-based morphometry (VBM) studies that assess gray matter (GM) abnormalities in different phenotypes or separate clinical characteristics of MDD. Methods: We reviewed studies in the PubMed and Scopus databases that assessed clinical and VBM associations in MDD phenotypes. Results: 15 articles were included in the review, analyzing GM abnormalities in MDD with melancholic, psychotic, and cognitive disturbances, suicidality, negative affectivity, and anhedonia. Melancholic MDD was associated with reductions in GM volume in the left insula and the right thalamus. In psychotic MDD, GM reduction in the right dorsolateral prefrontal cortex (DLPFC) was found. GM abnormalities in the cognitive MDD phenotype varied by domain of dysfunction. A decrease in GM density in the left hippocampus was linked to disturbances in verbal memory. Executive dysfunction correlated with GM thinning in the right medial and inferior frontal gyri, cingulate cortex, and hippocampus. GM volumes in the right medial frontal cortex showed a positive correlation with attention/vigilance. MDD suicidality was associated with reductions in GM volume in the frontal, parietal, and temporal regions, the insula, the lentiform nucleus, the midbrain, and the cerebellum. MDD patients with genetic suicidal risk showed decreased GM density in the fronto-striato-limbic network, caudate, and rostral anterior cingulate. MDD suicidal attempters had decreased GM volume in the right and left amygdala and ventral/medial/dorsal prefrontal cortex. Atrophy in the right DLPFC and right ventrolateral prefrontal cortex was linked to suicidal thoughts. Negative affectivity was correlated with GM diminishing in the right parahippocampal gyrus and amygdala. Ruminations were associated with GM thinning in the right superior temporal gyrus. Emotionally distorted thinking styles were linked to GM reductions in the left precentral gyrus. The severity of anhedonia in MDD was correlated with reduced GM volume in the putamen and cerebellum. Conclusion: Decreased GM volumes in MDD phenotypes, along with distinct clinical characteristics of MDD, may indicate involvement of specific regions in the pathogenesis of certain MDD symptomatology. Further studies are needed to examine clinical and morphological correlations in other MDD phenotypes.