Aberrant grey matter volume in responsive and treatment-resistant patients with Major Depressive Disorder: two coordinate based meta-analyses of whole-brain sMRI studies

Major Depressive Disorder (MDD) is a mental disease caused by many complex factors (psycho-social, biological, genetic factors), but, despite decades of research, its etiopathogenesis has not yet been fully elucidated. Moreover, not all patients respond to the pharmacological treatment, which is the first-choice therapy for MDD. Treatment-resistant depression (TRD) is the diagnostic label for the occurrence of an inadequate response to an adequate antidepressant therapy. To investigate the neural correlates of MDD and TRD, neuroimaging techniques represent a powerful, in vivo, and noninvasive approach; in particular, structural Magnetic Resonance Imaging (sMRI) can identify morphological alterations in Grey Matter Volume (GMV) underpinning the pathophysiology of MDD and can help to shed light on the still unclear mechanisms linking depression, structural abnormalities, and treatment responsiveness. The present thesis consists of two coordinate based meta-analyses of whole-brain voxel-based morphometry (VBM) studies on GMV structural alterations occurring in MDD and TRD patients with respect to healthy controls (HC) with a particular focus on treatment responsiveness. VBM is a well-established, whole-brain, automatic, and unbiased tool that allows comparisons of focal differences in brain anatomy between groups, using the statistical approach of parametric mapping. A systematic literature search was performed in PubMed up to January 2022. Sixty-seven studies were included in the first meta-analysis, and seven in the second one. Comparisons were the followings: 3,532 MDD patients showing GMV atrophy vs. 4,224 HC; 1,846 MDD patients showing GMV hypertrophy vs. 2,483 HC; 245 TRD patients vs. 258 HC. An activation likelihood estimation (ALE) analysis and a coordinate-based mapping approach were used to identify common brain structural alterations among patients. GMV was significantly reduced in the fusiform gyrus and the declive in respondent MDD patients, and in the anterior cingulate in TRD ones. We only found hypertrophy in MDD patients located in the parahippocampal gyrus. A hypothesis for structural differences between respondent and refractory patients has been suggested. The project aims to contribute to identify consistent GMV anomalies in MDD and to elucidate the difference in these alterations between patients who respond and who don’t respond to drug treatment, for which findings are yet inconsistent.