Meta-Analysis of Brain Volumetric Abnormalities in Patients with Remitted Major Depressive Disorder

Abstract

Although patients with major depressive disorder (MDD) achieve remission after antidepressant treatment, >90% of those in remission have at least one residual depressive symptom, which may be due to neural damage linked with MDD. To better understand the structural impairments in patients with remitted MDD, we conducted a meta-analysis comparing grey matter volume (GMV) abnormalities between patients with remitted MDD and healthy controls (HCs). There were 11 cross-sectional datasets that investigated 275 patients with remitted MDD versus 437 HCs, and 7 longitudinal datasets that investigated 167 patients with remitted MDD. We found that GMV in the left insula, inferior parietal gyri, amygdala, and right superior parietal gyrus was decreased in patients with remitted MDD than in HCs. Additionally, patients with remitted MDD had lower GMV in the bilateral gyrus rectus than those in the nonremission state. Moreover, increased GMV in the bilateral anterior cingulate cortex, right striatum, middle temporal gyrus, and superior frontal gyrus was observed in patients with remitted MDD than in HCs. Furthermore, patients with remitted MDD had a larger GMV in the bilateral median cingulate/paracingulate gyri, left striatum, putamen, amygdala, hippocampus, and parahippocampal gyrus at follow-up than at baseline. Based on the brain morphological abnormalities in patients with remitted MDD after electroconvulsive therapy and pharmacological treatment, we proposed a schematic diagram of targeted intervention approaches for residual symptoms. In summary, our findings provide neurobiology-based evidence for multitarget treatment of depression to reduce residual symptoms and improve social function in patients with MDD.

Figure 1

Flow chart of literature search and selection in the meta-analysis. Abbreviations: HCs: healthy controls; MDD: major depressive disorder; n: number.

Figure 2

Meta-analysis results of GMV difference in patients with remitted MDD compared with HCs. The areas of decreased GMV compared with HC are displayed in blue, and the areas of increased GMV are displayed in red. Abbreviations: ACC: anterior cingulate cortex; AMY: amygdala; GMV: grey matter volumes; HCs: healthy controls; IFG: inferior frontal gyrus; INS: insula; IPG: inferior parietal gyri; L: left; MCC: median cingulate cortex; MDD: major depressive disorder; MTG: middle temporal gyrus; R: right; SPG: superior parietal gyrus; STG: superior temporal gyrus; STR: striatum.

Figure 3

GMV changes in patients with remitted MDD in longitudinal studies. The areas of lower GMV in patients with remitted MDD than that of those in the nonremission state are displayed in blue, and the areas of increased GMV are displayed in red. Abbreviations: AMY: amygdala; GMV: grey matter volumes; GR: gyrus rectus; HCs: healthy controls; HP: hippocampus; L: left; MCC: median cingulate cortex; MDD: major depressive disorder; PHP: parahippocampal gyrus; PUT: putamen; R: right; STR: striatum.

Figure 4

Brain location of novel and emerging treatment for residual symptoms in patients with remitted MDD. Abbreviations: ACC: anterior cingulate cortex; INS: insula; IPG: inferior parietal gyri; MDD: major depressive disorder; rTMS: repetitive transcranial magnetic stimulation; SFG: superior frontal gyrus; SPG: superior parietal gyrus; STG: superior temporal gyrus; STR: striatum; TPJ: temporoparietal junction.