Longitudinal comorbidity of depression and cognitive impairment has been reported by number of epidemiological studies but the underlying mechanisms explaining the link between affective problems and cognitive decline are not very well understood. Imaging studies have typically investigated patients with major depressive disorder (MDD) and mild cognitive impairment (MCI) separately and thus have not identified a structural brain signature common to these conditions that may illuminate potentially targetable shared biological mechanisms. We performed a meta-analysis of. 48 voxel-based morphometry (VBM) studies of individuals with MDD, MCI, and age-matched controls and demonstrated that MDD and MCI patients had shared volumetric reductions in a number of regions including the insula, superior temporal gyrus (STG), inferior frontal gyrus, amygdala, hippocampus, and thalamus. We suggest that the shared volumetric reductions in the insula and STG might reflect communication deficits and infrequent participation in mentally or socially stimulating activities, which have been described as risk factors for both MCI and MDD. We also suggest that the disease-specific structural changes might reflect the disease-specific symptoms such as poor integration of emotional information, feelings of helplessness and worthlessness, and anhedonia in MDD. These findings could contribute to better understanding of the origins of MDD-MCI comorbidity and facilitate development of early interventions.

Brain and Mind Research Programme Central European Institute of Technology Masaryk University 5 Kamenice Brno 62500 Czech Republic; Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health 250 College Street Toronto ON M5T 1L8 Canada

Brain and Mind Research Programme Central European Institute of Technology Masaryk University 5 Kamenice Brno 62500 Czech Republic; Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University 664 53 Pekarska Brno 65691 Czech Republic

Brain and Mind Research Programme Central European Institute of Technology Masaryk University 5 Kamenice Brno 62500 Czech Republic; Department of Psychiatry Faculty of Medicine Masaryk University and University Hospital Brno Jihlavská 20 Brno 62500 Czech Republic

Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health 250 College Street Toronto ON M5T 1L8 Canada

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