Brain volume abnormalities and neurocognitive deficits in diabetes mellitus: Points of pathophysiological commonality with mood disorders?

It is hypothesized that diabetes mellitus (DM) and mood disorders share points of pathophysiological commonality in the central nervous system. A PubMed search of all English-language articles published between 1966 and March 2009 was performed with the following search terms: depression, mood disorders, hippocampus, amygdala, central nervous system, brain, neuroimaging, volumetric, morphometric, and neurocognitive deficits, cross-referenced with DM. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. The primary author was principally responsible for adjudicating the merit of articles that were included. Volumetric studies indicate that individuals with Type 1/2 DM exhibit regional abnormalities in both cortical and subcortical (eg, hippocampus, amygdala) brain structures. The pattern of neurocognitive deficits documented in individuals with Type 1 DM overlap with Type 2 populations, with suggestions of discrete abnormalities unique to each phenotype. The pattern of volumetric and neurocognitive deficits in diabetic populations are highly similar to that reported in populations of individuals with major depressive disorder. The prevailing models of disease pathophysiology in DM and major depressive disorder are distinct. Notwithstanding, the common abnormalities observed in disparate effector systems (eg, insulin resistance, immunoinflammatory activation) as well as brain volume and neurocognitive performance provide the nexus for hypothesizing that both conditions are subserved by overlapping pathophysiology. This conception provides a novel framework for disease modeling and treatment development in mood disorder.