BACKGROUND: Obesity has been implicated in the pathophysiology of major 
depressive disorder (MDD), which prompted us to examine the possible association 
of obesity with cognitive function and brain structure in patients with MDD.
METHODS: Three hundred and seven patients with MDD and 294 healthy participants, 
matched for age, sex, ethnicity (Japanese), and handedness (right) were 
recruited for the study. Cognitive function was assessed using the Brief 
Assessment of Cognition in Schizophrenia (BACS). Gray and white matter 
structures were analyzed using voxel-based morphometry and diffusion tensor 
imaging in a subsample of patients (n = 114) whose magnetic resonance imaging 
(MRI) data were obtained using a 1.5 T MRI system.
RESULTS: Verbal memory, working memory, motor speed, attention, executive 
function, and BACS composite scores were lower for the MDD patients than for the 
healthy participants (p < 0.05). Among the patient group, working memory, motor 
speed, executive function, and BACS composite scores were lower in obese 
patients (body mass index ≥ 30, n = 17) than in non-obese patients (n = 290, p < 
0.05, corrected). MRI determined frontal, temporal, thalamic, and hippocampal 
volumes, and white matter fractional anisotropy values in the internal capsule 
and left optic radiation were reduced in obese patients (n = 7) compared with 
non-obese patients (n = 107, p < 0.05, corrected).
LIMITATIONS: Sample size for obese population was not very large.
CONCLUSIONS: Obesity is associated with decreased cognitive function, reduced 
gray matter volume, and impaired white matter integrity in cognition-related 
brain areas in patients with MDD.