Recent research on late-life depression (LLD) pathophysiology suggests the implication of abnormalities in cerebral white matter [1] and particularly in interhemispheric transfer [2]. Corpus callosum (CC) is the main brain interhemispheric commissure [3]. Hence, we investigated the association between baseline CC measures and risk of LDD.

We studied 467 non-demented individuals without LLD at baseline from a cohort of community-dwelling people aged 80 years or younger (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study follow-up. At baseline, T1-weighted magnetic resonance images were manually traced to measure the mid-sagittal areas of the anterior, mid and posterior CC. Multivariate Cox proportional hazards models stratified by sex were used to predict LLD incidence over 10 years.

A significant interaction between gender and CC size was found (P = 0.02). LLD incidence in elderly women, but not in men, was significantly associated with smaller anterior (HR 1.37 [1.05–1.79] P = 0.017), mid (HR 1.43 [1.09–1.86] P = 0.008), posterior (HR1.39 [1.12–1.74] P = 0.002) and total (HR 1.53 [1.16–2.00] P = 0.002) CC areas at baseline in Cox models adjusted for age, education, global cognitive impairment, ischemic pathologies, left-handedness, white matter lesion, intracranial volume and past depression.

The main limitation was the retrospective assessment of major depression.

Smaller CC size is a predictive factor of incident LLD over 10 years in elderly women. Our finding suggests a possible role of CC and reduced interhemispheric connectivity in LLD pathophysiology. Extensive explorations are needed to clarify the mechanisms leading to CC morphometric changes in mood disorders.