Patterns of Reduced Cortical Thickness in Late-Life Depression and Relationship to Psychotherapeutic Response

Objective: Cortical atrophy has been associated with late-life depression (LLD) and recent findings suggest that reduced right hemisphere cortical thickness is associated with familial risk for major depressive disorder, but cortical thickness abnormalities in LLD have not been explored. Furthermore, cortical atrophy has been posited as a contributor to poor antidepressant treatment response in LLD, but the impact of cortical thickness on psychotherapy response is unknown. This study was conducted to evaluate patterns of cortical thickness in LLD and in relation to psychotherapy treatment outcomes. Methods: Participants included 22 individuals with LLD and 12 age-matched comparison subjects. LLD participants completed 12 weeks of psychotherapy and treatment response was defined as a 50% reduction in depressive symptoms. All participants underwent magnetic resonance imaging of the brain, and cortical mapping of gray matter tissue thickness was calculated. Results: LLD individuals demonstrated thinner cortex than controls prominently in the right frontal, parietal, and temporal brain regions. Eleven participants (50%) exhibited positive psychotherapy response after 12 weeks of treatment. Psychotherapy nonresponders demonstrated thinner cortex in bilateral posterior cingulate and parahippocampal cortices, left paracentral, precuneus, cuneus, and insular cortices, and the right medial orbitofrontal and lateral occipital cortices relative to treatment responders. Conclusions: Our findings suggest more distributed right hemisphere cortical abnormalities in LLD than have been previously reported. In addition, our findings suggest that reduced bilateral cortical thickness may be an important phenotypic marker of individuals at higher risk for poor response to psychotherapy.