Gender Differences in Brain Structure of Elderly Patients with and without Depression

Helen Lavretsky, Psychiatry, Psychiatry, University of California- Los Angeles, Los Angeles, CA, USA

Objective: Frontal lobes and orbitofrontal sub-regions have been implicated in the pathophysiology of depression. Depressed elderly patients and normal controls, age 60 or older, were compared to examine gender differences in structural brain changes on MRI.

Design: Interest in such markers has been focused on their possible role in demonstrating disease-modifying effects of antidementia drugs.

Materials and Methods: Patients and controls were recruited from the ambulatory care programs in geriatric psychiatry at a University Hospital or through advertising, and closely matched by age and education. After signing the IRB approved informed consent form, they underwent a thorough neuropsychiatric, laboratory, and physical examination and the MRI scans. Volumetric measures of the total frontal lobe, and orbitofrontal sub-regions with corresponding gray and white matter volumes were corrected by the intracranial volume. Clinical measures of overall medical (CIRS) and cerebrovascular burden (CVRF), as well as comorbid psychiatric symptoms were obtained. A univariate and a multivariate analyses were used to evaluate the MRI brain changes by diagnosis and sex, controlling for age and medical burden (CIRS).

Results: The study samples were comprised of 35 patients with MDD (27 women; mean age 70.4 y.) and 25 controls (14 women; mean age 71.8 y.). In the univariate analysis, the depressed group had lower MMSE scores (p=0.008); greater severity of medical comorbidity (CIRS scores) (p=0.01), more severe apathy (P<0.0001) and poorer quality of life (P<0.0001) compared to the controls. The depressed group had lower right frontal white matter and orbitofrontal total and gray matter volumes than the controls (p<0.05). Men had smaller total frontal and total and gray matter volumes in the orbitofrontal sub-regions (p<0.01) compared with women. MMSE and CVRF did not differ between men and women. Diagnosis by sex interaction was observed after controlling for total medical burden.

Conclusion: Geriatric depression is associated with brain structural changes. However, sex differences in brain structural changes appear to play a role in geriatric depression, thereby, indicating that gender differences in neuroanatomy may be important in the pathophysiology of geriatric depression. The severity of medical burden may account for the observed diagnosis x sex interaction in brain volumes.