Investigators have shown that in geriatric depression, brain changes are associated with both vascular disease and medical burden. In addition, an accumulating body of research has evaluated the relationship between structural brain changes with age, gender and comorbidity.

Some researchers have reported that older men exhibit increased brain atrophy, placing them at increased risk of depression. Changing hormones may affect brain atrophy as well. Some reports suggest women on hormone replacement therapy (HRT) had more brain atrophy than non-users.

To explore the interrelationship of brain structure and gender in elderly depressed patients, Dr. Lavretsky and colleagues compared patients with major depression and age-matched normal controls. They evaluated regional brain volumes (total brain, frontal and orbito-frontal gray and white matter) using magnetic resonance imaging (MRI). They also assessed medical burden and neuropsychiatric symptoms. In a subset of patients, they explored the interrelationship of hormone replacement therapy with MRI variables.

Investigators recruited 82 subjects 60 years of age or older, including 41 with major depression (32 women) and 41 controls (20 women). The mean age was 70.5 years in the cases and 72.2 years in controls. They measured depression and quality of life using the short form-36 (SF-36) health questionnaire and the Hamilton Depression Scale. They estimated medical burden (vascular and non-vascular), psychomotor retardation, apathy and cognition using appropriate scales.

The depressed subjects were more apathetic than controls and had lower scores on the Mini-Mental State Exam. They also had poorer-quality of life on SF-36 measures. They were also more medically ill, but they did not have an increased number of cardiovascular risk factors. Multivariate analysis of these findings showed that men were more apathetic, more medically ill and had more psychomotor impairment compared with women. This was true for men in the depressed group and men in the control group.

Dr. Lavretsky reported that brain volumes were smaller in depressed men than in depressed women. Likewise, brain volume was smaller in men in the control group versus female controls.

Investigators also compared orbitofrontal volumes in the four groups. They found that depressed patients had lower orbitofrontal volumes than controls. In addition, men had lower orbitofrontal volumes than women in both the depressed and control groups.

There were 16 women in the study taking HRT. This included 8 depressed women and 8 controls. They found the women taking hormone replacement therapy were less apathetic. This was particularly true for the cognitive part of the Apathy Evaluation Scale (AES). This component of the AES evaluates interest and motivation (i.e. “Getting together with friends is important to her/him”). However, there was also evidence that women on HRT had lower brain volumes compared with those subjects not on HRT.

Based on these findings, Dr. Lavretsky and colleagues have hypothesized a hierarchy of relationships between these variables. The investigators will continue to evaluate gender differences in geriatric depression. In particular, they will explore the role of hormones in these complex relationships.