This study examined 91 elderly subjects with major depression and 31 elderly nondepressed comparison subjects. Fifty-four of the depressed subjects had an early-onset depression (EOD) and 37 had late-onset depression (LOD). Of note, 14 depressed subjects completed study procedures but could not conclusively identify an initial age of depression onset. These subjects were not included in the primary analyses but were included in secondary analyses examining the depressed and nondepressed cohorts, which did not dichotomize subjects by age of onset.
There were statistically significant group differences in age, education, and Mini-Mental State Exam (MMSE) score but not other demographic measures (). Using least squares means analyses, EOD subjects were significantly younger than LOD subjects (p = 0.0066), but there were no significant differences in comparisons with the nondepressed cohort. The LOD cohort also reported less education (p = 0.0052) and significantly lower MMSE scores (p= 0.0066) than the nondepressed cohort, but there were no significant group differences with the EOD cohort. Based on mean Montgomery-Asberg Depression Rating Scale (MADRS) scores, the majority of depressed subjects were symptomatic (); all LOD subjects exhibited a MADRS of 11 or greater, whereas only two EOD subjects exhibited a MADRS score less than 11.
Demographics and Statistical Analyses
In univariate analyses of MRI measures, significant group differences were noted in bilateral amygdala measures (). In these unadjusted comparisons, the nondepressed cohort exhibited significantly larger left and right amygdala volumes than both the EOD and LOD groups (all comparisons p <0.0001). Comparing amygdala volumes between the EOD and LOD cohorts, left amygdala volume did not differ significantly (p = 0.0522), but the EOD cohort did exhibit significantly larger right amygdala volume than the LOD cohort (p = 0.0423).
Initial multivariate models included not only age, sex, and cerebral volume but also education and MMSE score, as these variables differed between some cohorts. Neither education nor MMSE was significantly associated with amygdala volume, so were removed from the models. In parsimonious models controlling for age, sex, and cerebral volume, cohort continued to be significantly associated with amygdala volume bilaterally (left: F[2, 116]= 16.28, p <0.0001; right: F[2, 116]= 16.28, p <0.0001). Using least squares means analyses, both depressed cohorts exhibited significantly smaller amygdala volumes bilaterally than did the nondepressed cohort (all comparisons p <0.0001). However, the two EOD and LOD cohorts did not differ significantly (left: p = 0.0997; right: p = 0.1115). In these models, neither age nor sex was significantly associated with amygdala volume in either hemisphere; however, total cerebral volume exhibited a significant positive association with amygdala volume bilaterally (data not shown).
We also tested for differences between depressed and nondepressed cohorts, without dividing the depressed cohort on the basis of age of onset. For these analyses, we included the 14 subjects who did not have definitive ages of initial depression onset, resulting in a comparison of 105 elderly depressed subjects and 31 elderly nondepressed subjects. After controlling for age, sex, and total cerebral volume, the presence of depression continued to be significantly associated with smaller volume of both the left amygdala (F[1, 131]= 27.15, p<0.0001) and the right amygdala (F[1, 131]= 29.71, p<0.0001).