Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression

Abstract

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Fig. 1.

Hippocampal volume measurement using stereology.A, Coronal section through the hippocampus. Points within the hippocampus highlighted in red were selected from a randomly placed 5 × 5 mm² grid overlying the hippocampus and are simultaneously displayed in (A) coronal, (B) sagittal, and (C) horizontal views. Arrowindicates the caudate (A), and ↔ indicates the amygdala 171 (B). D, Cubic volumes containing the hippocampus were sectioned out from the total brain volume.

Fig. 2.

Left and right hippocampal gray matter volumes. The lines connect the hippocampal volumes for each subject pair consisting of subject with a history of major depression (post-depressed) and the age, gender, education, and height-matched case control; the mean and the SDs for each group are also shown.

Fig. 3.

Correlation between duration of depression and hippocampal volume. The Pearson correlation between cumulative lifetime total days of major depression was derived from the Diagnostic Interview for Genetic Studies using the Post Life Charting Method (Post et al., 1988) and the total hippocampal gray matter volumes.

Fig. 4.

Correlation between age and total hippocampal gray matter volumes corrected for depression duration. The correction factor was derived from a multiple regression ANOVA using age and depression duration as independent variables and hippocampal gray matter volume as the dependent variable (see Materials and Methods).

Fig. 5.

Correlations between hippocampal and amygdala volumes. A, The Pearson correlation between total hippocampal gray matter volume and the total amygdala core nuclei volume; B, the correlation between total hippocampal gray matter volume and total amygdala noncore volume in subjects with a history of major depression.