Depressed subjects ranged in age from 23 to 86 years (mean=50.8, SD=17.1), had a mean of 15.8 years of education (SD=3.3), and were a mean height of 64.7 inches (SD=2.3). The Hamilton depression scale scores (mean=6.7, SD=4.7) were consistent with the absence of current depression. Mean brain volumetric data for the depressed subjects were as follows: 4374 mm3 (SD=601) for total hippocampal gray matter volume; 2171 mm3 (SD=316) for left hippocampal gray matter volume; and 2203 mm3 (SD=315) for right hippocampal gray matter volume. The mean total cerebral cortical volume was 1057 cm3 (SD=152). For the comparison subjects, the mean total, left, and right hippocampal gray matter volumes were 4850 mm3 (SD=631), 2421 mm3 (SD=318), and 2429 mm3 (SD=326), respectively, with a mean total cerebral cortical volume of 1054 cm3 (SD=154). Mean left, right, and total hippocampal gray matter volumes were significantly smaller in depressed subjects than in comparison subjects, with average differences of 10% (t=3.5, df=37, p=0.001), 9% (t=3.0, df=37, p=0.005), and 10% (t=3.3, df=37, p=0.002), respectively. There were no significant between-group differences in age, education, height, or total cerebral cortical volume (all p>0.50).
Patients had a mean of 5.4 episodes of major depression (range=1–20) accounting for a lifetime mean of 1,341 days depressed (SD=1,096, range=56–4,561, median=1,112). The total number of days depressed was divided into the number of days untreated (mean=824, SD=834) and treated (mean=517 days, SD=606) with antidepressants. Untreated time depressed and total hippocampal gray matter volume were significantly and inversely related (F1). This was true for both left (beta=–0.21, R2=0.29; F=14.9, df=1, 36, p=0.0005) and right (beta=–0.18, R2=0.22; F=10.3, df=1, 36, p=0.003) hippocampal gray matter volume. No relationship was detected between the number of days depression went untreated and cerebral cortical volume or between the number of days a depressive episode was being treated and total hippocampal gray matter volume. The number of days of treated and untreated depression were not significantly correlated with each other (r=0.14, df=36, p=0.41). A comparison of correlated correlation coefficients (7) revealed that the number of days the depression went untreated was significantly more correlated with total hippocampal volume than was the number of treated depression days (z=1.82, p=0.03). No relationship was detected between lifetime exposure to antidepressants and total hippocampal volume. In a post hoc analysis, we conducted an ANCOVA with age, education, age at illness onset, and days of untreated depression (overall F=3.2, df=4, 32, p=0.02). In this model, there was no significant relationship between total hippocampal volume and age (p=0.67), education (p=0.15), or age at illness onset (p=0.66), whereas days of untreated depression was still significantly and inversely correlated with total hippocampal volume (p=0.008).