Subclinical depressive symptoms during late midlife and structural brain alterations: A longitudinal study of Danish men born in 1953

We explored whether depressive symptoms measured three times during midlife were associated with structural brain alterations quantified using magnetic resonance imaging measurements of volume, cortical thickness, and intensity texture. In 192 men born in 1953 with depressive symptoms measured at age 51, 56, and 59 years, magnetic resonance imaging was performed at age 59. All data processing was performed using the Freesurfer software package except for the texture‐scores that were computed using in‐house software. Structural brain alterations and associations between depressive symptoms and brain structure outcomes were tested using Pearson's correlation, t test, and linear regression. Depressive symptoms at age 51 showed clear inverse correlations with total gray matter, pallidum, and hippocampal volume with the strongest estimate for hippocampal volume ( r  = −.22, p  < .01). After exclusion of men ( n  = 3) with scores in the range of clinical depression the inverse correlation between depressive symptoms and hippocampal volume became insignificant ( r  = −13, p  = .08). Depressive symptoms at age 59 correlated positively with hippocampal and amygdala texture‐potential early markers of atrophy. Inverse relations with total gray matter and pallidum volumes lost significance when the analysis was adjusted for intracranial volume. In men, depressive symptoms at age 51 were associated with a reduced volume of the hippocampus at age 59 independent of later symptoms. Amygdala and hippocampal textures might be the early markers for brain alterations associated with depression in midlife.