Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study

Abstract

Background: Late-life depression is associated with decreased brain volumes, particularly in frontal and temporal areas. Evidence suggests that depressive symptoms at a subclinical level are also associated with brain atrophy in these regions, but most of these associations are based on cross-sectional data. Our objective was to investigate both cross-sectional and longitudinal relations between sub-threshold depressive symptoms and brain volumes in older adults and to examine whether these associations are modified by age.

Methods: In total, 110 dementia-free adults from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging aged 56 years and older at baseline participated in this study. Participants received annual evaluations for up to 9 years, during which structural magnetic resonance imaging (MRI) scans were acquired and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale.

Results: Mean depressive symptom scores over time were associated with grey matter volume reductions in the left temporal lobe. Depressive symptoms were associated with brain volume reductions with advancing age in the cingulate gyrus and orbitofrontal cortex. Moreover, individuals with higher mean depressive symptom scores showed a faster rate of volume decline in left frontal white matter. Depressive symptoms were not associated with hippocampus volumes.

Limitations: Limitations include the relative homogeneity of our primarily white and highly educated sample, the lack of information about age at onset of depressive symptoms and potential limitations of the automated brain volume registration.

Conclusion: Our results suggest that depressive symptoms, even at a subthreshold level, are associated with volume reductions in specific frontal and temporal brain regions, particularly with advancing age.

Fig. 1

Schematic of frontal and temporal regions of interest: (A) the orbitofrontal cortex is presented in blue, (B, C) white matter is in red, the cingulate gyrus is in green and the hippocampus is in yellow.

Fig. 2

Cross-sectional associations between mean depressive symptoms and brain volumes. These graphs depict brain regions for which statistical analyses revealed significant Center for Epidemiologic Studies Depression Scale (CES-D) and CES-D × baseline age effects, as shown in Table 4. Values reflect estimated scores computed from parameter estimates of the individual mixed-effects regression equations, including all main effects and significant interactions. Although depressive symptoms and age were continuous variables in all analyses, depressive symptoms and age groupings are depicted in the figure for ease of display. To show maximal differences, depressive symptoms groups are based on a cutoff at the 10th percentile of CES-D scores in our sample. Solid bar = average CES-D scores ≤ 10; striped bar = CES-D scores ≥ 11.

Fig. 3

Longitudinal association between mean depressive symptoms and left frontal white matter. In Table 4, this relation is reflected in the significant Center for Epidemiologic Studies Depression Scale (CES-D) by interval effect. (A) Values reflect estimated scores computed from parameter estimates of the individual mixed-effects regression equation, including all main effects and significant interactions. (B) Values represent the ratio of raw left frontal white matter volumes to total intracranial volume for a random selection of 10 participants with lower CES-D means and 10 participants with higher CES-D means. Although depressive symptoms were a continuous variable in all analyses, depressive symptoms groupings are depicted in the figure for ease of display. To show maximal differences, depressive symptoms groups are based on a cutoff at the 10th percentile of CES-D scores in our sample. Solid line = average CES-D scores ≤ 10; dotted line = CES-D scores ≥ 11.