Introduction. Late onset depressive symptoms (LODSs) frequently occur in elderly with cerebral small vessel disease (SVD). SVD cannot fully explain LODS; a contributing factor could be amygdala volume. We investigated the relation between amygdala volume and LODS, independent of SVD in 503 participants with symptomatic cerebral SVD. Methods. Patients underwent FLAIR and T1 scanning. Depressive symptoms were assessed with structured questionnaires; amygdala and WML were manually segmented. The relation between amygdala volume and LODS/EODS was investigated and adjusted for age, sex, intracranial volume, and SVD. Results. Patients with LODS had a significantly lower left amygdala volume than those without ( ), independent of SVD. Each decrease of total amygdala volume (by mL) was related to an increased risk of LODS ( ; 95% CI 1.02–3.08; ). Conclusion. Lower left amygdala volume is associated with LODS, independent of SVD. This may suggest differential mechanisms, in which individuals with a small amygdala might be vulnerable to develop LODS. 1. Introduction A first depressive episode at older age is defined as late onset depressive symptoms (LODSs). LODSs are usually defined by their occurrence after the age of 60 years, while early onset depressive symptoms (EODSs) appear before. The prevalence of LODS and EODS ranges from 10% to 32% [1–4] in the elderly population. Patients with EODS show a higher rate of family history of depression than patients with LODS; genetic factors appear to be important. While psychological and genetic factors presumably play an important role in EODS [5], there are probably other nongenetic factors that play a role in LODS [5, 6] such as structural changes in the brain [7, 8]. Population-based neuroimaging studies suggest a possible role for frequently occurring white matter lesions (WMLs) in the etiology of LODS [9–12]. Their dominant view is that WMLs disrupt white matter tracts connecting cortical and subcortical structures (e.g., frontostriatal circuits), which result in LODS [13, 14]. As WML are part of the cerebral small vessel disease (SVD) spectrum, also including lacunar infarcts, it could be that the association between WML and LODS is driven by lacunar infarcts as they reflect more severe structural damage than WML. In addition, SVD might not fully explain the presence of depressive symptoms in elderly as there are patients with LODS without SVD. A functional or structural change in the amygdala may explain the residual depressive symptoms as the amygdala is involved in mood regulation, and structural MRI studies
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