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May 10, 2026The International Journal of Neuropsychopharmacology0 citationsOpen Access

Late-onset major depression and subthreshold depressive symptoms as early clinical correlates of brain small vessel disease

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CMCalypso Α MitkaniTTThomas TegosVKVasilios Κ. Kimiskidis

Key Points

  • This study aims to explore the relationship between late-onset depression and subthreshold depressive symptoms in patients prior to the first lacunar stroke.
  • Evaluated 58 patients with their first lacunar ischemic stroke using MRI and psychiatric assessments.
  • Classified patients into groups based on depressive symptoms (LOD, SDS, combined, or none).
  • Applied Mann–Whitney U and Fisher’s Exact tests for statistical analysis.
  • 63.8% of patients exhibited either late-onset depression or subthreshold depressive symptoms prior to stroke.
  • Depressive symptoms typically started 5–7 years before the stroke, with average onset at age 55.5.
  • Higher prevalence of depressive symptoms was found in females (87.5%) compared to males (47.1%, p = 0.001).

Abstract

Abstract Background Late-onset depression (LOD) and subthreshold depressive symptoms (SDS) have been associated with cerebral small vessel disease (SVD), but the evidence regarding pre-stroke depression remains limited. This study examined the frequency of DSM-5 LOD and SDS prior to the first non-embolic lacunar stroke. Methods Fifty-eight patients (mean age 62.2 ± 8.2 years; 41.4% female) with a first lacunar ischemic stroke underwent MRI (T1, T2, FLAIR sequences) and psychiatric evaluation using the MINI, with data from caregivers and medical records. Patients were classified as having LOD (D), SDS (S), combined (S/D), or none (nD/S). Statistical analyses included Mann–Whitney U and Fisher’s Exact tests. Results Of the total sample, 63.8% (n = 37) exhibited LOD or SDS, with reported onset on average 5–7 years prior to stroke (mean onset age: 55.5 years). Females exhibited higher prevalence of depressive symptoms (87.5% vs. 47.1%, p = 0.001). Hypertension (75.7%) and dyslipidemia (62.2%) were the most common vascular risk factors. No patient had manic or hypomanic episodes. Conclusions Premorbid depressive symptoms were common and may precede the clinical manifestation of cerebrovascular disease. Given the retrospective and observational design, these findings should be regarded as hypothesis-generating rather than causal. Prospective longitudinal studies incorporating quantitative SVD imaging markers are required.

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Cite This Study

Mitkani et al. (2026) studied this question.

synapsesocial.com/papers/6a0021fec8f74e3340f9cf83https://doi.org/10.1093/ijnp/pyag024
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