Cerebral Small Vessel Disease and Depression Among Intracerebral Hemorrhage Survivors

Stroke. 2022 Feb;53(2):523-531. doi: 10.1161/STROKEAHA.121.035488. Epub 2021 Sep 30.


Background and purpose: Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment.

Methods: We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment.

Results: We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14-2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12-2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51-0.94]), and to benefit from antidepressant therapy (P=0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction P=0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH.

Conclusions: CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.

Keywords: cerebral hemorrhage; depression; magnetic resonance imaging; siderosis; survivors; white matter.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / therapeutic use
  • Biomarkers
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / diagnostic imaging
  • Cerebral Amyloid Angiopathy / epidemiology
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / epidemiology*
  • Cerebral Small Vessel Diseases / etiology*
  • Depression / drug therapy
  • Depression / epidemiology*
  • Depression / etiology*
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Depressive Disorder, Treatment-Resistant / epidemiology
  • Depressive Disorder, Treatment-Resistant / etiology
  • Female
  • Humans
  • Hypertension / complications
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Survival Analysis
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Antidepressive Agents
  • Biomarkers