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Human Genetics Clarifies the Relationship Between Depression and Alzheimer’s Disease

  • Hyun-Sik Yang
    Correspondence
    Address correspondence to Hyun-Sik Yang, M.D.
    Affiliations
    Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts
    Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
    Harvard Medical School, Boston, Massachusetts
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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      Depression and Alzheimer’s disease (AD) dementia are prevalent brain disorders that lead to an immense patient, caregiver, and societal suffering. Observational studies strongly support the association between depression and the risk of AD dementia (
      • Bellou V.
      • Belbasis L.
      • Tzoulaki I.
      • Middleton L.T.
      • Ioannidis J.P.A.
      • Evangelou E.
      Systematic evaluation of the associations between environmental risk factors and dementia: An umbrella review of systematic reviews and meta-analyses.
      ,
      • Livingston G.
      • Huntley J.
      • Sommerlad A.
      • Ames D.
      • Ballard C.
      • Banerjee S.
      • et al.
      Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.
      ). Still, confounders and reverse causation can impact observational studies (
      • Lawlor D.A.
      • Harbord R.M.
      • Sterne J.A.
      • Timpson N.
      • Davey Smith G.
      Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology.
      ), and the causal relationship between depression and AD dementia remains unclear. In the current issue of Biological Psychiatry, Harerimana et al. (
      • Harerimana N.V.
      • Liu Y.
      • Gerasimov E.S.
      • Duong D.
      • Beach T.G.
      • Reiman E.M.
      • et al.
      Genetic evidence supporting a causal role of depression in Alzheimer’s disease.
      ) leverage genetic associations to address these limitations and to clarify the causal relationship between depression and AD dementia.
      SEE CORRESPONDING ARTICLE ON PAGE 25
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