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

Abstract

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 ( 1 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. Alzheimers Dement. 2017; 13: 406-418 Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar , 2 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. Lancet. 2020; 396: 413-446 Abstract Full Text Full Text PDF PubMed Scopus (1510) Google Scholar ). Still, confounders and reverse causation can impact observational studies ( 3 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. Stat Med. 2008; 27: 1133-1163 Crossref PubMed Scopus (1446) Google Scholar ), and the causal relationship between depression and AD dementia remains unclear. In the current issue of Biological Psychiatry, Harerimana et al. ( 4 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. Biol Psychiatry. 2022; 92: 25-33 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ) leverage genetic associations to address these limitations and to clarify the causal relationship between depression and AD dementia. SEE CORRESPONDING ARTICLE ON PAGE 25 SEE CORRESPONDING ARTICLE ON PAGE 25 Genetic Evidence Supporting a Causal Role of Depression in Alzheimer’s DiseaseBiological PsychiatryVol. 92Issue 1PreviewDepression has been associated with a higher risk of Alzheimer’s disease (AD) in several prospective studies; however, mechanisms underlying this association remain unclear. Full-Text PDF