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No. 4 (2023)

ORIRGINAL RESEARCH

Associations of Polygenic Risk Scores for Autoimmune Diseases with Affective Disorders Phenotypes: In Search of New Mechanisms for Therapeutic Intervention

https://doi.org/10.21265/PSYPH.2023.54.33.001

Published 2023-12-30

  • G.V. Rukavishnikov
    • ,
  • E.D. Kasyanov
    • ,
  • A.S. Rakitko
    • ,
  • V.V. Ilinsky
    • ,
  • L.V. Malyshko
    • ,
  • N.G. Neznanov
    • ,
  • A.O. Kibitov
    • ,
  • G.E. Mazo

G.V. Rukavishnikov
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

E.D. Kasyanov
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

A.S. Rakitko
Genotek Ltd.

V.V. Ilinsky
Genotek Ltd.

L.V. Malyshko
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

N.G. Neznanov
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

A.O. Kibitov
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

G.E. Mazo
Federal State Budgetary Institution V. M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Heath of the Russian Federation

Abstract

Identification of shared etiopathogenetic links of depression and autoimmune diseases may be promising for the selection of new therapeutic targets, in particular in conditions resistant to antidepressant therapy.
The aim of this study was: to evaluate the associations of polygenic risk scores (PRS) for most prevalent autoimmune diseases with affective disorders phenotypes.
Material and methods. The study involved 4,520 clients of the Russian private genetics company “Genotek” (women — 50.4 %; average age of participants — 36.8 (S.D. = 9.8) years). Phenotyping results revealed the DSM criteria for depression in 17.8 % (n = 803) of participants; bipolar depression — in 8.1 % (n = 366); generalized anxiety disorder (GAD) — in 12.3 % (n = 557). A lifetime episode of anhedonia greater than 2 weeks was reported by 57.6 % (n = 2604) of participants. The PRS was used to analyze the genetic relationship between psychiatric disorders and autoimmune diseases. Considering epidemiological data, we selected three most prevalent autoimmune phenotypes to search for genetic associations: rheumatoid arthritis (RA), multiple sclerosis (MS) and Crohn's disease (CD).
Results. The GAD phenotype showed the largest number of significant associations for all autoimmune diseases. It was also shown that there were significant associations for RA with the phenotypes “Self-survey-depression”, “Self-survey-bipolar depression” and “Self-survey-GAD”; for CD with the phenotypes “Self-surveyanhedonia”, “Self-survey-GAD”; and MS with the “Self-survey-GAD” phenotype. Significant associations were found for the anhedonia phenotype and CD. When adjusted for multiple comparisons, significance was noted for the associations of RA with the “Self-survey-Depression” phenotype and CD and MS with the “Self-survey-GAD” phenotype.
Conclusion. Our study showed significant PRS associations for all types of autoimmune pathology. The identification of clear depressive phenotypes increases the likelihood of identifying specific associations for comorbid diseases, which provides more opportunities for their further use, including in the therapeutic process.

Keywords

therapeutic resistance, depression, autoimmune diseases, inflammation, polygenic risk scores, comorbidity

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