Association Between Polygenic Risk and Symptom Severity Change After Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder

Julia Bäckman; John Wallert; Matthew Halvorsen; Bjorn Roelstraete; Elles de Schipper; Nora I Strom; Thorstein Olsen Eide; Kira D Höffler; Manuel Mattheisen; Bjarne Hansen; Gerd Kvale; Kristen Hagen; Jan Haavik; Nordic OCD and Related Disorders Consortium (NORDiC); David Mataix-Cols; Christian Rück; James J Crowley

doi:10.1002/ajmg.b.33026

Association Between Polygenic Risk and Symptom Severity Change After Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder

Am J Med Genet B Neuropsychiatr Genet. 2025 Mar 7:e33026. doi: 10.1002/ajmg.b.33026. Online ahead of print.

Authors

Julia Bäckman¹, John Wallert¹, Matthew Halvorsen^{1

2}, Bjorn Roelstraete³, Elles de Schipper¹, Nora I Strom^{1

4

5

6}, Thorstein Olsen Eide^{7

8

9}, Kira D Höffler^{7

10

11}, Manuel Mattheisen^{5

6

12

13}, Bjarne Hansen^{7

9}, Gerd Kvale⁷, Kristen Hagen^{7

14

15}, Jan Haavik^{7

16}; Nordic OCD and Related Disorders Consortium (NORDiC); David Mataix-Cols^{1

15}, Christian Rück¹, James J Crowley^{1

2}

Collaborators

Nordic OCD and Related Disorders Consortium (NORDiC):
Julia Bäckman, Long Long Chen, James J Crowley, Elles de Schipper, Diana Pascal, Jan Haavik, Kristen Hagen, Matthew W Halvorsen, Bjarne Hansen, Kira D Höffler, Fredrik Johansson, Anna K Kähler, Elinor K Karlsson, Gerd Kvale, Paul Lichtenstein, Kerstin Lindblad-Toh, Manuel Mattheisen, David Mataix-Cols, Kathleen Morrill, Christian Rück, Thorstein Olsen Eide, Nora I Strom, John Wallert

Affiliations

¹ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
² Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
⁶ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁷ Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
⁸ Department of Psychiatry, Møre og Romsdal Hospital Trust, Molde, Norway.
⁹ Center for Crisis Psychology, University of Bergen, Bergen, Norway.
¹⁰ Department of Medical Genetics, Dr. Einar Martens Research Group for Biological Psychiatry, Haukeland University Hospital, Bergen, Norway.
¹¹ Department for Clinical Medicine, University of Bergen, Bergen, Norway.
¹² Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
¹³ Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁴ Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
¹⁵ Department of Clinical Sciences, Lund University, Lund, Sweden.
¹⁶ Department of Biomedicine, University of Bergen, Bergen, Norway.

PMID: 40052195
DOI: 10.1002/ajmg.b.33026

Abstract

A large proportion of patients undergoing cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) do not respond sufficiently to treatment. Identifying predictors for change in symptom severity after treatment could inform clinical decision-making, allow for better-tailored interventions, and avoid treatment failure. Prior research on predictors for treatment response has, however, yielded inconsistent findings with limited clinical utility. Here, we investigated the predictive power of nine polygenic risk scores (PRSs) for psychiatric and cognitive traits in 1598 OCD patients (1167 adults and 431 children/adolescents) treated with CBT in Sweden and Norway. We fitted linear mixed models adjusted for age, sex, genotyping batch, and the first five ancestry PCs to estimate associations between PRS and symptom severity change from pre- to post-treatment. The PRS for schizophrenia showed a modestly significant association with symptom change (β = 0.013, p = 0.04, R² = 0.10), indicating that a higher PRS for schizophrenia was associated with a smaller decrease in symptom severity. No other PRS were significantly associated with the outcome. While these results await replication and expansion, current PRS for psychiatric and cognitive phenotypes do not seem to contribute meaningfully to symptom severity change in CBT for OCD.

Keywords: cognitive behavior therapy; obsessive‐compulsive disorder; polygenic risk score; symptom severity.

Abstract

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