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The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia

Molecular Psychiatry (2023)Cite this article

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Abstract

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960–1995 with a first diagnosis of MD (n = 257,177), BD (n = 23,032), and SZ (n = 4248) from 2006 to 2018. Drug classes and Defined Daily Dose (DDD) were obtained from the Pharmacy register using the Anatomical Therapeutic Chemical system. We utilized the Familial Genetic Risk Scores (FGRS) calculated from morbidity risks in first- through fifth degree relatives. Treatment with antidepressants (AD) in MD, mood-stabilizers (MS) in BD, and antipsychotics (AP) in SZ were associated with significantly higher disorder-specific familial-genetic risks. Using dosage trajectory analysis of AD, MS, and AP treatment for MD, BD, and SZ, respectively, familial-genetic risk was positively associated with higher and/or increasing drug dosages over time. For MD and BD, examining cases started on the most common pharmacologic treatment class (SSRIs for MD and “other anti-epileptics” for BD), familial-genetic risks were significantly lower in those who did not versus did later receive treatment from other AD and MS classes, respectively. Higher familial-genetic risk for BD predicted switching AD medication in cases of MD. Among pharmacologically treated cases of BD, familial-genetic risk was significantly higher for those treated with lithium. In a large population-based patient cohort, we found evidence of a wide-spread association between higher familial-genetic risk and i) increased likelihood of receiving pharmacologic treatment but 2) responding more poorly to it—as indicated by a switching of medications -- and/or requiring higher doses. Further investigations into the clinical utility of genetic risk scores in the clinical managements of MD, BD, and SZ are warranted.

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Fig. 1: Genetic risk scores for cases of major depression who did versus did not receive antidepressants.
Fig. 2: Dosage trajectories and genetic risk scores for pharmacologic treatment of cases of depression, bipolar disorder and schizophrenia.
Fig. 3: Genetic risk scores for different sequences of antidepressant treatment.
Fig. 4: Genetic risk scores for cases of depression, bipolar disorder and schizophrenia who received only standard treatment versus were switched to a second agent.

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Data availability

Jan Sundquist MD, Ph.D. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Acknowledgements

Location of where work was done: Lund University, Virginia Commonwealth University.

Funding

This project was supported by grants from the Swedish Research Council (2020-01175).

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Authors and Affiliations

  1. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    Kenneth S. Kendler

  2. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    Kenneth S. Kendler

  3. Center for Primary Health Care Research, Lund University, Malmö, Sweden

    Henrik Ohlsson, Jan Sundquist & Kristina Sundquist

  4. Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jan Sundquist & Kristina Sundquist

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Contributions

KSK developed the hypothesis and HO performed the statistical analyses. KSK drafted the manuscript with input from JS, KS, and HO, who all reviewed the MS. JS and KS oversaw and kept updated the registry resources needed for these analyses.

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Correspondence to Kenneth S. Kendler.

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Kendler, K.S., Ohlsson, H., Sundquist, J. et al. The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02365-9

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