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A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy

Abstract

Depression during pregnancy affects 10–15% of women, and 5% of women take antidepressants during pregnancy. Clinical guidelines provide recommendations for selective serotonin reuptake inhibitor (SSRI) drug choice and dose based on CYP2D6 and CYP2C19 genotype; however, they are based on evidence from non-pregnant cohorts. This study aimed to test the hypothesis that women with function-altering variants (increased, decreased, or no function) in these pharmacogenes, taking SSRIs prenatally, would have more depression symptoms than women whose pharmacogenetic variants are associated with normal SSRI metabolism. Comprehensive CYP2D6 and CYP2C19 genotyping using a range of methods, including gene copy number analysis, was performed as secondary analyses on two longitudinal cohorts of pregnant women (= 83) taking the SSRIs paroxetine, citalopram, escitalopram, or sertraline. The Kruskal–Wallis test compared mean depression scores across four predicted metabolizer groups: poor (= 5), intermediate (= 10), normal (= 53), and ultrarapid (= 15). There were no significant differences between mean depression scores across the four metabolizer groups (H(3) = .73, = .87, eta-squared = .029, epsilon-squared = .0089). This is the first study of the relationship in pregnancy between CYP2C19 pharmacogenetic variations and depression symptoms in the context of SSRI use. Findings from this initial study do not support the clinical use of pharmacogenetic testing for SSRI use during the second or third trimesters of pregnancy, but these findings should be confirmed in larger cohorts. There is an urgent need for further research to clarify the utility of pharmacogenetic testing for pregnant women, especially as companies offering direct-to-consumer genetic testing expand their marketing efforts.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was conducted in partial fulfillment of the requirements of CH’s doctoral degree. We thank Fudan Miao and members of AG’s team for their support in genotyping these cohorts. We thank Dr. Arianne Albert for consulting on the statistical analysis. We thank all members of the Translational Psychiatric Genetics Group for their manifold support, insight, guidance, and commitment. We also extend our gratitude to all the volunteers who assisted with recruitment and data entry for these studies over the years. Finally, we would like to express our heartfelt appreciation for those who participated in these studies; without you, none of this would be possible.

Funding

CH received salary support from a Frederick Banting and Charles Best Canada Graduate Scholarship (CGS-D), a UBC Killam Doctoral Scholarship, and a UBC Four Year Fellowship Award. CJDR was supported by Michael Smith Foundation for Health Research scholar program. CN was supported by the Canada Research Chairs Program and Genome BC. JA was supported by the Canada Research Chairs Program, and BC Mental Health and Substance Use Services. TFO is the R. Howard Webster Professor, Brain Imaging and Child Development. Cohorts A (Austin PI) and O (Oberlander PI) were funded by the Canadian Institutes of Health Research (CIHR).

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Authors and Affiliations

Authors

Contributions

Manuscript writing: CH; revised for important intellectual contribution: JA; approved final version: all.

Research design: CH, JA, CN, LGB, DR

Data collection: CH, JA, CS, EM, RB, AI, PC, UB, DR, AG, CJDR, MH

Data analysis: CH, JA, GEBW, CN, CJDR, AG, TFO, UB, CS, EM, RB

Corresponding author

Correspondence to Jehannine Austin.

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Ethics approval

These studies were performed in line with the principles of the Declaration of Helsinki. Studies were approved by the UBC/Children’s and Women’s Hospital ethics boards (cohort A: H06–70145; cohort O1: H00-70500; cohort O2: H05-70629).

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Informed consent was obtained from all individual participants included in the studies.

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Not applicable (no identifying information for any participant is included in the manuscript).

Competing interests

The authors declare no competing interests.

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Hippman, C., Slomp, C., Morris, E. et al. A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy. Arch Womens Ment Health 25, 355–365 (2022). https://doi.org/10.1007/s00737-021-01149-w

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  • DOI: https://doi.org/10.1007/s00737-021-01149-w

Keywords

  • Depression
  • Pregnancy
  • Pharmacogenetics
  • Treatment
  • SSRI