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<p>Psychotropic medication use, unhealthy lifestyle behavior and polygenic risk for high BMI (PGS-BMI) may contribute to weight gain and thereby increase cardiovascular disease (CVD) risk in people with mental illness. Using a sample of UK Biobank participants, we examined associations of psychotropic use, lifestyle and PGS-BMI with two coprimary outcomes, BMI and incident CVD, using regression, interaction and mediation models. Among 496,662 participants (mean (s.d.) age = 56.5 (8.1) yr, 54.3% female), psychotropic medication use was positively associated with BMI relative to no use (<i>β</i> = 0.053, <i>R</i><sup>2</sup> = 0.019). This association was more pronounced for multiple psychotropic use than psychotropic monotherapy (9.12% and 5.08% BMI increases, respectively). Unhealthy lifestyle was associated with increased CVD risk among participants with psychotropic use (HR = 1.69, 95% CI = 1.59-1.80). Among users of psychotropics we found consistently positive and linear associations of increasing PGS-BMI and increasingly unhealthy lifestyle with higher BMI and CVD incidence, with highest CVD risks detected in people with high PGS-BMI and unhealthy lifestyle (HR relative to those not using psychotropics, with low PGS-BMI and healthy lifestyle, 3.33, 95% CI = 2.36-4.70). Among participants with a psychiatric diagnosis, CVD risk was not increased in those using psychotropics relative to those not using psychotropics (HR = 0.98, 95% CI = 0.92–1.05). These results suggest that, among psychotropic medication users, those with both a high PGS-BMI and unhealthy lifestyle had the highest BMI and CVD risk, whereas those with both a low PGS-BMI and healthy lifestyle had the lowest risk. Notably, the association between psychotropic medication use and CVD risk was modified by psychiatric diagnosis: among people with a psychiatric diagnosis, psychotropic medication use was not associated with increased CVD risk.</p>

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Psychotropic medication use, lifestyle, genetic risk for high BMI and the incidence of cardiovascular disease

  • 期刊论文

  • 发表日期：

    2026年5月6日

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  • Nini de Boer,
  • Iris Hanskamp,
  • Bochao Danae Lin,
  • Liese Boonstra,
  • Marte van der Horst,
  • Kristel van Eijk,
  • Marco P. Boks,
  • Wouter J. Peyrot,
  • Jos Twisk,
  • Thomas Goldschmidt,
  • Hanno Pijl,
  • Christiaan H. Vinkers,
  • Christoph U. Correll,
  • Marc De Hert,
  • Sinan Guloksuz,
  • Wiepke Cahn,
  • Jurjen J. Luykx

摘要

Psychotropic medication use, unhealthy lifestyle behavior and polygenic risk for high BMI (PGS-BMI) may contribute to weight gain and thereby increase cardiovascular disease (CVD) risk in people with mental illness. Using a sample of UK Biobank participants, we examined associations of psychotropic use, lifestyle and PGS-BMI with two coprimary outcomes, BMI and incident CVD, using regression, interaction and mediation models. Among 496,662 participants (mean (s.d.) age = 56.5 (8.1) yr, 54.3% female), psychotropic medication use was positively associated with BMI relative to no use (β = 0.053, R2 = 0.019). This association was more pronounced for multiple psychotropic use than psychotropic monotherapy (9.12% and 5.08% BMI increases, respectively). Unhealthy lifestyle was associated with increased CVD risk among participants with psychotropic use (HR = 1.69, 95% CI = 1.59-1.80). Among users of psychotropics we found consistently positive and linear associations of increasing PGS-BMI and increasingly unhealthy lifestyle with higher BMI and CVD incidence, with highest CVD risks detected in people with high PGS-BMI and unhealthy lifestyle (HR relative to those not using psychotropics, with low PGS-BMI and healthy lifestyle, 3.33, 95% CI = 2.36-4.70). Among participants with a psychiatric diagnosis, CVD risk was not increased in those using psychotropics relative to those not using psychotropics (HR = 0.98, 95% CI = 0.92–1.05). These results suggest that, among psychotropic medication users, those with both a high PGS-BMI and unhealthy lifestyle had the highest BMI and CVD risk, whereas those with both a low PGS-BMI and healthy lifestyle had the lowest risk. Notably, the association between psychotropic medication use and CVD risk was modified by psychiatric diagnosis: among people with a psychiatric diagnosis, psychotropic medication use was not associated with increased CVD risk.