Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort.

Autor: Piras M; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland. Marianna.piras@chuv.ch., Lin J; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA., Sadler MC; University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Ranjbar S; Psychiatric Epidemiology and Psychopathology Research Center, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Grosu C; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Laaboub N; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Preisig M; Psychiatric Epidemiology and Psychopathology Research Center, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Gamma F; Les Toises Psychiatry and Psychotherapy Center, Lausanne, Switzerland., Plessen KJ; Service of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., von Gunten A; Service of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Conus P; Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland., Kutalik Z; University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Eap CB; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Prilly, Switzerland. chinbin.eap@unil.ch.; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. chinbin.eap@unil.ch.; Center for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland. chinbin.eap@unil.ch.; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, Switzerland. chinbin.eap@unil.ch.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Nov 15; Vol. 14 (1), pp. 471. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1038/s41398-024-03177-3
Abstrakt: Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m 2 , respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.
Competing Interests: Competing interests CBE received honoraria for conferences from Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, andZeller in the past 3 years. The authors declare no competing interests. Ethics This study was carried out in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Vaud (CER-VD).
(© 2024. The Author(s).)
Databáze: MEDLINE
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