Antipsychotic-induced weight gain and metabolic effects show diurnal dependence and are reversible with time restricted feeding.


Journal

Schizophrenia (Heidelberg, Germany)
ISSN: 2754-6993
Titre abrégé: Schizophrenia (Heidelb)
Pays: Germany
ID NLM: 9918367987006676

Informations de publication

Date de publication:
30 Aug 2022
Historique:
received: 14 06 2022
accepted: 08 08 2022
entrez: 30 8 2022
pubmed: 31 8 2022
medline: 31 8 2022
Statut: epublish

Résumé

Antipsychotic drugs (AP) are highly efficacious treatments for psychiatric disorders but are associated with significant metabolic side-effects. The circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding, fasting and hormone regulation but how circadian rhythms interact with AP and its associated metabolic side-effects is not well-known. We hypothesized that time of AP dosing impacts the development of metabolic side-effects. Weight gain and metabolic side-effects were compared in C57Bl/6 mice and humans dosed with APs in either the morning or evening. In mice, AP dosing at the start of the light cycle/rest period (AM) resulted in significant increase in food intake and weight gain compared with equivalent dose before the onset of darkness/active period (PM). Time of AP dosing also impacted circadian gene expression, metabolic hormones and inflammatory pathways and their diurnal expression patterns. We also conducted a retrospective examination of weight and metabolic outcomes in patients who received risperidone (RIS) for the treatment of serious mental illness and observed a significant association between time of dosing and severity of RIS-induced metabolic side-effects. Time restricted feeding (TRF) has been shown in both mouse and some human studies to be an effective therapeutic intervention against obesity and metabolic disease. We demonstrate, for the first time, that TRF is an effective intervention to reduce AP-induced metabolic side effects in mice. These studies identify highly effective and translatable interventions with potential to mitigate AP-induced metabolic side effects.

Identifiants

pubmed: 36042214
doi: 10.1038/s41537-022-00276-2
pii: 10.1038/s41537-022-00276-2
pmc: PMC9427943
doi:

Types de publication

Journal Article

Langues

eng

Pagination

70

Subventions

Organisme : BLRD VA
ID : I01 BX003431
Pays : United States
Organisme : Department of Veterans Affairs | Veterans Affairs San Diego Healthcare System (VA San Diego Healthcare System)
ID : BX003431
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : R01DK117872

Informations de copyright

© 2022. The Author(s).

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Auteurs

Rizaldy C Zapata (RC)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Allison Silver (A)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Dongmin Yoon (D)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Besma Chaudry (B)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Avraham Libster (A)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

Michael J McCarthy (MJ)

Psychiatry Service, VA San Diego Healthcare, San Diego, CA, 92161, USA.
Department of Psychiatry and Center for Circadian Biology, University of California San Diego, La Jolla, CA, 92093, USA.

Olivia Osborn (O)

Division of Endocrinology and Metabolism, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. oosborn@ucsd.edu.

Classifications MeSH