Circadian and Sleep-Related Polygenic Scores in Relation to Lithium Treatment Response in Bipolar Disorder
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: Circadian rhythms are reflected through sleep-wake patterns and chronotype. Patients with bipolar disorder (BD) frequently exhibit disrupted sleep patterns and a tendency for evening chronotype. Also, genetic risk factors for BD partially overlap with those influencing sleep traits. Lithium (Li), the first-line therapy for BD, stabilizes circadian rhythms and promotes morningness in responders (Rp). This study aimed to evaluate whether the polygenic burden of sleep-related traits is associated with Li response in BD patients. METHODS: A total of 114 European ancestry BD patients were categorized as Li Rp (N = 79) or non-responders (N = 35), based on the reduction of 50% of the episodes. Polygenic scores (PGS) for chronotype, daytime dozing, ease of getting up, insomnia, morningness, napping, sleep duration, and snoring were calculated using PRS-CS. Associations between each PGS and Li response were tested using logistic regression models. Comparisons were made between the extreme quartiles of each PGS. RESULTS: The PGS for ease of getting up was significantly associated with Li response, explaining 9.989% of the variance based on Nagelkerke's pseudo-R2 (FDR-adjusted p value = 0.046). Additionally, individuals with a higher genetic predisposition for ease of getting up had increased odds of a good response (FDR-adjusted p value = 0.039; OR = 5.143; 95% CI = 1.537-17.209). CONCLUSION: The study suggests that a higher genetic predisposition for ease of getting up in the morning may increase the likelihood of responding to Li treatment in BD patients. Our study aligns with previous evidence, highlighting the importance of sleep and chronotype patterns in response to Li in BD patients. .
Source: Neuropsychobiology
DOI: 10.1159/000551565
Authors: Marina Zafrilla-López, Daniel Herrera-Escartín, Maria Guardiola-Ripoll, Arnau García-Fernández, Miriam Acosta-Díez, Anna Giménez-Palomo, Pilar A. Saiz, Maria Paz García-Portilla, Esther Jiménez, Sergi Papiol, Lourdes Fañanás, Victoria Ruiz, Patricia Gavín, Leticia González-Blanco, Eduard Vieta, Thomas G. Schulze, Mar Fatjó-Vilas, Antoni Benabarre, Marina Mitjans, Bárbara Arias
Institutions: Instituto de Salud Carlos III, Universitat de Barcelona, Institut Pere Mata, Institut de Recerca Biomèdica Catalunya Sud, Universitat Politècnica de Catalunya, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, Servicio de Salud del Principado de Asturias, Max Planck Institute of Psychiatry, Institut für Psychiatrische Phänomik und Genomik, Ludwig-Maximilians-Universität München, Institut de Biomedicina de la Universitat de Barcelona, Johns Hopkins University, SUNY Upstate Medical University, Johns Hopkins Medicine, Fidmag Sisters Hospitallers, Institut de Recerca Sant Joan de Déu
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7154632847