Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Publication date: Jul 11, 2023

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li was developed in the International Consortium of Lithium Genetics cohort (ConLiGen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li and lithium treatment response – defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P 

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Concepts Keywords
Genetic Bd
Glutamatergic Bipolar
Lithium Cholinergic
Models Continuous
Psychiatry Developed


Type Source Name
disease MESH bipolar disorder
disease MESH mental disorder
drug DRUGBANK Acetylcholine
disease MESH mania
disease MESH comorbidity
disease MESH suicide
disease MESH schizophrenia
drug DRUGBANK Coenzyme M
pathway REACTOME Translation

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