Circadian rhythm and lithium response in bipolar disorder: Insights from actigraphy and NR1D1 polymorphism

Lithium has long been used as a cornerstone mood stabilizer in the treatment of bipolar disorder (BD). However, reliable biomarkers that can predict which patients will respond better to lithium are still lacking. This study aims to evaluate the potential of NR1D1 gene SNP; rs2071427 and actigraphic measurements in predicting lithium response. Thirty-one patients diagnosed with BD at Selçuk University Faculty of Medicine and who were euthymic for at least 8 weeks were included in the study. Sleep-wake cycles and circadian rhythms of the participants were monitored by actigraph for approximately 1 week. For genetic analyses, the SNP rs2071427 variant of the NR1D1 gene was evaluated. A significant proportion of patients with homozygous (AA/GG) genotypes responded well to lithium, whereas some patients with heterozygous (AG) genotypes did not respond to lithium. Actigraphic data showed that there were marked variations in the sleep patterns of BD patients. The Morningness-Eveningness Questionnaire scale did not adequately discriminate the morning chronotype. Seasonal Pattern Assessment Questionnaire results showed that most patients had a seasonal pattern, but this was insufficient to predict response to lithium. This study once again demonstrates the need for new biomarkers to predict lithium response. The findings are an important step in the personalization of BD treatment and may improve treatment efficacy and minimize side effects by tailoring the treatment process to the individual characteristics of patients. Future studies should support these findings with larger sample groups and studies on different genetic markers.