Baseline NMR lipoprotein profiles in lithium-naïve bipolar disorder patients who later showed weight gain during lithium therapy: a pilot study

Lithium is a first-line treatment for bipolar disorder (BD), but weight gain is a common side effect, leading to physical comorbidities and reduced average life expectancy. Some individuals are predisposed to weight gain due to lithium therapy, indicating the need to explore metabolic differences to prevent health complications. This descriptive feasibility study aimed to explore metabolic parameters in lithium-naïve BD individuals who later gained weight during lithium therapy versus those who did not. Data from BD individuals (N = 10) were included, five of whom gained weight (≥ 5 kg) during lithium treatment and five who did not. Nuclear Magnetic Resonance spectroscopy was used to measure blood serum lipoprotein and inflammation parameters, as well as molecular metabolites before lithium treatment. Univariate t-tests and multivariate orthogonal partial least-squares discriminant analysis (oPLS-DA) were performed to observe metabolomic between-group differences. The multivariate oPLS-DA did not show significant differences between the groups, but data visualization suggested distinct metabolic profiles. Univariate analyses revealed significantly elevated lipoprotein parameters in the weight gain group, which did not remain significant after correction for multiple testing. Phenylalanine levels showed an observable but non-significant downward trend in the weight gain group (fold change = 0.40, p = .057). The findings suggest a link between weight gain during lithium therapy and altered lipoprotein metabolism, aligning with previous research. However, larger studies are needed to further explore the underlying mechanisms. These preliminary findings represent a stepping stone for personalized lithium treatment strategies, which could help mitigate adverse metabolic side effects and improve treatment adherence.