Identification of peripheral biomarkers through metabolomic analysis in patients with bipolar disorder treated with mood stabilizers: an exploratory study.

Importance: Bipolar disorder (BD) is mainly treated with mood stabilizers, among which lithium represents the gold standard. Despite its high clinical efficacy, the molecular players involved in lithium response and non-response remain partly unclear. Therefore, the identification of peripheral biomarkers would significantly improve the management of pharmacological interventions in BD.

Objective and design: In this study we sought to investigate the blood metabolome in patients with BD to identify biosignatures of treatment with different mood stabilizers as well as possible biomarkers of response to lithium.

Setting and participants: Blood metabolome was measured in a sample of 89 patients with BD either under prophylactic lithium treatment (n = 47), and characterized as responders (R) or non-responders (NR), or with other mood stabilizers (MS, n = 42). For each patient plasma metabolome was measured with 1H-NMR and GC-MS. Data were investigated with multivariate analyses accounting for covariates.

Results: Patients exposed to lithium or to other MS showed different, specific metabolic signatures, with different levels of metabolites belonging to pathways involved in glucose, pyruvate and glutamate metabolism, which were previously suggested to be implicated in BD and to be regulated by lithium. On the other hand, we were not able to identify significant differences in the metabolomic profile between responders and non-responders to lithium.

Conclusions and relevance: Findings from this exploratory study suggest that patients treated with lithium show distinctive metabolomic biosignatures, specifically pointing to energy metabolism and mitochondria functioning, thus potentially suggesting possible biosignatures of mood stabilizing treatments.