Abstract
For decades, lithium carbonate has been a cornerstone treatment for bipolar disorder and related conditions, yet its mechanism of action remains poorly understood. Previous studies have suggested that the two stable isotopes, 6 Li and 7 Li, with nuclear spins of 1 and 3/2, respectively, can produce distinct biological effects. Because nuclear spin can subtly alter the course of specific chemical reactions, these studies have motivated the exploration of whether lithium's isotopes might act through a spin-dependent mechanism. Here, we investigate the Radical Pair Mechanism in the flavin–ascorbyl system using DFT and spin-dynamics calculations. The ascorbyl radical, derived from vitamin C, is both abundant in the brain and long-lived, making it a more credible partner for flavin. We propose that lithium's nuclear spin modulates triplet yields in flavin–ascorbyl radical pairs, offering a quantum-based explanation for isotope-dependent effects. Whether these spin interactions play a clinical role remains to be determined, but the possibility is exciting and points toward a promising line of inquiry. Author summary Lithium is a long-standing treatment for bipolar disorder, yet how it acts in the brain is still not fully understood. Previous studies have shown that different lithium isotopes can have different effects on hyperactive behaviour. A critical difference between these isotopes lies in nuclear spin, a fundamental physical property described by quantum mechanics. It is thus appropriate to investigate potential links between nuclear spin phenomena and results obtained in rat experiments. We investigate a possible quantum-mechanical mechanism involving brief interactions between flavin and the ascorbyl radical. Using computational modelling, we show that lithium affects these interactions depending on its nuclear spin. The proposed model is consistent with experimental findings in rats and uses parameter values that are realistic for biological systems.