Lithium as a Neuroprotective Agent for Bipolar Disorder: An Overview

Lithium (Li⁺) is a first option treatment for adult acute episodes of Bipolar Disorder (BD) and for the prophylaxis of new depressed or manic episodes. It is also the preferred choice as maintenance treatment. Numerous studies have shown morphological abnormalities in the brains of BD patients, suggesting that this highly heritable disorder may exhibit progressive and deleterious changes in brain structure. Since treatment with Li⁺ ameliorates these abnormalities, it has been postulated that Li⁺ is a neuroprotective agent in the same way atypical antipsychotics are neuroprotective in patients diagnosed with schizophrenia spectrum disorders. Li⁺'s neuroprotective properties are related to its modulation of nerve growth factors, inflammation, mitochondrial function, oxidative stress, and programmed cell death mechanisms such as autophagy and apoptosis. Notwithstanding, it is not known whether Li⁺-induced neuroprotection is related to the inhibition of its putative molecular targets in a BD episode: the enzymes inositol-monophosphatase, (IMPase), glycogen-synthase-kinase 3β (GSK3), and Protein kinase C (PKC). Furthermore, it is uncertain whether these neuroprotective mechanisms are correlated with Li⁺'s clinical efficacy in maintaining mood stability. It is expected that in a nearby future, precision medicine approaches will improve diagnosis and expand treatment options. This will certainly contribute to ameliorating the medical and economic burden created by this devastating mood disorder.