Neuroprotective effects of lithium in neuropsychiatric disorders

The recognition of lithium as not only a mood stabilizer but also as an inducer of a broad neuroprotective effects bursts at the dawn of the previous millennium. The myriad of effects culminating in neuroprotection are explained by the discoveries of several key cell signaling-related enzymes being lithium inhibitable. These include glycogen synthase kinase-3, inositol monophosphatase, phosphoadenosylphosphate phosphatase, and Akt/beta-arrestin 2 (Akt). Processes associated with these enzymes include autophagy, BDNF cellular signaling, neuroinflammation, mitochondrial function, and apoptosis. The involvement of these processes in a variety of brain disorders beyond bipolar disorders, such as stroke, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, fragile X syndrome, amyotrophic lateral sclerosis, and multiple sclerosis raised the interest in exploring lithium’s potential neuroprotective property in these neurodegenerative and neurodevelopmental disorders. The first part of the chapter discusses lithium’s effects on the cellular processes detailed earlier. The second part deals with data regarding lithium’s effects on cellular and animal models of each of the previously mentioned disorders that, by and large, encouraged clinical trials of lithium in these brain disorders. Finally, we discuss lithium human studies in each of these central-nervous-system disorders.