Lithium salts are the most commonly used drug in the treatment of bipolar disorder, with proven effectiveness in reducing the risk of relapses. However, the narrow therapeutic range of concentrations and high risk of side effects require a closer look at their mechanisms of action. Lithium exhibits a neuroprotective effect in hippocampus and amygdala as well as the neurotoxic properties which are most evident in the cerebellum. The purpose of this paper is to review the literature on the neuroprotective and neurotoxic properties of lithium salts.
Neuroprotective properties of prolonged lithium treatment result from the inhibition of neuronal excitotoxicity by blocking the NMDA receptors, and anti-apoptotic action in the particular areas of the brain. In vitro studies have also found a positive effect on neurogenesis, which coincides with the morphometric studies in humans, where increased volume of grey matter in the prefrontal cortex and the limbic system was reported. A lot of research indicates, however, the occurrence of serious adverse effects of prolonged lithium therapy, not necessarily resulting from an overdose. Symptoms of chronic intoxication include both cognitive disorders, peripheral neuropathy giving rise to sensomotoric disturbances, and cerebellar dysfunctions. All of these are the aspects of the syndrome of irreversible lithium-effectuated neurotoxicity. Neuropathological studies indicate signiﬁ cant structural changes occurring mainly in the cerebellum, including the disappearance of the granular layer and Purkinje cells, with associated gliosis. These changes, caused by lithium toxicity, might be a signiﬁ cant factor impeding the determination of the aetiology of bipolar disorder, which also includes disturbances in the cerebellum, both at the structural and functional level.