Why is lithium effective in alleviating bipolar disorder?

Bipolar disorder (BD) is a unique disorder where the same patient exhibits depression and mania, states with polar opposite mood symptoms. Lithium is an alkali metal that is widely used for the treatment of BD. However, it is largely unknown why lithium can stabilize mood. Lithium is known to inhibit glycogen synthase kinase-3 beta (GSK3 beta). Interestingly, both in the glutamatergic system and GABAergic system, active GSK3 beta decreases neuronal excitability, whereas inhibition of GSK3 beta increases neuronal excitability, suggesting that activation of GSK3 beta leads to depressive mood, and inhibition of GSK3 beta leads to manic mood. The activity of GSK3 beta is regulated by many kinases and a phosphatase, and they are further controlled by several neurotransmitters and signaling molecules. Thus, these complicated control systems might make the swing of GSK3 beta activity, the swing of GSK3 beta activity makes the swing of neuronal excitability and finally resulting in the intrinsic swing of mood, usually observed in healthy human. BD is considered that the amplitude of the mood swing is enhanced by many factors. Lithium can dose-dependently decrease the amplitude of the swing of GSK3 beta activity. In addition, lithium also inhibits K+ channel activation, leading to the elongation of refractory period, resulting in the inhibition of neuronal excitability. Therefore, in depressive mood, lithium can increase neuronal activity via the inhibition of neuronal GSK3beta activity, and in manic mood, lithium can inhibit neuronal excitability via inhibiting K+ channel activation, therefore the amplitude of the mood swing is decreased, i.e. alleviating the depressive state and the manic state, resulting in the normalization of the mood swing.

Automated summary

Bipolar disorder is characterized by swings between depression and mania in patients, with lithium being a common treatment that stabilizes mood through inhibiting the activity of GSK3β kinase. The levels of GSK3β activity directly influence neuronal excitability, resulting in mood swings seen in individuals with BD.