台大心理系

Lithium was the first medication with mood-stabilizing and first-line treatment for both acute mania and depression episodes of bipolar disorder. Emerging evidence indicates that lithium directly and indirectly inhibited glycogen synthase kinase 3 (GSK3), which is one of key downstream kinases for Akt1. Accumulating evidence from human genetic and animal studies suggested that Akt1 contributed to susceptibility for neuropsychiatric, especially schizophrenia. However, recent study revealed that Akt1-deficit mice showed are insensitive to antipsychotic, but GSK3 inhibitor could have therapeutic potential. To evaluate the therapeutic potential and mechanism of lithium on the alleviation of schizophrenia-related deficits with Akt1 deficiency, a series of studies was conducted. First, using Taiwan national health insurance research database (NHIRD) surveyed that the usage rate of lithium was 10.66% and 6.63% in Taiwan schizophrenia inpatients and outpatients. Second, both AKT1/2 inhibitor and lithium were applied to evaluate their effect from P19 neural cell and primary cell culture. Inhibiting Akt resulted in a reduction of neurite length and lithium rescued the impairment. Third, female Akt1 heterozygous mutant (Akt1+/-) mice showed the sensorimotor gating deficit, depression-like behavior, and methamphetamine (Meth) induced stereotypic behavior. Then, chronic treatment of lithium alleviated the observed behavioral impairments in female Akt1+/- mice. Collectively, our findings implied the therapeutic potential of lithium for the treatment of schizophrenia and the importance of GSK3 as a new therapeutic target.