| First Author | Emamian ES | Year | 2004 |
| Journal | Nat Genet | Volume | 36 |
| Issue | 2 | Pages | 131-7 |
| PubMed ID | 14745448 | Mgi Jnum | J:185487 |
| Mgi Id | MGI:5428838 | Doi | 10.1038/ng1296 |
| Citation | Emamian ES, et al. (2004) Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36(2):131-7 |
| abstractText | AKT-GSK3beta signaling is a target of lithium and as such has been implicated in the pathogenesis of mood disorders. Here, we provide evidence that this signaling pathway also has a role in schizophrenia. Specifically, we present convergent evidence for a decrease in AKT1 protein levels and levels of phosphorylation of GSK3beta at Ser9 in the peripheral lymphocytes and brains of individuals with schizophrenia; a significant association between schizophrenia and an AKT1 haplotype associated with lower AKT1 protein levels; and a greater sensitivity to the sensorimotor gating-disruptive effect of amphetamine, conferred by AKT1 deficiency. Our findings support the proposal that alterations in AKT1-GSK3beta signaling contribute to schizophrenia pathogenesis and identify AKT1 as a potential schizophrenia susceptibility gene. Consistent with this proposal, we also show that haloperidol induces a stepwise increase in regulatory phosphorylation of AKT1 in the brains of treated mice that could compensate for an impaired function of this signaling pathway in schizophrenia. |
