These deficits were related to SNPs from 16 genes, several previously associated with schizophrenia risk and/or involved in normal central nervous system development, including AKT, PI3K, SLC6A4, DRD2, CHRM2, and ADORA2A.
Patients were genotyped for eight AKT1 Single Nucleotide Polymorphism (SNPs), which have been previously investigated for association with schizophrenia.
However, minuscule data exist on the role of different alleles of AKT1 in measurable quantitative endophenotypes, such as cognitive abilities and neuroanatomical features, showing deviations in schizophrenia and bipolar disorder.
Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia.
We examined eight polymorphisms spanning the AKT1 gene and their association with TD in our schizophrenia sample of 193 Caucasians, 76 of which with TD.
We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia.
Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder.
Our study suggests that AKT1 is a susceptibility gene for schizophrenia in the Chinese population and that the AKT1 gene may play no major role in the therapeutic response to antipsychotics or in chlorpromazine-induced extrapyramidal syndrome.
Our findings did not confirm the association of AKT1 SNP2/3/4 TCG haplotype with the risk of schizophrenia as reported in the original study but showed the evidence of association with a different haplotype, AKT1 five-SNP AGCAG haplotype, with the risk of schizophrenia in Iranian population.
For other genes, disrupted in schizophrenia (DISC1), D-amino acid oxidase activator (DAOA), regulator of G-protein signalling 4 (RGS4) and V-AKT murine thymoma viral oncogene homolog 1 (AKT1) the data are promising but not yet compelling.
Most exciting have been recent associations of schizophrenia with specific genes, such as neuregulin-1, dysbindin-1, and AKT-1, which are vital to synaptic development, neurotransmission, and plasticity.
The replication of association of variants in the AKT1 gene in a family sample with similar ethnical background as in the original study adds further evidence for involvement of AKT1 in development of schizophrenic disorders.
While our previous data on GSK-3beta in postmortem brain and the recent report that there is impaired AKT1-GSK-3beta signaling in schizophrenia suggest that changes in pathways involving protein kinases such as AKT1 and GSK-3beta in schizophrenia are complex, our present data do not provide strong evidence in support of the involvement of GSK-3beta in schizophrenia.
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.