The study provides convergent evidence that alterations in AKT1-GSK3β signaling pathways contribute to the pathogenesis of schizophrenia. Key findings include: 1. **Reduced AKT1 Protein Levels**: Individuals with schizophrenia had significantly lower levels of AKT1 protein in their peripheral lymphocytes and brains compared to controls. 2. **Reduced Phosphorylation of GSK3β**: There was a significant decrease in the phosphorylation of GSK3β at Ser9 in the lymphocytes and brains of individuals with schizophrenia. 3. **Association with AKT1 Haplotype**: A specific AKT1 haplotype associated with lower AKT1 protein levels was preferentially transmitted to individuals with schizophrenia. 4. **Sensitivity to Amphetamine**: Individuals with schizophrenia showed greater sensitivity to the sensorimotor gating-disruptive effects of amphetamine, which was partially mitigated by haloperidol treatment. These findings suggest that AKT1-GSK3β signaling is impaired in schizophrenia and that AKT1 may be a susceptibility gene for the disorder. The study also highlights the potential role of antipsychotic medications in compensating for impaired AKT1-GSK3β signaling, providing insights into the mechanisms of these treatments.The study provides convergent evidence that alterations in AKT1-GSK3β signaling pathways contribute to the pathogenesis of schizophrenia. Key findings include: 1. **Reduced AKT1 Protein Levels**: Individuals with schizophrenia had significantly lower levels of AKT1 protein in their peripheral lymphocytes and brains compared to controls. 2. **Reduced Phosphorylation of GSK3β**: There was a significant decrease in the phosphorylation of GSK3β at Ser9 in the lymphocytes and brains of individuals with schizophrenia. 3. **Association with AKT1 Haplotype**: A specific AKT1 haplotype associated with lower AKT1 protein levels was preferentially transmitted to individuals with schizophrenia. 4. **Sensitivity to Amphetamine**: Individuals with schizophrenia showed greater sensitivity to the sensorimotor gating-disruptive effects of amphetamine, which was partially mitigated by haloperidol treatment. These findings suggest that AKT1-GSK3β signaling is impaired in schizophrenia and that AKT1 may be a susceptibility gene for the disorder. The study also highlights the potential role of antipsychotic medications in compensating for impaired AKT1-GSK3β signaling, providing insights into the mechanisms of these treatments.