The Association Study of AKT1 Genotype, Lymphocyte AKT1 Expression Level, and Neuropsychological Performance Deficit in Schizophrenic Patients
Date Issued
2007
Date
2007
Author(s)
Lee, Ming-Yih
DOI
zh-TW
Abstract
Schizophrenia is a devastating neuropsychiatric disorder. The pathophysiological mechanism is still unknown. The study of Emamian et al. (2004) got a fruitful achievement and established the hypothesis that the AKT1- GSK3β signaling pathway was possibly involved in the pathogenesis of schizophrenia. However, there left questions unanswered: which characteristics of schizophrenia are related to AKT1 protein function impairment? In animal models, AKT1 plays crucial role in working memory formation. Individuals with schizophrenia also show performance deficits on a wide range of working memory tasks. We hypothesize that the AKT1 protein function is associated with the sustained attention/ working memory performance deficit of schizophrenia patients.
This study aims to answer the following questions: (1) to see if schizophrenia patients have lower AKT1 protein level in EBV- transformed lymphocytes; (2) to find out which subgroup of schizophrenia patients have lower level of AKT1 protein; (3) to see if any specific risk haplotype is associated with lower AKT1 protein expression level; (4) to clarify the relationship between the AKT1 protein level and the attention/ working memory task performance.
We genotyped six SNPs of AKT1 gene on 95 schizophrenic patients and 62 normal controls and measured their AKT1 protein level of the EBV- transformed peripheral lymphocytes by ELISA. We find that schizophrenic patients have significantly lower AKT1 protein level than controls (p=0.023). The AKT1 level of the patients from the multiplex families, i.e., more than 2 affected siblings within a family, were significantly lower than that of the patients from the simplex families, i.e., only one patient within a family, and normal controls. There is no significant difference in either allele or genotype frequency of the six SNPs between patients and controls. There is no significant association between the AKT1 level and the genotypes or haplotypes. The AKT1 level is not correlated to the performance of CPT, but is significantly correlated to the performance of digit span backward repetition tasks (r= 0.283, p=0.004).
We conclude that the AKT1 protein level is related to the genetic loadings of schizophrenia. Namely, the higher genetic loading, the lower the AKT1 level. Our result failed to support the hypothesis that AKT1 level is correlated to the performance of sustained attention. Our result however support the hypothesis that the AKT1 level is correlated to working memory performance. There is no significant association between AKT1 gene and schizophrenia. The AKT1 level is not associated with the AKT1 genotypes and haplotypes. Therefore, the decrease of AKT1 level in schizophrenia may not be the direct result of AKT1 gene, but the secondary change due to alterations of other associated molecules on the AKT1 pathway.
Subjects
精神分裂症
AKT1基因
持續注意力測驗
工作記憶
schizophrenia
AKT1
Continueous Performance Test
Working Memory
Type
text