AKT1 and neurocognition in schizophrenia.
OBJECTIVE
Previous research has shown conflicting results for the significance of five v-akt murine thymoma viral oncogene homolog 1 (AKT1) single-nucleotide polymorphisms (SNPs) to the aetiology of schizophrenia. Neurocognition is a plausible endophenotype for schizophrenia and it was reasoned that the lack of agreement might be due to variability in neurocognition across studies. Therefore, the association of genetic variation in AKT1 with neurocognition was investigated in patients with schizophrenia.


METHODS
The same five SNPs used in previous studies of the etiology of schizophrenia (rs2494732, rs2498799, rs3730358, rs1130214, [corrected] and rs3803300) were genotyped in 641 individuals with schizophrenia who had participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. The primary dependent variable was a neurocognitive composite score and exploratory analyses investigated five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance).


RESULTS
There were no significant asymptotic or empirical associations between any SNP and the neurocognitive composite score. The authors also investigated the association of five-SNP haplotypes with the neurocognitive composite score. A marginally significant association was observed for the neurocognitive composite score with one of the five-SNP haplotypes (global score statistic 19.51, df = 9, permutation p = 0.02). Exploratory analyses of five domain scores (processing speed, reasoning, verbal memory, working memory, and vigilance) were non-significant for all five SNPs.


CONCLUSIONS
Results published to date for an association between genetic variation in AKT1 with schizophrenia are inconsistent. The results suggest that the AKT1 markers studied are not associated with neurocognition in schizophrenia, and do not support unassessed variation in neurocognitive scores as a reason for this discrepancy.
Pinheiro
Andrea Poyastro
AP
Department of Psychiatry, University of North Carolina at Chapel Hill, NC, USA.
Keefe
Richard S E
RS
Skelly
Tara
T
Olarte
Megan
M
Leviel
Keren
K
Lange
Leslie A
LA
Lange
Ethan M
EM
Stroup
T Scott
TS
Lieberman
Jeffrey
J
Sullivan
Patrick F
PF
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*; D005260:Female; D023281:Genomics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D016896:Treatment Outcome
C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt