Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins.
AKT1, encoding the protein kinase B, has been associated with the genetic etiology of schizophrenia and bipolar disorder. 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. We evaluated the contribution of AKT1 to quantitative cognitive traits and 3D high-resolution neuroanatomical images in a Finnish twin sample consisting of 298 twins: 61 pairs with schizophrenia (8 concordant), 31 pairs with bipolar disorder (5 concordant) and 65 control pairs matched for age, sex and demographics. An AKT1 allele defined by the SNP rs1130214 located in the UTR of the gene revealed association with cognitive traits related to verbal learning and memory (P = 0.0005 for a composite index). This association was further fortified by a higher degree of resemblance of verbal memory capacity in pairs sharing the rs1130214 genotype compared to pairs not sharing the genotype. Furthermore, the same allele was also associated with decreased gray matter density in medial and dorsolateral prefrontal cortex (P < 0.05). Our findings support the role of AKT1 in the genetic background of cognitive and anatomical features, known to be affected by psychotic disorders. The established association of the same allelic variant of AKT1 with both cognitive and neuroanatomical aberrations could suggest that AKT1 exerts its effect on verbal learning and memory via neural networks involving prefrontal cortex.
Pietiläinen
Olli P H
OP
FIMM, Institute for Molecular Medicine Finland and National Public Health Institute, Biomedicum, Helsinki, Finland.
Paunio
Tiina
T
Loukola
Anu
A
Tuulio-Henriksson
Annamari
A
Kieseppä
Tuula
T
Thompson
Paul
P
Toga
Arthur W
AW
van Erp
Theo G M
TG
Silventoinen
Karri
K
Soronen
Pia
P
Hennah
William
W
Turunen
Joni A
JA
Wedenoja
Juho
J
Palo
Outi M
OM
Silander
Kaisa
K
Lönnqvist
Jouko
J
Kaprio
Jaakko
J
Cannon
Tyrone D
TD
Peltonen
Leena
L
D000328:Adult; D000465:Algorithms; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000033:anatomy & histology* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014427:Twins / Q000235:genetics* / Q000502:physiology*; D014706:Verbal Learning / Q000502:physiology*
C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt