RGD Reference Report - Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. - Rat Genome Database

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Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia.

Authors: Emamian, ES  Hall, D  Birnbaum, MJ  Karayiorgou, M  Gogos, JA 
Citation: Emamian ES, etal., Nat Genet 2004 Feb;36(2):131-7. Epub 2004 Jan 25.
RGD ID: 1358369
Pubmed: PMID:14745448   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1296   (Journal Full-text)

AKT-GSK3beta signaling is a target of lithium and as such has been implicated in the pathogenesis of mood disorders. Here, we provide evidence that this signaling pathway also has a role in schizophrenia. Specifically, we present convergent evidence for a decrease in AKT1 protein levels and levels of phosphorylation of GSK3beta at Ser9 in the peripheral lymphocytes and brains of individuals with schizophrenia; a significant association between schizophrenia and an AKT1 haplotype associated with lower AKT1 protein levels; and a greater sensitivity to the sensorimotor gating-disruptive effect of amphetamine, conferred by AKT1 deficiency. Our findings support the proposal that alterations in AKT1-GSK3beta signaling contribute to schizophrenia pathogenesis and identify AKT1 as a potential schizophrenia susceptibility gene. 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
schizophrenia  IAGP 1358369 RGD 
schizophrenia  ISOAKT1 (Homo sapiens)1358369; 1358369 RGD 
schizophrenia  IDA 1358369protein:decreased serine phosphorylation:frontal cortex RGD 
schizophrenia  ISOGSK3B (Homo sapiens)1358369; 1358369protein:decreased serine phosphorylation:frontal cortex RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)
GSK3B  (glycogen synthase kinase 3 beta)


Additional Information