Glycogen synthase kinase-3 overexpression replicates electroretinogram anomalies of offspring at high genetic risk for schizophrenia and bipolar disorder.

Publication Type:

Journal Article


Biol Psychiatry, Volume 76, Issue 2, p.93-100 (2014)


Animals, Biomarkers, Bipolar Disorder, Electroretinography, Female, Genetic Predisposition to Disease, Glycogen Synthase Kinase 3, Male, Mice, Mice, Transgenic, Retina, Risk Factors, Schizophrenia


<p><b>BACKGROUND: </b>Electroretinogram (ERG) anomalies occur in patients with psychiatric disorders and represent potential biomarkers for diagnosis. For instance, decreased rod ERG (b-wave amplitude at Vmax) is a biological endophenotype in young offspring at high genetic risk (HR) for schizophrenia (SZ) and bipolar disorder (BD). Also, a decrease in cone a-wave and rod a- and b- wave was observed in SZ patients. However, the biological underpinning of these anomalies remains unknown. Several genetic variants associated with enhanced risk for SZ and/or BD can activate glycogen synthase kinase-3 isozymes (GSK3α and β). Here we examined the potential contribution of GSK3α and β in the modulation of the ERG.</p><p><b>METHODS: </b>Cone and rod ERGs were recorded in mice having increased (prpGSK3β mice) or reduced (GSK3β(+/-) mice) GSK3β expression and in GSK3α knockout (KO) mice.</p><p><b>RESULTS: </b>In prpGSK3β mice, we observed a decrease in rod b-wave amplitude at Vmax, whereas enhanced b-wave amplitude at Vmax was found in GSK3β(+/-) mice. An increase in cone a- and b-wave amplitude at Vmax and in rod b-wave amplitude at Vmax was observed in GSK3α-KO mice.</p><p><b>CONCLUSIONS: </b>GSK3 expression modulates some ERG parameters. The phenotype observed in prpGSK3β mice is consistent with observations made in HRs. ERG anomalies observed in GSK3β(+/-) and GSK3α-KO mice confirm an association between the rod and cone b-wave amplitude and the expression of GSK3 isozymes. Changes in GSK3 expression or activity may explain some ERG anomalies in HRs and patients, thus supporting the biological validity of ERG measurements as a valuable biomarker for psychiatric research.</p>

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