Rampino, A;
Torretta, S;
Gelao, B;
Veneziani, F;
Iacoviello, M;
Marakhovskaya, A;
Masellis, R;
... Blasi, G; + view all
(2021)
Evidence of an interaction between FXR1 and GSK3 beta polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics.
European Psychiatry
, 64
(1)
, Article e39. 10.1192/j.eurpsy.2021.26.
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Abstract
Background: Genome-Wide Association Studies (GWASs) have identified several genes associated with Schizophrenia (SCZ) and exponentially increased knowledge on the genetic basis of the disease. In addition, products of GWAS genes interact with neuronal factors coded by genes lacking association, such that this interaction may confer risk for specific phenotypes of this brain disorder. In this regard, fragile X mental retardation syndrome-related 1 (FXR1) gene has been GWAS associated with SCZ. FXR1 protein is regulated by glycogen synthase kinase-3β (GSK3β), which has been implicated in pathophysiology of SCZ and response to antipsychotics (APs). rs496250 and rs12630592, two eQTLs (Expression Quantitative Trait Loci) of FXR1 and GSK3β, respectively, interact on emotion stability and amygdala/prefrontal cortex activity during emotion processing. These two phenotypes are associated with Negative Symptoms (NSs) of SCZ suggesting that the interaction between these SNPs may also affect NS severity and responsiveness to medication. Methods: To test this hypothesis, in two independent samples of patients with SCZ, we investigated rs496250 by rs12630592 interaction on NS severity and response to APs. We also tested a putative link between APs administration and FXR1 expression, as already reported for GSK3β expression. Results: We found that rs496250 and rs12630592 interact on NS severity. We also found evidence suggesting interaction of these polymorphisms also on response to APs. This interaction was not present when looking at positive and general psychopathology scores. Furthermore, chronic olanzapine administration led to a reduction of FXR1 expression in mouse frontal cortex. Discussion: Our findings suggest that, like GSK3β, FXR1 is affected by APs while shedding new light on the role of the FXR1/GSK3β pathway for NSs of SCZ.
| Type: | Article |
|---|---|
| Title: | Evidence of an interaction between FXR1 and GSK3 beta polymorphisms on levels of Negative Symptoms of Schizophrenia and their response to antipsychotics |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1192/j.eurpsy.2021.26 |
| Publisher version: | http://dx.doi.org/10.1192/j.eurpsy.2021.26 |
| Language: | English |
| Additional information: | © The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association. This is an Open Access article, distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivatives licence (http:// creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work. |
| Keywords: | FXR1, GSK3 beta, Negative Symptoms, Schizophrenia, treatment with antipsychotics, GLYCOGEN-SYNTHASE KINASE-3, GENOME-WIDE ASSOCIATION, PREFRONTAL CORTEX, DOPAMINE, RECEPTOR, DRUGS, MOOD, PHARMACOLOGY, DISRUPTION, ACTIVATION |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10134263 |
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