Background: The inhibitory GABAergic system has shown an association with
multiple psychiatric disorders. The type A GABA receptors are an integral component of
this system, and in recent years, evidence has accumulated to support an essential role in
disease etiology for one of the receptor genes GABRB2 which encodes for the receptor β2
Objective: To summarize the different lines of evidence supporting the important role of
GABRB2 in psychiatric disorders, with a particular focus on schizophrenia, and evaluate
the recently-proposed GABRB2-origin of schizophrenia hypothesis.
Results: In terms of genetics, Single Nucleotide Polymorphisms (SNPs) in GABRB2 have
been associated with a number of psychiatric disorders, and some of the associations have
remained significant following meta-analysis. Importantly, expression and alternative
splicing of the gene was shown to be dependent on the genotypes of the associated SNPs,
and receptors containing the long isoform displayed functional differences compared to
those containing the short isoform. Moreover, differential epigenetic regulation and imprinting
imbalance of the gene were observed in schizophrenic patients compared to
healthy subjects. Finally, recent findings from a Gabrb2-knockout mouse model demonstrated
that knockout of the gene alone was sufficient to induce a wide range of schizophrenia-
like symptoms and comorbid phenotypes.
Conclusion: The different lines of evidence coalesce to strongly support the recentlyproposed
GABRB2-origin of schizophrenia hypothesis, and GABRB2 may also have a potential
role in cognition, the dysfunction of which is common to many psychiatric disorders.