A GRIK4 variant conferring protection against bipolar disorder modulates hippocampal function

The GRIK4 gene encodes the kainate glutamate receptor subunit, KA1, which is expressed at high levels in the hippocampus.1, 2 Cytogenetic and associated studies have shown that genetic variation in GRIK4 alters risk for bipolar disorder and schizophrenia.3 Recently a common insertion–deletion (indel) variant was identified in the 3′ untranslated region (3′UTR) of the GRIK4 gene, which alters GRIK4 expression in the hippocampus and confers protection against bipolar disorder.4 Here we show that the same GRIK4 variant modulates hippocampal activity as assessed by functional magnetic resonance imaging.