title: Effect of variation in diacylglycerol kinase η (DGKH) gene on brain function in a cohort at familial risk of bipolar disorder.
abstract: Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH's risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high-risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype.
authors: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. heather.whalley@ed.ac.uk
authors: Heather C
authors: HC
authors: Whalley
authors: Martina
authors: M
authors: Papmeyer
authors: Liana
authors: L
authors: Romaniuk
authors: Eve C
authors: EC
authors: Johnstone
authors: Jeremy
authors: J
authors: Hall
authors: Stephen M
authors: SM
authors: Lawrie
authors: Jessika E
authors: JE
authors: Sussmann
authors: Andrew M
authors: AM
authors: McIntosh
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D019852:Diacylglycerol Kinase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019852:Diacylglycerol Kinase