title: A gene-brain-cognition pathway: prefrontal activity mediates the effect of COMT on cognitive control and IQ.
abstract: A core thesis of cognitive neurogenetic research is that genetic effects on cognitive ability are mediated by specific neural functions, however, demonstrating neural mediation has proved elusive. Pairwise relationships between genetic variation and brain function have yielded heterogeneous findings to date. This heterogeneity indicates that a multiple mediator modeling approach may be useful to account for complex relationships involving function at multiple brain regions. This is relevant not only for characterizing healthy cognition but for modeling the complex neural pathways by which disease-related genetic effects are transmitted to disordered cognitive phenotypes in psychiatric illness. Here, in 160 genotyped functional magnetic resonance imaging participants, we used a multiple mediator model to test a gene-brain-cognition pathway by which activity in 4 prefrontal brain regions mediates the effects of catechol-O-methyltransferase (COMT) gene on cognitive control and IQ. Results provide evidence for gene-brain-cognition mediation and help delineate a pathway by which gene expression contributes to intelligence.
authors.affiliation: Department of Psychology, Georgetown University, Washington, DC 20057, USA. aeg58@georgetown.edu
authors.forename: Adam E
authors.initials: AE
authors.lastname: Green
authors.forename: David J M
authors.initials: DJ
authors.lastname: Kraemer
authors.forename: Colin G
authors.initials: CG
authors.lastname: Deyoung
authors.forename: John A
authors.initials: JA
authors.lastname: Fossella
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Gray
mesh_terms: D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase