title: Genes encoding heterotrimeric G-proteins are associated with gray matter volume variations in the medial frontal cortex.
abstract: G-protein-coupled signal transduction mediates most cellular responses to hormones and neurotransmitters; this signaling system transduces a large variety of extracellular stimuli into neurons and is the most widely used mechanism for cell communication at the synaptic level. The heterotrimeric G-proteins have been well established as key regulators of neuronal growth, differentiation, and function. More recently, the heterotrimeric G-protein genes group was associated with general cognitive ability. Although heterotrimeric G-proteins are linked to both cognitive ability and neuron signaling, it is unknown whether heterotrimeric G-proteins are also important for brain structure. We tested for association between local cerebral gray matter volume and the heterotrimeric G-protein genes group in 294 subjects; a replication analysis was performed in an independent sample of 238 subjects. Voxel-based morphometry revealed a strong replicated association between 2 genes encoding heterotrimeric G-proteins with specific local increase in medial frontal cortex volume, an area known to be involved in cognitive control and negative affect. This finding suggests that heterotrimeric G-proteins might modulate medial frontal cortex gray matter volume. The differences in gray matter volume due to variations in genes encoding G-proteins may be explained by the role of G-proteins in prenatal and postnatal neocortex development.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neurosciences Campus Amsterdam, VU University, 1081HV Amsterdam, the Netherlands.
authors.forename: Iván
authors.initials: I
authors.lastname: Chavarría-Siles
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.forename: Esther
authors.initials: E
authors.lastname: Lips
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias-Vasquez
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005625:Frontal Lobe / Q000033:anatomy & histology* / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D019204:GTP-Binding Proteins