title: Associations between genetic risk, functional brain network organization and neuroticism.
abstract: Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, PO Box 196, 9700, AD, Groningen, the Netherlands. m.n.servaas@umcg.nl.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Servaas
authors.affiliation: MRC Cognition and Brain Sciences Unit, University of Cambridge, 15 Chaucer Road, Cambridge, CB2 7EF, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Geerligs
authors.affiliation: Interdisciplinary Center for Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700, RB, Groningen, the Netherlands.
authors.forename: Jojanneke A
authors.initials: JA
authors.lastname: Bastiaansen
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, PO Box 196, 9700, AD, Groningen, the Netherlands.
authors.forename: Remco J
authors.initials: RJ
authors.lastname: Renken
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, PO Box 196, 9700, AD, Groningen, the Netherlands.
authors.forename: Jan-Bernard C
authors.initials: JC
authors.lastname: Marsman
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700, RB, Groningen, the Netherlands.
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.affiliation: Interdisciplinary Center for Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700, RB, Groningen, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Ormel
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University of Groningen, University Medical Center Groningen, PO Box 196, 9700, AD, Groningen, the Netherlands.|Department of Psychology, University of Groningen, Grote Kruisstraat 2, 9712, TS, Groningen, the Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Aleman
authors.affiliation: Interdisciplinary Center for Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700, RB, Groningen, the Netherlands.
authors.forename: Harriëtte
authors.initials: H
authors.lastname: Riese
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D000075384:Neuroticism / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D012146:Rest; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Functional connectivity; Genetics; Graph theory; Personality; Resting-state functional magnetic resonance imaging (rs-fMRI)