title: Testing differential susceptibility: Plasticity genes, the social environment, and their interplay in adolescent response inhibition.
abstract: Impaired inhibitory control is a key feature of attention-deficit/hyperactivity disorder (ADHD). We investigated gene-environment interaction (GxE) as a possible contributing factor to response inhibition variation in context of the differential susceptibility theory. This states individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments.
  
  
  
  Behavioural and neural measures of response inhibition were assessed during a Stop-signal task in participants with (N = 197) and without (N = 295) ADHD, from N = 278 families (age M = 17.18, SD =3.65). We examined GxE between candidate plasticity genes (DAT1, 5-HTT, DRD4) and social environments (maternal expressed emotion, peer affiliation).
  
  
  
  A DRD4 × Positive peer affiliation interaction was found on the right fusiform gyrus (rFG) activation during successful inhibition. Further, 5-HTT short allele carriers showed increased rFG activation during failed inhibitions. Maternal warmth and positive peer affiliation were positively associated with right inferior frontal cortex activation during successful inhibition. Deviant peer affiliation was positively related to the error rate.
  
  
  
  While a pattern of differential genetic susceptibility was found, more clarity on the role of the FG during response inhibition is warranted before firm conclusions can be made. Positive and negative social environments were related to inhibitory control. This extends previous research emphasizing adverse environments.
authors.affiliation: a Department of Cognitive Neuroscience , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.|b Karakter Child and Adolescent Psychiatry University Centre , Nijmegen , The Netherlands.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Richards
authors.affiliation: c Department of Human Genetics , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.|d Department of Psychiatry , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias Vásquez
authors.affiliation: a Department of Cognitive Neuroscience , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: van Rooij
authors.affiliation: e Department of Psychiatry , University of Groningen, University Medical Center Groningen , The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: van der Meer
authors.affiliation: c Department of Human Genetics , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.|d Department of Psychiatry , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: e Department of Psychiatry , University of Groningen, University Medical Center Groningen , The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: f Department of Clinical Neuropsychology , VU University Amsterdam , Amsterdam , The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Heslenfeld
authors.affiliation: f Department of Clinical Neuropsychology , VU University Amsterdam , Amsterdam , The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.affiliation: g SUNY Upstate Medical University Center, Departments of Psychiatry and of Neuroscience and Physiology, Syracuse , USA and the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen , Bergen , Norway.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: e Department of Psychiatry , University of Groningen, University Medical Center Groningen , The Netherlands.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: a Department of Cognitive Neuroscience , Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen , The Netherlands.|b Karakter Child and Adolescent Psychiatry University Centre , Nijmegen , The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D019260:Expressed Emotion / Q000502:physiology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007266:Inhibition, Psychological; D007398:Interpersonal Relations; D008279:Magnetic Resonance Imaging; D008297:Male; D009034:Mother-Child Relations; D009473:Neuronal Plasticity / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4
keywords: ADHD; functional MRI; gene–environment interaction; response inhibition; social environment