title: 5-HTTLPR-environment interplay and its effects on neural reactivity in adolescents.
abstract: It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11 years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity.
authors.affiliation: Developmental and Life-course Research Group, Department of Psychiatry, University of Cambridge, Cambridge, CB2 8AD, UK. nickwalsh100@gmail.com
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Walsh
authors.forename: Tim
authors.initials: T
authors.lastname: Dalgleish
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Dunn
authors.forename: Rosemary
authors.initials: R
authors.lastname: Abbott
authors.forename: Michelle C
authors.initials: MC
authors.lastname: St Clair
authors.forename: Matthew
authors.initials: M
authors.lastname: Owens
authors.forename: Graeme
authors.initials: G
authors.lastname: Fairchild
authors.forename: William S
authors.initials: WS
authors.lastname: Kerslake
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Hiscox
authors.forename: Luca
authors.initials: L
authors.lastname: Passamonti
authors.forename: Michael
authors.initials: M
authors.lastname: Ewbank
authors.forename: Maria
authors.initials: M
authors.lastname: Ban
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Calder
authors.forename: Ian M
authors.initials: IM
authors.lastname: Goodyer
mesh_terms: D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins