5-HTTLPR–environment interplay and its effects on neural reactivity in adolescents

• Published in: NeuroImage (Orlando, Fla.) Vol. 63; no. 3; pp. 1670 - 1680
• Main Authors: Walsh, Nicholas D., Dalgleish, Tim, Dunn, Valerie J., Abbott, Rosemary, St Clair, Michelle C., Owens, Matthew, Fairchild, Graeme, Kerslake, William S., Hiscox, Lucy V., Passamonti, Luca, Ewbank, Michael, Ban, Maria, Calder, Andrew J., Goodyer, Ian M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-11-2012; Elsevier Limited; Academic Press
• Subjects: 5-HTTLPR; Adolescent; Amygdala; Brain; Brain - physiopathology; Brain Mapping; Childhood adversity; Faces; Female; Functional magnetic resonance imaging; Gene-Environment Interaction; Genotype; Humans; Magnetic Resonance Imaging; Male; Medical imaging; Recent negative life events; Serotonin Plasma Membrane Transport Proteins - genetics; Stress, Psychological - complications; Stress, Psychological - genetics; Studies; Teenagers; Childhood adversity; Recent negative life events; 5-HTTLPR; Amygdala; SLC6A4; fMRI; RNLE; CAMEEI; PH; Functional magnetic resonance imaging; MFQ; SAI; K-SADS-PL; CA; Faces
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2012.07.067

It is not known how 5-HTTLPR genotype×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 11years 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.
► Tested hypothesis that amygdala is neural locus for 5-HTTLPR×environment interaction ► Additive effects of 5-HTTLPR genotype and recent life events on amygdala reactivity ► Genotype×childhood adversity interaction on neural reactivity in lingual gyrus ► Two forms of environmental adversities interplay with 5-HTTLPR and neural reactivity. ► No support for hypothesized G×E interaction on amygdala reactivity