title: Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence.
abstract: The S and LG alleles of the serotonin transporter-linked polymorphic region (5-HTTLPR) lower serotonin transporter expression. These low-expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala-prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces depression that emerges in adolescence, whereas decreased serotonin transporter that occurs later in development ameliorates depression. However, no brain imaging research has yet investigated the moderating influence of human development on the link between 5-HTTLPR and effect-related brain function. We investigated the age-related effect of 5-HTTLPR on amygdala activation and amygdala-prefrontal cortex connectivity using a well-replicated probe, an emotional face task, in children and adolescents aged 9-19 years. A significant genotype-by-age interaction predicted amygdala activation, such that the low-expressing genotype (S/S and S/LG ) group showed a greater increase in amygdala activation with age compared to the higher expressing (LA /LA and S/LA ) group. Additionally, compared to the higher expressing group, the low-expressing genotype group exhibited decreased connectivity between the right amygdala and ventromedial prefrontal cortex with age. Findings indicate that low-expressing genotypes may not result in the corticolimbic profile associated with depression risk until later adolescence.
authors.affiliation: Department of Psychology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jillian Lee
authors.initials: JL
authors.lastname: Wiggins
authors.forename: Jirair K
authors.initials: JK
authors.lastname: Bedoyan
authors.forename: Melisa
authors.initials: M
authors.lastname: Carrasco
authors.forename: Johnna R
authors.initials: JR
authors.lastname: Swartz
authors.forename: Donna M
authors.initials: DM
authors.lastname: Martin
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Monk
mesh_terms: D000293:Adolescent; D000375:Aging / Q000235:genetics*; D000679:Amygdala / Q000098:blood supply / Q000502:physiology*; D002648:Child; D004644:Emotions / Q000502:physiology; D005145:Face; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000098:blood supply / Q000502:physiology*; D011601:Psychophysics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen
keywords: 5-HTTLPR; affect; connectivity; development; emotion; functional MRI; imaging genetics