title: Serotonin transporter genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults.
abstract: Recent attempts to understand the biological bases of depression vulnerability have revealed that both the short allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) and activity in the amygdala are associated with depression. Other studies have reported amygdala hyperactivity associated with the 5-HTTLPR short allele, linking the genetic and neuroimaging lines of research and suggesting a mechanism whereby the short allele confers depression risk. However, fewer investigations have examined the associations among depression, 5-HTTLPR variability, and amygdala activation in a single study. The current study thus investigated whether 5-HTTLPR genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults. Regional cerebral blood flow was measured with perfusion fMRI during a task-free scan. We hypothesized differential associations between depressive symptoms and amygdala activity among individuals homozygous for the short allele and individuals homozygous for the long allele. Both whole brain analyses and region-of-interest analyses confirmed this prediction, revealing a significant negative association among the long allele group and a trend of positive association among the short allele group. These results complement existing reports of short allele related amygdala hyperactivity and suggest an additional neurobiological mechanism whereby the 5-HTTLPR is associated with psychiatric outcomes.
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA. gillihan@mail.med.upenn.edu
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Gillihan
authors.forename: Hengyi
authors.initials: H
authors.lastname: Rao
authors.forename: Lauretta
authors.initials: L
authors.lastname: Brennan
authors.forename: Danny J J
authors.initials: DJ
authors.lastname: Wang
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.forename: Geena Mary V
authors.initials: GM
authors.lastname: Sankoorikal
authors.forename: Edward S
authors.initials: ES
authors.lastname: Brodkin
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Farah
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D003863:Depression / Q000235:genetics* / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood; D010552:Personality Assessment; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen