The serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressor.

TitleThe serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressor.
Publication TypeJournal Article
Year of Publication2008
AuthorsKalin, NH, Shelton, SE, Fox, AS, Rogers, J, Oakes, TR, Davidson, RJ
JournalMol Psychiatry
Volume13
Issue11
Pagination1021-7
Date Published2008 Nov
ISSN1476-5578
KeywordsAnimals, Behavior, Animal, Brain, Brain Mapping, Disease Models, Animal, Female, Fluorodeoxyglucose F18, Genotype, Macaca mulatta, Male, Phenotype, Polymorphism, Genetic, Positron-Emission Tomography, Serotonin Plasma Membrane Transport Proteins, Stress, Psychological
Abstract

A variant allele in the promoter region of the serotonin transporter gene, SLC6A4, the s allele, is associated with increased vulnerability to develop anxiety-related traits and depression. Furthermore, functional magnetic resonance imaging (fMRI) studies reveal that s carriers have increased amygdala reactivity in response to aversive stimuli, which is thought to be an intermediate phenotype mediating the influences of the s allele on emotionality. We used high-resolution microPET [18F]fluoro-2-deoxy-D-glucose (FDG) scanning to assess regional brain metabolic activity in rhesus monkeys to further explore s allele-related intermediate phenotypes. Rhesus monkeys provide an excellent model to understand mechanisms underlying human anxiety, and FDG microPET allows for the assessment of brain activity associated with naturalistic environments outside the scanner. During FDG uptake, monkeys were exposed to different ethologically relevant stressful situations (relocation and threat) as well as to the less stressful familiar environment of their home cage. The s carriers displayed increased orbitofrontal cortex activity in response to both relocation and threat. However, during relocation they displayed increased amygdala reactivity and in response to threat they displayed increased reactivity of the bed nucleus of the stria terminalis. No increase in the activity of any of these regions occurred when the animals were administered FDG in their home cages. These findings demonstrate context-dependent intermediate phenotypes in s carriers that provide a framework for understanding the mechanisms underlying the vulnerabilities of s-allele carriers exposed to different types of stressors.

DOI10.1038/mp.2008.37
Alternate JournalMol. Psychiatry
PubMed ID18414408
PubMed Central IDPMC2785009
Grant ListP51 RR000167 / RR / NCRR NIH HHS / United States
P50 MH069315-050002 / MH / NIMH NIH HHS / United States
MH069315 / MH / NIMH NIH HHS / United States
P50 MH052354-100003 / MH / NIMH NIH HHS / United States
MH046729 / MH / NIMH NIH HHS / United States
R01 MH046729-17 / MH / NIMH NIH HHS / United States
P50 MH069315 / MH / NIMH NIH HHS / United States
R01 MH046729 / MH / NIMH NIH HHS / United States
P50 MH052354 / MH / NIMH NIH HHS / United States
MH052354 / MH / NIMH NIH HHS / United States