Early experience and serotonin transporter gene variation interact to influence primate CNS function

Mol Psychiatry. 2002;7(1):118-22. doi: 10.1038/sj.mp.4000949.


Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Brain / physiopathology*
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Choriocarcinoma / pathology
  • Female
  • Genes, Reporter
  • Genotype
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Luciferases / biosynthesis
  • Macaca mulatta / genetics
  • Macaca mulatta / physiology*
  • Macaca mulatta / psychology
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Membrane Transport Proteins*
  • Minisatellite Repeats*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Peer Group
  • Promoter Regions, Genetic / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Serotonin / physiology
  • Serotonin Plasma Membrane Transport Proteins
  • Social Environment*
  • Stress, Psychological / cerebrospinal fluid
  • Stress, Psychological / genetics
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology
  • Surrogate Mothers
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Uterine Neoplasms / pathology


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Luciferases