Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders?

Biol Psychiatry. 1998 Aug 1;44(3):179-92. doi: 10.1016/s0006-3223(98)00121-8.


Serotonin (5-HT) is an important regulator of morphogenetic activities during early central nervous system development, including cell proliferation, migration, and differentiation. The 5-HT transporter (5-HTT) plays a pivotal role in brain 5-HT homeostasis. It is also the initial target for both antidepressant drugs and drugs of abuse, some of which are potent neurotoxins. A polymorphism in the 5'-flanking regulatory region of the 5-HTT gene that results in allelic variation of 5-HTT expression is associated with anxiety-related personality traits and may influence the risk of developing affective disorders. Progress in 5-HTT gene inactivation studies are also changing views of the relevance of adaptive 5-HT uptake function in brain development and plasticity as well as processes underlying drug dependence and neurodegeneration. Despite evidence for a potential role of the 5-HTT in the integration of synaptic connections in the mammalian brain during development, adult life, and old age, detailed knowledge of the molecular mechanisms involved in these fine-tuning processes is just beginning to emerge. Integration of various strategies, including molecular genetic, transgenic, and gene transfer techniques, will allow elucidation of the 5-HTT's role in brain development, plasticity, and degeneration as well as in affective illness, drug abuse, and dementia.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alcoholism / genetics
  • Animals
  • Brain / embryology
  • Brain / physiopathology
  • Carrier Proteins / genetics*
  • Dementia / genetics*
  • Female
  • Gene Expression / physiology
  • Genetic Variation / genetics*
  • Humans
  • Infant, Newborn
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Mood Disorders / genetics*
  • Nerve Degeneration / embryology
  • Nerve Degeneration / genetics*
  • Nerve Tissue Proteins*
  • Neuronal Plasticity / genetics
  • Personality / genetics
  • Pregnancy
  • Risk Factors
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin