A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide

Arch Gen Psychiatry. 2000 Aug;57(8):729-38. doi: 10.1001/archpsyc.57.8.729.


Background: Major depression and suicide are associated with fewer serotonin transporter (5-HTT) sites. The 5'-flanking promoter region of the 5-HTT gene has a biallelic insertion/deletion (5-HTTLPR). We assayed prefrontal cortical (PFC) 5-HTT binding in major depression and suicide and examine the relationship to the 5-HTTLPR allele.

Methods: Postmortem brain samples from 220 individuals were genotyped for the 5-HTTLPR polymorphism. Binding of 5-HTT was assayed by quantitative autoradiography in the PFC of a subset of subjects (n = 159). Clinical information, including DSM-III-R Axis I diagnoses, was obtained by psychological autopsy and medical chart review.

Results: Binding to 5-HTT was lower in the ventral PFC of suicides compared with nonsuicides and was lower throughout the PFC of subjects with a history of major depression. The 5-HTTLPR genotype was associated with major depression but not with suicide or 5-HTT binding.

Conclusions: A diffuse reduction of 5-HTT binding in the PFC of individuals with major depression may reflect a widespread impairment of serotonergic function consistent with the range of psychopathologic features in major depression. The localized reduction in 5-HTT binding in the ventral PFC of suicides may reflect reduced serotonin input to that brain region, underlying the predisposition to act on suicidal thoughts. The 5-HTTLPR genotype was not related to the level of 5-HTT binding and does not explain why 5-HTT binding is lower in major depression or suicide. Arch Gen Psychiatry. 2000;57:729-738

Publication types

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

MeSH terms

  • Adult
  • Autoradiography
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics*
  • Depressive Disorder / psychology
  • Female
  • Gene Expression
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Mental Disorders / diagnosis
  • Mental Disorders / genetics
  • Middle Aged
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic*
  • Prefrontal Cortex / metabolism*
  • Promoter Regions, Genetic / genetics*
  • Serotonin / genetics*
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Sex Factors
  • Suicide / psychology
  • Suicide / statistics & numerical data*


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