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

Author(s): Huang, J. Y., Underwood, M. D., Kassir, S. A., Oppenheim, S., Kelly, T. M., Dwork, A. J., Arango, V.

Journal/Book: Arch Gen Psychiat. 2000; 57: 515 N State St, Chicago, IL 60610, USA. Amer Medical Assoc. 729-738.

Abstract: 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.

Note: Review Mann JJ, New York State Psychiat Inst & Hosp, Dept Neurosci, Mental Hlth Clin Res Ctr Study Sucidal Behav, 1051 Riverside Dr, Box 42, New York,NY 10032 USA

Keyword(s): BIPOLAR AFFECTIVE-DISORDER; CEREBROSPINAL-FLUID MONOAMINE; TRYPTOPHAN-HYDROXYLASE GENE; TRITIATED IMIPRAMINE BINDING; BIOGENIC AMINE METABOLITES; H-3 PAROXETINE BINDING; MESSENGER-RNA; ASSOCIATION ANALYSIS; RECEPTOR-BINDING; FRONTAL-CORTEX

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