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J. John Mann, MD; Yung-yu Huang, MS; Mark D. Underwood, PhD; Suham A. Kassir, MS; Sara Oppenheim, PhD; Thomas M. Kelly, PhD; Andrew J. Dwork, MD; Victoria Arango, PhD

Arch Gen Psychiatry. 2000;57:729-738.

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.

From the Mental Health Clinical Research Center for the Study of Suicidal Behavior, Department of Neuroscience, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY.

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