THE ARTICLE by Mann and coworkers1 demonstrates, with a respectably large sample size, the association of major depression and suicide with low levels of serotonin transporter (5-HTT) binding in the prefrontal cortex. This extends these authors' previous demonstration of low levels of 5-HTT binding in prefrontal cortex from those who had committed suicide reported in a smaller sample size.2 Furthermore, the authors demonstrate, for the first time, that the anatomy of 5-HTT loss in the prefrontal cortex of subjects with major depression is more widespread than that found in those who commit suicide. The recent identification of a polymorphism in the promoter region of the human 5-HTT gene3 (5-HTTLPR) and the demonstration that the short promoter form has lower activity4 led these authors to logically examine the possible association of reduced 5-HTT in depression and suicide with the short-form (less active) 5-HTTLPR. As cited in their article, there is considerable controversy over whether this promoter polymorphism is associated with affective disorders. The findings of Mann and coworkers provide little evidence supporting a role of the less active short 5-HTTLPR in mood disorders. Their observations also suggest that low levels of 5-HTT binding found in major depression and suicide are not associated with a preponderance of the short 5-HTTLPR.
Ordway GA. Searching for the Chicken's Egg in Transporter Gene Polymorphisms. Arch Gen Psychiatry. 2000;57(8):739–740. doi:10.1001/archpsyc.57.8.739