ROLE OF THE SEROTONIN TRANSPORTER PROMOTER POLYMORPHISM IN PSYCHIATRIC DISORDERS

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Dysfunctions in serotonergic pathways may underlie several psychiatric disorders. The serotonin transporter (5-HTT) plays a critical role in the termination of serotonergic neurotransmission by Na-dependent uptake of serotonin by the presynaptic neuron. 5-HTT also represents the initial site of action of certain antidepressant drugs and neurotoxins. A functionally significant polymorphism in the 5-HTT promoter was identified (5HTTLPR). The polymorphism affects 5-HTT transcription and, ultimately, 5-HTT function. Frequency of the 5-HTTLPR was determined in a variety of clinical psychiatric populations including alcoholics; linkage and association studies were performed. Positive linkage was detected between 5-HTTLPR and the two anxiety-related personality traits available on the TPQ, at least partially replicating the reported association of this variant to behavior (see bibliography). In contrast, no association was found in Italian patients with obsessive compulsive disorders, panic disorders and eating disorders. However, two additional disease-specific findings were made: 1) in a collaboration with A. Malhotra and D. Pickar, 5-HTTLPR was found to be significantly associated with BPRS-rated psychoticism in schizophrenia and 2) in a collaboration with N. Rosenthal, HTTLPR was significantly linked with seasonal affective disorder and seasonality rating in SAD patients.