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 in vitro 5-HTT transcription and, ultimately, 5-HTT function. We have shown that the """"""""s"""""""" allele is also associated with lower in vivo serotonin transporter availability in brain. This was accomplished using B-CIT in a SPECT study of normal controls and alcoholics. 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.
| Heinz, A; Goldman, D; Jones, D W et al. (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-9 |
| Schuckit, M A; Mazzanti, C; Smith, T L et al. (1999) Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biol Psychiatry 45:647-51 |
