Serotonin transporter phenotypes

Goldstein JA, Ishizaki T, Chiba K, et al (1997) Frequencies of the defective CYP2C19 ahe-les responsible for the mephenytoin poor metabohzer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 7 59-64 Greenberg BD, McMahon FJ, Murphy DL (1998) Serotonin transporter candidate gene studies in affective disorders and personality promises and potential pitfahs [guest editorial]. Mol Psychiatry 3 186-189... 

Based on existing findings, there are many important hypotheses in pediatric psychopharmacogenetics. Selective serotonin transporter inhibitors have been shown to have efficacy in double-blind studies in children and/ or adolescents in the treatment of autism, major depression, OCD, and anxiety disorders. Given the association of the serotonin transporter promoter variant with SSRI treatment response in adult depression (Smeraldi et ah, 1998), all of the SSRI-responsive phenotypes should be tested for promoter variant influence on response using family-based or population-based controlled association studies. The report of strong 5-HTTLPR allelic effects on SSRI-induced mania (Mundo et ah, 2000) is of special interest given frequent SSRI-induced activation in children. 

Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabohtes. J Pharmacol Exp Ther 283 1305-1322 Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, Murphy DL (2003) Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 8 933-936... 

Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol. Psychiatry 2002 7 118-122. Crawley JN, Belknap JK, Collins A, Crabbe JC, Erankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, et al. Behavioral phenotypes of inbred mouse strains implications and recommendations for molecular studies. Psychopharmacology (Berl) 1997 132 107-124. 

The neurotransmitter phenotype, (i.e., what type of neurotransmitter is stored and ultimately will be released from the synaptic bouton) is determined by the identity of the neurotransmitter transporter that resides on the synaptic vesicle membrane. Although some exceptions to the rule may exist all synaptic vesicles of a given neuron normally will express only one transporter type and thus will have a dehned neurotransmitter phenotype (this concept is enveloped in what is known as Dale s principle see also Reference 19). To date, four major vesicular transporter systems have been characterized that support synaptic vesicle uptake of glutamate (VGLUT 1-3), GABA and glycine (VGAT), acetylcholine (VAChT), and monoamines such as dopamine, norepinephrine, and serotonin (VMAT 1 and 2). Vesicles that store and release neuropeptides do not have specific transporters to load and concentrate the peptides but, instead, are formed with the peptides already contained within. 

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