Serotonin transporter disorders

Rawson RA, Gonzales R, Brethen P Treatment of methamphetamine use disorders an update. J Subst Abuse Treat 23 145—150, 2002a Rawson RA, Huber A, Brethen P, et al Status of methamphetamine users 2—5 years after outpatient treatment. J Addict Dis 21 107—119, 2002b Reneman L, Lavalaye J, Schmand B, et al Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymetham-phetamine (MDMA or ecstasy ) preliminary findings (comment). Arch Gen Psychiatry 58 901—906, 2001... 

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

Greenberg, B. D., McMahon, F. J. et al. (1998). Serotonin transporter candidate gene studies in affective disorders and personality promises and potential pitfalls. Mol. Psychiatry, 3(3), 186-9. 

Yu, Y. W., Tsai, S. J. etal. (2002). Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol. Psychiatry, 7(10), 1115-19. 

Durham, L. K., Webb, S. M., Milos, P. M., Clary, C. M. Seymour, A. B. (2004). The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology, 174, 525-9. 

Serretti, A., Malitas, R N., Mandelli, L. etal. (2004). Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders. Pharmacoge-nomics /., 4(4), 267-73. 

Smeraldi, E., Benedetti, F. Zanardi, R. (2002). Serotonin transporter promoter genotype and illness recurrence in mood disorders. Eur. Neuropsychopharmacol. 12, 73-5. 

Mundo E, Walker M, Cate T, Macciar-di F, Kennedy JL. The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder preliminary findings. Arch Gen Psychiatry 2001 58 539-544. 

Some failures will be due to the presence of variants in drug handling. Patients who are rapid acetylators of isoniazid have a slower antituberculous response than slow acetylators (Evans and Clarke, 1961). Asthmatics who do not respond well to (32-agonist bronchodilators may have fewer functioning p2-adrenergic receptors (Drysdale et al., 2000). Variations in the synthesis or structure of the serotonin transporter protein, which is involved in selective reuptake of serotonin by presynaptic neurons, may explain why some patients with depressive disorders respond to selective serotonin reuptake inhibitors and others do not (Steimer et al., 2001). 

Furlong, R.A., et al., "Analysis and Meta-Analysis of Two Serotonin Transporter Gene Polymorphisms in Bipolar and Unipolar Affective Disorders," Am. ]. Med. Genet., 81, 58-63 (1998). 

Monoamine reuptake inhibitors elevate extracellular levels of serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) in the brain by binding to one or more of the transporters responsible for reuptake, namely the serotonin transporter (SERT), the norepinephrine transporter (NET) and the dopamine transporter (DAT), thereby blocking the reuptake of the neurotransmitter(s) from the synaptic cleft [1], Monoamine reuptake inhibitors are an established drug class that has proven utility for the treatment of a number of CNS disorders, especially major depressive disorder (MDD). 

Billett EA, Richter MA, King N, Heils A, Lesch KP, Kennedy JL (1997) Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Mol Psychiatry 2 403-406... 

McDougle CJ, Epperson CN, Price LH, Gelernter J (1998) Evidence for hnkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry 3 270-273... 

Ohara K, Nagai M, Suzuki Y, Ochiai M (1998a) Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene. Psychiatry Res 81 277-279 Ohara K, Nagai M, Suzuki Y, Ochiai M (1998b) No association between anxiety disorders and catechol-O-methyltransferase polymorphism. Psychiatry Res 80 145-148... 

Ohara K, Suzuki Y, Ochiai M, Tsukamoto T, Tani K (1999) A variable-number-tandem-repeat of the serotonin transporter gene and anxiety disorders. Prog Neuropsychopharmacol... 

Gelernter J, Cubells JF, Kidd JR, Pakstis AJ, Kidd KK (1999) Population studies of polymorphisms of the serotonin transporter protein gene. Am J Med Genet 88 61-66 Hahn MK, Blakely RD (2002) Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders. Pharmacogenomics J 2 217-235 HeUs A, Teufel A, Petri S, et al (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66 2621-2624... 

Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression implications for therapy. J Affect Disord 62 77-91 Ito K, Yoshida K, Sato K, et al (2002) A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine. Psychiatry... 

Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ (2002) Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 7 1115-1119 Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E (2000) Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. J Clin Psychopharmacol 20 105-107 Zanardi R, Serretti A, Rossini D, et al (2001) Factors affecting fluvoxamine antidepressant activity influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 50 323-330... 

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. 

Hanna, G.L., Himle, J.A., Curtis, G.C., Koram, D.Q., Weele, J.V.V., Leventhal, B.L., and Cook, E.H., Jr. (1998) Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder. Neuropsychopharmacology 18 102-111. 

Kim, S.J., Cox, N., Courchesne, R., Lord, C., Corsello, C., Natacha Akshoomoff, N., Guter, S., Leventhal, B.L., Courchesne, E., and Cook, E.H. (2002) Transmission disequilibrium mapping in the serotonin transporter gene (SLC6A4) region in autistic disorder. Amer J Hum Genet 2002, in press. 

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