Anxiety serotonin transporter

In addition to the deficiency of the cholinergic neurotransmission observed in AD and correlated with cognitive function disorders, AD patients also suffer from depression and anxiety. Serotonin transporters (SERT) inhibitors... 

Lesch, K. P., Bengel, D., Heils, A. etal. (1996). Association of anxiety related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527-31. 

Holmes A, Lit Q, Mimphy DL, Gold E, Crawley JN (2003) Abnormal anxiety-related behavior in serotonin transporter null mutant mice the influence of genetic backgroimd. Genes Brain Behav 2 365-380... 

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... 

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. 

Mazzanti, C.M., Lappalainen, J., Long, J.C., Bengel, D., Naukkari-nen, H., Eggert, M., Virkkunen, M., Linnoila, M., and Goldman, D. (1998) Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Arch Gen Psychiatry 55 936-940. 

Osher, Y., Hamer, D., and Benjamin,. (2000). Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs. Mol Psychiatry 5 216-219. 

Fluoxetine Highly selective blockade of serotonin transporter (SERT) little effect on norepinephrine transporter (NET) Acute increase of serotonergic synaptic activity slower changes in several signaling pathways and neurotrophic activity Major depression, anxiety disorders panic disorder obsessive-compulsive disorder post-traumatic stress disorder perimenopausal vasomotor symptoms eating disorder (bulimia) Half-lives from 15-75 h oral activity Toxicity Well tolerated but cause sexual dysfunction Interactions Some CYP inhibition (fluoxetine 2D6, 3A4 fluvoxamine 1A2 paroxetine 2D6)... 

Several studies have discussed the relationship between serum cholesterol and suicide, violence, anxiety disorders, depressive disorders, and schizophrenia [1-3]. Some of these papers suggested that low or lowering cholesterol levels could cause or worsen depressive symptoms and increase the risks of suicide and violence death. There are many reports that discussed the relationships between the lipid profiles, depression, and suicide from the viewpoints of decreased serotonergic transmission on suicide behavior [4, 5], lower serum cholesterol and serotonin levels [6, 7], serum cholesterol levels and polymorphism in the promoter region of the serotonin transporter gene for depression and suicide [8-10], low serum cholesterol and suicide risk [11, 12], and serotonergic receptor function [13, 14]. These studies supported the hypothesis that reduced cholesterol levels resulted in reduced central serotonin transmission. 

Holmes A, Yang RJ, Lesch KP, Crawley JN, Murphy DL. Mice lacking the serotonin transporter exhibit 5-HT(lA) receptor-mediated abnormalities in tests for anxiety-like behavior. Neuropsychopharmacology 2003 28(12) 2077-2088. 

Keywords Dopamine transporter Norepinephrine transporter Serotonin transporter Polymorphism Attention deficit h5rperactivity disorder Parkinson s disease Addiction Anxiety Depression Autism... 

Just H, Sitte HH, Schmid JA, Freissmuth M, Kudlacek O (2004) Identification of an additional interaction domain in transmembrane domains 11 and 12 that supports oligomer formation in the human serotonin transporter. J Biol Chem 279 6650-6657 Keller NR, Diediich A, Appalsamy M, Miller LC, Caron MG, McDonald MP, Shelton RC, Blakely RD, Robertson D (2006) Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension. Neuroscience 139 931-946... 

Katsuragi S, Kunugi H, Sano A, Tsutsumi T, Isogawa K, Nanko S, Akiyoshi J. Association between serotonin transporter gene polymorphism and anxiety-related traits. Biol. Psychiatry 1999 45 368-370. 

Sen S, Burmeister M, Ghosh D. Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 127 85-89. 

Schinka JA, Busch RM, Robichaux-Keene N. A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol. Psychiatry 2004 9 197-202. 

Munafo MR, Clark T, Flint J. Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits A meta-analysis. Mol. Psychiatry 2005 10 415-419. 

Through their widespread blockade of the serotonin transporter, the S SRIs are known to increase serotonin levels at virtually every synapse in the CNS, yet the exact neuronal pathways and receptors through which their anxiolytic effect is ultimately produced remain unclear (166). To date, 15 different 5HT receptor subtypes have been identified (170). Of these, seven subtypes have been implicated to a greater or lesser degree in anxiety the 5HT-1A, 5HT-1B/D, 5HT-2A/B/C, and 5HT-3... 

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