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Genetic variation in brain-derived neurotrophic factor is associated with serotonin transporter but not serotonin-1A receptor availability in men.

Journal article
Authors Susanne Henningsson
Jacqueline Borg
Johan Lundberg
Jessica Bah Rösman
Mats Lindström
Erik Ryding
Hristina Jovanovic
Tomoyuki Saijo
Makoto Inoue
Ingmar Rosén
Lil Träskman-Bendz
Lars Farde
Elias Eriksson
Published in Biological psychiatry
Volume 66
Issue 5
Pages 477-85
ISSN 1873-2402
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 477-85
Language en
Links dx.doi.org/10.1016/j.biopsych.2009....
Keywords genetic neurotrophic factor serotonin transporter men
Subject categories Pharmacology and Toxicology

Abstract

BACKGROUND: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). METHODS: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [(11)C]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [(11)C]WAY-100635. RESULTS: Several single nucleotide polymorphisms were associated with [(11)C]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [(11)C]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with (123)I-beta-CIT as ligand. CONCLUSIONS: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.

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