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Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder
- Source :
- Furmark, T, Marteinsdottir, I, Frick, A, Heurling, K, Tillfors, M, Appel, L, Antoni, G, Hartvig, P, Fischer, H, Roland Långström, B, Eriksson, E & Fredrikson, M 2016, ' Serotonin synthesis rate and the tryptophan hydroxylase-2 : G-703T polymorphism in social anxiety disorder ', Journal of Psychopharmacology, vol. 30, no. 10, pp. 1028-1035 . https://doi.org/10.1177/0269881116648317
- Publication Year :
- 2016
-
Abstract
- It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -11C]tryptophan, [11C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [11C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.
- Subjects :
- 0301 basic medicine
Male
Neurology
positron emission tomography
Tryptophan Hydroxylase
Hippocampus
Serotonin/metabolism
Basal Ganglia
0302 clinical medicine
Polymorphism (computer science)
Pharmacology (medical)
Polymorphism, Genetic/genetics
[ C]5-HTP
Social anxiety
anxiety
Amygdala
Anxiety Disorders
Psychiatry and Mental health
Phobia, Social/genetics
Anxiety
Female
medicine.symptom
Tryptophan Hydroxylase/genetics
Psychology
Amygdala/metabolism
Clinical psychology
Adult
medicine.medical_specialty
Serotonin
Serotonin synthesis
Genotype
brain
Hippocampus/metabolism
Gyrus Cinguli
03 medical and health sciences
Young Adult
Internal medicine
medicine
Serotonin synthesis [C-11]5-HTP brain anxiety gene positron emission tomography human tryptophan-hydroxylase-2 gene predicts amygdala reactivity positron-emission-tomography human brain in-vivo transporter phobia system stress pet Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry
Humans
gene
Alleles
Pharmacology
Polymorphism, Genetic
Gyrus Cinguli/metabolism
Phobia, Social
Tryptophan hydroxylase
030104 developmental biology
Endocrinology
Basal Ganglia/metabolism
Anxiety Disorders/genetics
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14617285
- Volume :
- 30
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of psychopharmacology (Oxford, England)
- Accession number :
- edsair.doi.dedup.....b003efdcacc89fe26e097e4b0c5d4504