دورية أكاديمية
أعرض في EDS

Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders.

التفاصيل البيبلوغرافية
العنوان: Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders.
المؤلفون: Spagnolo PA; Human Motor Control Section, Medical Neurology Branch, National Institute on Nuerological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA vera.spagnolo@nih.gov., Norato G; Office of Biostatistics, National Institute on Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA, Bethesda, Maryland, USA., Maurer CW; Department of Neurology, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, USA., Goldman D; National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA., Hodgkinson C; National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA., Horovitz S; Human Motor Control Section, Medical Neurology Branch, National Institute on Nuerological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Hallett M; Human Motor Control Section, Medical Neurology Branch, National Institute on Nuerological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
المصدر: Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2020 Aug; Vol. 91 (8), pp. 814-821. Date of Electronic Publication: 2020 Jun 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Country of Publication: England NLM ID: 2985191R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-330X (Electronic) Linking ISSN: 00223050 NLM ISO Abbreviation: J Neurol Neurosurg Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: London : BMJ Publishing Group
Original Publication: London : British Medical Association
مواضيع طبية MeSH: Adult Survivors of Child Adverse Events*, Conversion Disorder/*genetics , Movement Disorders/*genetics , Tryptophan Hydroxylase/*genetics, Adult ; Amygdala/physiopathology ; Case-Control Studies ; Conversion Disorder/etiology ; Conversion Disorder/physiopathology ; Female ; Gene-Environment Interaction ; Genetic Association Studies ; Genetic Predisposition to Disease/genetics ; Homozygote ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Movement Disorders/etiology ; Movement Disorders/physiopathology ; Polymorphism, Single Nucleotide/genetics ; Prefrontal Cortex/physiopathology ; Psychiatric Status Rating Scales ; Surveys and Questionnaires
مستخلص: Background: Functional movement disorders (FMDs), part of the wide spectrum of functional neurological disorders (conversion disorders), are common and often associated with a poor prognosis. Nevertheless, little is known about their neurobiological underpinnings, particularly with regard to the contribution of genetic factors. Because FMD and stress-related disorders share a common core of biobehavioural manifestations, we investigated whether variants in stress-related genes also contributed, directly and interactively with childhood trauma, to the clinical and circuit-level phenotypes of FMD.
Methods: Sixty-nine patients with a 'clinically defined' diagnosis of FMD were genotyped for 18 single-nucleotide polymorphisms (SNPs) from 14 candidate genes. FMD clinical characteristics, psychiatric comorbidity and symptomatology, and childhood trauma exposure were assessed. Resting-state functional connectivity data were obtained in a subgroup of 38 patients with FMD and 38 age-matched and sex-matched healthy controls. Amygdala-frontal connectivity was analysed using a whole-brain seed-based approach.
Results: Among the SNPs analysed, a tryptophan hydroxylase 2 ( TPH2 ) gene polymorphism-G703T-significantly predicted clinical and neurocircuitry manifestations of FMD. Relative to GG homozygotes, T carriers were characterised by earlier FMD age of onset and decreased connectivity between the right amygdala and the middle frontal gyrus. Furthermore, the TPH2 genotype showed a significant interaction with childhood trauma in predicting worse symptom severity.
Conclusions: This is, to our knowledge, the first study showing that the TPH2 genotype may modulate FMD both directly and interactively with childhood trauma. Because both this polymorphism and early-life stress alter serotonin levels, our findings support a potential molecular mechanism modulating FMD phenotype.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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المشرفين على المادة: EC 1.14.16.4 (TPH2 protein, human)
EC 1.14.16.4 (Tryptophan Hydroxylase)
تواريخ الأحداث: Date Created: 20200625 Date Completed: 20210119 Latest Revision: 20231111
رمز التحديث: 20231111
مُعرف محوري في PubMed: PMC7402460
DOI: 10.1136/jnnp-2019-322636
PMID: 32576619
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-330X
DOI:10.1136/jnnp-2019-322636