دورية أكاديمية
Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders.
العنوان: | Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders. |
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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 |
تدمد: | 1468-330X |
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DOI: | 10.1136/jnnp-2019-322636 |