Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders.
J Neurol Neurosurg Psychiatry
; 91(8): 814-821, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32576619
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triptófano Hidroxilasa
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Trastornos de Conversión
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Adultos Sobrevivientes de Eventos Adversos Infantiles
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Trastornos del Movimiento
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurol Neurosurg Psychiatry
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos