Early-life trauma endophenotypes and brain circuit–gene expression relationships in functional neurological (conversion) disorder

Abstract

Early-life trauma endophenotypes and brain circuit-gene expression relationships in functional neurological (conversion) disorder. Molecular Psychiatry.

Activation of Functional Brain Networks in Children With Psychogenic Non-epileptic Seizures

“…Because cortisol modulates gene expression in the brain and tissues, the flowon effects of maltreatment include neuroplasticity changes that change brain structure and function. In a recent neuroimaginggene expression study in adult patients with FND, Diez et al (2020) found that physical abuse correlated with increases in functional connectivity between limbic regions and motor cortices (Diez et al, 2020). In the current study, the change in functional organization-an increase in network metrics in the gamma band-arguably reflects a pattern of activation in the face of stress that predisposes children to PNES.…”

“…Over the last decades, neuroscience studies have expanded our understanding of the neurobiology of FND. The working hypothesis from these studies is that FND symptoms emerge when stress-physical or emotional-triggers excessive activation of the brain stress systems (regions processing salience, arousal, and emotional states), which, in turn, disrupts motor-and sensory-processing regions (Blakemore et al, 2016;Kozlowska, 2017;Pick et al, 2018;Diez et al, 2020). PNES, which are paroxysmal, have been hypothesized to emerge in the context of neural network instability (Knyazeva et al, 2011;Barzegaran et al, 2012Barzegaran et al, , 2016Szaflarski and LaFrance, 2018).…”

Psychological Profiles and Clinical Clusters of Patients Diagnosed With Functional Neurological Disorder

“…Neurobiological and neurodevelopmental abnormalities are hypothesized to include an altered sense of self-agency affecting sense of voluntariness of movement, loss of “intentional binding” or the subjective sense of movement and its sensory consequences, as well as bias in evaluating prior information (the Bayesian prior) modifying internal predictions about the subject's world especially in terms of motor control ( 21 ). It has also been postulated that prior physical trauma changes the coupling of the amygdala and insula to the motor cortex ( 23 ) providing a model neurodevelopmental endophenotype of a brain network that is prone to functional dysconnectivity. There was certainly a high proportion (9%) of patients across the whole cohort of 288 who had a comorbid neurodevelopmental disorder (ADHD, ASD or intellectual impairment).…”

Transcriptional Signatures of Synaptic Vesicle Genes Define Myotonic Dystrophy Type I Neurodegeneration

“…To date, its use has shed some light on several fundamental aspects of the brain and their association with the transcriptome, such as myelination 54 , hierarchical cortical organization 55 , visuomotor integration 33 or large-scale connectivity 31,56,57 . In addition it has provided data regarding pathologies, suggesting novel molecular mechanisms underlying some disorders, such as Autism Spectrum Disorder 58 or functional neurological disorder 59 . It is important to emphasize that our methodology, assessing the relationships between brain images associated with neurodegeneration and the entire transcriptome is complementary to other techniques, such as genome-wide association studies (GWAS) 60 , simultaneously addressing genotype-phenotype associations from hundreds of thousands to millions of genetic variants in a data-driven manner.…”