Effects of TPH2 gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders, 2020, Hallett et al

[Andy]

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.

Open access, https://jnnp.bmj.com/content/early/2020/06/23/jnnp-2019-322636

 

[InitialConditions]

is it still functional if gene polymorphisms are implicated and there are changes in neurocircuitry!?

 

[Mithriel]

This is typical of the confusion surrounding FNDs. If it is a genetic disorder which makes the stress system inefficient then it is not a case of emotions being "converted" into physical problems. It is perfectly acceptable to find that there is damage to the brain so that the stress pathways are corrupted. Maybe CBT to reduce stress would be a helpful treatment but this means that FND is a physical disease caused by damage to the brain, not a new name for hysteria.

All their research is designed as confirmation studies with one mistake layered in another. There evidence for clinically defining patients is flawed so that it is just an opinion that says they are right. A couple of signs in neurological examination are taken as positive proof that th epatient has FND but they have never offered any biological (or psychological for that matter) pathways by which FND would lead to these repeatable problems with neurological pathways.

There have been no studies which have shown positive outcomes such as complete recovery to pre illness levels of health in anyone given CBT and they have not given any plausible accounts of why FND, which they consider a single disorder, should express itself in such wildy different ways in different patients.

It's rubbish but they present it in such a way that doctors who take it at face value will believe in it and that is a very frightening thought.

 

[rvallee]

What if instead research funding was spent on smart useful research?

How about that? Instead of whatever this junk is? Because this is egregious misuse of institutional funds, fiscally irresponsible. Adult oversight is badly needed here.