Preprint The Energetic Stress Marker GDF15 is Induced by Acute Psychosocial Stress, 2024, Huang et al

Preprint
Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases


Abstract

GDF15 (growth differentiation factor 15) is a marker of cellular energetic stress linked to physical-mental illness, aging, and mortality. However, questions remain about its dynamic properties and measurability in human biofluids other than blood.

Here, we examine the natural dynamics and psychobiological regulation of plasma and saliva GDF15 in four human studies representing 4,749 samples from 188 individuals. We show that GDF15 protein is detectable in saliva (8% of plasma concentration), likely produced by salivary glands secretory duct cells. Plasma and saliva GDF15 levels are not correlated. Using a brief laboratory socio-evaluative stressor paradigm, we find that psychological stress increases plasma (+3.4-5.3%) and saliva GDF15 (+45%) with distinct kinetics, within minutes. Moreover, saliva GDF15 exhibits a robust awakening response, declining by ~42-92% within 30-45 minutes from its peak level at the time of waking up. Clinically, individuals with genetic mitochondrial OxPhos diseases show elevated baseline plasma and saliva GDF15, and post-stress GDF15 levels in both biofluids correlate with multi-system disease severity, exercise intolerance, and the subjective experience of fatigue.

Taken together, our data establish the dynamic properties of saliva GDF15, reveal it as a stress-sensitive, and as a clinically relevant marker of mitochondrial diseases. These findings point to a shared psychobiological pathway integrating metabolic and mental stress.

https://www.biorxiv.org/content/10.1101/2024.04.19.590241v1

 

Preprint
The Energetic Stress Marker GDF15 is Induced by Acute Psychosocial Stress

Abstract
GDF15 (growth differentiation factor 15) is a marker of cellular and mitochondrial energetic stress linked to physical-mental illness, aging, and mortality.

Here, we describe the psychobiological regulation of plasma and saliva GDF15 in four human studies including 3,599 samples from 148 healthy individuals. We report two main observations establishing GDF15 as a novel tractable biomarker of psychosocial stress. 1) In two experimental laboratory studies, socio-evaluative stress rapidly elevates GDF15 and lactate, two molecular markers of energetic/reductive stress. 2) Similar to other stress-related metabolic hormones, we also find that saliva GDF15 exhibit a robust awakening response, being highest at the time of waking up and declining by ~42-92% within 30-45 minutes.

These data position GDF15 as a dynamic biomarker of psychosocial stress accessible in human blood and saliva, pointing towards a shared psychobiological pathway linking mental and mitochondrial energetic stress. These foundational observations open the door to large-scale studies using GDF15 to non-invasively probe how acute psychosocial factors promote cellular and mitochondrial and energetic stress contributing to the stress-disease cascade across the lifespan.
LINK

 

Can someone give me an example of what "physical-mental illness" is and how it might present? It sounds like it is a new substitute term for MUS or FND.

Ageing is something nobody can avoid unless they die young. Is that going to be psychologised now? You're getting old so you must be mentally ill and making up your symptoms?

Mortality is also something people can't avoid although it can be delayed with a healthy lifestyle in many people if they are lucky and have the right genes and don't get illnesses that don't go away.

I've seen researchers desperate to medicalise lots of normal behaviours and happenings and based on the abstract this is yet another one.

 

This is preprint v4 of Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases (2024, Preprint: BioRxiv)

 

PTSD developing after being in a car accident or a physical illness is one. Mental illness causing fatigue, insomnia and other physical symptoms like pain.

 

I suspected this when Alzheimer’s or dementia got moved under mental health (pretty sure the former was either neuro or gerontology) and gps started not understanding that cognitive fatigue in a stroke isn’t mental illness as they understood it but eg someone was just the same in their thinking just couldn’t speak it the same because of where their injury was.

those moves were justified ambiguously with sometimes people trying to say ‘it’s just because the symptom seems to be mental’ and other times saying ‘it’s only when they get eg depression alongside’

but instead of it being a stroke therapist referring to someone who might have had some expertise that might have included the but ‘psych’ but was neuro and psychology (as in cognitive psychology) it ended up I think being a way to suggest that symptoms that are physical are psychiatric and would benefit from therapy delivered by clinical psych - a totally different area and could therefore just be people looking at certain mental illnesses.

I’m unaware of psychiatry making eg great strides into how dementia works or Parkinson’s as an underlying condition so would be intrigued to know more eg from @hibiscuswahine how this line could be better-defined.

it’s not hard for gps to do psychometric tests to discern if it’s a cognitive symptom of an illness that needs a different specialist or is depression etc but I think this ‘ it’s all just under ‘mental health’’ Has been used to send people off thinking that place will have ALL the specialists so is more accurate (to assess the specifics of what they have and which specialism needs to deal with it) but I don’t know if sometimes these can end up being on the other end somewhere the patient arrives somewhere only equipped to rule in or out fir eg CBT fir anxiety or depression in the worst cases, or what else has moved there etc. it’s confusing to me what sits under what now and if it’s consistent.

to then justify this as ok ‘cos some might also have depression which means if you get a big enough sample and don’t care about size of improvement and have non-specific measures you can claim it helps all or is even a treatment’ seems to be the latest sales pitch. Sad that at best if ever rectified it could take a long time for someone to complete that loop to ‘prove the negative tgat should be assumed anyway’ and those years might have been very lynchpin.

I don’t know how the muddying of these terms can be undone as nearly every term seems to have been captured. And even things like sleep or being knocked out is ending up under generic categories tgat don’t quite fit

 

It would intriguing to see the full references and actually see if they are comprehensive of what it’s linked to

you are correct that listing these three things in particular just sounds like ‘is correlated with being older’ and I’d be intrigued whether that is really the confounding causation so far ie die’s said research actually look at the other two with age somehow controlled for/out of that equation?

 

Always depends on what the definition of words mean.

And how everyone reacts differently to this. To me this is a 0 out of any scale on the stress rating. It's play-acting, there is no stake at all, it would be less demanding than playing a hard level in a video game. It kind of mirrors the context of a job interview, which I know a lot of people describe as stressful, but I've never related to that, this is not something that is equal for everyone.

Effort, maybe, but to extrapolate to this the concept of every day stress, which more often than not can be substituted with exertion and actually gain meaning from it, is ridiculous.

I guess they had mice do a mirror and camera thing?

This idea that you can reduce complex physiological systems to a single molecule is absurd. It's the same as the failed serotonin hypothesis, or anytime someone uses the words "dopamine hit", which makes me cringe every time.

This ain't science, folks. It's just ridiculous.

 

@bobbler. In answer to your questions: Psychiatry doesn't research the aetiology of Dementia, Parkinson's etc, researchers do this. Psychiatry may do treatment trials for meds.

We don't have much to do with the treatment of Parkinson's Disease - that is still in the specialty of medicine. Some, but not all, people with Parkinson's Disease, develop a subcortical dementia.

Physicians/GP's may call on a clinical psychologist to do psychometric testing of cognition or use validated screening tests for cognition eg MOCA/MMSE and with imaging and history, are able to make a diagnosis of dementia themselves. If there is no major behavioural or psychiatric symptoms eg depression, psychosis, they continue to be cared for in Medicine (Geriatrics). If there is uncertainty in the diagnosis they will refer the patient to a psychogeriatrician.

Psychogeriatric Psychiatry is a super/sub- specialty of Psychiatry. They have advanced training in neurodegenerative disease, cognition, and the diagnosis of cognitive disorders, (dementia being one such diagnosis), and prescribing any proven medication to prevent deterioration available to them within their country. But also the training in the treatment of behavioural and psychiatric disorders arising from neurodegenerative diseases. (Though all psychiatrists get some training in this specialty) This can be by prescribing psychiatric medicines, that is outside the expertise of GP's/physician, and suggesting and sometimes using some psychological techniques/therapies if a person with eg. early dementia- develops depression. Also psychogeriatricians (in my country) can use the mental health act to detain and treat people with neurodegenerative diseases who are a serious risk to themselves or others or due to serious self-neglect. General psychiatrists can do this too but it is usually psychogeriatricians who then take over their care, sometimes sharing the care with physicians to manage any physical concerns.

Most of the time, GP's will do the basic cognitive tests they are taught in training. These are screening tests, they are pretty basic but they are used in the decision making process when put with the history from the patient and family/carers. They are also used to monitor treatment. Psychiatrist's do slightly more advanced testing but not like a full neuropsychological test which needs to be done by a clinical psychologist.

 

So basically if I get this right? They did a playacting test, and rated people by how stressed they think they got in the test. Then, they saw that people who seemed more stressed had different levels of a molecule than calmer people? They then assumed this meant the molecule was a marker of stress and lack or mental resilience or something?

This seems like it has way too many different factors to assume a causation. Like, maybe abnormal levels of that molecule is a sign of poorer physical health, which means people are more susceptible to stress, but the molecule doesn’t have anything to do with stress itself.

This seems to be an interesting study that finds an interesting correlation. I don’t know why they have to ruin it by making unfounded causation claims, something all too common in the medical field it seems.