Thread by @SamWeb29

✨Sharing "Identification of bio psychological trait markers in functional neurological disorders"✨, published #OpenAccess in @Brain1878 with @LoukasSerafeim @SelmaAybek

Some of the highlights below 🧵. (1/16)
academic.oup.com/brain/advance-…

Recent pathophysiological models in functional neurological disorders (#FND) focus on a multifactorial origin integrating predisposing, precipitating and preceding risk factors.

But what does that mean?
(2/16)

thelancet.com/journals/laneu…

Can biopsychosocial vulnerability factors potentially explain the development of FND symptoms in a subgroup of (biologically) vulnerable individuals with certain psychosocial risk factors? (3/16).

jnnp.bmj.com/content/90/7/8…

Negative life events have often been linked to FND, but are not a requirement for the diagnosis (anymore).
thelancet.com/journals/lanps…

Also, type and timing seem to play an important role in pathophysiological mechanisms. (4/16)

➡️10.1176/appi.ajp.2013.12070957

Various Neuroimaging studies investigated the relationship between negative life events and FND symptoms.

Some important findings:
➡️10.1001/jamapsychiatry.2013.2842
➡️10.1136/jnnp-2016-314998
➡️10.1038/s41380-020-0665-0

(5/16)

frontiersin.org/articles/10.33…

But what happens to the brain when "stressed"?

Responses to stress are mediated by the so called "hypothalamus-pituitary-adrenal" (HPA) axis, eventually leading to the release of cortisol - a hormone important for homeostasis, so that the body is "in balance"⚖️.
(6/16)

Current models suggest two potential mechanisms:

1 - Prolonged exposure to stress can cause a down regulation of the stress response

➡️ A reduction in cortisol secretion can be observed
(7/16)

2 - On the other side, cortisol is suspected to have a neurotoxic effect⚡️ especially on regions highly sensitive to stress, such as the prefrontal cortex, the hippocampus and the amygdala.
... and they might shrink (8/16)

sciencedirect.com/science/articl…

And why is this important for FND?

We could show that FND patients have a flatter cortisol awakening response (CAR) compared to healthy controls!

➡️ The CAR occurs naturally and has been linked to the "daily" hippocampus' preparation of the HPA axis to react to stress.
(9/16)

In FND, we could show that the reduced CAR was associated not only with severity but also duration of past emotional neglect!

❗️This suggests some sort of long-term maladaptive habituation of the HPA-axis in FND as a response to prolonged emotional stress/neglect ❗️
(10/16)

Could prolonged stress have affected the hippocampus?

❗️Indeed, we could show that FND patients had a significantly reduced hippocampal (and amygdala) volume ❗️
(11/16)

In healthy controls, we found that higher cortisol levels were associated with smaller brain volumes.

This would support the neurotoxicity hypothesis ⚡️- but only in healthy controls, and not in FND ❗️
(12/16)

We suggest that a reduced hippocampal volume potentially represents a biological vulnerability factor for FND in the form of a "stress-diathesis" model, which refers to having a predisposition to a condition which might be activated through stress 🧬.
(13/16)

A causal relationship between HPA axis dysfunction, negative life events and brain structural alterations remains to be discovered. 🧠🔬

Imaging-based and physiological biomarkers could support the diagnostic process and could help eliminating the societal bias!
(14/16)

A big thank to all FND patients who enthusiastically volunteered for this study, and my colleagues and the reviewers for their valuable feedback! 🙏
(15/16)

Check out the paper to discover more! 🧠📖🤓
(16/16)

@FndPortal @FNDSociety @FNDHope @MedscapePsych @FndRecovery @FND_Together @ConnectFnd @PsychiatryAdv @inselgruppe @unibern @unifr @EPFL_en @clin_neurobern

academic.oup.com/brain/advance-…