Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex, 2024, Joseph et al.

SNT Gatchaman

SNT Gatchaman

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Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex
Anna Joseph; Gaston Baslet; Mary A O’Neal; Ginger Polich; Irene Gonsalvez; Andrea N Christoforou; Barbara A Dworetzky; Primavera A Spagnolo

BACKGROUND
Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging as one potential mechanism. To begin to understand the role of immune dysfunctions in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex.

METHODS
Using a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by the presence of psychiatric comorbidities.

RESULTS
The overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p= 0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p’s < 0.05).

CONCLUSIONS
This study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterised by distinct dysregulations in immune response.


Link | PDF (Journal of Neurology, Neurosurgery & Psychiatry)
 
The primary limitation of the current study is its retrospective nature, which precludes any causal inferences regarding the association between FND and ADs.
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Recent findings suggest that FND is associated with neuroendocrine and immune abnormalities.
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referencing Perez in their intro Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis (2021, The Journal of Neuropsychiatry and Clinical Neurosciences) —

Specifically, patients with this disorder show blunted morning cortisol secretion, alterations in peripheral inflammatory markers, such as C reactive protein, interferon-gamma, interleukin-6, tumour necrosis factor-alpha and presence of antiganglionic acetylcholine receptor antibodies associated with autonomic dysfunction.
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Finding

Connective tissue disorders and autoimmune endocrine diseases were the most common ADs observed in our FND sample. We further found that the prevalence of ADs was significantly higher in female patients with FND and in those with co-occurring MDD and/or PTSD. However, prevalence rates of ADs were greater than those observed in the general population even in the absence of psychiatric comorbidities, thus supporting a link between FND and immune dysfunction.
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These findings are in line with previous studies reporting that, compared with healthy controls, patients with FND have elevated levels of pro-inflammatory molecules, including IL-1, IL-6, IFN-γ and TNF-α and increased levels of immunoglobulins and C reactive protein. These observations suggest that FND may be characterised by a low-grade inflammatory state, which could serve as one molecular mechanism underlying several brain and behavioural alterations associated with this disorder.
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To better characterise this association, it will be critical to determine whether the relationship between FND and ADs is bidirectional, and whether changes in inflammatory response precede or follows the development of FND.
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We further observed that the proportion of women diagnosed with ADs in our cohort was significantly higher than men, both in the overall sample and in the subgroups of interest (patients with and without comorbid MDD and/or PTSD), mirroring the sex bias in the prevalence of ADs observed in the general population. This bias likely reflects sex differences in immune response, which is influenced by a complex interplay between sex hormones, sex chromosomes, immune-related genes and environmental exposure. [...] Evidence that immunopathogenic mechanisms are also implicated in FND may provide critical insights into the biological underpinnings of the well-documented but often poorly explained predominant prevalence of FND among females. As such, future studies investigating inflammatory processes in patients with FND should specifically consider the role of biological sex.
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We also found that the association between FND and ADs was stronger in presence of psychiatric comorbidities (MDD and/ or PTSD). Indeed, patients affected by these psychiatric disorders exhibit abnormal levels of cytokines and have an increased vulnerability for ADs. [...] However, in subjects without psychiatric comorbidities, the prevalence of ADs was still significantly greater than that observed in the general population. As such, the link between immune dysregulation and FND may be independent of, yet probably amplified by, the presence of psychiatric comorbidities. A compelling question is whether specific alterations in immune response and/or inflammatory marker profiles are associated with FND compared to other disorders and could, therefore represent an FND-specific disease biomarker.
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to understand whether FND is characterised by distinct dysregulations in immune response.

In which case the whole concept of 'functional' is not only irrelevant, but downright dangerous and should be dropped immediately.
 
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