Fibromyalgia and, perhaps, What Happened to the Missing Females with Autism

This post is about a condition about Fibromyalgia, a condition that affects 2-4% of the population. It affects women eight times more often than men, but it does, bizarrely, appear to be related to autism and is seen by some as a comorbidity.  I would go further and suggest that perhaps I have stumbled upon the missing females with autism. 

When you look at all the proposed drugs and supplements, there is a 90% overlap between the two conditions, even things like low dose naltrexone and flavonoids, like quercetin, crop up.

As we have seen earlier in this blog, autism is a disease related to the auto-immune system and inflammatory pathways.  There are many other diseases with similar origins, one example being arthritis.  Fibromyalgia tends to get lumped together with arthritis.  Families with autism present tend to have higher levels of arthritis and there are even some overlapping therapies, such as vagus nerve stimulation.

Fibromyalgia caught my attention, because it seems to be uncannily closely related to autism, but there are some distinct differences.  Classic “full-on” fibromyalgia is a disease about pain, whereas in autism people tend to have a high pain threshold.  Nonetheless, if you Google “Fibromyalgia with Autism” you will find no shortage of people suffering from both and pondering a connection.

Comorbidities are interesting, because they can indicate possible new therapies.  The people researching fibromyalgia are not generally the same people as the autism researchers.  The underlying pathologies though are very likely overlapping, even though neither is fully understood.

Fibromyalgia is neither degenerative nor curable, but it is treatable.

Here is a link to an article by a US doctor who came to the same conclusion.  (The article itself is not great)

Symptoms of Fibromyalgia

We can split these into two categories, pain-related and pain-unrelated.  In the case of autism we should look at pain-unrelated, but in the case of relatives we should look at both.  You will probably be able to diagnose a non-autistic family member with symptoms of this syndrome.

 
Pain-related:-

·        Widespread muscle pain and joint pain, the effects of these symptoms varies from person to person and from day to day.  Many people have flare-ups.  There are specific pain areas, and these are shown below:

 

·        Long-term studies suggest that it is not progressive, it does not cause permanent damage to your muscles, bones, joints or organs.

 

Pain-unrelated:-

This is a long list and typically only some will apply to any one person:-

·        Cognitive dysfunction, such as:

o   Difficulty following directions when driving

o   Losing your train of thought in the middle of a sentence

o   Difficulty paying attention

o   Memory problems

o   Difficulty expressing ideas in words

·        Depression, anxiety, irritability,  overreaction, anger outbursts, unpredictable mood swings, phobias and personality changes

·        Difficulty swallowing

·        Headaches

·        Restless leg syndrome

·        Sensitivity to the cold, and/or having cold hands and feet

·        Palpitations

·        Chest pain and costochondritis    

·        Sensitivity to light and noise intolerance.

·        Clumsy walking, dropping things

·        Hair loss

Fibromyalgia vs autism

There are some other similarities/differences with autism.

·        It often takes years to get a diagnosis and some doctors do not believe the condition exists

·        There is a specialist doctor that should know about it – the Rheumatologist, although Neurologists sometimes get involved

·        It is not curable, but it is treatable

·        It is usually diagnosed on very subjective measures

·        A blood test does now exist in the US  - the FM/a test  

The firm with the blood test is called, interestingly, “Epigenetics”.  If you make a blood test for Fibromyalgia, there is a good chance that the same researchers could develop one for autism.  They are measuring the level of pro-inflammatory cytokines.

The test is expensive, about $750.  Who knows how accurate the result is; they claim 99%.

In the UK, the National Health Service maintains that no test for Fibromyalgia exists.

A Neuro-immuno-endocrine disorder

Evidence exists that fibromyalgia is a neuro-immuno-endocrine disorder. Elevations in substance P, IL-6 and IL-8 as well as corticotropin-releasing hormone have been found in the cerebral spinal fluid of fibromyalgia suffering individuals. Increased numbers of mast cell numbers have been found in skin biopsies of some individuals with fibromyalgia.

Theoharides, who I have quoted extensively in early post on mast cells and autism, appears here too:- 

Fibromyalgia--new concepts of pathogenesis and treatment.

Lucas HJ, Brauch CM, Settas L, Theoharides TC.

Abstract

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.

Treatment

Classic treatment involves tricyclic antidepressants, which are actually very closely related to the early antihistamine drugs. 

Even though low brain serotonin is a feature of the disease, counter-intuitively, it has been found that serotonin-3 receptor antagonists are effective; this is the opposite of what was expected.  Tropisetron is a favoured antagonist, but there are several others.  Tropisetron is also a α₇-nicotinic receptor agonist, which you may recall, I highlighted as interesting in posts on the cholinergic system and autism.

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

This blog is about autism, so let us go back to a previous paper I looked at.

Nicotinic Acetylcholine Receptor Alterations in Autism Spectrum Disorders – Biomarkers and Therapeutic Targets

 

In that paper tropisetron is put forward as a potential autism treatment.

 

10.1.2 ᾳ7 nAChRs

It is possible to use ᾳ7 nAChR agonists to treat neuroinflammation in ASD. There is strong evidence that activation of the ᾳ7 nAChR expressed on monocytes and macrophage, by inhibiting NF-kappaB nuclear translocation, suppresses cytokine release by them, and that this cholinergic anti-inflammatory pathway that provides a bidirectional link between the nervous and immune system, inhibits the innate immune response. Hence, a reasonable case can be made for the use of ᾳ7 nAChR agonists to treat neuroinflammation in ASD.

A second candidate drug, Tropisetron is a partial agonist of the ᾳ7 nAChR. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. In a clinical trial with 33 schizophrenic patients administration of tropisetron, without placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. In mice, the early postnatal period represents a critical time window essential for brain development. The administration of tropisetron from postnatal days 2-12

(P2-P12) in mice did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays.

 

It is the non-conventional treatments that overlap with autism, things like GH, IGF-1 and low dose naltrexone etc.  The interesting therapies relate to treating the non-pain symptoms. There are many such therapies and some have been used for decades, one or two may be interesting for autism; they may indeed be more effective in autism that in fibromyalgia.  There is even an overlap with therapies I am already investigating.