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Somatic comorbidities in ADHD

Somatic comorbidities in ADHD

Adults with the highest 10% of ADHD symptom severity according to ADHD-E were 10.62 times more likely to experience distress due to physical complaints and 6.80 times more likely to experience distress due to somatization than those not affected.1

The following list of somatic disorders that occur comorbidly with ADHD is sorted in descending order of frequency of occurrence in ADHD sufferers. The headings indicate the percentage of occurrence of this comorbidity in ADHD sufferers (compared to non-affected persons).

The percentages in the headings indicate the frequency of comorbidity in ADHD. Example: 48% of ADHD sufferers suffer from musculoskeletal disorders, compared to 21.6% of those not affected by ADHD.

1. Sleep problems - children: 68.7 % (compared to 47.1 %)

A Chinese study of 23,791 schoolchildren found that 68.7% of children with ADHD had poor sleep quality compared to 47.1% of children without ADHD.2

2. Chronic pain / neck / shoulder pain (up to 66 % compared to 10 - 20 %)

One study found that gene variants that correlate with neck or shoulder pain can causally increase the risk of ADHD.3
A meta-study found an ADHD prevalence of 15 to 25 % in children with chronic pain (without headaches), i.e. 2 to 5 times higher.4

Conversely, children with ADHD showed a prevalence of chronic pain of up to 66% (at least weekly pain for more than 3 months). Stimulant treatment reduced the rate of chronic pain. Another study found a reduced perception of pain in adolescents with ADHD, which disappeared with stimulant treatment.4

An adult ADHD sufferer reported a massive reduction in his decades of massive neck/shoulder tension when he drastically reduced his alcohol consumption.

3. Diseases of the musculoskeletal system - 48 % (compared to 21.6 %)

  • In adults with ADHD: 48.4 %5
  • For those not affected: 21.6%5
    = 2 times the risk

Skeletal problems were found6

  • In 31% of adults with ADHD
  • In 16 % of adults without ADHD:

One study found that gene variants that correlate with synovitis (inflammation of the joint lining) and tenosynovitis (inflammation of the tendon sheath) can causally increase the risk of ADHD. Conversely, ADHD gene variants appear to increase the risk of carpal tunnel syndrome.3

4. Allergies - 26 to 45% (compared to 15 to 18%)

Allergies occur more frequently in people with ADHD than in those not affected.7 This correlation was already established by Marshall in 1989 and attributed to acetylcholine hypersensitivity and adrenaline hypersensitivity in the autonomic nervous system.8 Pelsser, Buitelaar et al. found that ADHD can (also) be triggered by allergic and non-allergic hypersensitivity9

In 100 children with ADHD (average age 9 years), 35% were found to have an allergy. Of those with comorbidities, 43 % had a hay dust allergy, 37.5 % various pollen allergies, 25 % a combined allergic rhinitis and bronchial asthma, 8 % urticaria and 2 % asthma. Interestingly, allergies were only found in ADHD-C, but not in the ADHD-HI or ADHD-I subtype. In addition, boys with ADHD were significantly more frequently affected by a comorbid allergy than girls. Allergies correlated with increased ADHD symptom severity. Allergies appeared on average at the age of 4 years, ADHD on average at the age of 6 years. Among those with ADHD, 16% showed a positive skin prick test compared to 5% of controls. A high total IgE was found in 45% of those with ADHD and 18% of those without10
Among 23,791 Chinese schoolchildren, 26.1% of children with ADHD were found to have allergies, compared to 15.2% of children without ADHD2
Japanese children with developmental disorders were found to have a 3.22 to 3.87-fold risk of allergies.11
One study did not find an increased risk of allergies with ADHD.12

Successful treatment of allergic rhinitis in children significantly reduces their ADHD symptoms, but not in children with non-allergic rhinitis.1314

Allergies are usually the result of excessive cortisol levels. Cortisol inhibits the promotion of inflammation triggered by CRH (first stage of the HPA axis) through inflammatory cytokines and instead promotes other immune defense mechanisms that are directed against extracellular stressors - such as bacteria or allergens.
An excessive cortisol level or an overshooting of the cortisol response can lead to an overreaction of the immune system to external substances that are not actually dangerous - an allergy.
More information on the immunological effect of cortisol can be found at Adrenal cortex (3rd stage)
Disturbances in stress hormone levels, especially cortisol, are common in ADHD. Cortisol in ADHD
There is also a connection between allergies and histamine,15
. Histamine interferes with the dopamine metabolism and, like almost all ADHD medications, increases histamine levels. and in some cases increases the breakdown of histamine itself .

5. Cardiovascular problems 43% (vs. 18%)

In adults with ADHD:
* 43 %6
In adults without ADHD:
* 18 %6

6. Premature ejaculation (41.6 % compared to 5 %)

A study of 48 people suffering from lifelong premature ejaculation and 40 people without this disorder also found ADHD in 41.6% of those affected, and 5% of those not affected.16
Of those affected with premature ejaculation and ADHD, 2/3 were of the ADHD-HI subtype with predominant hyperactivity/impulsivity, which is otherwise only found in 8.3% of ADHD sufferers.

7. Gastrointestinal disorders - 40 % (compared to 20 %)

  • In adults with ADHD:
    • 41,1 %17
    • 39 %6
  • For those not affected:
    • 21,6 %5
      • 19 %6
        = 2 times the risk

8. Diseases of the upper airways

8.1. Upper respiratory tract diseases in children - 40 % (compared to 33.4 %)

  • In children with ADHD: 40.1 %17
  • For those not affected: 33.4 %17
    = 1.3 times the risk

3.6% of those affected by chronic rhinosinusitis who had undergone endoscopic sinus surgery were taking ADHD medication, compared to 2% of those not affected. Antidepressant use was also roughly doubled at 22.1 % compared to 11.3 %.18

8.2. Upper respiratory diseases in adults - 33.7 % (compared to 15.2 %)

  • In adults with ADHD: 33.7 %17
  • For those not affected: 15.2 %5
    = 2 times the risk

One study found that ADHD gene variants can causally increase the risk of chronic obstructive pulmonary disease.3

9. Metabolic disorders - 36.2 % (compared to 19 %)

  • In adults with ADHD: 36.5 %19
  • For those not affected: 19.0%17
    = 2 times the risk

10. Skin diseases, neurodermatitis, eczema, psoriasis - 32.4 % (compared to 10 to 25.5 %)

  • In children with ADHD: 32.4 %17
  • In non-affected people: 25.5%17; 10 - 20% in children, 2 - 3% in adults, with an increased incidence in urban areas20
    = approx. 1.5 times the risk in children20 which should also explain 9% of all ADHD cases.
  • People with ADHD suffer from atopic dermatitis (= atopic eczema) more frequently than average21 A study found a 5.06-fold risk of atopic dermatitis in Japanese children with ADHD.11 An evaluation of the German KIGGS study found an increased risk of approx. 67% (Exp(β) = 1.672).22 Exp(β) corresponds to the OR.23
  • Conversely, neurodermatitis sufferers have an increased risk of mental disorders such as ADHD 24 25 26 2728
    • A study of Indian children with atopic dermatitis found rates of29
      • Inattention: 29.5 %
      • Hyperactivity: 20 %
  • Epidemiological data show that the worldwide prevalence of atopic dermatitis and ADHD has increased in parallel. Several cross-sectional studies have indicated a common occurrence and a temporal common origin in those affected20
  • One study found no genetic causality of atopic dermatitis for ADHD or of ADHD for atopic dermatitis30
  • Atopic immune disorders could be the result of an excessive immune response due to reduced cortisol levels. Cortisol inhibits the inflammation initially promoted by CRH (first stage of the HPA axis) by means of inflammatory cytokines. If the release of cortisol (third stage of the HPA axis) is too low, the inflammation is not sufficiently inhibited.31
  • 90% of lichen sufferers had mental disorders, compared to 20% of non-affected people. Lichen sufferers had an ADHD prevalence of 36.6%.32
  • In a mouse model for atopic dermatitis, a study found chronically increased HPA axis function and dopamine and noradrenaline changes in the locus coeruleus, PFC and striatum, which are typical of ADHD. Melatonin was also reduced20
    • The finding could confirm our view that chronic stress mediates its symptoms in the same way as ADHD, namely through reduced dopamine and noradrenaline levels in the brain areas mentioned.

More information on the immunological effect of cortisol can be found at Adrenal cortex (3rd stage)

Disturbances in stress hormone levels, particularly cortisol, are common in ADHD.
Cortisol in ADHD

One study found increased risks for ADHD sufferers:33

  • Atopic dermatitis: OR = 1.53
  • Urticaria (hives): OR = 1.39

We also find it interesting that inflammation is often accompanied by greatly increased adenosine levels.34 At the same time, A2A and A3 receptors are overexpressed in lymphocytes in chronic autoimmune rheumatic diseases. A2A and A3 agonists inhibited the activation of NF-κB, the release of typical proinflammatory cytokines and the concentration of metalloproteinases, which are involved in the inflammatory reactions in chronic autoimmune rheumatic diseases.35 Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it is at least theoretically conceivable that inflammation could also cause ADHD symptoms through an increased adenosine level. More about adenosine at Adenosine In the chapter Neurological aspects.

11. Infectious diseases - 31.2 % (compared to 25.9 %)

  • In children with ADHD: 31.2 %17
  • For those not affected: 25.9 %5
    = 1.3 times the risk

12. Ear diseases - 31.1 % (compared to 23.7 %)

  • In children with ADHD: 31.1 %17
  • For those not affected: 23.7 %17
    = 1.7 times the risk

A Chinese study of 23,791 schoolchildren found that 6.7% of children with ADHD had had otitis media, compared to 3.8% of children without ADHD2
Since the previous presence was probably queried, this is less a comorbidity than a risk factor.
An evaluation of the German KIGGS study found an increased risk of approx. 57% (Exp(β) = 1.57).22 Exp(β) corresponds to the OR.(([Noymer: Why is exp(β) the odds ratio?]

13. Lung problems 31 % (compared to 16 %)

In adults with ADHD:
* 31 %6
In adults without ADHD:
* 16 %6

14. Sleep apnea 30 % (compared to 4 %)

30% of people with ADHD suffer from sleep apnea.36
Sleep apnea leads to a lack of oxygen. Oxygen deficiency (hypoxia) impairs the dopaminergic system.
In the general population, 3 to 7 % of men and 2 to 5 % of women have obstructive sleep apnea.37
An individual case study reports an improvement in ADHD symptoms after treatment of sleep apnea.38

15. Obesity - Germany: 22.1 % (compared to 10.2 %); USA: 41.4 % (compared to 21.6 %)

The frequency of obesity in ADHD sufferers has doubled in the USA from 21.6% without ADHD to 41.4% with ADHD39 (albeit at extremely different starting levels) and in Germany from 10.2% without ADHD to 22.1% with ADHD.40
A meta-study of 42 studies with n = 728,136 participants found:41

  • Obesity increases the risk of ADHD in children by 20% (OR = 1.20) and in adults by 55% (OR = 1.55)
  • ADHD increases the risk of obesity in children by 40 % (10.3 % compared to 7.4 %) and in adults by 70 % (28.2 % compared to 16.4 %)

An Israeli cohort study found obesity to be almost twice as common in adolescents with severe ADHD (13.5%) as in those without, and about 30% more common in mild ADHD-HI than in those without.42

A meta-analysis of 16 studies with n = 14,981 cases and n = 128,916 controls showed an increased risk of overweight and obesity for:43

  • Children with ADHD: by 56
    • Boys with ADHD: by 45
  • People in Asia: by 225 %
  • People in Europe: by 85 %
  • Affected people who do not take medication: by 54 %

A Chinese study of 23,791 schoolchildren found that 32.6% of children with ADHD were overweight or obese, compared to 29.6% of children without ADHD.2 The figures for overweight were 15.9% and for obesity 11.9%, but not broken down by ADHD status. As the figures for obesity were not reported separately, they are not comparable.

According to Winkler, 30 to 60 % of all severe obesity cases are linked to ADHD.44

In adult psychiatric clinical patients with ADHD, the prevalence of obesity is 24.5% and of other eating disorders 11.2%45 Other sources do not provide percentages in the accessible abstracts.46

ADHD treatment of ADHD sufferers with obesity resulted in a weight loss of over 12.3%, while in the control group of non-ADHD obese patients there was a weight gain of 2.8%.47

Winkler reports that a weight gain of less than 5% is already considered a success in pure obesity treatment,48 so that a weight loss of more than 12% seems downright sensational.

More on this under -&gt ADHD, obesity and eating disorders In the chapter Treatment / Comorbidities.

16. Tonsil or adenoid hypertrophy / enlarged tonsils or adenoids - 20.0 % (compared to 11.1 %)

A Chinese study of 23,791 schoolchildren found that 20.0% of children with ADHD had enlarged tonsils or adenoids, compared to 11.1% of children without ADHD2
Adenotonsillar hypertrophy is the main cause of obstructive sleep apnea in childhood. Obstructive sleep apnea, in turn, is a possible cause of ADHD symptoms.

17. Asthma - 16.2 to 16.9 % (compared to 9.7 to 11.5 %)

A meta-analysis found asthma in 16.9% of ADHD sufferers compared to 11.5% of non-ADHD sufferers49 A cohort study found 16.2% compared to 9.7%.50 Asthma correlated with the total number of ADHD-HI symptoms and with the total number of hyperactivity/impulsivity symptoms, but less so with inattention symptoms.
A 12-year bidirectional cohort study found a 17% increased risk of ADHD due to asthma and a 10% increased risk of asthma due to ADHD.51

A Swedish cohort study with N = 1,575,377 people found an ADHD prevalence of 8.8 % in asthma sufferers compared to 5.6 % in non-asthma sufferers.52 In another study, children with asthma had a 70% increased risk of also having ADHD. The risk of ODD was also increased (360%), but not the risk of CD.53 Another study found ADHD in 11.3% of asthma sufferers54

There appears to be genetic overlap between ADHD (and major depression) and asthma.5550
One study found increased risks for ADHD sufferers:33

  • Asthma: 1.53-fold risk (OR)
  • Allergic rhinitis: OR = 1.59
  • Atopic dermatitis: OR = 1.53
  • Urticaria (hives): OR = 1.39

Another study found even higher values. Japanese children with ADHD had a 3.72-fold risk of bronchial asthma and a 5.06-fold risk of atopic dermatitis.11

17.1. Links from asthma to ADHD:

We currently have two hypotheses as to the neurophysiological pathway by which asthma could be linked to ADHD.

17.1.1. Adenosine

It seems interesting to us that asthma and inflammatory diseases are often associated with highly elevated adenosine levels 3456

At the same time, A2A and A3 receptors are overexpressed in lymphocytes in chronic autoimmune rheumatic diseases. A2A and A3 agonists inhibited the activation of NF-κB, the release of typical proinflammatory cytokines and the concentration of metalloproteinases, which are involved in the inflammatory reactions in chronic autoimmune rheumatic diseases35
Treating children with asthma with theophylline (an adenosine A1 and A2 antagonist) also improved their ADHD symptoms.
Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it is at least theoretically conceivable that asthma and inflammatory diseases could also cause ADHD symptoms due to an increased adenosine level. More about adenosine at Adenosine In the Neurological aspects chapter, and also there at Theophylline for ADHD

Consistent with this, successful treatment of allergic rhinitis in children significantly reduces their ADHD symptoms, but not those of children with non-allergic rhinitis.1314

17.1.2. Hypoxia (lack of oxygen)

Oxygen deficiency is known to interfere with the dopamine balance. Oxygen deficiency at birth is known to be a possible cause of ADHD.
Asthma, which is highly comorbid with ADHD, is associated with intermittent hypoxia57
Sleep apnea is also known to trigger ADHD symptoms and is also associated with intermittent hypoxia.

Hypoxia and stress - interaction between HIF and glucocorticoids

A sufficient oxygen supply and the regulation of oxygen homeostasis are essential for the survival of aerobic organisms (such as humans). Oxygen deficiency can be caused by inadequate respiratory oxygenation, low hemoglobin levels or insufficient blood flow. In the absence of oxygen, cells change their protein activity or their transcriptional and post-transcriptional organization and activate a variety of genes involved in various biological processes such as cell survival and proliferation, glucose metabolism and angiogenesis.
Oxygen homeostasis is regulated in particular by the HIF. HIF are transcription factors. HIFs are heterodimers with α and β subunits. The three oxygen-sensitive α-subunits HIF1α, HIF2α and HIF3α of mammals accumulate in hypoxia. The β-subunit (also called aryl hydrocarbon receptor nuclear translocator, ARNT) is not affected by hypoxia.
There is an interaction between hypoxia-dependent signaling pathways and glucocorticiods or the glucocorticoid receptor (GR). A functional role of hypoxia and HIF1α in the regulation of GR mRNA and protein expression has been reported. This suggests a reciprocal influence of HIF and GR58

18. Underweight (China: 19.9 %, compared to 14.3 %)

A Chinese study of 23,791 schoolchildren found:2

  • Stunted
    • In 9.8% of children with ADHD
    • Without 5.9 % of children without ADHD
  • Underweight
    • In 3.0 % of children with ADHD
    • Without 2.9 % of children without ADHD
  • Emaciation
    • In 7.1% of children with ADHD
    • Without 5.5 % of children without ADHD

19. Injuries 19 % (compared to 13.7 %)

A cohort study found injuries in 19% of ADHD sufferers (across the entire age range) and in 22.7% of ADHD sufferers with other mental comorbidities, compared to 13.7% in the control group. The risk of injury was therefore 33% higher with pure ADHD.
The number of comorbid mental illnesses correlated with an increased risk of injury in ADHD patients. The risk of injury was highest in ADHD patients with comorbid schizophrenia, followed by bipolar disorder and obsessive-compulsive disorder. Comorbid ASD lowered the risk of injury.59

19. Diabetes

It seems interesting to us that diabetes is often associated with greatly increased adenosine levels.34 Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it is at least theoretically conceivable that diabetes could also cause ADHD symptoms due to increased adenosine levels. More about adenosine at Adenosine In the chapter Neurological aspects.

19.1. Type 1 diabetes - 12% to 35% (vs. 9.5%)

The ADHD rate is higher among adolescents with type 1 diabetes. One study found ADHD in 12% of adolescents with type 1 diabetes mellitus.60 A review reported a 35% increased risk of ADHD61

The worldwide prevalence of type 1 diabetes is 9.5%.62

19.2. Type 2 diabetes - 3.9% (compared to 1.62%)

According to a large Swedish cohort study, type 2 diabetes was found in 3.90% (men: 4.32%; women: 3.58%) of adults with ADHD compared to 1.62% (men: 1.96%; women: 1.28%) of those without the disorder.63 Another large registry study found a 2.29-fold risk of type 2 diabetes in ADHD sufferers.64

One study found that gene variants that correlate with diabetes 2 can causally increase the risk of ADHD.3 A genetic predisposition to ADHD or depression also increased the risk of type 2 diabetes, just as a genetic predisposition to type 2 diabetes increased the risk of ADHD (by 9%)65

20. Premature birth suffered - 8.7 % (compared to 5.5 %)

A Chinese study of 23,791 schoolchildren found that 8.7% of children with ADHD were born prematurely, compared to 5.5% of children without ADHD2
This is not a comorbidity, but a risk factor.

21. High blood pressure - 8.5 % (compared to 4.5 %)

According to a large Swedish cohort study, high blood pressure was found in 8.51% (men: 9.57%, women: 7.39%) of adults with ADHD compared to 4.48% (men: 4.98%, women: 3.98%) of those without the disorder.63

22. Gastroesophageal reflux - 4.3 % (compared to 0.6 %)

A Chinese study of 23,791 schoolchildren found that 4.3% of children with ADHD suffered from gastroesophageal reflux (ascending gastric juice), compared to 0.6% of children without ADHD2

23. Visual disturbances - up to 2.4 % (compared to 1.3 %)

A large study found that children with ADHD-HI have significantly higher prevalences of eye disorders:66

  • Farsightedness, hypermetropia (2.4 % in ADHD, 1.3 % in non-affected persons, OR 1.82)
  • Poor eyesight, amblyopia (1.6 % in ADHD, 0.9 % in non-affected persons, OR 1.89)
  • Manifest strabismus, heterotropia (1.1 % in ADHD, 0.5 % in non-affected persons, OR 2.01)
  • Astigmatism (0.2 % in ADHD, 0.1 % in non-affected persons, OR 1.73)+

One study indicates an increased problem due to reduced eye fluid in ADHD. This also existed when taking MPH.67

24. Celiac disease (gluten intolerance)

One study found an increased ADHD prevalence of 16%,68 a review confirmed a correlation between celiac disease and ADHD.69
A larger study found an ADHD prevalence of 1.4% in children with coeliac disease and an overall reduced prevalence of mental disorders70
A study reports a link between ADHD symptoms and a non-gluten-free diet in children with celiac disease.71
One study found no correlation between celiac disease and ADHD.72

Celiac disease appears to correlate with reduced levels of dopamine, norepinephrine and serotonin in the cerebrospinal fluid.737475

25. Psychogenic and functional breathing disorders (PFBD)

One study found ADHD in 17.3% of children affected by PBFD, tic disorders in 15.4%, specific phobias in 15.4%, a somatic symptom disorder in 11.5% and 51.9% showed clinical features of tic disorders.76

26. Cerebral palsy / spasticity

Cerebral palsy can be a consequence of encephalitis, in which the dopaminergic cells have been destroyed. The result is a severe dopamine deficiency. Treatment with L-dopa can help in such cases.
A study of 213 children with cerebral palsy found a suspicion of ADHD in 50%, which was confirmed in 23%.77 This corresponds to a 4.6-fold risk of ADHD in cerebral palsy.

27. Iron deficiency anemia

One study found that gene variants that correlate with iron deficiency anemia (a blood count disorder) can causally increase the risk of ADHD.3

28. Raynaud’s syndrome

Raynaud’s syndrome is a circulatory disorder of the extremities. Fingers become pale or even blue and cold from the tips due to spasmodic constriction of the blood vessels.
Raynaud’s problems are a more common comorbidity in people with ADHD.
Raynaud’s is treated with alpha-1-adrenoceptor antagonists, e.g. prazosin or tamsulosin (highly selective at the prostate alpha-1-adrenoceptors).
As we understand it, the ADHD-I problem of decision-making problems and daydreaming results from too frequent shutdowns of the PFC. Dietrich calls this posteriorization of behavioural control78. These PFC shutdowns are triggered by excessive noradrenaline stress responses and cortisol stress responses at alpha-1 adrenoceptors, which are typical of the excessive endocrine stress response of ADHD-I.
Firstly, this raises the question of whether Raynaud’s problems occur more frequently in ADHD-I than in ADHD-HI.

We recall at least one ADHD-I sufferer who had significant Raynaud’s and hypertension, which was exacerbated by MPH and was less evident on Elvanse.

29. Hyperthyroidism / hyperthyroidism

Other synonyms are hyperthyroidism, hyperthyroidism, thyroid hormone poisoning.

Military personnel with hyperthyroidism were 70% more likely to have ADHD.79 68.3% of those affected had first been diagnosed with ADHD and only later received a diagnosis of hyperthyroidism.
Another study found a 2.53-fold risk (OR) of autoimmune disorders of the thyroid hormone system in ADHD sufferers.33

30. Endometriosis

Women with endometriosis had double the risk (OR 1.98) of ADHD than their sisters without endometriosis.80

31. Polyarthritis

One study found that gene variants that correlate with polyarthritis can causally increase the risk of ADHD.3

32. Colitis

One study found a 2.31-fold risk (OR) of ulcerative colitis in ADHD sufferers.81

In this context, we find it interesting that colitis is often associated with highly elevated adenosine levels.34 Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it is at least theoretically conceivable that colitis could also cause ADHD symptoms due to increased adenosine levels. More about adenosine at Adenosine In the chapter Neurological aspects.

33. Ankylosing spondylitis / ankylosing spondylitis

One study found a 2.78-fold risk (OR) of ankylosing spondylitis in people with ADHD.81

In this context, we find it interesting that ankylosing spondylitis is often associated with greatly increased expression of A2A and A3 adenosine receptors in the lymphocytes.35

34. Ehlers-Danlos syndrome (EDS)

Ehlers-Danlos syndrome is a group of rare diseases of the connective tissue that are associated with overstretchable skin, joints and ligaments, among other things.
Many of those affected by EDS suffer from psychiatric comorbidities:82

  • Speech disorders: 63.2 %
  • ADHD: 52.4 %
  • Anxiety: 51.2 %
  • Learning disorders: 42.4 %
  • Depression: 30.2 %

The following presentation is fundamentally based on Hamonet (2019).8384

EDS is hereditary and is passed on to all children, even if only one parent is affected.
EDS affects both sexes, although women often show more severe symptoms.
Diagnosis is made on the basis of several characteristic features and can be confirmed by electron microscopy.

Diagnostic symptoms:

The presence of 5 of the 8 diagnostic symptoms mentioned is said to indicate Ehlers-Danlos with a sensitivity of 99.7 %. Unfortunately, we were unable to find the 3 publications mentioned by Hamonet.83

  • Chronic pain
    • on the whole body, also on
      • Gums
      • Oesophagus
      • Vagina
      • Testicles
    • often stubbornly resistant to treatment
    • very variable
    • crisis-like exacerbations, influenced by exercise, hormonal factors, weather
  • Exhaustion / fatigue
    • often already in the morning
    • can become stronger at any time of day
  • motor disorders
    • Clumsiness
    • Collisions with obstacles
    • Dropping objects
    • Fall
  • Joint instability
    • Sprains
    • Dislocations
    • Subluxations (“cracking noises” in the joints)
  • Thin skin
    • soft to the touch
    • transparent
      • Veins visible on the back and above the breasts
    • fragile
      • Injuries and frequent abrasions
    • heals poorly
      • long healing time
      • very visible scars
    • Electric shocks on contact with metal objects due to loss of protection against static electricity
    • Stretch marks
      • often arise early
      • are diffuse
      • extensive
    • Skin is elastic
      • by a length that is half the length that the thumb can pinch (Ehlers)
      • Extensibility not recognizable in case of hypersensitivity or tissue oedema
      • particularly affected:
        • Cheeks
        • upper eyelids
        • Neck
        • Elbow
      • Forearm
        • Back of the hand
        • Belly
        • Arch of foot
    • Flexible cartilage
      • Ears (sometimes “sticking out”)
      • Nose
  • Joint hypermobility
    • due to slack ligaments
    • Shoulders
    • Hips
    • lower end of the ulna
    • may decrease with increasing age
    • Joint hypermobility not a compelling symptom
      • Elbows, knees, ankles, soles of the feet can be restricted by muscle contractions
      • especially for small children
      • difficult to determine with joint pain
    • Joint MRIs often negative, with severe clinical symptoms
  • Diffuse bleeding
    • cutaneous (small areas of bleeding into the skin, ecchymoses)
    • even with minimal trauma
    • often unnoticed
      • genital
      • Gums when brushing teeth
      • nasal
      • urinal
      • rectal (often facilitated by hemorrhoids).
  • Increased sensitivity
    • acoustic hypersensitivity (hyperacusis)
      if necessary:
    • Balance (dizziness)
    • Odor (hyperosmia)
    • Skin (aversion to clothing labels, rough fabrics)
    • Photophobia
      • Light sensitivity
      • Glare from car headlights
  • Reflux (heartburn)

Other symptoms83, unless they correlate with ADHD:

  • Scoliosis
    • quite often
    • moderate (10 to 15 degrees)
    • rarely progressive
    • not painful
  • Intervertebral discs
    • reduced in height due to their laxity
    • easily confused with herniated discs
  • Dystonia (disorder of unconscious “automatic” motor control)
    • very often
    • easily misdiagnosed as epilepsy, spasmophilia, hysteria
    • involuntary muscle contractions that cause twitching movements
    • Fasciculations
      • Face (eye area), thigh muscles, forearms
      • visible spontaneous muscle contractions
      • recognizable as trembling
      • without displacement of the extremity) of the face
    • Trembling at rest or during movement
    • alternating repetitive movements
    • sudden relaxation of areas
  • Dysautonomy
    • proprioceptive disorder (regulatory disorder caused by the sympathetic nervous system)
    • Temperature regulation
      • vasomotor disorders
      • Cold extremities, feet, nose, ears, hands
        • easily confused with Raynaud’s syndrome
      • Sweating
      • Chills
      • unexplained fever
      • Hot flushes
      • Vasodilation (dilated blood vessels)
        • on extremities, face
        • with pain and local swelling
    • Secretion formation disturbed
      • Nose, cheek, throat, larynx, bronchi
      • Dryness or hypersecretion possible
    • Problems of the “internal organs” (arteries, veins, lymph vessels, gastrointestinal tract, ureterovesico-sphincteric system, pharyngo-laryngotracheo-bronchial motor function)
      • due to proprioceptive dysfunctions
  • cardiovascular
    • Tachycardia
      • often lead to painful and stressful palpitations
    • additional systoles
      • often lead to precordial pain
    • Unstable blood pressure
      • mostly low with hypotension
      • Blood pressure spikes (easily mistaken for high blood pressure)
      • Postural Orthostatic Syndrome (POTS)
        • Discomfort and very soft legs when standing or getting up
        • Falls
        • Loss of consciousness
    • Arterial aneurysms
    • Venous insufficiency
    • Leakage of the valves in cardiac ultrasound often without symptoms
    • Heart failure very rare
  • Digestive problems
    • Ingestion
    • Dysphagia
    • Belching
    • retrosternal burning sensation (behind the breastbone in the middle of the chest) when swallowing
    • Flatulence
    • Constipation, diarrhea or both
    • Anal incontinence
    • Gastroesophageal reflux
    • endoscopic examination contraindicated
      • due to the increased risk of serious accidents (bleeding and / or perforation)
      • due to the increased vulnerability of the mucous membrane in the digestive tract
    • Gallbladder stones are common due to the increased distension and low contractility of the gallbladder
  • Respiratory symptoms
    • Shortness of breath due to exertion (climbing stairs) in more than 80 % of those affected
      • Hyperventilation syndrome due to reduced blood C02 content
      • Blockages caused by pain-related restricted inspiration of the diaphragm muscle due to dysfunctional rib movements caused by weak connective tissue
        • easy to confuse with asthma attack
        • bony-cartilaginous lower end of the sternum (xiphoid) often very painful (“Ehlers point”)
    • Bronchial irritation, especially in children
    • Bronchial infections of the upper respiratory tract
    • Oxygen deficiency (hypoxia) in the brain and muscles
      • Hypoxia could, in our opinion, be the causative reason for frequently comorbid ADHD
      • Blood oxygen levels rarely change even during 6-minute tests
      • Oxygen therapy relieves migraines, fatigue, sleep and cognitive disorders, dystonia
      • Frequent pauses in breathing (also during sleep, sleep apnea)
  • Mouth area
    • Teeth
      • bad teeth with inclusions, overlaps, fragility, hypermobility
      • Dentures difficult
    • Gums
      • sensitive and painful
      • Bleeding
    • Tongue
      • Hyperlax
      • can twist itself
      • can sometimes reach the tip of the nose (Görlin sign)
    • Pine
      • temporary temporomandibular joint pain
      • Subluxations or dislocations
      • Bruxism with tooth wear
    • Palate
      • ogival
  • Urogenital area
    • Bladder problems
    • Sphincter problems
    • Childhood
      • Getting clean is often delayed
    • Adults
      • Decrease in the need to urinate
        • sometimes catheterization is necessary
      • Frequent urge to urinate
        • partly with incontinence (leakage)
      • Burning frequently
        • easily confused with infections
      • Perineal insufficiencies with prolapse
        • especially after pregnancy.
  • Sexual / reproductive problems
    • Women
      • Dyspareunia (sexual dysfunction)
        • usually burning or cramp-like pain in the genital area during sexual intercourse
        • almost always no orgasm
        • in 50 % of female EDS sufferers
        • Xylocaine gel locally is helpful
      • Menstruation
        • abundant and very painful
      • Birth
        • Difficult birth
          • frequent uterine contractions without spontaneous opening of the cervix
          • PDAs are sometimes ineffective, need exact dose
          • Bleeding frequently
          • Caesarean sections should be avoided
    • Men
      • Pain during erection or ejaculation
      • Testicular ectopia
  • Cysts, nodules
    • joints, breasts, thyroid gland, liver, pancreas, intracranial, mastoid, etc.)
    • often disappear spontaneously
    • do not degenerate
    • Volume increases in the area of the ganglia without direct consequences
  • Endocrine symptoms
    • Thyroid gland
    • Adrenal glands
    • Salivary and lacrimal glands
  • Mast cell activation syndrome
    • Indications frequent
      • superficial and deep urticaria
      • Flush
      • non-specific exanthema, especially after a shower
      • Pruritus
    • Factors
      • increased stress
      • Trauma, including surgical trauma (mainly orthopaedic surgery)
      • climatic factors (wet cold)
      • hormonal factors (pregnancy, birth)
      • Restriction of physical activity and immobilization of a joint.
  • Anemia
  • Iron deficiency
    • in most hemorrhagic forms
  • Platelets may be reduced.
  • Electromyograms unremarkable
  • Speech disorders
    • 63.2 % of Ehlers-Danlos sufferers have speech disorders82

Other Ehlers-Danlos symptoms83, which are also ADHD symptoms or frequently occur with ADHD.
We think that the cause of ADHD symptoms could be hypoxia caused by Ehlers-Danlos. Visual problems are also more common with hypoxia.

  • ADHD
    • 52.4% of Ehlers-Danlos sufferers have ADHD82
      The following features are classic ADHD symptoms and, in our opinion, are likely to be caused by hypoxia.
  • Cognitive disorders
    • Impaired working memory
      • Executive functions impaired
        • Organization
        • Management of daily life
        • Sequence of individual steps for multi-step activities
  • Attention deficit disorders
    • A wealth of ideas
    • sudden change of subject
    • from “stick to stick”
    • Multitasking
    • increased creativity
  • Concentration disturbed
    • Difficulties with sustained concentration
    • Difficulties in spatial orientation
  • intellectual level unimpaired
  • social problems
    • Result of a confrontation between a normal brain and a body that delivers messages that are difficult to interpret
    • Withdrawal into oneself
  • Dysorthographies, dyspraxia, dyslexia
  • Strong emotionality
    - high understanding of others
    - high empathy for the suffering of others
  • Food intake / metabolism
    • Food intolerances (lactose, gluten…)
    • Drug intolerance
    • Appetite disorders
    • Overweight frequently
  • Visual disturbances very common
    • In our opinion, visual disturbances could be the result of hypoxia, which we also suspect to be the cause of frequently comorbid ADHD
    • Lesions of the retina or cornea (rare)
    • Photophobia
      • Light sensitivity
      • Glare from car headlights
    • binocular visual disturbances very common
      • synchronous motor control of eyes and eyes with head movements more difficult
  • Learning disorders
    • 42.4% of Ehlers-Danlos sufferers have learning disorders82
  • Sleep disorders
    • Difficulty falling asleep and sleeping through the night very frequently (also with ADHD)
    • Hypersomnia rare
    • sometimes reinforced by
      • severe pain at night
      • Muscle unloading (“restless legs”)
      • Contractures of painful expression of dystonia
    • Frequent nightmares
    • Sleepwalking, especially in children
  • Fear
    • 51.2% of people with Ehlers-Danlos suffer from anxiety82
    • Anxiety is a common comorbidity of ADHD
  • Depression
    • 30.2 % of Ehlers-Danlos sufferers have depression82
    • Depression is a common comorbidity of ADHD
  • Vitamin D deficiency
    • also frequently occurs with ADHD
  • Ehlers-Danlos main symptoms
    of the main diagnostic symptoms of Ehlers-Danlos mentioned above, the following are correlated with ADHD:
    • chronic pain
      • significantly increased prevalence in SADHS
      • especially shoulder/neck area
    • motor disorders
      • Clumsiness
      • Collisions with obstacles
      • Dropping objects
      • Fall
    • increased sensitivity
      • not limited to hyperacusis in ADHD
    • Reflux
      - 7 times higher in ADHD compared to non-affected people

35. Ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency85 occurs in around 1 / 30,000 people and is caused by a genetic defect in the OTC gene. There are also gene mutations with a residual enzyme activity, so these may not be diagnosed immediately. Those affected develop typical neuropsychological complications such as86

  • Developmental delay
  • Learning disability
  • mental disability
  • Attention deficit/hyperactivity disorder
  • Deficits in the executive function

36. CYP2C19 ultra-metabolizer

One study found no correlation between different metabolization gene variants of CYP2D6 or CYP2C19 on drug response (of stimulants) in ADHD, but an increased rate of CYP2C19 ultra-metabolizers among ADHD sufferers.87
CYP2C19*17 is present in approx. 20 % of the Caucasian population and is associated with increased degradation.
CYP2C19 metabolizes various drugs:888990

  • Arachidonic acid (a quadruply unsaturated omega-6 fatty acid) to epoxyeicosatrienoic acids (EETs)
  • Linoleic acid (an essential, double-unsaturated omega-6 fatty acid) to 9,10-epoxy-octadecaenoic acid (other names: vernolic acid, linoleic acid-9:10-oxide, leukotoxin) and 12,13-epoxy-octadecaenoic acid (other names: coronary acid, linoleic acid-12,13-oxide, isoleukotoxin)
  • Docosahexaenoic acid (DHA, represents 95% of omega-3 fatty acids) to epoxydocosapentaenoic acids (EDPs)
  • Eicosapentaenoic acid (polyunsaturated omega-3 fatty acid) to epoxyeicosatetraenoic acids (EEQs)

37. Alopecia areata (hair loss)

Alopecia areata (hair loss) correlated with a 3.03-fold risk of ADHD.91

38. Lipedema

One study reports that ADHD is 42% more common in women with lipedema than in women without lipedema.92 However, the study suffers from a strange use of the ASRS.

39. Hidradenitis suppurativa

Other names: Acne inversa, Acne inversa, Acne triad, Acne tetrade, Morbus Verneuil, Pyodermia fistulans sinifica93

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is associated with psychiatric comorbidity.
Among 52,909 Danish blood donors, 1.9% were found to have hidradenitis suppurativa. Of these, 7.4 % showed ADHD symptoms, compared to 3.5 % of participants without hidradenitis suppurativa. The risk of ADHD was increased by 85% after adjustment for confounding factors.94

40. Hearing loss

The frequency of ADHD in children with (partial or complete) hearing loss was significantly higher (12.1%) than in the control group (3.6%).95

41. Albinism

Albinism is associated with a genetic defect in the melanin balance. One study reported an ADHD prevalence of 21.8% in children with albinism.96

42. Herpes simplex

An evaluation of the German KIGGS study found an increased risk of approx. 48% (Exp(β) = 1.48).22 Exp(β) corresponds to the OR.(([Noymer: Why is exp(β) the odds ratio?]

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