Somatic Comorbidities in ADHD

Among adults in the top 10% of ADHD symptom severity according to the ADHS-E scale, distress caused by physical symptoms occurred 10.62 times more frequently and distress caused by somatization occurred 6.80 times more frequently than among those without ADHD.¹

The following list of somatic disorders that co-occur with ADHD is sorted in descending order of frequency of occurrence among people with ADHD. The headings indicate the percentage of people with ADHD who have this comorbidity (compared to people without ADHD).

The percentages in the headings indicate the prevalence of comorbid conditions in ADHD. Example: 48% of people with ADHD suffer from musculoskeletal disorders, compared to 21.6% of people without ADHD.

1. Chronic Pain¶

1.1. Chronic pain (up to 86% vs. 21% to 50%)¶

See the following section on Chronic Pain / Muscle Tension in ADHD in the Symptoms chapter.

1.2. Fibromyalgia Co-occurring with ADHD (+233%)¶

Fibromyalgia (“muscle fiber pain”) is a chronic syndrome characterized by pain in various parts of the body. It is accompanied by sleep disturbances, fatigue, morning stiffness, and difficulty concentrating. Fibromyalgia is not an inflammatory disease, but rather primarily a disorder of pain perception and processing.
The prevalence of fibromyalgia ranges from 0.5 to 5.8 percent. In Germany, it is 2 percent (2013—it is unclear which diagnostic criteria were used).

Among people with ADHD, the risk of fibromyalgia is 3.33 (OR), which is a 233% increase.²

Among adults with fibromyalgia, a chronic pain disorder, the reported prevalence of ADHD is

• 44.72%³
• 32.3% during childhood among adult women with fibromyalgia⁴
• 29.5% among adult women (N = 78) compared with 7.4% among adult women without fibromyalgia (N = 54)⁵⁶
• 25%⁷
• 24.5%⁸
  To the extent that the studies cited did not yet use the American College of Rheumatology’s 2010-revised diagnostic criteria for fibromyalgia—which, compared to the previous 1990 criteria, do not⁹, the comorbidity rate is likely to be significantly higher.

Cognitive symptoms in fibromyalgia are attributable to dysfunction in the prefrontal cortex. These include, for example:⁹¹⁰

• Slower reaction time
• the inability to filter out irrelevant information
• Difficulty dividing one’s attention
• Memory problems
• Vocabulary problems
• not: slowed-down thinking

Emotional dysregulation, sleep problems, and mood issues are also primary symptoms of fibromyalgia.⁹ All of these are also symptoms of ADHD.

ADHD in childhood is a predictor of fibromyalgia in adulthood.¹¹
Fibromyalgia may also be linked to a history of PTSD and ASD¹², which are themselves often comorbid with ADHD.

Stimulants are helpful for both fibromyalgia and ADHD.¹³¹⁴
With regard to fibromyalgia, there are reports of effective treatment with very low doses of naltrexone. The treatment is said to be virtually free of side effects.¹⁵¹⁶ A person with ADHD told us that the low-dose naltrexone also helped alleviate their co-occurring ADHD symptoms.
The following are also reported as possible treatment options:

• Kratom.¹⁷ Kratom is also used as a self-treatment for ADHD. Due to its potential for dependence and a reported risk of seizures, kratom should be avoided.
• Low-dose medical cannabis^{1819 20 21 22 23 24 25} Cannabis is also used to treat ADHD.

1.3. Pathways Leading to Chronic Pain, Increased Muscle Tone, and Fibromyalgia¶

For more on this, see Chronic Pain and Muscle Tension in ADHD—Neurophysiological Correlates

2. Sleep problems—Children: 68.7% (compared to 47.1%)—Adults: +138%¶

A Chinese study of 23,791 schoolchildren found that 68.7% of children with ADHD had poor sleep quality, compared with 47.1% of children without ADHD.²⁶
A study reports a 2.38-fold increased risk of sleep-related disorders in individuals with ADHD.²

For more details, see:

• Sleep Problems in ADHD—Symptoms
• Sleep Problems in ADHD—Neurophysiological Correlates
• Sleep Problems in ADHD - Treatment

3. Musculoskeletal disorders - 48% (compared to 21.6%)¶

• among adults with ADHD: 48.4%²⁷
• Among those not affected: 21.6%²⁷
  = twice the risk

The following skeletal problems were found:²⁸

• in 31% of adults with ADHD
• Among 16% of adults without ADHD:

A study found that gene variants associated with synovitis (inflammation of the joint lining) and tenosynovitis (inflammation of the tendon sheath) may causally increase the risk of ADHD. Conversely, ADHD gene variants appear to increase the risk of carpal tunnel syndrome.²⁹

4. Allergies—26 to 45% (compared with 15 to 18%)¶

Allergies are more common in people with ADHD than in those without the condition.³⁰ This association was first identified by Marshall as early as 1989 and attributed to acetylcholine hypersensitivity and adrenaline hyposensitivity in the autonomic nervous system.³¹ Pelsser, Buitelaar, et al. found that ADHD can (also) be triggered by allergic and non-allergic hypersensitivity.³²

Among 100 children with ADHD (average age 9 years), 35% were found to have an allergy. Among people with comorbid conditions, 43% had a hay fever allergy, 37.5% had various pollen allergies, 25% had a combination of allergic rhinitis and bronchial asthma, 8% had urticaria, and 2% had asthma. Interestingly, allergies were found only in the ADHD-C subtype, but not in the ADHD-HI or ADHD-I subtypes. In addition, boys with ADHD were significantly more likely to have a comorbid allergy than girls. Allergies correlated with increased severity of ADHD symptoms. Allergies typically first appeared at an average age of 4 years, while ADHD typically first appeared at an average age of 6 years. Among people with ADHD, 16% tested positive on a skin prick test, compared to 5% of the control group. Elevated total IgE levels were found in 45% of people with ADHD and 18% of people without ADHD.³³
Among 23,791 Chinese schoolchildren, 26.1% of those with ADHD had allergies, compared with 15.2% of children without ADHD.²⁶
Among N = 18,558 participants, urticaria was found in 5.00% of people with ADHD compared to 4.22% (+19%) of people without ADHD. Allergic urticaria was found in 3.26% of people with ADHD compared to 2.73% of people without ADHD (+20%). The ADHD group was more likely to take systemic and topical antihistamines as well as systemic corticosteroids.³⁴

Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 43.4% reported having allergies, compared with 27.8% of those without ADHD (+56.1%).³⁵
Japanese children with developmental disorders were found to have a 3.22- to 3.87-fold increased risk of allergies.³⁶
A study found no increased risk of allergies in children with ADHD.³⁷
Elementary school children in China with one allergy had a 2.2-fold increased risk of ADHD; for those with multiple allergies, the risk of ADHD was 3.15 times higher.³⁸
Children with ADHD had a 14% higher risk of allergies.³⁹

The prevalence of allergic rhinitis rises from infancy through adolescence to between 12.5% and 43.6%, and then declines again with age.⁴⁰
Among elementary school children in China with allergic rhinitis, 7.7% had ADHD; among those without allergic rhinitis, the rate was 4.1%.³⁸⁴¹
Successful treatment of allergic rhinitis in children significantly reduces their ADHD symptoms, but this is not the case for children with nonallergic rhinitis.⁴²⁴³

ADHD is associated with an increased risk of rhinitis:

• 1.51-fold increased risk across all studies (systematic review, k = 8 meta-analyses, n = 15,197, N = 83,438)⁴⁴
• 1.30-fold increased risk when limited to gold-standard studies (systematic review, k = 5 meta-analyses, n = 12,234, N = 45,391)⁴⁴

Allergies are usually consequences of elevated cortisol levels. Cortisol inhibits the promotion of inflammation triggered by CRH (the first increment of the HPA axis) via inflammatory cytokines and instead promotes other immune defense mechanisms that target extracellular stressors—such as bacteria or allergens.
Elevated cortisol levels or an excessive cortisol response can lead to an overreaction of the immune system to external substances that are not actually dangerous—an allergy.
For more information on the immunological effects of cortisol, visit ⇒ Adrenal cortex (3rd increment)
Disorders in stress hormone levels, particularly cortisol, are common in ADHD. ⇒ Cortisol in ADHD
In addition, there is a link between allergies and histamine.⁴⁵
Histamine interferes with dopamine metabolism, just as nearly all ADHD medications increase histamine levels.

5. Cardiovascular problems: 38% to 43% (compared to 18% to 24%)¶

2.38 times the risk: 43% of adults with ADHD, compared with 18% of adults without ADHD, had cardiovascular problems.²⁸
2.1-fold risk: ADHD was associated with a 2.1-fold risk (HR) for all types of cardiovascular disease, even after adjusting for the use of stimulants and other psychotropic medications. During an average follow-up period of 11.80 years, 38.05% of people with ADHD and 23.57% of people without ADHD received at least one diagnosis of a cardiovascular disease. ⁴⁶

Among 3,440 children with heart problems, there were⁴⁷

• 20.4% with ADHD
• 22.1% have an anxiety disorder
• 19.6% have learning difficulties

A meta-analysis of Mendelian randomization studies, which can be used to establish the direction of causality between correlated effects, showed (meta-analysis, k = 14)⁴⁸

• A genetic predisposition to ADHD increased the risk of coronary heart disease, heart failure, and various types of strokes.
• A genetic predisposition to ASS increased the risk of atrial fibrillation and heart failure
• Atrial fibrillation was found to have a causal association with an increased risk of ADHD

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

Among people with ADHD who had suffered from premature ejaculation throughout their lives, 41.6% also had ADHD, compared with 5% of those who did not have the condition.⁴⁹
Among people with premature ejaculation and ADHD, two-thirds had the ADHD-HI subtype characterized primarily by hyperactivity and impulsivity, which is otherwise found in only 8.3% of people with ADHD.

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

• For people with ADHD:
  • 41.1%⁵⁰
  • 39%²⁸
• for those not affected:
  • 21.6%²⁷
    • 19%²⁸
      = twice the risk

For ADHD, the following was found (meta-analysis, k = 11, N = 3,851,163)⁵¹

• a 25% increased risk of gastrointestinal disorders
• a 63% increased risk of irritable bowel syndrome (IBS)

8. Upper Respiratory Tract Disorders¶

8.1. Upper respiratory tract infections in children—40% (compared to 33.4%)¶

• among children with ADHD: 40.1%⁵⁰
• Among those not affected: 33.4%⁵⁰
  = 1.3 times the risk

3.6% of people with chronic rhinosinusitis who had undergone endoscopic sinus surgery were taking ADHD medication, compared with 2% of persons without ADHD. The use of antidepressants was also roughly double, at 22.1% compared to 11.3%.⁵²

8.2. Upper respiratory tract diseases in adults — 33.7% (compared with 15.2%)¶

• Among adults with ADHD: 33.7%⁵⁰
• Among those not affected: 15.2%²⁷
  = twice the risk

A study found that ADHD gene variants may causally increase the risk of chronic obstructive pulmonary disease.²⁹

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

• Among adults with ADHD: 36.5%⁵³
• Among those not affected: 19.0%⁵⁰
  = twice the risk

10. Skin diseases, atopic dermatitis, eczema, psoriasis—32.4% (compared to 10 to 25.5%)¶

• among children with ADHD: 32.4%⁵⁰
• Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 16.7% reported skin conditions (particularly male adolescents), compared with 8.1% of those without ADHD (+106%).³⁵
• Among those not affected: 25.5%⁵⁰; 10–20% among children, 2–3% among adults, with a higher incidence in urban areas.⁵⁴
  = the risk is approximately 1.5 times higher in children⁵⁴, which is said to account for 9% of all ADHD cases.
• People with ADHD are more likely than average to suffer from neurodermatitis (= atopic eczema)⁵⁵
  • Japanese children with ADHD have a 5.06-fold increased risk of atopic dermatitis³⁶
  • 1.67-fold increased risk among German children (KIGGS study: Exp(β) = 1.672).⁵⁶ Exp(β) corresponds to the OR.⁵⁷
  • 1.41-fold increased risk across all studies (systematic review, k = 7 meta-analyses, N = 802,099)⁴⁴
  • 1.30-fold increased risk when limited to gold-standard studies (systematic review, k = 8 meta-analyses, N = 802,099)⁴⁴
• Conversely, people with atopic dermatitis have an increased risk of mental disorders such as ADHD.^5859606162
  • A study of Indian children with atopic dermatitis found rates of⁶³
    • Inattention: 29.5%
    • Hyperactivity: 20%
  • A study of N = 44 children and adolescents with atopic dermatitis who had not been diagnosed with ADHD (but for whom an ADHD diagnosis had not been ruled out) showed many ADHD-related symptoms but no attention problems⁶⁴
    • average attention span on the CPT-3 (although it is unknown whether the participants were particularly motivated or unmotivated, which can have a significant impact on attention tests for ADHD)
    • increased sensitivity, stimulus-avoidance behavior, or hyposensitivity
    • increased sleep problems
    • increased incidence of comorbid anxiety disorders
    • increased incidence of comorbid depression
• Epidemiological data show that the global prevalence of atopic dermatitis and ADHD has risen in parallel. Several cross-sectional studies have indicated that these conditions often occur together and develop at the same time in people with ADHD.⁵⁴
• A study found no genetic causal relationship between atopic dermatitis and ADHD, or between ADHD and atopic dermatitis⁶⁵
• Atopic immune disorders may be due to an excessive immune response resulting from low cortisol levels. Cortisol counteracts the inflammation initially triggered by CRH (the first increment of the HPA axis) through inflammatory cytokines. If cortisol secretion (the third increment of the HPA axis) is too low, the inflammation is not sufficiently suppressed.⁶⁶
• 90% of people with vitiligo (patches of depigmentation) exhibited mental disorders, compared to 20% of those without the condition. The prevalence of ADHD among people with vitiligo was 36.6%.⁶⁷
• In a mouse model of atopic dermatitis, a study found chronically elevated HPA axis activity and changes in dopamine and norepinephrine levels in the locus coeruleus, prefrontal cortex, and striatum—changes typical of ADHD. In addition, melatonin levels were reduced.⁵⁴
  • These findings could support our view that chronic stress produces its symptoms in the same way as ADHD, namely through reduced levels of dopamine and norepinephrine in the aforementioned brain regions.

For more information on the immunological effects of cortisol, visit ⇒ Adrenal cortex (3rd increment)

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

A study found that people with ADHD have an increased risk of:⁶⁸

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

We also find it interesting that inflammation is often associated with significantly elevated adenosine levels.⁶⁹ 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 pro-inflammatory cytokines, and the concentration of metalloproteinases involved in inflammatory reactions in chronic autoimmune rheumatic diseases.⁷⁰ Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it would be conceivable, at least in theory, that inflammation could also cause ADHD symptoms through elevated adenosine levels. More on adenosine at ⇒ Adenosine In the chapter “Neurological Aspects.”

A case report describes a boy with recurrent generalized pustular psoriasis (GPP), comorbid epilepsy, hyperactivity, and hypoproteinemia. He had a combination of the homozygous IL36RN: c.115 + 6T > C mutation and the heterozygous c.227C > T(p.P76L) variant. Treatment with the anti-IL-36 antibody spesolimab led to a complete and rapid improvement. Pustules, erythema, and scaling improved within one week. After six months of treatment with pesolizumab, the child’s electroencephalogram returned to normal, and all clinical symptoms of hyperactivity and epilepsy—such as inattention, excessive activity, and emotional instability—improved significantly.⁷¹ This is another example of secondary ADHD.

11. Infectious diseases - 31.2% (up from 25.9%)¶

• among children with ADHD: 31.2%⁵⁰
• Among those not affected: 25.9%²⁷
  = 1.3 times the risk

12. Ear disorders - 31.1% (compared to 23.7%)¶

• among children with ADHD: 31.1%⁵⁰
• Among those not affected: 23.7%⁵⁰
  = 1.7 times the risk

A Chinese study of 23,791 schoolchildren found that 6.7% of children with ADHD had had an ear infection (otitis media), compared with 3.8% of children without ADHD.²⁶
Since the patient was likely asked about a history of this condition, it is less a comorbidity than a risk factor.
An analysis of the German KIGGS study found an approximately 57% increased risk (Exp(β) = 1.57).⁵⁶ Exp(β) corresponds to the OR.

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

For adults with ADHD:

• 31%²⁸
  For adults without ADHD:
• 16%²⁸

14. Sleep apnea—up to 30% (compared to 4%)¶

23.3% of children with ADHD⁷² and up to 30% of people with ADHD⁷³ suffer from sleep apnea.

The majority of children with ADHD and sleep apnea had moderate-to-severe sleep apnea. The presence of moderate-to-severe sleep apnea significantly altered the outcomes for children with ADHD compared to children with ADHD and mild sleep apnea⁷⁴

• the time it takes to fall asleep
• total sleep duration
• various sleep-related behaviors, such as difficulty falling asleep and difficulty waking up in the morning
• increased inattention
• increased hyperactivity
• increased behavioral problems

Sleep apnea leads to a lack of oxygen. A lack of oxygen (hypoxia) impairs the dopaminergic system.
In the general population, 3 to 7% of men and 2 to 5% of women have obstructive sleep apnea.⁷⁵
A case study reports an improvement in ADHD symptoms following treatment for sleep apnea.⁷⁶

Sleep apnea is usually treated with a sleep mask. If a sleep mask is not tolerated, there are alternative treatment options.⁷⁷

15. Cerebral Palsy / Spasticity 15% to 23% (vs. 8%)¶

Studies have found that cerebral palsy is associated with a risk of ADHD of

• 36.4% of children with cerebral palsy had ADHD, compared with 9.1% of children without the condition.⁷⁸
• 50% were suspected of having ADHD, which was confirmed in 23% (N = 213, based on comprehensive screenings and neuropsychiatric evaluations)⁷⁹ This corresponds to a 4.6-fold increased risk of ADHD in children with cerebral palsy.
• a 52% increased lifetime risk of ADHD (OR 1.52)⁸⁰
• 23% on health registry data⁸¹
• 21% on health registry data⁸²
• 19.9% vs. 10.5% in the parent report⁸³
• 19.5% in the parent report⁸⁴
• 19.5% in the parent report (+150%)⁸⁵
• 18.1% of children and adolescents with cerebral palsy had been diagnosed with ADHD, according to health registry data⁸²
  • Children and adolescents with bilateral spastic cerebral palsy were 42% less likely to have ADHD (aOR: 0.58)
• 15.91% of children with CP vs. 7.89% of children without CP, according to parental reports⁸⁶
• 15.4% in the parent report⁸⁷
• 15% vs. 8.7% in the parent report⁸⁸
• 4.1% of health registry data⁸⁹

Many people with ADHD were initially misdiagnosed with cerebral palsy.⁹⁰⁹¹
More about dopamine transporter deficiency syndrome (DTDS) in the article Psychiatric Comorbidities in ADHD L-Dopa is said to be helpful for DTDS.

Cerebral palsy can be a consequence of encephalitis that has destroyed dopaminergic cells. This leads to a severe dopamine deficiency. Treatment with L-dopa can be helpful in such cases.
In contrast, L-dopa is not effective for cerebral palsy caused by complications during childbirth.

16. Obesity—Germany: 22.1% (compared to 10.2%); U.S.: 41.4% (compared to 21.6%)¶

The doubling of the prevalence of obesity among people with ADHD is (albeit from extremely different baseline levels) in the U.S., where it ranges from 21.6% among those without ADHD to 41.4% among those with ADHD⁹², as well as in Germany, where it ranges from 10.2% among those without ADHD to 22.1% among those with ADHD.⁹³
A meta-analysis of 42 studies with N = 728,136 participants found:⁹⁴

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

ADHD is associated with an increased risk of obesity:
* 1.32-fold increased risk across all studies (systematic review, k = 43 meta-analyses, n = 74,476, N = 1,390,311)⁴⁴
* 1.81-fold increased risk when limited to gold-standard studies (systematic review, k = 5 meta-analyses, n = 19,511, N = 499,744)⁴⁴
* An Israeli cohort study found that obesity was nearly twice as common—at 13.5%—among adolescents with severe ADHD than among those without the condition, and about 30% more common among those with mild ADHD-HI than among those without the condition.⁹⁵

A meta-analysis of 16 studies with N = 14,981 cases and N = 128,916 controls found an increased risk of being overweight or obese for:⁹⁶

• Children with ADHD: by 56%
  • Boys with ADHD: by 45%
• People in Asia: 225%
• People in Europe: by 85%
• People with ADHD 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 with 29.6% of children without ADHD.²⁶ The figures reported were 15.9% for being overweight and 11.9% for obesity, but these were not broken down by ADHD status. Since the figures for obesity were not reported separately, they are not comparable.

According to Winkler, 30 to 60 percent of all cases of severe obesity are linked to ADHD.⁹⁷

Among adult psychiatric inpatients with ADHD, the prevalence of obesity is 24.5% and that of other eating disorders is 11.2%⁹⁸ Other sources do not provide percentages in the available abstracts.⁹⁹

Treatment for ADHD in people with ADHD and obesity resulted in weight loss of more than 12.3%, while the control group of obese patients without ADHD experienced a 2.8% weight gain.¹⁰⁰
Winkler reports that in obesity treatment alone, a weight gain of less than 5% is already considered a success,¹⁰¹ so that weight loss of more than 12% is nothing short of sensational.

For more information, see -> ADHD, Obesity, and Eating Disorders in the chapter on Treatment / Comorbidities.

17. Tonsillar 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 with 11.1% of children without ADHD.²⁶
Adenotonsillar hypertrophy is the leading cause of obstructive sleep apnea in childhood. Obstructive sleep apnea, in turn, is a possible cause of ADHD symptoms.

18. Asthma—16.2 to 16.9% (compared with 9.7 to 11.5%)¶

A meta-analysis found that 16.9% of people with ADHD had asthma, compared with 11.5% of those without ADHD¹⁰²; a cohort study reported rates of 16.2% versus 9.7%.¹⁰³ 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 associated with asthma, as well as a 10% increased risk of asthma associated with ADHD.¹⁰⁴

A Swedish cohort study involving N = 1,575,377 participants found an ADHD prevalence of 8.8% among people with asthma, compared to 5.6% among those without asthma.¹⁰⁵ In another study, children with asthma had a 70% increased risk of also having ADHD. The risk of ODD was also increased (360%), but the risk of CD was not.¹⁰⁶ Another study found ADHD in 11.3% of people with asthma.¹⁰⁷

There appear to be genetic overlaps between ADHD (and major depression) and asthma.¹⁰⁸¹⁰³
A study found that people with ADHD have an increased risk of:⁶⁸

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

ADHD is associated with an increased risk of asthma:

• 1.55-fold increased risk across all studies (systematic review, k = 29 meta-analyses, n = 572,114, N = 4,822,797)⁴⁴
• 1.47-fold increased risk when limited to gold-standard studies (systematic review, k = 8 meta-analyses, n = 12,577, N = 77,300)⁴⁴

Japanese children with ADHD had a 3.72-fold increased risk of bronchial asthma and a 5.06-fold increased risk of atopic dermatitis.³⁶
Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 24.7% reported having asthma, compared with 16.0% of those without ADHD (+54.3%).³⁵

In cases of comorbid asthma and ADHD, IL-6 levels were elevated, but C-reactive protein levels were apparently not.¹⁰⁹

A study found no causal relationship between atopic dermatitis and ADHD, or between ADHD and atopic dermatitis, among Europeans.¹¹⁰

18.1. Links Between Asthma and ADHD:¶

We currently have two hypotheses regarding the neurophysiological mechanism through which asthma might be linked to ADHD.

18.1.1. Adenosine¶

We find it interesting that asthma and inflammatory diseases are often associated with significantly elevated adenosine levels.⁶⁹¹¹¹

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 involved in the inflammatory responses associated with chronic autoimmune rheumatic diseases.⁷⁰
Treatment of people with ADHD who have asthma using 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 would be conceivable—at least in theory—that asthma and inflammatory diseases could also cause ADHD symptoms through elevated adenosine levels. Learn more about adenosine at ⇒ Adenosine In the chapter “Neurological Aspects,” as well as there at ⇒ Theophylline and ADHD

Consistent with this, successful treatment of allergic rhinitis in children significantly reduces their ADHD symptoms, but not those in children with nonallergic rhinitis.⁴²⁴³ Similarly, an improvement in ADHD symptoms following successful treatment of comorbid asthma was reported in a single case.¹¹²

18.1.2. Hypoxia (oxygen deficiency)¶

It is well known that oxygen deprivation affects dopamine levels. Oxygen deprivation during birth is known to be a possible cause of ADHD.
Asthma, which is frequently comorbid with ADHD, is associated with intermittent hypoxia.¹¹³
Sleep apnea is also known to trigger ADHD symptoms and is likewise associated with intermittent hypoxia.

Hypoxia causes upregulation of tyrosine hydroxylase in the locus coeruleus of newborn mice.¹¹⁵

19. Migraine¶

Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 10.8% reported having migraines (particularly girls), compared with 7.5% of those without ADHD (+44%).³⁵

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

A Chinese study of 23,791 schoolchildren found that:²⁶

• Stunted growth
  • in 9.8% of children with ADHD
  • excluding 5.9% of children without ADHD
• Underweight
  • in 3.0% of children with ADHD
  • excluding 2.9% of children without ADHD
• Emaciation
  • in 7.1% of children with ADHD
  • excluding 5.5% of children without ADHD

21. Injuries: 19% (up from 13.7%)¶

A cohort study found that 19% of people with ADHD (across all age groups) and 22.7% of people with ADHD and additional mental health comorbidities had sustained injuries, compared with 13.7% in the control group. The risk of injury was thus 33% higher in cases of ADHD alone.
The number of comorbid mental disorders was associated with an increased risk of injury among patients with ADHD. The risk of injury was highest among ADHD patients with comorbid schizophrenia, followed by those with bipolar disorder and obsessive-compulsive disorder. Comorbid ASD reduced the risk of injury.¹¹⁶

22. Diabetes¶

We find it interesting that diabetes is often associated with significantly elevated adenosine levels.⁶⁹ Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it would be at least theoretically conceivable that diabetes could also cause ADHD symptoms through elevated adenosine levels. More on adenosine at ⇒ Adenosine In the chapter “Neurological Aspects.”

22.1. Type 1 diabetes—12% to 35% (compared to 9.5%)¶

The prevalence of ADHD is higher among adolescents with type 1 diabetes. One study found that 12% of adolescents with type 1 diabetes had ADHD.¹¹⁷ A review reported a 35% increased risk of ADHD.¹¹⁸

The global prevalence of type 1 diabetes is 9.5%.¹¹⁹

22.2. 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 people with ADHD, compared to 1.62% (men: 1.96%; women: 1.28%) of people without ADHD.¹²⁰ Another large registry study found a 2.29-fold increased risk of type 2 diabetes among people with ADHD.¹²¹

A study found that genetic variants associated with type 2 diabetes may causally increase the risk of ADHD.²⁹ 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%).¹²²

23. Experienced a preterm birth - 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 with 5.5% of children without ADHD.²⁶
This is not a comorbidity, but rather a risk factor.

24. 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 people with ADHD, compared with 4.48% (men: 4.98%, women: 3.98%) of those without ADHD.¹²⁰

A meta-analysis of Mendelian randomization studies—which can be used to establish the direction of causality between correlated effects—found no genetic link between high blood pressure and ADHD or ASD (meta-analysis, k = 14)⁴⁸

25. 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 (stomach acid flowing back up), compared with 0.6% of children without ADHD.²⁶

26. Short stature - 3.2% (compared to 0.9%)¶

In a nationally representative U.S. longitudinal cohort, 3.2% of children with ADHD in 4th grade had short stature (height below the 3rd percentile), compared with 0.9% of children without ADHD, after adjusting for gender, parental income, and parental education level—a 3.88-fold higher probability (OR 3.88; 95% CI 1.69 to 8.88). In kindergarten and in 2nd grade, the difference was not significant. (Cohort study, N = 7,063, n = 298 with ADHD in 4th grade, E 2b)¹²³

26.1. Prevalence of ADHD itself¶

The height z-score for children with ADHD in 2nd and 4th grade was lower than for those without ADHD (difference in 4th grade: 0.26; 95% CI 0.08 to 0.44), and the BMI-z score from kindergarten through 4th grade (difference in 4th grade: 0.28; 95% CI 0.07 to 0.50). Children who had already been diagnosed with ADHD in kindergarten grew more slowly through 4th grade (difference in height z-score growth 0.23; 95% CI 0.04 to 0.42) and gained less BMI (0.16; 95% CI 0.03 to 0.29). In kindergarten, only 16 of these 139 children (12%) were on medication, so the baseline findings are largely independent of medication use. (Cohort study, N = 7,063, n = 139 with ADHD in kindergarten, E 2b)¹²³

26.2. Additional dose of medication¶

Within the ADHD group, a longer duration of ADHD medication use (2 to 4 years versus 0 to 2 years or no medication) was associated with a lower z-score for height in 4th grade (β −0.231; 95% CI −0.387 to −0.075) and with less height gain from kindergarten through 4th grade (β −0.187; 95% CI −0.248 to −0.126). For the BMI-z score, the result was β −0.234 (95% CI −0.358 to −0.109), and for BMI growth, β −0.154 (95% CI −0.222 to −0.086).
In a cross-sectional analysis, children with ADHD who were on medication and those who were not differed only in 2nd grade (length z-score 0.47; 95% CI 0.45 to 0.49; BMI-z-score 0.47; 95% CI 0.02 to 0.91), but not in kindergarten or in 4th grade. The probability of short stature was not increased among children with ADHD who were on medication (4th grade OR 2.71; 95% CI 0.32 to 23.17). In 2nd grade, this comparison could not be calculated because none of the 55 children with ADHD who were not on medication had short stature. (Cohort study, N = 7,063, n = 139 with ADHD in kindergarten, of whom n = 228 were on medication in 4th grade, E 2b)¹²³

26.3. Classification¶

The difference attributable to ADHD itself (about 0.26 standard deviations in 4th grade) and the difference by increment in duration of medication use (about 0.23 standard deviations) are similarly large. However, these two values come from different models—one from a comparison with children without ADHD, the other from a comparison within the ADHD group. They cannot be added together. (ADxS assessment)

The duration of medication use was not randomized. Children who took medication for a longer period likely had more severe ADHD. The effect of the medication is therefore biased upward, while the prevalence of ADHD itself is correspondingly biased downward. (ADxS assessment)

The study relied solely on parental reports for diagnoses and medication, without specifying the active ingredient, dosage, or distinguishing between stimulants and non-stimulants, and without considering parental height. The finding regarding short stature is based on only 8 people with ADHD. (Cohort study, N = 7,063, E 2b)¹²³

27. Vision problems—up to 2.4% (compared to 1.3%)¶

A large study found that children with ADHD-HI have significantly higher rates of eye disorders:¹²⁴

• Farsightedness, hyperopia (2.4% among those with ADHD, 1.3% among those without ADHD, OR 1.82)
• Low vision, amblyopia (1.6% among those with ADHD, 0.9% among those without ADHD, OR 1.89)
• Obvious strabismus, heterotropia (1.1% in individuals with ADHD, 0.5% in those without ADHD, OR 2.01)
• Astigmatism (0.2% in individuals with ADHD, 0.1% in those without ADHD, OR 1.73)+

A study points to an increased risk associated with reduced intraocular fluid in ADHD. This risk persisted even when taking MPH.¹²⁵

28. Celiac Disease (Gluten Intolerance)¶

Gluten is a protein found in wheat. Gluten intolerance can manifest in various ways—such as

• chronic intestinal inflammation¹²⁶
• IgE-mediated food allergy (wheat allergy)¹²⁷
• Non-celiac, non-wheat allergy wheat sensitivity (NZNWWS), also known as non-celiac gluten sensitivity (NCGS) or non-celiac wheat sensitivity (NZWS)^128129130
  • not detectable by immunological methods
  • Possible symptoms
    • intestinal
      • Flatulence
      • Flatulence
      • Abdominal pain
    • Headaches
    • Fatigue
    • Depression
    • Attention Disorders
    • Skin problems
    • Respiratory problems
    • Throat problems
    • Eye problems
  • Possible triggers
    • Gluten (even if you don’t have celiac disease)
    • fermentable oligo-, di-, and monosaccharides
    • Polyols (FODMAPs)
    • Exorphins
    • Wheat germ agglutinin
    • Amylase-trypsin inhibitors
  • A gluten-free diet improves symptoms

Gluten may be a contributing factor in ADHD, but it is not “the” cause of ADHD.

Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 2.4% reported gluten intolerance, compared to 1.6% of those without ADHD (+50%).³⁵ A small study found an increased prevalence of ADHD of 16% among individuals with celiac disease.¹³¹ Another small study of 67 children with ADHD found that 10 of them had gluten intolerance.¹³² A gluten-free diet improved ADHD symptoms in these children.
Reviews confirmed a correlation between celiac disease and ADHD.¹³³¹³⁴

A study found a 16% prevalence of ADHD among children with celiac disease, which is more than twice as high as would be expected in children without celiac disease.¹³⁵A link was reported between ADHD symptoms and a non-gluten-free diet in children with celiac disease.¹³⁶

One study found no correlation between celiac disease and ADHD,¹³⁷ while another found no genetic association.¹³⁸

A large-scale study found a prevalence of ADHD of 1.4% among children with celiac disease and, overall, a lower prevalence of mental disorders.¹³⁹

There is evidence that the risk of serious mental disorders increases approximately fourfold in people with celiac disease.¹⁴⁰ A study of a branded product for ASD found that a gluten- and casein-free diet reduced ASD-associated gastrointestinal symptoms and improved antisocial behavior.¹⁴¹ Both gluten-free and ketogenic diets can affect the gut microbiome.¹⁴²

A very small pilot study involving N = 6 children with ADHD who did not have serum markers for celiac disease and who followed a gluten-free diet for 4 months reported a significant reduction in digestive symptoms and headaches in all participants. ADHD symptoms improved in 3 of the children. CPT-II scores did not change significantly.¹⁴³
Celiac disease appears to be associated with reduced levels of dopamine, norepinephrine, and serotonin in the cerebrospinal fluid.^144145146

29. Psychogenic and Functional Respiratory Disorders (PFBD)¶

A study found that among people with PBFD, 17.3% had ADHD, 15.4% had tic disorders, 15.4% had specific phobias, 11.5% had a somatic symptom disorder, and 51.9% exhibited clinical features of tic disorders.¹⁴⁷

30. Iron-Deficiency Anemia¶

A study found that genetic variants associated with iron-deficiency anemia (a blood disorder) may causally increase the risk of ADHD.²⁹

31. Raynaud’s Syndrome¶

Raynaud’s syndrome is a circulatory disorder affecting the extremities. The fingertips turn pale or even blue and become cold due to spasmodic constriction of the blood vessels.
Raynaud’s syndrome is a common comorbidity among people with ADHD. ADHD medications can trigger or worsen Raynaud’s syndrome.¹⁴⁸ We are aware of cases in which Raynaud’s was triggered by caffeine consumption while taking ADHD medication and resolved after caffeine was eliminated from the diet.
Raynaud’s syndrome is treated, among other things, with alpha-1-adrenoceptor antagonists, such as prazosin or tamsulosin (which is highly selective for prostate alpha-1-adrenoceptors).

As we understand it, the ADHD-I issues of decision-making problems and daydreaming stem from overly frequent deactivation of the PFC. Dietrich refers to this as “posteriorization of behavioral control”¹⁴⁹. These PFC shutdowns are triggered by excessive norepinephrine and cortisol stress responses at alpha-1 adrenoceptors, which are characteristic of the heightened endocrine stress response seen in ADHD-I.
This raises, first, the question of whether Raynaud’s symptoms occur more frequently in ADHD-I than in ADHD-HI.

We recall at least one person with ADHD-I who suffered significantly from Raynaud’s phenomenon and high blood pressure, which were exacerbated by MPH but were less pronounced while taking Vyvanse.

32. Hyperthyroidism¶

Other synonyms include hyperthyroidism, hyperthyroidism, and thyroid hormone toxicity.

Among military personnel with hyperthyroidism, the likelihood of ADHD was 70% higher.¹⁵⁰ 68.3% of people with ADHD had first been diagnosed with ADHD and only later received a diagnosis of hyperthyroidism.
Another study found that people with ADHD had a 2.53-fold increased risk (OR) of autoimmune disorders of the thyroid hormone system.⁶⁸

33. Endometriosis¶

Women with endometriosis had a twofold increased risk (OR 1.98) of ADHD compared with their sisters without endometriosis.¹⁵¹

34. Polyarthritis (rheumatoid arthritis)¶

A study found that genetic variants associated with polyarthritis may causally increase the risk of ADHD.²⁹

Of 1,608 adolescents, 5.5% had been diagnosed with ADHD. Among them, 1.3% reported having rheumatic diseases, compared with 1.1% of those without ADHD (+18.2%).³⁵

35. Colitis¶

A study found that people with ADHD had a 2.31-fold increased risk (OR) of ulcerative colitis.⁶⁸

In this context, we find it interesting that colitis is often associated with significantly elevated adenosine levels.⁶⁹ Adenosine inhibits dopamine, particularly in the striatum and other brain regions relevant to ADHD. In this respect, it would be conceivable—at least in theory—that colitis could also cause ADHD symptoms through elevated adenosine levels. Learn more about adenosine at ⇒ Adenosine In the chapter Neurological Aspects.

Furthermore, colitis is associated with hypoxia. Hypoxia, in turn, correlates with inflammation, which in turn correlates with ADHD.¹⁵²

36. Ankylosing Spondylitis¶

A study found that people with ADHD have a 2.78-fold increased risk (OR) of ankylosing spondylitis / Bechterew’s disease.⁶⁸

In this context, we find it interesting that ankylosing spondylitis is often associated with a marked increase in the expression of A2A and A3 adenosine receptors in lymphocytes.⁷⁰

37. Ehlers-Danlos Syndrome (EDS)¶

Ehlers-Danlos syndrome is a group of rare connective tissue disorders characterized by, among other things, hyperelastic skin, joints, and ligaments.
Many people with EDS suffer from psychiatric comorbidities:¹⁵³

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

The increased prevalence of ADHD in cases of hypermobility is also discussed elsewhere.¹⁵⁴

The following presentation is based primarily on Hamonet (2019).¹⁵⁵¹⁵⁶

EDS is hereditary and is passed on to all children, even if only one parent is affected.
EDS affects both genders, although women often experience more severe symptoms.
The diagnosis is based on several characteristic features and can be confirmed by electron microscopy.

Diagnostic symptoms:

The presence of 5 of the 8 diagnostic symptoms listed is said to indicate Ehlers-Danlos syndrome with a sensitivity of 99.7%. Unfortunately, we were unable to locate the 3 publications cited by Hamonet in this regard.¹⁵⁵

• Chronic Pain
  • all over the body, including
    • Gums
    • Esophagus
    • Vagina
    • testicles
  • often stubbornly resistant to treatment
  • very versatile
  • acute flare-ups triggered by physical activity, hormonal factors, or the weather
• Exhaustion / Fatigue
  • often as early as the morning
  • can get stronger at any time of day
• motor disorders
  • Blunders
  • Collisions with obstacles
  • Dropping objects
  • Falls
• Joint Instability
  • Sprains
  • Dislocations
  • Subluxations (“cracking” sounds in the joints)
• Thin Skin
  • feels soft to the touch
  • transparent
    • Veins visible on the back and above the breasts
  • fragile
    • Injuries and frequent scrapes
  • heals poorly
    • long recovery time
    • very visible scars
  • Electric shocks upon contact with metal objects due to a loss of protection against static electricity
  • Stretch marks
    • often develop early
    • are diffuse
    • comprehensive
  • Skin is elastic
    • a length equal to half the length that the thumb can pinch (Ehlers)
    • Elasticity is not apparent in cases of hypersensitivity or tissue edema
    • particularly affected:
      • Cheeks
      • upper eyelids
      • Neck
      • Elbow
    • Forearm
      • Back of the hand
      • Stomach
      • Top of the foot
  • Flexible cartilage
    • Ears (sometimes “protruding”)
    • Nose
• Joint hypermobility
  • due to loose ligaments
  • Shoulders
  • Hips
  • lower end of the cubit
  • may decrease with age
  • Joint hypermobility is not a definitive symptom
    • Movement in the elbows, knees, ankles, and soles of the feet may be restricted due to muscle contractions
    • especially with young children
    • difficult to diagnose in cases of joint pain
  • Joint MRIs are often negative, even in cases of severe clinical symptoms
• Diffuse hemorrhages
  • cutaneous (small areas of bleeding into the skin, ecchymoses)
  • even with minimal trauma
  • often goes unnoticed
    • genital
    • Gums when brushing your teeth
    • nasal
    • urinal
    • rectal (often caused by hemorrhoids).
• Increased sensitivity
  • Acoustic hypersensitivity (hyperacusis)
    if applicable, also:
  • Balance (Dizziness)
  • Sense of smell (hyperosmia)
  • Skin (sensitivity to clothing tags, rough fabrics)
  • Photophobia
    • Sensitivity to light
    • Glare from car headlights
• Reflux (heartburn)

Other symptoms¹⁵⁵, provided they are not related to ADHD:

• Scoliosis
  • quite often
  • moderate (10 to 15 degrees)
  • rarely progressive
  • not painful
• Intervertebral discs
  • reduced due to their laxity in height
  • easily confused with herniated discs
• Dystonia (a disorder of unconscious “automatic” motor control)
  • very common
  • often misdiagnosed as epilepsy, spasmophilia, or hysteria
  • involuntary muscle contractions that cause twitching movements
  • Fasciculations
    • Face (eye area), thigh muscles, forearms
    • visible spontaneous muscle contractions
    • recognizable as a tremor
    • without displacement of the facial features
  • Tremors at rest or during movement
  • alternating, repetitive movements
  • sudden relaxation of specific areas
• Dysautonomia
  • proprioceptive disorder (regulatory disorder caused by the sympathetic nervous system)
  • Temperature control
    • vasomotor disorders
    • Cold extremities, feet, nose, ears, hands
      • easily confused with Raynaud’s syndrome
    • Sweating
    • Chills
    • unexplained fever
    • Hot flashes
    • Vasodilation (dilated blood vessels)
      • on the extremities, face
      • accompanied by pain and localized swelling
  • Impaired secretion
    • Nose, cheek, throat, larynx, bronchi
    • Dryness or hypersecretion is possible
  • Problems with the “internal organs” (arteries, veins, lymphatic vessels, gastrointestinal tract, ureterovesicophincteric system, pharyngolaryngotracheobronchial motility)
    • due to proprioceptive dysfunction
• cardiovascular
  • Tachycardias
    • often lead to painful and distressing heart palpitations
  • additional systoles
    • often cause precordial pain
  • Unstable blood pressure
    • usually low, with hypotension
    • Blood pressure spikes (which are easily confused with high blood pressure)
    • Postural Orthostatic Syndrome (POTS)
      • Discomfort and very weak legs when standing or getting up
      • Falls
      • Loss of consciousness
  • Arterial aneurysms
  • Venous insufficiency
  • Valve regurgitation often causes no symptoms on an echocardiogram
  • Heart failure is very rare
• Digestive problems
  • Ingestion
  • Dysphagia
  • Belching
  • retrosternal burning (behind the sternum, in the center of the chest) when swallowing
  • Flatulence
  • Constipation, diarrhea, or both
  • Anal incontinence
  • Gastroesophageal reflux
  • Endoscopic examination is contraindicated
    • due to the increased risk of serious complications (bleeding and/or perforation)
    • due to the increased vulnerability of the mucous membrane in the digestive tract
  • Gallbladder stones are common due to increased distension and reduced contractility of the gallbladder
• Respiratory symptoms
  • Shortness of breath during exertion (climbing stairs) in more than 80% of people with ADHD
    • Hyperventilation syndrome caused by low blood CO2 levels
    • Blockages caused by pain-induced restriction of diaphragmatic inspiration due to dysfunctional rib movements resulting from weak connective tissue
      • easily mistaken for an asthma attack
      • The bony-cartilaginous lower end of the sternum (xiphoid process) is often very painful (“Ehlers’ point”)
  • Bronchial irritation, especially in children
  • Bronchial infections of the upper respiratory tract
  • Lack of oxygen (hypoxia) in the brain and muscles
    • In our view, hypoxia could be the underlying cause of ADHD, which is often comorbid with other conditions
    • Blood oxygen levels rarely change, even during 6-minute tests
    • Oxygen therapy alleviates migraines, fatigue, sleep and cognitive disorders, and dystonia
    • Frequent pauses in breathing (including during sleep; sleep apnea)
• mouth area
  • Teeth
    • Poor-quality teeth with inclusions, crowding, fragility, and hypermobility
    • Difficulty with dental prostheses
  • Gums
    • sensitive and painful
    • Bleeding
  • Tongue
    • Hyperlax
    • can twist on its own
    • may occasionally reach the tip of the nose (Görlin’s sign)
  • Jaw
    • temporary temporomandibular joint pain
    • Subluxations or dislocations
    • Bruxism with tooth wear
  • Palate
    • pointed arch
• Urogenital region
  • Bladder problems
  • Sphincter problems
  • Childhood
    • Toilet training is often delayed
  • Adults
    • Decreased urge to urinate
      • Catheterization is sometimes necessary
    • Frequent urge to urinate
      • sometimes accompanied by incontinence (leakage)
    • Frequent burning
      • easy to confuse with infections
    • Perineal insufficiency with prolapse
      • especially after pregnancy.
• Sexual and reproductive health issues
  • Women
    • Dyspareunia (sexual dysfunction)
      • usually a burning or cramping pain in the genital area during sexual intercourse
      • almost always failing to reach orgasm
      • in 50% of people with EDS
      • Xylocaine topical gel is helpful
    • Menstruation
      • profuse and very painful
    • Birth
      • Difficult birth
        • Frequent uterine contractions without spontaneous dilation of the cervix
        • PDAs are sometimes ineffective and require precise dosing
        • Frequent bleeding
        • Cesarean sections should be avoided
  • Men
    • Pain during an erection or ejaculation
    • Testicular ectopia
• Cysts, nodules
  • in joints, breasts, the thyroid gland, the liver, the pancreas, intracranially, in the mastoid, etc.)
  • often disappear on their own
  • do not degenerate
  • Enlargement of the ganglia without any direct consequences
• Endocrine symptoms
  • Thyroid gland
  • Adrenal glands
  • Salivary and lacrimal glands
• Mast Cell Activation Syndrome
  • Frequent evidence
    • superficial and deep urticaria
    • Flush
    • nonspecific rash, especially after a shower
    • Pruritus
  • Factors
    • increased stress
    • Trauma, including surgical trauma (primarily orthopedic surgery)
    • climatic factors (damp cold)
    • hormonal factors (pregnancy, childbirth)
    • Restriction of physical activity and immobilization of a joint.
• Anemia
• Iron deficiency
  • in most hemorrhagic forms
• Platelet counts may be low.
• Electromyograms are normal
• Speech disorders
  • 63.2% of people with Ehlers-Danlos syndrome have speech disorders¹⁵³

Other Ehlers-Danlos symptoms¹⁵⁵ that are also ADHD symptoms or frequently occur in people with ADHD:

• ADHD
  • 52.4% of people with Ehlers-Danlos syndrome have ADHD¹⁵³
    The following characteristics are classic ADHD symptoms and, in our opinion, are likely caused by hypoxia.
• Cognitive disorders
  • Impaired working memory
    • Impaired executive functions
      • Organization
      • Managing daily life
      • Order of priority for individual steps in multi-step tasks
• Attention Disorders
  • A wealth of ideas
  • sudden changes in topic
  • from one thing to the next
  • Multitasking
  • increased creativity
• Difficulty concentrating
  • Difficulty maintaining concentration
  • Difficulties with spatial orientation
• intellectual capacity remains unaffected
• social problems
  • The result of a normal brain being confronted with a body that sends messages that are difficult to interpret
  • Withdrawal into oneself
• Dysorthography, dyspraxia, dyslexia
• Highly emotional
  • a deep understanding of others
  • a deep sense of empathy for the suffering of others
• Food Intake / Metabolism
  • Food intolerances (lactose, gluten…)
  • Drug intolerance
  • Appetite disorders
  • Being overweight is common
• Vision problems are very common
  • In our view, visual disturbances could be a consequence of hypoxia, which we also suspect is the cause of ADHD, a condition that is often comorbid
  • Lesions of the retina or cornea (rare)
  • Photophobia
    • Sensitivity to light
    • Glare from car headlights
  • Binocular vision problems are very common
    • Synchronized motor control of the eyes and coordination of the eyes with head movements is difficult
• Learning Disabilities
  • 42.4% of people with Ehlers-Danlos syndrome have learning disabilities¹⁵³
• Sleep Disorders
  • Difficulty falling asleep and staying asleep is very common (as it is with ADHD)
  • Hypersomnia is rare
  • sometimes reinforced by
    • severe pain at night
    • Muscle twitching (“restless legs”)
    • Contractures as a painful manifestation of dystonia
  • Frequent nightmares
  • Sleepwalking, especially in children
• Anxiety
  • 51.2% of people with ADHD experience anxiety¹⁵³
  • Anxiety is a common comorbidity of ADHD
• Depression
  • 30.2% of people with ADHD experience depression¹⁵³
  • Depression is a common comorbidity of ADHD
• Vitamin D deficiency
  • is also common in ADHD
• Main Symptoms of Ehlers-Danlos Syndrome
  Of the main diagnostic symptoms of Ehlers-Danlos syndrome mentioned above, the following are correlated with ADHD:
  • chronic pain
    • significantly higher prevalence in SADHS
    • especially the shoulder and neck area
  • motor disorders
    • Blunders
    • Collisions with obstacles
    • Dropping objects
    • Falls
  • increased sensitivity
    • in ADHD, it is not limited to hyperacusis
  • Reflux
    • 7 times higher in people with ADHD compared to those without the condition

We are considering the possibility that the cause of ADHD symptoms could be hypoxia resulting from Ehlers-Danlos syndrome. Vision problems are also more common in cases of hypoxia.

38. Ornithine transcarbamylase deficiency¶

Ornithine transcarbamylase deficiency (¹⁵⁷ ) occurs in approximately 1 in 30,000 people and is caused by a genetic defect in the OTC gene. There are also gene mutations that result in residual enzyme activity, so these may not be diagnosed immediately. People with ADHD develop typical neuropsychological complications such as¹⁵⁸

• Developmental delay
• Learning disability
• intellectual disability
• Attention-Deficit/Hyperactivity Disorder
• Deficits in executive function

39. CYP2C19 ultra-metabolizers¶

One study found no association between different metabolic gene variants of CYP2D6 or CYP2C19 and response to medication (stimulants) in ADHD; but did find an increased proportion of CYP2C19 ultra-metabolizers among people with ADHD.¹⁵⁹
CYP2C19*e 17 is present in approximately 20% of the Caucasian population and is associated with increased metabolism.
In addition to various medications, CYP2C19 metabolizes:^160161162

• Arachidonic acid (a quadruple-unsaturated omega-6 fatty acid) to epoxy eicosatrienoic acids (EETs)
• Linoleic acid (an essential, polyunsaturated omega-6 fatty acid) to 9,10-epoxy-octadecenoic acid (other names: vernolic acid, linoleic acid 9:10 oxide, leukotoxin) and 12,13-epoxyoctadecenoic acid (other names: coronary acid, linoleic acid 12,13-oxide, isoleukotoxin)
• Docosahexaenoic acid (DHA, which accounts for 95% of omega-3 fatty acids) to epoxydocosapentaenoic acids (EDPs)
• Eicosapentaenoic acid (a polyunsaturated omega-3 fatty acid) to epoxyeicosatetraenoic acids (EEQs)

40. Alopecia areata (hair loss)¶

Alopecia areata (hair loss) was associated with a 3.03-fold increased risk of ADHD.¹⁶³

41. Lipedema¶

A study reports that ADHD is 42% more common in women with lipedema than in women without lipedema.¹⁶⁴¹⁶⁵

42. Hidradenitis suppurativa¶

Other names: Acne inversa, Acne inversa, Acne triad, Acne tetrad, Verneuil’s disease, Pyodermia fistulans sinifica¹⁶⁶

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition associated with psychiatric comorbidities.
Among 52,909 Danish blood donors, 1.9% were found to have hidradenitis suppurativa. Of these, 7.4% exhibited ADHD symptoms, compared with 3.5% of participants without hidradenitis suppurativa. After adjusting for confounding factors, the risk of ADHD was 85% higher.¹⁶⁷

43. Hearing Loss¶

The prevalence of ADHD among children with (partial or complete) hearing loss—at 12.1%—was significantly higher than in the control group (3.6%).¹⁶⁸

44. Albinism¶

Albinism is associated with a genetic defect in melanin production. One study reported a prevalence of ADHD of 21.8% among children with albinism.¹⁶⁹

45. Herpes simplex¶

An analysis of the German KIGGS study found an approximately 48% increased risk (Exp(β) = 1.48).⁵⁶ Exp(β) corresponds to the OR.⁵⁷

46. Neuromuscular Dysregulation¶

ADHD was associated with a 15% increased risk of neuromuscular dysregulation (including muscular dystrophy). This was not the case for mood disorders, anxiety disorders, or personality disorders.¹⁷⁰

47. Increased intima-media thickness of the carotid artery wall (CIMT)¶

Carotid intima-media thickness (the thickness of the two inner layers of the carotid artery—the intima and media; carotid intima-media thickness, IMT) is used to diagnose the extent of atherosclerotic vascular disease in the carotid artery.
In cases of ADHD, there was evidence of increased CIMT.¹⁷¹

48. Sever’s disease (calcaneal apophysitis)¶

Sever’s disease (calcaneal apophysitis, Morbus Sever) is an inflammation of the growth plate (apophysis) in the heel bone (calcaneus) that causes pain when weight is placed on the heel.
Sever’s disease is an inflammation of the growth plate (apophysis) on the heel bone (calcaneus), often caused by overuse or repetitive stress, particularly in physically active children between the ages of 8 and 15, since the growth plate of the heel bone is still open during this period.

Eighty-eight children with Sever’s disease (including 57 boys) and 90 controls were screened for ADHD using the DSM-IV. The prevalence of ADHD in the Sever’s disease cohort was 70.5%, compared with 13.3% in the control group. A large number of the patients diagnosed with ADHD among the Morbus Sever patients did not participate in sports.¹⁷²

49. Urinary Stones in Children¶

A study reports a high incidence of urinary stones (urolithiasis, mineral deposits [stones] in the urinary tract) among children with ADHD who were receiving medication and lived in a food desert.¹⁷³ A “food desert” refers to areas where access to fresh fruits and vegetables is limited. In the U.S., 39 million people live in food deserts, particularly in low-income areas and in states with a strong agricultural sector.

50. Sturge-Weber Syndrome¶

Sturge-Weber syndrome results from a somatic mutation in the GNAQ gene during early development. This mutation occurs spontaneously. Since it does not affect germ cells, it is not hereditary.
The prevalence is 1 in 20,000 to 1 in 50,000 among live births.
Symptoms include red discoloration of the skin on the face, which also affects the eyelids.
Sturge-Weber syndrome is associated with an increased incidence of

• Epilepsy
• Brain atrophy, accompanied by developmental delays ranging up to cognitive impairment as a result of cerebral circulatory disorders caused by calcification of the angiomas
• migraine-like headaches.
• Hemiparesis (paralysis on one side of the body) with a risk of underdevelopment or stunted growth (hypotrophy) of the affected limb(s).
• Eye diseases (e.g., glaucoma)
• Neurologically caused visual field defects
• Anxiety¹⁷⁴
• ASS¹⁷⁴
• psychotic symptoms¹⁷⁴
• ADHD¹⁷⁴

51. Vocal cord nodules¶

Children with vocal cord nodules exhibited more behavioral problems and were more likely to have ADHD.¹⁷⁵

52. Headaches¶

ADHD is associated with an increased risk of headaches:

• 1.58-fold increased risk across all studies (systematic review, k = 8 meta-analyses, n = 4,480, N = 19,419)⁴⁴
• 2.43-fold increased risk when limited to gold-standard studies (review, k = 1 meta-analysis, n = 139, N = 1,308)⁴⁴