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Somatic comorbidities in ADHD

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Somatic comorbidities in ADHD

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

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

The percentages in the headings indicate the frequency of comorbidity in ADHD. Example: 48% of ADHD sufferers have musculoskeletal disorders, compared to 21.6% of non-ADHD sufferers.

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

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

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

One study found that gene variants that correlate with neck or shoulder pain may causally increase ADHD risk.3
A meta-study found an ADHD prevalence of 15% to 25% in children with chronic pain (excluding headaches), a 2 to 5-fold increase.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 decreased pain perception in adolescents with ADHD, which disappeared with stimulant treatment.4

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

3. Musculoskeletal disorders - 48 % (vs. 21.6 %)

  • In adult ADHD sufferers: 48.4 %5
  • For non-affected persons: 21.6 %5
    = 2 times the risk

One study found that gene variants correlating with synovitis (inflammation of the synovial membrane) and tenosynovitis (tendonitis) may causally increase ADHD risk. Conversely, ADHD gene variants appear to increase the risk of carpal tunnel syndrome.3

4. Allergies - 45% (vs. 18%)

Allergies are more common in ADHD than in non-affected individuals.6
Among 100 children with ADHD (average age 9 years), one study found allergy in 35%. Of the comorbidly affected, 43% had hay allergy, 37.5% had various pollen allergies, 25% had combined allergic rhinitis and bronchial asthma, 8% had urticaria, and 2% had asthma. Interestingly, allergies were found only in ADHD-C, but not in the ADHD-HI or ADHD-I subtype. In addition, boys with ADHD were significantly more likely to have comorbid allergy than girls. Allergies correlated with increased ADHD symptom severity. Allergies presented at an average age of 4 years, ADHD at an average age of 6 years. Among ADHD sufferers, 16% showed a positive skin prick test compared with 5% of controls. A high total IgE was found in 45% of ADHD sufferers and 18% non-affected7
A Chinese study of 23,791 school children found that 26.1% of children with ADHD had allergies, compared with 15.2% of children without ADHD2
One study found a 3.22 to 3.87 -fold risk of allergies in Japanese children with developmental disabilities.8

Allergies are usually a consequence of excessive cortisol levels. Cortisol inhibits the inflammatory cytokines triggered by CRH (first stage of the HPA axis) and instead promotes other immune defense mechanisms 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 actually not really dangerous - an allergy.
For more details on the immunological effect of cortisol, see ⇒ Adrenal cortex (3rd stage)

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

5. Premature ejaculation (41.6% vs. 5%)

A study of 48 individuals with lifelong premature ejaculation and 40 individuals without the disorder also found ADHD in 41.6 of those affected and 5% of those not affected.9
Of those with premature ejaculation and ADHD, 2/3 were of the ADHD-HI subtype with predominant hyperactivity/impulsivity, otherwise found in only 8.3% of ADHD sufferers.

6. Gastrointestinal disorders - 41.1% (vs. 21.6%)

  • In adult ADHD sufferers: 41.1 %10
  • For non-affected persons: 21.6 %5
    = 2 times the risk

7. Diseases of the upper respiratory tract

7.1. Upper respiratory diseases in children - 40% (vs. 33.4%)

  • In ADHD-affected children: 40.1 %10
  • For non-affected persons: 33.4 %10
    = 1.3 times the risk

7.2. Upper respiratory diseases in adults - 33.7% (vs. 15.2%)

  • In adult ADHD sufferers: 33.7 %10
  • For non-affected persons: 15.2 %5
    = 2 times the risk

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

8. Metabolic disorders - 36.2 % (vs. 19 %)

  • Among adults with ADHD: 36.511
  • For non-affected persons: 19.0 %10
    = 2 times the risk

9. Skin diseases, neurodermatitis, eczema, lichen - 32,4 % (vs. 10 to 25,5 %)

  • In children with ADHD: 32.4%10
  • In unaffected individuals: 25.5%10; 10-20% in children, 2-3% in adults, with higher incidence in urban environments12
    = about 1.5 times the risk in children12 which is supposed to explain 9% of all ADHD cases.
  • ADHD sufferers have an above-average incidence of atopic dermatitis (= atopic eczema)13 A study found a 5.06-fold risk of atopic dermatitis in Japanese children with ADHD.8
  • Conversely, atopic dermatitis sufferers are at increased risk for mental health disorders such as ADHD 14 15 16 1718
    • A study of Indian children with atopic dermatitis found rates of19
      • 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 indicated a co-occurrence and a temporal co-emergence in affected individuals12
  • Atopic immune disorders could be due to an exaggerated immune response due to lowered cortisol levels. Cortisol inhibits the inflammation initially promoted by CRH (first stage of the HPA axis) by means of inflammatory cytokines. If cortisol release (third stage of the HPA axis) is too low, inflammation is not sufficiently inhibited.20
  • Those affected by lichen showed mental disorders in 90%, compared to 20% of non-affected individuals. Lichen sufferers had an ADHD prevalence of 36.6%.21
  • In a mouse model of atopic dermatitis, one study found chronically increased HPA axis function and dopamine and norepinephrine changes in locus coeruleus, PFC, and striatum typical of ADHD. In addition, melatonin was decreased12
    • The finding may confirm our view that chronic stress mediates its symptoms in the same way as ADHD, namely through decreased levels of dopamine and norepinephrine in the aforementioned brain areas.

For more details on the immunological effect of cortisol, see ⇒ Adrenal cortex (3rd stage)

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

One study found increased risks in ADHD sufferers for:22

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

We further find it interesting that inflammation is often accompanied by highly elevated levels of adenosine.23 At the same time, A2A and A3 receptors are overexpressed in lymphocytes in chronic autoimmune rheumatic diseases. A2A and A3 agonists inhibited NF-κB activation, release of typical proinflammatory cytokines, and levels of metalloproteinases involved in inflammatory responses in chronic autoimmune rheumatic diseases.24 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 inflammation could also cause ADHD symptoms through elevated levels of adenosine. For more on adenosine, see ⇒ Adenosine In the chapter Neurological Aspects.

10. Infectious diseases - 31.2 % (vs. 25.9 %)

  • In children with ADHD: 31.2 %10
  • For non-affected persons: 25.9 %5
    = 1.3 times the risk

11. Ear diseases - 31.1 % (vs. 23.7 %)

  • In children with ADHD: 31.1 %10
  • For non-affected persons: 23.7 %10
    = 1.7 times the risk

A Chinese study of 23,791 school children found that 6.7% of children with ADHD had had otitis media, compared with 3.8% of children without ADHD2
Since past presence is likely to have been queried, this is less of a comorbidity and more of a risk factor.

12. Obesity - D: 22.1% (vs. 10.2%); U.S.: 41.4% (vs. 21.6%)

The doubling of the prevalence of obesity in ADHD sufferers has occurred (albeit at extremely different starting levels) in the USA from 21.6% without ADHD to 41.4% with ADHD25 as has occurred in Germany from 10.2% without ADHD to 22.1% with ADHD.26
An Israeli cohort study found obesity to be almost twice as common in adolescents with severe ADHD as in those not affected, at 13.5%, and about 30% more common in those with mild ADHD-HI than in those not affected.27

A Chinese study of 23,791 school children found that 32.6% of children with ADHD had overweight or obesity, compared with 29.6% of children without ADHD.2 For overweight, 15.9% were cited, and for obesity, 11.9% were cited, but not separated by ADHD status. Since the figures for obesity were not given separately, they are not comparable.

According to Winkler, 30% to 60% of all severe obesity cases are linked to ADHD.28

Among adult psychiatric clinical patients with ADHD, the prevalence of obesity is 24.5% and of other eating disorders is 11.2%29 Other sources do not cite percentages in accessible abstracts.30

ADHD treatment of ADHD sufferers with obesity resulted in a weight loss of over 12.3%, while the control group of non-ADHD obese patients experienced a weight gain of 2.8%.31

Winkler reports that in pure obesity treatment, a weight gain of less than 5% is already considered a success,32 so that a weight loss of more than 12% seems downright sensational.

Read more at -&gt ADHD, overweight and eating disorders In the chapter Treatment / Comorbidities.

13. Tonsillar or adenoid hypertrophy / enlarged tonsils or adenoids - 20.0% (vs. 11.1%)

A Chinese study of 23,791 school children found that 20.0% of children with ADHD had enlarged tonsils or adenoids, compared with 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.

14. Asthma - 16.2% (vs. 9.7%)

In ADHD sufferers, a cohort study found asthma in 16.2%, compared with 9.7% in nonaffected individuals.33 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 from asthma and a 10% increased risk of asthma from ADHD.34
In another study, children with asthma had a 70% increased risk of concomitant ADHD. The risk of ODD was also increased (360%), but not the risk of CD.35 Another study found ADHD in 11.3% of asthma sufferers36
There appears to be genetic overlap between ADHD (and major depression) with asthma.3733
One study found increased risks in ADHD sufferers for:22

  • 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 levels. Japanese children with ADHD had a 3.72-fold risk of bronchial asthma and a 5.06-fold risk of atopic dermatitis.8

It seems interesting to us that asthma and inflammatory diseases are often associated with highly elevated levels of adenosine.2338 At the same time, A2A and A3 receptors are overexpressed in lymphocytes in chronic autoimmune rheumatic diseases. A2A and A3 agonists inhibited NF-κB activation, release of typical proinflammatory cytokines, and levels of metalloproteinases involved in inflammatory responses in chronic autoimmune rheumatic diseases.24 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 asthma and inflammatory diseases could also cause ADHD symptoms through elevated levels of adenosine. For more on adenosine, see ⇒ Adenosine In the Neurological Aspects chapter.
In conclusion, successful treatment of allergic rhinitis in children significantly reduces their ADHD symptoms, but not those of children with non-allergic rhinitis.39

15. Underweight, etc. - in China: 19.9% (vs. 14.3%)

A Chinese study of 23,791 school children found:2

  • Stunting (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

16. Injuries 19 % (vs. 13.7 %)

A cohort study found injuries in 19% of ADHD sufferers (across the age range) and in 22.7% of ADHD sufferers with other mental health comorbidities, compared with 13.7% in the control group. The risk of injury was thus increased by 33% in pure ADHD.
The number of comorbid mental illnesses correlated with increased risk of injury in ADHD patients. The risk of injury was most elevated in ADHD patients with comorbid schizophrenia, followed by bipolar disorder and obsessive-compulsive disorder. Comorbid ASD decreased the risk of injury.40

17. Celiac disease (gluten intolerance)

One study found an increased ADHD prevalence of 16%,41 a review confirmed a correlation of celiac disease and ADHD.42
A larger study found a 1.4% prevalence of ADHD and an overall reduced prevalence of mental disorders in children with celiac disease43
A study reports an association between ADHD symptoms and non-gluten-free diet in children with celiac disease.44

Celiac disease appears to correlate with decreased levels of dopamine, norepinephrine, and serotonin in brain CSF.454647

18. Diabetes

It seems interesting to us that diabetes is often associated with highly elevated levels of adenosine.23 Adenosine inhibits dopamine, especially in the striatum and other brain regions relevant for ADHD. In this respect, it would be at least theoretically conceivable that diabetes could also cause ADHD symptoms through elevated levels of adenosine. For more on adenosine, see ⇒ Adenosine In the chapter Neurological Aspects.

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

Among adolescents with diabetes 1, the rate of ADHD is increased. One study found ADHD in 12% of adolescents with type 1 diabetes mellitus.48 One review reported a 35% increased risk of ADHD49

The global prevalence of type 1 diabetes is 9.5%.50

18.2. Type 2 diabetes - 3.9% (vs. 1.62%)

Type 2 diabetes was found in 3.90% (males: 4.32%; females: 3.58%) of adult ADHD sufferers compared with 1.62% (males: 1.96%; females: 1.28%) of nonaffected individuals, according to a large Swedish cohort study.51 Another large registry study found a 2.29-fold risk of type 2 diabetes in ADHD sufferers.52

One study found that gene variants correlated with diabetes 2 may causally increase ADHD risk.3 A gene 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%)53

19. Premature birth suffered - 8.7% (vs. 5.5%)

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

20. Hypertension - 8.5% (vs. 4.5%)

Hypertension was found in 8.51% (males: 9.57%, females: 7.39%) of adult ADHD sufferers versus 4.48% (males: 4.98%, females: 3.98%) of nonaffected individuals, according to a large Swedish cohort study.51

21. Gastroesophageal reflux - 4.3% (vs. 0.6%)

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

22. Visual disturbances - up to 2.4% (vs. 1.3%)

One large study found that children with ADHD-HI have significantly higher prevalences of eye disorders:54

  • Farsightedness, hypermetropia (2.4% in ADHD, 1.3% in unaffected, OR 1.82)
  • Low vision, amblyopia (1.6% in ADHD, 0.9% in unaffected, OR 1.89)
  • Manifest strabismus, heterotropia (1.1% in ADHD, 0.5% in unaffected, OR 2.01)
  • Corneal curvature, astigmatism (0.2% in ADHD, 0.1% in unaffected, OR 1.73)+

One study indicates an increased problem due to decreased ocular fluid in ADHD. This also existed when taking MPH.55

23. Psychogenic and Functional Breathing Disorders (PFBD)

Among children affected by PBFD, one study found ADHD in 17.3%, tic disorders in 15.4%, specific phobias in 15.4%, somatic symptom disorder in 11.5%, and 51.9% showed clinical features of tic disorders.56

24. Cerebral palsy / spasticity

Cerebral palsy may be a consequence of encephalitis in which the dopaminergic cells have been destroyed. The result is a severe lack of dopamine. Treatment with L-dopa can help in such cases.
A study of 213 children with cerebral palsy found suspected ADHD in 50%, which was confirmed in 23%.57 This corresponds to a 4.6-fold risk of ADHD in cerebral palsy.

25. Iron Deficiency Anemia

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

26. 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 blood vessels.
Raynaud’s problems are a more common comorbidity in ADHD sufferers.
Raynaud’s disease is treated with alpha-1-adrenoceptor antagonists, e.g., prazosin or tamsulosin (highly selective at prostatic alpha-1-adrenoceptors), among others.
As we understand it, the ADHD-I problems of decision-making problems and daydreaming result from too frequent shutdowns of the PFC. Dietrich calls this posteriorization of behavioral control58. These PFC shutdowns are triggered by excessive noradrenal stress responses and cortisol stress responses at alpha-1 adrenoceptors, typical of the excessive endocrine stress response of ADHD-I.
This raises, first, the question of whether Raynaud’s problems are more common in ADHD-I than in ADHD-HI.

We recall at least one ADHD-I sufferer who suffered significantly from Raynaud’s and hypertension, which was exacerbated by MPH and less evident under Elvanse.

27. Hyperthyroidism / Hyperthyroidism

Other synonyms include hyperthyroidism, hyperthyroidism, thyroid hormone toxicity.

Military personnel with hyperthyroidism were 70% more likely to have ADHD.59 68.3% of those affected had first received their ADHD diagnosis and only later received their diagnosis of hyperthyroidism.
Another study found a 2.53-fold risk (OR) for autoimmune thyroid hormone disorders in ADHD sufferers.22

28. Endometriosis

Women with endometriosis had a doubled risk (OR 1.98) of ADHD than their sisters without endometriosis.60

29. Polyarthritis

One study found that gene variants correlated with polyarthritis may causally increase ADHD risk.3

30. Colitis

One study found a 2.31-fold risk (OR) for ulcerative colitis in ADHD sufferers.61

It seems interesting to us in this context that colitis is often accompanied by strongly elevated adenosine levels.23 Adenosine inhibits dopamine, especially in the striatum and other brain regions relevant for ADHD. In this respect, it would be at least theoretically conceivable that colitis could also cause ADHD symptoms through elevated levels of adenosine. For more on adenosine, see ⇒ Adenosine In the chapter Neurological Aspects.

31. Bekhterev’s disease / ankylosing spondylitis

One study found a 2.78-fold risk (OR) of ankylosing spondylitis / ankylosing spondylitis in ADHD sufferers.61

In this context, it seems interesting to us that ankylosing spondylitis is often associated with strongly increased expression of A2A and A3 adenosine receptors in lymphocytes.24

32. Ehlers-Danlos syndrome (EDS)

Ehlers-Danlos syndrome is a group of rare diseases of the connective tissue, which are associated with overstretchable skin, joints and ligaments.
Of those with EDS, many suffer from psychiatric comorbidities:62

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

33. Ornithine transcarbamylase deficiency

Ornithine transcarbamylase deficiency63 occurs in approximately 1 / 30,000 people and is due to a genetic defect in the OTC gene. Gene mutations with residual enzyme activity also exist, so they may not be diagnosed immediately. Affected individuals develop typical neuropsychological complications such as64

  • Developmental delay
  • Learning Disability
  • mental disability
  • Attention Deficit/Hyperactivity Disorder
  • Deficits in the executive function

34. CYP2C19 ultra-metabolizer

One study found no association between different metabolization gene variants of CYP2D6 or CYP2C19 on drug responsiveness (of stimulants) in ADHD, but an increased rate of CYP2C19 ultra-metabolizers among ADHD sufferers.65

35. Alopecia areata (hair loss)

Alopecia areata (hair loss) correlated with a 3.03-fold risk of ADHD.66

36. Lipedema

One study reports that ADHD is 42% more common in women with lipedema than in women without lipedema.67 However, the study suffers from a strange use of the ASRS.

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