Primary organic disorders

Author: Ulrich Brennecke
Review: Dipl.-Psych. Waldemar Zdero

Sorted by prevalence (frequency of occurrence) in descending order. The prevalence indicates the frequency of the Disorder itself, not the frequency or likelihood of ADHD in the Disorder. For example, the prevalence of deficiency symptoms is quite high, but the influence of their elimination on ADHD symptoms is not significant.

• 1. Post-concussion syndrome (Consequences of a concussion) (11 to 80 %)
• 2. Deficiency symptoms (5 to 30 %)
  • 2.1. Vitamin D3 (30 %)
  • 2.2. Vitamin B12 deficiency (5 % to 30 %)
  • 2.3. Zinc deficiency (11 %)
  • 2.4. Iron deficiency (10 %)
  • 2.5. Other possible deficiency symptoms
• 3. Mild Cognitive Impairment (MCI; 7 to 25 %; ADHD + 250 %)
• 4. Snoring (10 % to 20 %; ADHD + 300 %)
• 5. Migraine (women: 18 %, men 6 %)
• 6. Thyroid problems (cumulative 7 to 14 % in women, 2.75 to 3.5 % in men)
  • 6.1. Hyperthyroidism (women 1 - 2 %, men 0.25 - 0.5 %)
  • 6.2. Underactive thyroid / hypothyroidism (from 60 years approx. 2 %)
  • 6.3. Hashimoto’s thyroiditis (women 4.5 - 9.5 %, men 0.5 - 1 %)
  • 6.4. Thyroid hormone resistance (RTH) / thyroid hormone action defect (THAD)
• 7. Lack of sleep (12.5% in children)
• 8. Restless legs syndrome (children 2 %, adults 5 to 10 %)
• 9. Interrupted breathing during sleep (sleep apnea; 4 % to 9 %)
• 10. Prenatal damage due to alcohol, FAS (0.8 to 8.2 %)
• 11. Allergies (asthma 4% to 8%, food allergies 4%)
• 12. Hydrocephalus (0.4 - 0.8 %; from 65 years 3 %)
• 13. Seizure disorder
  • 13.1. Epilepsy: 0.5 to 1 %
  • 13.2. Status epilepticus during sleep (ESES)
• 14. Histamine intolerance, histamine intolerance (1 %, of which 80 % adults)
• 15. ME/CFS, myalgic encephalomyelitis / chronic fatigue (0.42 % to 0.75 %)
• 16. Prolactinomas (0.02 - 0.05 %)
• 17. Consequences of severe brain infections (cumulative 0.04% to 0.15%)
  • 17.1. Encephalitis (cumulative 0.03 %)
  • 17.2. Bacterial infections (cumulative 0.01% in women, 0.12% in men)
• 18. Turner syndrome (0.04 %; ADHD + 225 %)
• 19. Perinatal hypoxemia (0.001 to 0.009 %)
• 20. Congenital myopathy (0.005 %) and neuropathy (2 % to 8 %)
• 21. Cortisol disorders (cumulative 0.0042 to 0.0048 %)
  • 21.1. Hypocortisolism (adrenal insufficiency) (0.004 %)
  • 21.2. Hypercortisolism (Cushing’s syndrome) (0.0002 to 0.0008 %)
• 22. Moyamoya (0.0001 % to 0.0009 %)
• 23. Hamartoma of the hypothalamus (0.0005 %)
• 24. Visual and hearing impairment
• 25. Lesions of the left cerebral hemisphere / right PFC
• 26. Organic brain damage
• 27. Traumatic or space-occupying cerebral disorders / other psychoorganic syndromes with cerebral damage and/or mental retardation

1. Post-concussion syndrome (Consequences of a concussion) (11 to 80 %)¶

Another name: post-concussion syndrome

Prevalence: probably in 1 / 10 patients with mild traumatic brain injury¹
A concussion is the mildest form of traumatic brain injury. In the USA, an incidence of 1.15 % is assumed for concussion (3.8 million / 331 million). This would put the incidence of postconcussion syndrome at around 0.115% per year.
The prevalence is between 11 and 80 %.²

In uninjured adolescent athletes, ADHD appears to mimic postcommotional syndrome. Persons with ADHD report more symptoms of postconcussion syndrome than non-concussed people.³ The scores of people with ADHD without concussion on the ImPACT (a test that measures evidence of concussion) were significantly worse than those of non-concussed people⁴
One study reported prolonged times to recovery from concussion in ADHD⁵, another found no differences in progression⁶
One study found no clustering of ADHD in 12-/13-year-old athletes with concussion.⁷ Adolescents with ADHD did not have an increased prevalence of diagnosed or unreported concussion.⁸

ADHD was associated with 50% longer concussion recovery in one study.⁹ Other studies found no association between concussion severity or concussion recovery and ADHD.¹⁰¹¹

2. Deficiency symptoms (5 to 30 %)¶

2.1. Vitamin D3 (30 %)¶

Prevalence of D3 deficiency:¹²¹³
* 30.2 % inadequately supplied
* 38.4 % sufficiently supplied
* 31.4 % in need of improvement or oversupplied

• A vitamin D3 deficiency also appears to be very common in ADHD.¹⁴ D3 supplementation is recommended, especially in the fall/winter.

• D3 requires fat for absorption, i.e. ingestion requires that the preparations contain fat or that food is consumed at the same time. A glass of milk should suffice for this.

2.2. Vitamin B12 deficiency (5 % to 30 %)¶

Prevalence of B12 deficiency:¹⁵¹³

• Young adults 5 to 10 %
• Older adults 10 to 30 %

• At an older age, concentration and attention problems due to B12 deficiency are almost phenotypical.
• B12 can be administered more safely by means of injections.
• In the meantime, B12 is also available in tablet form.
• Foods with a potentially high B12 content (spinel algae), on the other hand, cannot be dosed reliably enough.

2.3. Zinc deficiency (11 %)¶

Zinc deficiency can exacerbate symptoms of existing ADHD.¹⁶

• Prevalence of zinc deficiency:
  • Population-wide
    • Europe: 11 %¹³
  • Healthy children from 1 to 3 years:
    • Western Europe: 31.3 %¹⁷
  • in children under five years of age (Disease Control Priorities in Developing Countries 2006).
    • East Asia/Pacific: 7 %
    • Eastern Europe and Central Asia: 10%
    • Latin America and the Caribbean: 33 %
    • Middle East and North Africa: 46 %
    • Sub-Saharan Africa: 50 %
    • South Asia: 79 %
• Zinc deficiency manifests itself in a lack of T and B lymphocytes, among other things
• Zinc deficiency often goes hand in hand with vitamin A deficiency
• Zinc is involved in the Ada repair protein. This repairs (demethylates) methylated phosphate linkers in the DNA by transferring the methyl group to the cysteinate-S¹⁸

2.4. Iron deficiency (10 %)¶

The prevalence of iron deficiency is difficult to determine because there is little reliable epidemiologic data on this topic, and it is also related to various related pathologic entities such as anemia, iron deficiency anemia, and isolated iron deficiency without anemia.

• Worldwide: 50 %¹⁹
  • for women: 37% (42% and 25% for children)
    • non-pregnant women: 33 %
    • pregnant women: 40 %
    • In around 50% of cases, this is due to severe iron deficiency.
  • large differences depending on age, gender and world region
• Europe: 5-10 %²⁰
  • Women of childbearing age: approx. 20 %
  • Other risk groups: Infants and young children
  • Adolescents from 13 to 15: 4-8 %; mainly storage iron deficiency without iron deficiency anemia

Symptoms of iron deficiency are¹⁹

• Tiredness
• Muscle weakness
• reduced physical performance
• Changes in mood and emotional behavior

Today, iron status is determined on the basis of serum ferritin. Low serum ferritin concentrations are a marker for low iron stores. Normal or elevated serum ferritin levels, on the other hand, do not rule out iron deficiency in the case of infections or inflammation.²¹²²

Iron deficiency affects the dopamine metabolism¹⁹

• This could be particularly harmful in infants and young adults with changes in the mesolimbic signaling pathway [30]. Iron is involved in dopaminergic signaling pathways and dopaminergic neurotransmission.
• Iron deficiency in the substantia nigra could result in reduced tyrosine hydroxylase activity and thus impaired dopamine synthesis.
• The SERT influences dopaminergic signaling
  • through its modulation of intracerebral iron homeostasis. The SERT-dependent decrease in intracerebral iron concentration influences dopaminergic and noradrenergic neurotransmission because iron is required for the conversion of phenylalanine to L-tyrosine and L-tyrosine to L-dopa and thus co-regulates dopamine synthesis.
  • by the (reversible) decrease in the density of dopaminergic D2 receptors and presynaptic DAT, which ensure presynaptic reuptake.
• Striatum:
  • Increased dopamine levels
  • Tyrosine hydroxylase increased
  • D1 receptors increased
  • Transferrin receptors increased
  • D2 receptors reduced
  • Adenosine-1 receptor reduced

2.5. Other possible deficiency symptoms¶

• Vitamin B6
• Magnesium
• Iodine

3. Mild Cognitive Impairment (MCI; 7 to 25 %; ADHD + 250 %)¶

Prevalence: 7 % to 25 %.

Mild Cognitive Impairment is a mild cognitive impairment that goes beyond the normal mental decline in old age, but does not yet constitute dementia.
A small study of n = 36 MCI persons with ADHD with an average age of 72 years found ADHD in 25 %.²³

4. Snoring (10 % to 20 %; ADHD + 300 %)¶

Prevalence of snoring: 30% in men, 10% in women, increasing with age

In contrast, a study of n = 512 snoring children and adolescents (70% of whom were overweight or obese and 35% with an increased obstructive AHI >3/h) found that of the snoring children²⁴

• 36 % showed hyperactivity/impulsivity
• 24 % showed emotional dysregulation

This would indicate a 300% increased risk of ADHD.
Surprisingly, the reduced oxygen supply due to sleep apnea did not correlate significantly with hyperactivity/impulsivity or emotional dysregulation, while the measure correlated with the volume of snoring.

5. Migraine (women: 18 %, men 6 %)¶

Prevalence women 18 %, men 6 %
The overall symptom picture usually differs significantly from ADHD and is barely permanent.

6. Thyroid problems (cumulative 7 to 14 % in women, 2.75 to 3.5 % in men)¶

Among other cognitive deficits, hyperthyroidism can also cause inattention and hyperarousal. Depending on the degree of hypothyroidism, the cognitive effects can range from mild impairment of memory and attention to complete dementia.²⁵²⁶

The THRA gene encodes the thyroid receptor alpha, TRα1, TRHB the thyroid receptor isoforms TRβ1 and TRβ2.
The pituitary hormone TSH (thyroid-stimulating hormone) stimulates the thyroid gland to produce thyroxine (T4; prohormone) and then triiodothyronine (T3). The thyroid hormones (T3 and T4) in the blood in turn regulate the pituitary release of TSH within the hypothalamic-pituitary-thyroid axis, which is mediated by the receptor isoform TRβ2.

See also the guidelines of the ADHD Working Group of Pediatricians and Adolescent Doctors, as of 2014.²⁷

6.1. Hyperthyroidism (women 1 - 2 %, men 0.25 - 0.5 %)¶

Prevalence: 1-2 % in women, 0.25 - 0.5 % in men²⁸²⁹³⁰

ADHD-like symptoms can be:³¹

• Nervousness
• Aggression
• Irritability
• Increased anxiety up to and including fearfulness
• (Extreme) jumpiness
• Difficulty to relax
• Sleep disorders
• Hyperactivity³²

Other symptoms that are not typical of ADHD can be:³¹

• Sweating
• Palpitations
• Atrial fibrillation
• (Severe) tremor
• Diarrhea
• Severe weight loss
• Tiredness
• Weakness
• Additionally occurring psychosis
• High blood pressure³²
• Oily skin³²
• Hyperventilation³²
• Cravings³²
• TSH low, fT3 high, fT4 high

6.2. Underactive thyroid / hypothyroidism (from 60 years approx. 2 %)¶

From the age of 60, around 2% of the population are affected by hypothyroidism.³⁰

ADHD-like symptoms can result from hypothyroidism³³
Hypothyroidism becomes more common with increasing age (usually a consequence of Hashimoto’s autoimmune thyroiditis).

Hypothyroidism often develops slowly, which is why symptoms are difficult to recognize.

Healthy 4-year-old children with thyroid-stimulating hormone levels in the upper normal range have a higher risk of ADHD than children with low free thyroxine levels. Thyroid disorders are more common in women than in men. As ADHD continues to show a possible association with thyroid hormone receptor insensitivity (see below), a role of thyroid hormones in the development and manifestation of ADHD in women and girls should be further investigated.³⁴

Symptoms of an underactive thyroid can include³²

• Constipation
• Weight gain
• Blemished skin
• Freeze
• Lack of drive
• Weepiness
• Increased need for sleep
• Low blood pressure
• Difficult breathing
• Loss of appetite
• TSH high, fT3 low, fT4 low

Hyperthyroidism does not preclude treatment with methylphenidate, but requires particular caution, especially strict monitoring of thyroid levels, pulse and blood pressure.

6.3. Hashimoto’s thyroiditis (women 4.5 - 9.5 %, men 0.5 - 1 %)¶

Hashimoto’s (Hashimoto’s lymphomatous goiter) is an autoimmune disorder that causes hypothyroidism³³
The prevalence of Hashimoto’s in Germany is around 5 to 10 %. Prevalence and incidence increase with age. Women in the 3rd-5th decade of life are affected about 10 to 20 times more frequently than men.³⁵

ADHD-like symptoms can be:³¹

• Depressive moods
  • Apathy
  • Rapid exhaustion
  • Concentration disorders.

Other symptoms that are not typical of ADHD can be:³¹

• Tiredness
  • In extreme cases: delusions / suicidal thoughts
  • Weight gain
  • Slowed heartbeat
  • Slowed reflexes
  • Decreased libido.

It is reported that adrenal insufficiency (reduced cortisol production by the adrenal gland) often leads to thyroid insufficiency. Treatment of the thyroid gland with thyroxine then increases the cortisol demand on the adrenal gland. However, if the adrenal gland is already so weakened that the increased cortisol production completely overwhelms it, a collapse of the adrenal gland can result, which further reduces cortisol production, which is why the adrenal gland should be considered and treated before thyroxine treatment.³⁶

An attenuated cortisol stress response is often present in ADHD-HI. *⇒ Cortisol and other stress hormones in ADHD *This could be a sign of mild adrenal insufficiency. However, this is often likely to be caused by pituitary weakness due to CRH receptor downregulation. To differentiate from adrenal insufficiency, see ⇒ Hypocortisolism (adrenal cortical insufficiency) In this article.
However, adrenal collapse due to thyroxine therapy is not reported as typical in ADHD.

6.4. Thyroid hormone resistance (RTH) / thyroid hormone action defect (THAD)¶

The β-thyroid receptors (TRβ) in the pituitary gland control the down-regulation of thyroid stimulating hormone (TSH), which leads to reduced production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

Thyroid hormone resistance (RTH) / thyroid hormone action deficiency (THAD) is an overall rare, hereditary syndrome, but the most common syndrome with reduced sensitivity to thyroid hormones.³⁷
Mutations in the β gene of the thyroid receptor (Thrb, formerly just called RTH) can impair the receptors’ ability to bind T3³⁸
There is an imbalance between

• the resistance of tissues that predominantly express thyroid hormone receptor β isoforms 1 and 2 and
• overstimulation of tissues that mainly express the thyroid hormone receptor α isoform
  In functional receptors, the mutant receptors form homo- and heterodimers that lack the ability to act on genomic response elements. The result of this dominant negative effect is that TSH is not downregulated (thyroid hormone resistance (RTH)).

THRB mutation thyroid hormone resistance has the following typical symptoms:

• normal³⁹⁴⁰ or elevated levels of triiodothyronine/free thyroxine and non-suppressed thyroid-stimulating hormone³⁷⁴⁰
• Sinus tachycardia³⁷⁴¹ at rest⁴⁰
• Short stature⁴⁰
• Osteoporosis⁴⁰
• Hearing loss
• Goitre⁴¹³⁹ or goitre (enlargement of the thyroid gland)³⁷
• ADHD³⁷³⁹
  • in 70 % of children with thyroid hormone resistance⁴²
  • entire spectrum of ADHD symptoms
  • Foggy Brain³⁹
  • suggests that mechanisms downstream of the TRβ receptor may be responsible for the manifestation of behavioral phenotypes in both disorders

THRA mutation thyroid hormone resistance has the following typical symptoms:³⁷

• mental retardation of varying degrees
• Short stature with reduced subischial leg length
• chronic constipation
• Bradycardia

7. Lack of sleep (12.5% in children)¶

The prevalence of chronic sleep deprivation in children was 12.5%.⁴³

Sleep deprivation can be caused organically or psychologically.
Massive sleep deprivation can trigger inattentive or hyperactive/impulsive⁴⁴ symptoms that can be confused with ADHD, such as

• severe fatigue
  • Microsleep
  • Feeling of exhaustion
• Weak drive
• Concentration problems
• Memory problems, forgetfulness
• Mood swings
  • increased irritability
  • depressive mood
• Discomfort
• increased susceptibility to infections
• Headaches, migraines
• Circulatory problems
• Drowsiness on waking
• Weight gain, increased hunger, overweight
• Concentration problems
• Muscle pain
• Skin problems
• burning and/or dry eyes
• increased shivering

People who have suffered from sleep deprivation for many years (some have suffered from it since school days) may not always be able to confidently attribute the symptoms to sleep deprivation and may need several months of adequate sleep to lose the Consequences of sleep deprivation.⁴⁴

8. Restless legs syndrome (children 2 %, adults 5 to 10 %)¶

Prevalence:⁴⁵

• Children 2 %
• Adults 5 - 10 %

Restless legs correlates with ADHD symptoms.³⁰⁴⁶
Intensive sugar consumption can cause twitching in the limbs (especially in the legs) - especially in people who do not tolerate sugar well - which is similar to a mild form of restless legs and can make it difficult to fall asleep.

A lower frequency of D4.7R is suspected in restless legs, while this gene variant is more common in ADHD.⁴⁷

In restless legs, treatment with L-dopa is often helpful in the short term, but can be detrimental in the long term.
Treatment with D4 agonists is also being discussed⁴⁷

9. Interrupted breathing during sleep (sleep apnea; 4 % to 9 %)¶

Prevalence of sleep apnea: 9 % in men and 4 % in women.
Prevalence of snoring: 30% in men, 10% in women, increasing with age
Breathing interruptions in children’s sleep can trigger cognitive stress, causing symptoms that resemble ADHD.⁴⁹

One study found a correlation of sleep apnea with decreased amplitude of the N3 component on the FC electrode, with no significant difference in ADHD questionnaire scores and behavior.⁵⁰

Treatment options include lifestyle changes, adenotonsillectomy, upper airway stenting, continuous positive airway pressure (CPAP) therapy.⁵¹

10. Prenatal damage due to alcohol, FAS (0.8 to 8.2 %)¶

Other names: Fetal alcohol syndrome, embryofetal alcohol syndrome, alcohol effects, FAE, FAS, FASD, alcohol embryopathy

Prevalence: 0.8 to 8.2 % of all births, with around 10 % of all cases developing full symptoms.⁵² Long-term studies of children with FAS (fetal alcohol syndrome) found that 47.2 %⁵³, 67.6 %⁵⁴ or 70 %⁵⁵ also had ADHD.

Around 15 to 30% of all mothers continue to drink alcohol during pregnancy.⁵² The risk to the unborn child is considerable.
This problem is also considered a possible cause of ADHD.⁵⁶ The risk of ADHD among people with FAE/FAS was increased 10-fold.⁵⁷

11. Allergies (asthma 4% to 8%, food allergies 4%)¶

There is a clear comorbidity between allergy and ADHD, especially asthma⁶² and food allergies⁶³.
There is also a strong comorbidity between food allergies and ASD.⁶⁴
The severity of atopic symptoms correlated with the severity of ADHD symptoms (meta-analysis, k = 38, n = 117,181,049).⁶⁵

Prevalence of asthma: 4 to 8 %
Prevalence of food allergies: 4%

An IL-4 receptor antibody (dupilumab) reduced the need for ADHD medication in children with atopic dermatitis and ADHD⁶⁶
Allergy medications can alleviate ADHD symptoms in patients with comorbid allergies.⁶⁷⁶⁸⁶⁹

One of the main mediators of allergic reactions in atopic dermatitis, allergic asthma and rhinitis is the cytokine IL-4.
IL-4, given in the second week of life, increased hyperactivity and impulsivity in mice. Allergic asthma in early life also increased hyperactivity and impulsivity.⁷⁰⁷¹

12. Hydrocephalus (0.4 - 0.8 %; from 65 years 3 %)¶

Prevalence: 0.4 - 0.8 %, > 65 years: approx. 3 %⁷²

Children with hydrocephalus have an almost threefold risk of ADHD.⁷³
In old age, hydrocephalus often occurs comorbidly with Alzheimer’s disease and vascular dementia.

13. Seizure disorder¶

13.1. Epilepsy: 0.5 to 1 %¶

The prevalence of epilepsy is 0.5 to 1 %.⁷⁴

Source²⁷

• Pyknolepsy³⁰
• Seizure disorder with absences or complex partial seizures³⁰⁴⁶
• Epilepsy-related seizures (absences)⁷⁵

13.2. Status epilepticus during sleep (ESES)¶

Other names: Bioelectric status epilepticus during sleep, CSWS, CSWS syndrome, ESES syndrome, Epileptic encephalopathy with continuous spike-wave discharges during slow-wave sleep
Prevalence: unknown. Orphane Disorder (rare).⁷⁶

Epilepsy with continuous spike-wave discharges during sleep (CSWS) is a rare epileptic encephalopathy in children. It is characterized by seizures, electroencephalographic patterns of status epilepticus during sleep (ESES) and cognitive developmental regression.⁷⁷

ESES is associated with symptoms similar to ADHD. In one study, treatment with ACTH reduced ADHD symptoms by an average of 67%.⁷⁸ Another study by the same authors found similar improvements with ACTH in ADHD and stuttering.⁷⁹

14. Histamine intolerance, histamine intolerance (1 %, of which 80 % adults)¶

The prevalence of histamine intolerance is given as 1%. However, 80% of people with ADHD are said to be adults.⁸⁰
The main physical symptoms of histamine intolerance are⁸¹⁸²⁸³

• Psychological symptoms
  • Depression
  • depressive moods
  • Winter depression
  • Mood swings
  • States of exhaustion
  • increased sensitivity (acoustic, visual, tactile, temperature, emotional, etc.)
  • Sleep disorders, wakefulness
  • Tension, restlessness, agitation, arousal, nervousness, overexcitement

• Nervous system
  • Headache, cluster headache
  • Migraine
  • Dizziness (vertigo), seasickness, motion sickness

• Muscle tension

• Endocrine system
  • Menstrual cramps: Period pain, menstrual pain, dysmenorrhea
  • Increased PMS symptoms
• Digestive tract, gastrointestinal tract
  • Diarrhea (diarrhea, soft stools, diarrhea), indigestion
  • Abdominal cramps, stomach pain
  • Flatulence, meteorism, bloating, intestinal winds, flatulence
  • Recurrent cystitis
  • Nausea, nausea
  • Vomiting, vomitus
• Cardiovascular system
  • Palpitations (synonyms: rapid heartbeat, tachycardia), up to and including panic attacks
  • Low blood pressure, sudden drop in blood pressure (hypotension, drop in blood pressure)]
  • Additional heartbeats (extra beats, extrasystoles)
  • Cardiac arrhythmia, heart stumbling, arrhythmias, heart problems
  • Palpitations, palpitations
• Skin, mucous membranes, respiratory tract
  • Stuffy or runny nose (synonyms: blocked nose, runny nose, runny nose, rhinorrhea, non-allergic rhinitis, runny nose, nasal obstruction)
  • Sneezing, sneezing irritation
  • Narrowing of the airways (synonyms: Bronchoconstriction, bronchoconstriction, bronchial constriction and bronchial obstruction): e.g. shortness of breath (breathlessness, dyspnea), asthma, bronchospasm
  • Flushing, red face, flush
  • Itching, pruritus, scratching
  • Erythema, reddening of the skin
  • Hives, nettle rash, urticaria, urticarial exanthema
  • Edema, water retention, swelling of the eyelids
  • Conjunctivitis, inflammation of the conjunctiva of the eye, eye inflammation

15. ME/CFS, myalgic encephalomyelitis / chronic fatigue (0.42 % to 0.75 %)¶

Myalgic encephalomyelitis / chronic fatigue syndrome is a severe neuroimmunological disease. A high degree of physical disability is a common consequence.⁸⁴

Prevalence:
0.42 % for adults, 0.75 % for children
17 million people with ADHD worldwide
250.000 people with ADHD (including 40,000 children / adolescents) in Germany before the COVID-19 pandemic (0.31 %)
500.000 people with ADHD after the COVID-19 pandemic (0.62 %)
25 % can no longer leave the house
60 % are unable to work

ME/CFS is an independent, complex clinical picture. The symptom of fatigue, on the other hand, is a common accompanying symptom of chronic inflammatory diseases.

Symptoms of ME/CFS:

• physical symptoms
  • severe fatigue (physical weakness)
    • significant restriction of the activity level
  • Muscle twitching
  • Muscle cramps
  • massive sleep disorders
• autonomic symptoms
  • Orthostatic intolerance
    • Palpitations
    • Dizziness
    • Drowsiness
    • Fluctuations in blood pressure
  • Consequences: e.g. no longer able to stand or sit for long periods of time
• immunological symptoms
  • strong feeling of illness
  • painful and swollen lymph nodes
  • Sore throat
  • Respiratory tract infections
  • increased susceptibility to infections
• Post-exertional malaise (PEM)
  • pronounced and persistent intensification of all symptoms after minor physical or mental exertion
  • pronounced weakness
  • Muscle pain
  • flu-like symptoms
  • Deterioration of the general condition
  • typically occurs even after low levels of stress
    • Brushing your teeth
    • Showers
    • Cooking
    • walk a few steps
  • in severely affected people, even turning over in bed or the presence of another person in the room can trigger PEM
• Pain symptoms
  • pronounced pain
    • Muscle pain
    • Joint pain
    • Headache
• neurocognitive symptoms
  • “Brain Fog”
    • Concentration problems
    • Memory problems
    • Word-finding disorders
  • Increased sensitivity
    • Hypersensitivity to sensory stimuli
    • Very severely affected people often have to lie in darkened rooms and can only communicate in a whisper

Trigger:

• Infectious diseases
  • Epstein-Barr virus
  • Influenza
  • SARS
  • COVID-19
• Gonorrhea
• Endometriosis and PDMS
• Nutrient deficiencies (vitamins, trace elements)

Path:

• unexplained
• possible:
  • Autoimmune disease
  • severe disorder of the energy metabolism

Biomarkers:

• none known

Diagnostics:

• using established clinical criteria catalogs

Treatment:

• there is currently no approved curative treatment or cure
• Pacing
  • helps with ME/CFS as well as with ADHD or ASA
  • Overloading is “punished more severely” with ME/CFS

Differences between ME/CFS and ADHD / ASD / depression:

• ADHD: problems usually already as children, but no later than 16 to 18; ME/CFS: problems usually not already throughout life
• ME/CFS: gradual, usually undulating deterioration over years until at some point there is no energy left at all
• no depressive states
  • no strong deterioration in sentiment
  • Depression: severe cognitive impairment and reduced drive; ME/CFS: cognitive impairment due to temporary or permanent “brain fog”
  • Ability to vibrate is preserved in ME/CFS
  • People with ADHD do not perceive themselves as depressed and do not appear depressed
  • Depression; drive is lacking and is missed; ME/CFS: drive present, energy for implementation is lacking or implementation leads to overload (sometimes only hours later)

Martin Winkler considers exhaustion in ADHD in the context of a regulation-dynamic model. He distinguishes between ADHD / neurodivergence:

• Cognitive exhaustion
  • Consequences: Mental fatigue due to constant demands on attention and concentration, especially in inappropriate environments
    • reduced performance
    • reduced attention span
    • increased distractibility
• Emotional exhaustion
  • Emotional regulation requires increased effort
    • Consequences: depletion of emotional resources
      • increased irritability
      • Mood swings
      • Feeling of being overwhelmed
• Physical exhaustion
  • Constant tension and effort to concentrate / control impulsive behavior,
    • Consequences: physical exhaustion
• Exhaustion due to adaptation requirements / masking
  • Increased cognitive / emotional resources to adapt to social norms and expectations
    • Consequences: specific adaptation requirement exhaustion

16. Prolactinomas (0.02 - 0.05 %)¶

Prevalence: 30 to 50 / 100000 (0.02 to 0.05 %)

Prolactinomas are prolactin-secreting (benign) tumors
⇒ ADHD neurotransmitters - messenger substances

17. Consequences of severe brain infections (cumulative 0.04% to 0.15%)¶

Sources⁷⁵⁸⁵⁴⁶

17.1. Encephalitis (cumulative 0.03 %)¶

Prevalence:⁸⁶
Autoimmune encephalitis 13.7/100,000 (0.0137 %)
infectious encephalitis 11.6/100,000 (0.0116 %)
viral encephalitis 8.3/100,000 (0.0083 %)

Brain infection with inflammatory changes caused by invading microorganisms.
Encephalitis destroys the cells in the substantia nigra that produce dopamine.
The people with ADHD affected by the encephalitis epidemic from 1914 to 1917 showed typical symptoms of ADHD as the disease progressed. Children developed hyperactive motor skills, adults Parkinson’s symptoms.
The symptoms are consequences of the dopamine deficiency that characterizes ADHD. These symptoms have been reproduced in animal experiments as a result of impaired dopamine production.⁸⁷

See also Viral infections as a cause of ADHD in the article Age-independent physical stress as an environmental cause of ADHD in the chapter Development.

17.2. Bacterial infections (cumulative 0.01% in women, 0.12% in men)¶

• Meningitis: inflammation of the meninges
  • Prevalence: 0.5 / 100,000 (0.0005 %)⁸⁸
• Brain abscesses: 0.3-1.3 /100,000 per year (0.0003% to 0.0013%)
  • Local infection of the brain tissue. Begins as focal encephalitis (cerebral phlegmon, “cerebritis”). Gradually develops into a collection of pus with a connective tissue capsule
• Syphilis (prevalence 11.5 / 100,000 (0.115 %) in men, 0.9/100,000 (0.009 %) in women)

18. Turner syndrome (0.04 %; ADHD + 225 %)¶

Prevalence: 1 in 2500 girls born alive =
Turner syndrome is a genetic disorder in girls and women in which one X chromosome is completely or partially missing (chromosomal aberration).
Turner syndrome was found:⁸⁹

• ADHD at 26 %
• Anxiety disorder at 26 % (+ 225 % compared to the 8 % for girls in the USA⁹⁰.)
• Dyscalculia at 18 %
• ASS at 16 %
• a lower mean non-verbal IQ (performance intelligence quotient, PIQ) compared to the verbal IQ (VIQ)

19. Perinatal hypoxemia (0.001 to 0.009 %)¶

Prevalence: 1 to 9 / 100,000 (0.001 to 0.009 %)((Hypoxic-ischemic encephalopathy (HIE), Orpha.net))

Oxygen deprivation during birth is one of the main causes of early childhood brain damage (ECBD).
In animal experiments, led to the death of dopamine-producing cells in the substantia nigra and thus to a decrease in dopamine levels of up to 70 %.⁹¹
Hypoxemia is associated with excess adenosine. Adenosine inhibits dopamine.

20. Congenital myopathy (0.005 %) and neuropathy (2 % to 8 %)¶

The prevalence of congenital myopathy is 1 / 20,000 live births (0.005 %).

One person with ADHD reported that his suspected ADHD was mistaken and that he had congenital myopathy and neuropathy instead.

21. Cortisol disorders (cumulative 0.0042 to 0.0048 %)¶

21.1. Hypocortisolism (adrenal insufficiency) (0.004 %)¶

Sources:⁹²⁹³

Addison’s disease: Prevalence: 4/100,000 (0.004 %).
Weaker forms are much more common.

Since the basal cortisol level is slightly reduced in ADHD (in ADHD-HI as in ADHD-I), ADHD could be described as very weak adrenal insufficiency (adrenal insufficiency).

21.2. Hypercortisolism (Cushing’s syndrome) (0.0002 to 0.0008 %)¶

Prevalence: 8/1,000,000 in men (0.0008%), 2/1,000,000 in women (0.0002%)⁹⁴

• ACTH-dependent form (80% of cases)
  • Micro- or macroadenoma of the anterior pituitary gland produces ACTH (= Cushing’s disease)
  • (mostly malignant) tumors outside the pituitary gland (often bronchial carcinomas) as the cause of ectopic ACTH production
• ACTH-independent form (20% of cases)
  Overproduction of glucocorticoids (cortisol) and mineralocorticoids by the adrenal cortex
  • Adrenal cortical adenoma (pure cortisol overproduction)
  • Adrenal carcinoma (increased cortisol and androgen production)
  • Nodular hyperplasia of the adrenal cortex

22. Moyamoya (0.0001 % to 0.0009 %)¶

Moyamoya is particularly common in Japan.
Prevalence
Worldwide: 1 / 1,000,000 to 9 / 1,000,000 (0.0001 % to 0.0009 %)⁹⁵
Japan: 1 / 30,000 to 1 / 9,500 (0.0033 % to 0.0105 %)
Incidence Japan: 1 / 280,000 to 1 / 89,000

Moyamoya is a narrowing or occlusion of cerebral arteries that leads to relative anemia (stroke and transient ischemic attack) in the brain. Many small compensatory vessels form as bypass circuits.
Moyamoya can be associated with symptoms that can be confused with ADHD.⁹⁶

23. Hamartoma of the hypothalamus (0.0005 %)¶

Prevalence: 1 / 200,000 (0.0005 %)⁹⁷

A hamartoma is a tumor-like, benign tissue change due to incorrectly differentiated or dispersed germinal tissue. A hypothalamic hamartoma can produce a variety of hormones and cause ADHD symptoms, conduct disorder, oppositional defiant disorder, antisocial behavior, tantrums, intellectual regression, cognitive disorders, premature puberty, obesity and epilepsy. 60% of people with ADHD develop externalizing disorders (especially in boys and epilepsy) and 30% develop internalizing disorders.⁹⁸⁹⁹ MPH can significantly improve ADHD triggered by a hypothalamic hamartoma, as can treatment with a gonadotropin-releasing hormone (GnRH) analog.¹⁰⁰ In severe cases, stereotactic laser surgery may be helpful.¹⁰¹

24. Visual and hearing impairment¶

Sources²⁷³⁰

25. Lesions of the left cerebral hemisphere / right PFC¶

• Attention selection impairs¹⁰²
  • E.g. in situations that require quick decisions between relevant and irrelevant stimuli
  • Frequently increased number of errors in choice-response tasks or extended response times

Lesions of the OFC have been known since the case of Phineas Gage (Harlow 1848) and are associated with specific symptoms:¹⁰³

• often dramatic changes in personality
• impulsive
  • often reckless, risky behavior
  • frequent conflicts with the law
  • disinhibited in terms of instinctive behaviors
  • Problems with drive control
• irritable
• quarrelsome
• Tendency to crude humor
• Disregard for social and moral principles
• severe attention deficit disorder
  • strong distractibility due to external or internal stimuli

The OFC normally has inhibitory functions. These take place via efferents to:¹⁰³

• Hypothalamus
• Basal ganglia
• other neocortical areas, e.g. in the PFC

Patients with lesions of the right frontal cortex often show ADHD-like behavior.¹⁰⁴

26. Organic brain damage¶

Source³⁰

27. Traumatic or space-occupying cerebral disorders / other psychoorganic syndromes with cerebral damage and/or mental retardation¶

Source²⁷