6. Diseases as Risk Factors for ADHD

Author: Ulrich Brennecke
Review (2024): Waldemar Zdero, M.A. in Psychology

Traumatic physical or psychological experiences during childhood can be a contributing factor to ADHD.
This article discusses medical conditions as risk factors for ADHD.

For infants and children:
Exposure to secondhand smoke, air pollution (particularly fine particulate matter and nitrogen oxides), and various pollutants such as lead, manganese, or phthalates is associated with an increased risk of ADHD.
Surgical procedures under anesthesia, atopic dermatitis, bacterial infections, and concussions are risk factors for ADHD, as are stressful childhood psychological experiences such as trauma, chronic stress, or growing up in a children’s home.
A lack of attachment from the mother or parents during childhood, maternal stress during childhood, or the parents’ mental health issues increase the risk of ADHD in children, as do low socioeconomic status, low educational attainment, or parental unemployment.
Starting school earlier and being the youngest child in the class are additional risk factors.

During puberty:
High levels of stress during adolescence are considered a risk factor for ADHD persisting into adulthood.

The percentage values indicate the extent to which the risk of ADHD correlates with the respective factor. These figures do not imply that the respective factor is a causal cause.

6.1. Infections and Infectious Diseases¶

An infection is the entry of microorganisms (viruses, fungi, bacteria, parasites) into an organism, followed by their colonization and reproduction.
In a broader sense, infectious diseases are also imprecisely referred to as “infections.”¹

A higher infection burden may have a cumulative association with psychiatric disorders that goes beyond what has been described for individual infections. Susceptibility to infections is reflected in the infection burden (the number of specific types or sites of infection). An increased infection burden correlates with an increased risk of:²

• ADHD
• ASS
• bipolar disorders
• Depression
• Schizophrenia
• total number of psychiatric diagnoses.
  A modest but significant heritability was found for the infection burden (h2 = 0.0221), as well as a high degree of genetic correlation between it and the overall psychiatric diagnosis (rg = 0.4298). Evidence was also found for a genetic causality of the total infection on the overall psychiatric diagnosis.

6.1.1. Infections during the first year of life (+16% to +77%)¶

A registry-based cohort study (n = 2,885,662, of whom n = 1,864,660 were full siblings) found a slight 16% increase in the risk of ADHD associated with childhood infections during the first year of life (ASD + 12%, tics + 12%, intellectual disability + 63%), which disappeared when adjusted for ADHD and tics using twins as a control group.³
Severe infections during the first week of life increased the risk of ADHD treated with medication between the ages of 8 and 14 by 12%. Meningitis during the first week of life increased the risk of ADHD, as defined here, by 77% and the risk of ASD by 105%.⁴

6.1.2. Bacterial infections (up to +593%)¶

Severe bacterial infectious diseases during childhood or adolescence dramatically increase the risk of serious mental disorders (HR):⁵

• ASS: 13.80
• ADHD: 6.93
  • ADHD medication use: 11.81
• Tic disorder: 6.19
• OCD: 3.93
• Bipolar disorder: 2.50
• Depressive disorders: 1.93
  • Antidepressant use: 2.96
  • Mood stabilizer intake: 4.51
  • Use of atypical antipsychotics: 4.23
• Schizophrenia⁶

Among the bacterial species studied (streptococci, staphylococci, Pseudomonas, Klebsiella, Haemophilus, mycoplasmas, tuberculosis, meningococci, Escherichia, Chlamydia, and scrub typhus), streptococci were associated with the most clinical presentations. ADHD was associated with eight bacterial infections.⁵

6.1.2.1. Bacterial meningitis (inflammation of the meninges) (+40% to +180%)¶

The consequences of bacterial meningitis (but not of enteroviral meningitis) were an increased risk of ADHD or of taking ADHD medication:⁷

• Meningitis in the first 90 days of life:
  • 2.8-fold increased risk of ADHD (aHR 2.8, +180%)
  • 2.2 times more likely to take ADHD medication
  • 1.9-fold increased risk of ASD
  • Behavioral and emotional disorders (2 categories)
  • Learning and intellectual development disorders: 4.2 times
• Meningitis between 90 days and 18 years of age:
  • 1.4 times higher risk of ADHD (+40%)
  • ADHD medication use: 1.5 times
  • Learning and intellectual development disorders: 1.5 times

All 21 people with tuberculous meningitis exhibited ADHD symptoms.⁸ Given a population prevalence of 8%, this would represent a 1,150% increase in risk.
In a recent study of 78 children with tuberculous meningitis, the same authors found that only 13.5% of the children had a clinical Total Problem Score on the CBCL (above 70) and 20.6% had clinical Social Problems Scores. The ADHD score was significantly elevated in the group, although no conclusion was drawn regarding the number of people with ADHD.⁹

The prevalence of Streptococcus agalactiae (Group B Streptococcus, GBS) infection among infants was 0.07%.
GBS caused:¹⁰

• increased infant mortality (19.41 times higher)
• Long-term neurological developmental disorders (3.49 times)

GBS meningitis increased the risk of¹⁰

• ADHD
• cerebral palsy
• Epilepsy
• Hearing impairment
• profound and specific developmental disorders

6.1.2.2. Periodontal Disease¶

Periodontitis is a bacterial infection of the gums caused by the bacterium P. gingivalis, which secretes toxins. Periodontitis is described as a risk factor for ADHD.¹¹

6.1.2.3. Antibiotics in the first years of life (up to +33%)¶

In a very large study, antibiotic use during a child’s second year of life increased the risk of ADHD by 20 to 33% and the risk of sleep problems by 24 to 50%.¹² An even larger study from Korea found a dose-dependent 10% increase in the risk of ADHD, with prenatal and early childhood administration together further increasing the risk.¹³
Another very large study found that the risk of ADHD increased all the more as¹⁴

• the earlier the first course of antibiotics was administered (under 2 years old, 2 to 5 years old, 5 to 8 years old) and
• the longer the course of antibiotics lasted (less than 7 days, 7 to 14 days, more than 14 days):

ADHD prevalence among children who received antibiotics at the following ages / for the following durations:	under 2 years	2–5 years	5–8 years
< 7 Days	10.53%	7.33%	5.18%
7–14 days	10.66%	8.80%	7.25%
&gt; 14 days	11.47%	11.11%	8.83%

A small study found more frequent behavioral problems and depressive symptoms in 3 1/2-year-old children who had received antibiotics during their first year of life.¹⁵ Two other studies found no increased risk of mental disorders associated with antibiotic use during the first 1 ¹⁶ to 2¹⁷ years of life.
One study found no increased risk of ADHD, but did find an increased risk of asthma, food allergies, and allergic rhinitis (hay fever),¹⁸ which are known to be associated with an increased risk of ADHD.

Antibiotic use during the first three years of life reduces the diversity, stability, and composition of the microbiome:¹⁹

• reduced frequency of genera
  • Bacteroides
  • Bifidobacterium
  • Lactobacillus
  • Staphylococcus
  • Sediminibacterium
• increased incidence of
  • Members of the Enterobacteriaceae family
  • of the genus Enterococcus

As the microbiome matures, several processes in the central nervous system—such as synaptogenesis, myelination, and synaptic pruning—take place, and these can be influenced by microbiome-associated metabolites.¹⁹

Antibiotic exposure during the first years of life increased the child’s risk of: (meta-analysis, k = 30, n = 7,047,853)²⁰

• ADHD: +33%
  • not significant in studies that used sibling control groups
• Depression: +29%
  • not significant in studies that used sibling control groups
• ASS: +19%

A cohort study found no significant increase in the risk of ADHD or ASD associated with antibiotic use during the first two years of life.²¹

6.1.3. Viral Infections¶

The Powassan flavivirus is transmitted by ticks and, in rare cases, causes encephalitis in humans. Six children with Powassan virus encephalitis, who were diagnosed between the ages of 14 months and 11 years, all suffered permanent neurological sequelae, including:²²

• Seizures
• Movement disorders
• Behavioral problems
• ADHD
• Learning difficulties
• Anxiety
• Sleep disorders

6.1.3.1. Enteroviruses in general (up to +182%)¶

(Non-polio) enteroviruses account for just over half of all cases of aseptic meningitis, making them one of the most significant known causes.²³ In addition to encephalitis²⁴, (non-polio) enteroviruses also frequently cause febrile illnesses, hand-foot-and-mouth disease, herpangina, aseptic meningitis, and encephalitis, as well as, on occasion, severe and life-threatening infections such as myocarditis or neonatal sepsis.

Enteroviruses are considered a possible cause of ADHD.²⁵
A study found an increased risk of ADHD associated with mild enterovirus infections (16%) and severe enterovirus infections (182%).²⁶

6.1.3.2. Enterovirus A71 (EV-A71) (+200%)¶

A longitudinal study of 43 adolescents who had a central nervous system infection with enterovirus A71 (EV-A71) between the ages of 6 and 18 found that 34.9% had ADHD. This indicates that the risk of ADHD is more than tripled. In addition, increased autistic symptoms were observed. There was no increase in other psychiatric diagnoses.²⁷²⁸ Another study found ADHD to be particularly common when the A71 infection was accompanied by cardiopulmonary failure.²⁹
EV-A71 often causes weakness, limb atrophy, seizures, hand, foot, and mouth disease, encephalitis, and reduced intelligence.

6.1.3.3. HIV (+150% to +1,000%)¶

A study of children and adolescents with HIV who were in stable health found ADHD symptoms in 20% of them.³⁰
A 2007 study of 100 African children aged 5 and older with HIV found ADHD symptoms in 88% of the participants: 26% had ADHD-I, 38% had ADHD-HI, and 24% had ADHD-C. In addition, the prevalence of ODD ranged from 9.5% (teacher assessment) to 12% (parent assessment). Sixty percent of the caregivers were themselves infected with HIV.³¹
Assuming a population prevalence of 8%, this would result in a +150% to +1,000% increase in ADHD prevalence.

6.1.3.4. Herpes zoster encephalitis¶

In one isolated case, ADHD was mentioned in connection with zoster encephalitis.³²

6.1.3.5. Human Endogenous Retroviruses (HERV)¶

The Topic Human Endogenous Retroviruses (HERV) and ADHD Is discussed in the chapter “ ” due to its high heritability Origin in the article Genetic and Epigenetic Causes of ADHD – Introduction

6.1.4. Parasitic Infections¶

A study of 100 children with ADHD and 100 healthy children found a correlation between ADHD and:³³

• Toxoplasma
• Toxocara
• Cryptosporidium parvum
• Giardia lamblia
• Entamoeba histolytica
  No difference was found with regard to Schistosoma (coccidian parasites).

6.2. Traumatic Brain Injuries (up to +529%)¶

Traumatic brain injuries (TBI) are estimated internationally at 349 per 100,000 person-years. One in two people will suffer a traumatic brain injury at some point in their lives. Traumatic brain injuries have the highest incidence and prevalence of all common neurological disorders and have been linked in studies to consequences such as neurodegenerative diseases, cognitive impairments, stroke, psychiatric disorders, and increased mortality.³⁴

Traumatic brain injuries can trigger secondary ADHD.³⁵
The severity of brain injuries correlates with significantly higher ADHD symptoms. Changes in the morphometry of the default mode network (DMN) caused by brain injuries predict higher ADHD symptoms 12 months after the injury, whereas the morphometry of the Salience Network (SN) and the Central Executive Network (CEN) did not constitute significant independent predictors.³⁶

A systematic review of k = 24 meta-analyses found a correlation between the risk of ADHD and previous traumatic brain injuries:³⁴

• mild traumatic brain injury: +18%, not statistically significant, n = 4,098 participants
• moderate traumatic brain injury: +266%, not statistically significant, n = 117
• Severe traumatic brain injury: +529%, statistically significant, n = 5,092

It remains unclear to what extent traumatic brain injuries in ADHD are the consequences of the increased likelihood of accidents and injuries associated with ADHD.
In one study, 30% of boys and 15% of girls with traumatic brain injury had previously been diagnosed with ADHD.³⁷ This study also suggests incorporating physical activity and providing resources to help girls cope with school-related stress into their rehabilitation programs. For boys, cognitive support and strategies for managing ADHD may be more effective.

ADHD was associated with an increased incidence of traumatic brain injuries^{3839 40} and otolaryngological trauma.⁴¹
A study examined mild (concussion) and severe traumatic brain injuries occurring before the age of 10. The incidence was 1,156 per 100,000 person-years. At age 19, the risk of ADHD was 68% higher, and the risk of a learning disability was 29% higher.⁴²
In cases of more severe traumatic brain injury, the association was not statistically significant. In an analysis of cases with possible traumatic brain injury (corresponding to a concussion), the result was significant (105% increased risk of ADHD, 42% increased risk of learning disabilities). The risk in adulthood was particularly elevated among children with the least severe injuries.
In purely correlational studies, however, it remains unclear to what extent traumatic brain injuries are a consequence of ADHD (increased risk of accidents) or whether ADHD is a consequence of traumatic brain injuries (secondary ADHD).

Among 1,709 ice hockey players aged 11 to 17, the rate of concussions correlated with higher self-reported and parent-reported scores for attention problems. Only self-reported hyperactivity—not parent-reported hyperactivity—was also significantly correlated with concussions. A T-score ≥ 60, which combines scores for attention problems and hyperactivity (an estimate of probable ADHD), was not significantly associated with the frequency of injuries or concussions.⁴³

A Finnish nationwide retrospective cohort study (1998 to 2018) of patients with pediatric traumatic brain injury (n > 126,000) found a significant association between pediatric traumatic brain injury and post-traumatic use of ADHD medications during a 20-year follow-up period, with the association being particularly pronounced after 4 years.⁴⁴
The proposed mechanism of action was neurodegeneration resulting from traumatic brain injury, followed by neuroinflammation and oxidative stress, which could impair brain development and neurotransmitter function and increase the risk of neurodevelopmental disorders.⁴⁵

6.3. Craniosynostosis (+500%)¶

Craniosynostosis is the premature fusion of the skull sutures. In one study, the majority of children with craniosynostosis also exhibited ADHD symptoms. Maternal smoking during pregnancy significantly increased the risk of craniosynostosis.⁴⁶
Approximately one in two children who underwent surgery for metopic synostosis (trigonocephaly or metopic craniosynostosis) at 9.5 (± 7.9) months of age showed at least borderline levels of hyperactivity and inattention at 10.3 (± 3.5) years, at least borderline levels of hyperactivity and inattention.⁴⁷ A higher age at the time of surgery was associated with poorer executive functions.
A study found that 42.6% of those who had undergone surgery for craniosynostosis as children had high scores on the CAARS-2 ADHD Index at age 16 and older.⁴⁸
Craniosynostosis is associated with a significantly increased risk of ADHD symptoms.⁴⁹

6.4. Epilepsy (up to +470%)¶

Epilepsy is a physical neurological disorder,
One study found a 5.7-fold increased risk of ADHD in children with epilepsy (41.5% vs. 7.3%). In most of these children, ADHD was diagnosed after their epilepsy had subsided and they had stopped taking epilepsy medication.⁵⁰ Another study found that 43.3% of children with epilepsy had ADHD or a learning disability.⁵¹ One study reported a prevalence of 11.2% for ADHD and 19.1% for ASD among children with epilepsy aged 7 years.⁵²

Among children with infection-related epilepsy (FIRES), 33.3% exhibited symptoms of inattention, 53.3% exhibited aggression, and 20% exhibited mood problems.⁵³

For West syndrome (infantile spasms, BNS epilepsy), which occurs in infants, the prevalence of ADHD has been reported to be 15%.⁵⁴

6.5. Phenylketonuria (PKU) (+375%)¶

See the section below on Monogenic Causes of ADHD.

6.6. Sleep-Related Breathing Disorders (SBAS, SDB, SRBD) (up to +350%)¶

Other names: Sleep-disordered breathing (SDB), Sleep-related breathing disorder (SRBD).⁵⁵

Sleep-related breathing disorders (SBAS), as an umbrella term, include, among other things,

• primary snoring (snoring alone, without other sleep-related breathing disorders)
• Upper Airway Resistance Syndrome⁵⁶
• Obstructive sleep apnea (OSA)⁵⁷⁵⁸
• central sleep apnea (CSA)
• Sleep-Related Gas Exchange Disorders (SAGEA)

SBAS is most common between the ages of 2 and 8, presumably due to the relative size of the lymphatic tissue compared to the diameter of the airways.⁵⁹

6.6.1. Sleep-Related Breathing Disorders in General¶

6.6.1.1. Prevalence of Sleep-Related Breathing Disorders¶

The prevalence of sleep-related breathing disorders (SBAS) was found to be

• Children:
  • 12%⁶⁰
  • 10% (study of n = 227 children aged 4 to 2 years)⁵⁹
• Children and adolescents (ages 6 to 17)
  • 10%⁶¹
• Children and adolescents (ages 5 to 16) undergoing orthodontic treatment:⁵⁸
  • SBAS: 10.8% vs. 5% in healthy controls
  • Snoring: 13.3%
  • Drowsiness: 17.9%
• Teens
  • 7%⁶²
    • male: 5.8%
    • female: 8%
    • weekly: 6%⁶²
  • 5.8% without obesity⁶²
    • 12.8% with obesity
• Population
  • Ages 30 to 60, AHI of 5 or higher⁶³
    • 9% among women
    • 24% among men
  • 20%⁶⁴
  • 23.4% among women⁶⁵
    • 3- to 4-fold increase in postmenopausal women compared with premenopausal women⁶⁶
  • Average age 59 years, AHI 15 or higher⁶⁵
    • 49.7% among men
    • The median AHI for the general population was 6.9/h for women and 14.9/h for men⁶⁵
  • ages 30 to 69 (meta-analysis, k = 17)⁶⁷
    • Germany
      • 60.1% AHI of 5 or higher
      • AHI of 32.9% or higher starting at age 15
    • France
      • 72.1% AHI of 5 or higher
      • AHI of 36.3% or higher starting at age 15
    • Austria
      • 48.7% AHI of 5 or higher
      • AHI of 28.4% or higher starting at age 15
    • Switzerland
      • 72.4% AHI of 5 or higher
      • AHI of 36.6% or higher starting at age 15
    • Denmark
      • 48.9% AHI of 5 or higher
      • AHI of 28.5% or higher starting at age 15
    • Sweden
      • 17.0% AHI from 5 onward
      • AHI of 12.7% or higher starting at age 15
    • United States
      • AHI of 33.2% or higher
      • 14.5% AHI at age 15 and older
• inpatients in psychiatric care
  • 23.9%⁶⁸
• Prevalence of SBAS (apnea-hypopnea index (AHI), respiratory disturbance index (RDI), or oxygen desaturation index (ODI) of 5 or more per hour):⁶⁶
  • 24.0% to 83.8% among men
  • 9.0% to 76.6% among women
• Prevalence of moderate-to-severe SBAS (AHI, RDI, or ODI of 15 or more per hour)⁶⁶
  • 7.2% to 67.2% among men
  • 4.0% to 50.9% among women

SBD is associated with hearing problems.
44.8% of children who habitually snored had recurrent middle ear infections⁶⁹
Middle ear infection is associated with SBD and the resulting hypoxia.⁷⁰ Children with middle ear infection and effusion are more likely to have significant OSA symptoms.⁷¹
Middle ear infections are exacerbated by a lack of oxygen.^7273747576

Mild SBAS that went untreated resolved on its own:

• among 70.8% of children and adolescents aged 6 to 17⁶¹
• in 65% of children aged 5 to 9 with mild OSA⁷⁷
• Among 52.9% of children with an AHI of 2 or higher, the condition persists into adolescence⁷⁸
• 100% of children with an AHI of 5 or higher through adolescence; below that,⁷⁸
  • 50% partial remission for an AHI of 2 to 4
  • 50% achieved a reduction in AHI to below 2

In cases of moderate or severe OSAS (AHI ≥ 5), spontaneous remission is less common. Obesity, a high BMI, persistent tonsillar hypertrophy, male gender, or African American ethnicity are unfavorable predictors of spontaneous remission of OSAS.⁷⁹

6.6.1.2. Oxygen Supply for SBAS¶

TOI: mean nocturnal tissue oxygen index

Unlike in adults, the TOI during sleep in children with SBAS does not appear to differ from that of healthy controls.⁸⁰
In cases of apnea and hypopnea, the decrease in TOI is preceded by peripheral and systemic desaturation.
TOI Falls More Sharply

• in cases of apnea as well as hypopnea
• during REM sleep than during other sleep stages
• in younger children than in older children
• in children with a high AHI rather than a low AHI

A study of 65 children with SBAS examined 540 obstructive and mixed apneas, 172 central apneas, and 393 obstructive hypopneas.⁸¹

• SpO2 decreased by an average of 4.1% (± 3.1%)
• TOI decreased by an average of 3.4% (± 2.8%)
• TOI declined more sharply
  • in cases of apnea (cessation of breathing) compared to obstructive hypopnea (reduced depth of breathing, shallower breathing)
  • in cases of moderate to severe SBAS compared to mild SBAS
  • in children up to 6 years of age compared to older children
    • Explanatory models: lower residual functional capacity, higher oxygen consumption, and immaturity of cerebral autoregulation in children⁸⁰
• Decreases in TOI correlated significantly with, regardless of the type of event,
  • Decreases in SpO2
  • Duration of the event
  • Age

A study of 60 children with SBAS analyzed 493 central and 399 obstructive events:⁸²

• Central oxygenation and heart rate changed more significantly during central events (apneas) than during obstructive events
• The changes were greater during NREM sleep than during REM sleep
• TOI changed more significantly among 3- to 6-year-olds than among 7- to 12-year-olds
• Heart rate fluctuated more among 7- to 12-year-olds than among 3- to 6-year-olds

Two studies found different results:

• Cerebral oxygenation did not correlate with the severity of SBAS. Primary snoring was associated with significantly poorer cerebral oxygenation than mild or severe OSA. Sleep disturbances, male gender, arousal index, and NREM sleep correlate with reduced cerebral oxygenation. An increase in mean arterial blood pressure, older age, higher blood oxygen saturation, and REM sleep were associated with higher cerebral oxygenation.⁸³
• SBAS in children aged 7 to 12 was associated with a significant increase (in cases of primary snoring, AHI ≤ 1) or a tendency toward an increase (in cases of mild and severe OSA) in cerebral oxygenation (TOI). This could possibly be a compensatory response to reduced arterial oxygen saturation during an apnea (cerebral autoregulation). In children aged 3 to 6 years, cerebral oxygen levels remained unchanged, regardless of the severity of SBAS. Cerebral oxygen levels did not correlate with cognitive deficits but did correlate with behavioral problems in children aged 7 to 12 years. In contrast to cerebral oxygenation, the oxygen extraction rate (O2-ER or FTOE, which measures tissue oxygen consumption) was lower in all SBAS groups during all sleep stages compared to controls. The SpO2 value was the same across all groups.⁸⁴

In adults, obstructive respiratory events (particularly during REM sleep and in relation to the duration of the event) were associated with⁸⁰

• Decrease in O2Hb
• TOI Acceptance
• Increase in HHb
• Increase in tHb

In adults, cerebral oxygen supply changed⁸⁵

• more pronounced during obstructive apneas than during obstructive hypopneas
• more severe in cases of severe OSA than in cases of mild or moderate OSA

Repeated drops in oxygen levels during sleep can damage the brainstem’s respiratory control centers, particularly during critical developmental stages, which can lead to long-term problems such as unstable breathing, cardiovascular strain, or neurological issues.⁸⁶

Hyperactivity was correlated with reduced blood oxygen saturation.⁸⁷

Hypoxia is a relevant developmental pathway for ADHD.⁸⁸

Neural inflammation may be another common pathway in the development of ADHD and SBAS.⁸⁹⁹⁰

6.6.1.3. ADHD in SBAS¶

One review reports a 50% correlation between ADHD and SBAS.⁸⁹
SBAS shows a moderate correlation with ADHD symptoms (Hedges’ g = 0.57, 95% confidence interval: 0.36–0.78; p = 0.000001). A high AHI was associated with lower effect sizes. (Meta-analysis, k = 18, n = 2,518)⁹¹ Adenotonsillectomy was associated with a reduction in ADHD symptoms 2–13 months after surgery (Hedges’ g = 0.43; SMD; 95% confidence interval = 0.30–0.55; p < 0.001; n = 529).

The risk of ADHD is increased in SBAS:⁹²

• by 1,106% for moderate and severe sleep problems⁹³
• by 759% (31.8% vs. 3.8% among children and adolescents aged 5 to 16) in orthodontic treatment:⁵⁸
  • Nocturnal enuresis: 13.6% vs. 0%
  • Overweight: 18.2% vs. 2.7%
• by 393% for mild sleep problems⁹³
• by 150% to 200%⁹⁴
• by more than 100%⁹⁵
• in children with SBAS
  • Hyperactivity^{9697 98 99}
    • increased by 150%¹⁰⁰
    • increased by 57%¹⁰¹
    • The cutoff on the BASC-2 PRF scale for hyperactivity was exceeded 6.82 times more often in children with persistent SBD compared to those who never had SBD (+582%)¹⁰²
  • Inattention^{10296 99}
    • increased by 110%¹⁰⁰
    • increased by 89%¹⁰¹
    • Elevated levels of¹⁰³ in NEPSY
  • Hyperactivity and inattention improved significantly following an adenotonsillectomy.
• Impaired executive functions
  • for 5-year-old children¹⁰⁴
  • on NEPSY¹⁰³
• Impaired memory functions
  • for 5-year-old children¹⁰⁴
• impaired general intellectual abilities
  • for 5-year-old children¹⁰⁴
• externalizing symptoms⁹⁶
  • for children ages 7 to 12 (CBCL and BRIEF)¹⁰⁵
  • The cutoff on the BASC-2 PRF scale for externalizing problems was exceeded 3.29 times more often in cases of persistent SBD compared to those who never had SBD (+229%)¹⁰²#
• Aggressiveness¹⁰²⁹⁶
  • increased by 110%¹⁰⁰
• reduced social skills¹⁰²
• impaired communication skills¹⁰²
• reduced adaptability¹⁰²
• Behavioral symptoms⁹⁹
  • (but no cognitive symptoms) in children aged 3 to 5¹⁰⁶
  • for children ages 7 to 12 (CBCL and BRIEF)¹⁰⁵
• internalizing symptoms⁹⁶
  • for children ages 7 to 12 (CBCL and BRIEF)¹⁰⁵

Children with Robin sequence (Pierre Robin sequence, PRS) suffer from a congenital combination of malformations:

• Underdeveloped lower jaw (micrognathia)
• tongue that falls backward (glossoptosis)
• resulting breathing difficulties caused by a blockage of the upper airways
• often accompanied by a cleft palate, which exacerbates breathing and feeding problems
• ADHD symptoms as a possible consequence of breathing difficulties¹⁰⁷
• PRS is a common feature of Stickler syndrome, a genetic disorder that causes underdevelopment of the midface

Among children aged 4 to 12 who visited a dental clinic, SBAS was associated with a more than 7.35-fold increased risk of ADHD medication, a 40% increased risk of asthma medication, and a 12.5-fold increased risk of other medications.⁵⁹

• SBAS continued to correlate with:⁵⁹
  • Allergies: 4.9 times
  • Developmental disorders: 4.94 times
  • Behavioral disorders: 3.94 times
  • Difficulty sleeping through the night: 3 to 6 times
  • Mouth breathing: 4.7 to 5 times
  • Snoring: 3 times
    • 70% of children with SBAS snore frequently¹¹⁰
  • fewer complications experienced during their own childbirth
  • 83.3% of parents reported that they snore, compared with 52.2% of parents of children without SBAS
• The use of ADHD medication was found to have a low-to-moderate correlation with mouth breathing (Phi = 0.216)
• Mouth breathing was moderately to strongly correlated with snoring (Phi = 0.386, p < 0.001).

Polysomnography studies found a correlation between ADHD and sleep-related disorders only in terms of increased nighttime movements.¹¹¹¹¹² Polysomnography is a sleep laboratory examination that measures brain waves (EEG), eye movements (EOG), heart activity (ECG), respiration, oxygen saturation, muscle activity (EMG), and body position.

A study reports increased snoring and breathing pauses in children with Down syndrome.¹¹³ Down syndrome is associated with a 50% prevalence of ADHD. For more information, see Monogenic Causes of ADHD.

A genomic correlation was found between ADHD and insomnia, daytime napping, daytime sleepiness, snoring, and short and long sleep duration. Insomnia, daytime sleepiness, and snoring shared genes with ADHD that are involved in neurobiological functions and regulatory signaling pathways.¹¹⁴

The upper quartile for the SBAS apnea-hypopnea index (AHI greater than 20.6/h) correlated (independently in each case) with⁶⁵

• metabolic syndrome (OR 2.80)
• Diabetes (OR 2.00)
• Depression (OR 1.92)
• High blood pressure (OR 1.60)

Children with ADHD are more likely to exhibit SBAS symptoms.¹¹⁵

6.6.1.4. Adenotonsillectomy for SBAS and Changes in ADHD Symptoms¶

Children aged 6 to 12 with SBAS showed a correlation between the lowest blood oxygen saturation levels and performance on the Modified Wisconsin Card Sorting Test. An adenotonsillectomy significantly improved the apnea-hypopnea index (AHI) and improved the mean scores on most neurocognitive and behavioral measures, although residual deficits persisted even after 6 months. However, nearly half of the children continued to suffer from SBAS. A baseline AHI > 5/h and complete resolution of SBAS (postoperative AHI < 1/h) correlated with improvement in more subscales than a baseline AHI < 5/h or incomplete resolution of SBAS. The impairment of neurocognitive performance in SBAS appears to be attributable more to hypoxemia than to the frequency of SBAS events.¹¹⁶
Children with SBAS who had undergone an adenotonsillectomy¹¹⁷

• showed, prior to surgery, compared to those not affected
  • common ADHD (DSM-IV)
  • frequent hyperactivity
  • increased inattention on cognitive tests
  • increased sleepiness in the Multiple Sleep Latency Test; more sleepy
• showed significant improvements in all measures after surgery and no longer differed from those without the condition
• The improvements could not be predicted by polysomnographic measurements prior to surgery

Among 64 children with SBAS (ages 3 to 12), there was a significant improvement in quality of life 4 years after adenotonsillectomy, but no improvement in behavior as measured by the CBCL.¹¹⁸
Among 20 children with OSA (ages 3 to 13), a significant improvement in ADHD symptoms, behavior, and snoring was observed 4.5 years after an adenotonsillectomy.¹¹⁹

Among 54 children with sleep-related gas exchange disorders (SAGEA), surgical tonsillectomy and adenoidectomy resulted in a statistically significant improvement in school performance, whereas performance remained unchanged in children who did not undergo surgery.¹²⁰

Children with mild (Apnea-Hypopnea Index (AHI) below 6 or Apnea Index (AI) below 1) SBAS (mean AHI of 3.1) and children with OSA (AHI of 5 or higher or AI of 1 or higher) (average AHI 25.3; range 10 to 48) showed no differences in BASC scores prior to adenotonsillectomy. After surgery, both groups showed a significant improvement in the behavioral symptom index, as well as in the BASC scales for atypicality, depression, hyperactivity, and somatization.¹²¹

Differences in Observation: Symptom Perception vs. Polysomnographic Measurement

Several studies have found that the severity of symptoms reported by parents or teachers correlates only to a limited extent with the results of polysomnographic measurements.

SBAS in children aged 5 to 17 showed the following results for the five domains of executive function (meta-analysis: k = 14, n = 1,697)¹²²

• during polysomnographic testing
  • 0.43 Generativity (SMD)
  • the other four areas of executive functions (vigilance, inhibition, working memory, and task switching) were not significantly
• for questionnaire surveys
  • significant for all three measured domains of executive functions, ranging from SMD 0.64 to 1.06
    • 0.64 Inhibition (SMD in the parent report)
    • 1.06 Working Memory (SMD as reported by parents)
    • 0.86 task switches (SMD in the parent report)
• The severity of SBAS did not affect executive functions

Children aged 7 to 12 years, who were divided based on nocturnal polysomnography into a control group (N = 34); primary snoring (PS: N = 55), mild obstructive sleep apnea (mild OSA: N = 22), and moderate-to-severe OSA (MS OSA: n = 16) showed deficits in working memory on the Behavior Rating Inventory of Executive Function (BRIEF) across all severity levels of SBAS. While a computer-based test (playing card recognition, CogHealth) found no difference between SBAS and controls, the mild OSA group performed significantly worse than the primary snoring group. Parents of children with primary snoring, however, reported more severe working memory deficits than those indicated by the objective measurement.¹²³

Among children aged 5 to 9 years with adenotonsillar hypertrophy and diagnosed sleep apnea, 42% no longer met the diagnostic criteria for sleep apnea after 7 months without surgery. This remission was statistically significantly more common among children with a lower AHI, better oxygen saturation, smaller waist circumference, a higher-positioned soft palate, smaller neck circumference, and non-black skin color. However, of the 167 children with baseline PSQ scores ≥ 0.33, only 15% achieved symptomatic remission. Symptomatic remission was predicted by low PSQ and PSQ snoring subscale scores, the absence of habitual snoring, loud snoring, observed apneas, or smokers in the household, a higher quality of life, fewer ADHD symptoms, and female gender. Only lower PSQ and snoring scores were independent predictors.
In summary, while a “wait-and-see” approach to polysomnography is often associated with the OSAS diagnosis being dropped, it is rarely associated with a significant improvement in symptoms.¹²⁴

Children aged 3 to 5 with SBD showed the following in a follow-up examination 3 years later:¹²⁵

• 60% of the children treated showed a resolution of SBAS
• 40% of the untreated children showed a resolution of SBAS
• “Cured” was defined as: a maximum OAHI of 1 per hour, no snoring observed during polysomnography, and no report of habitual snoring by the parents
• No cognitive differences between the “recovered,” “unrecovered,” and “control group”
• Behavioral functions were significantly worse in children with an initial diagnosis of SBAS compared to controls, regardless of whether they had recovered
• Changes in OAHI did not predict cognitive or behavioral outcomes
• A reduction in nighttime arousal, regardless of whether a complete recovery occurred, was associated with improved attention and reduced aggression

6.6.1.5. Risk Factors for Sleep-Related Breathing Disorders¶

Risk factors for sleep-related breathing disorders, particularly sleep apnea, include¹²⁶

• Sleep Mask (Standard Treatment)

• Alcohol
• Obesity
  • elongated soft palate
  • Retraction of the lower jaw
  • Fat deposits in the tongue and lateral pharyngeal wall

6.6.2. Snoring (up to +350%)¶

Primary snoring (snoring without OSA) differs from obstructive sleep apnea in terms of the number of hypopneas per hour.
Primary snoring is defined as an AHI of 1 or less, while OSA is defined as an AHI greater than 1.

6.6.2.1. Prevalence of Snoring¶

6.6.2.2. Snoring and ADHD Symptoms¶

Habitual snoring predicted hyperactivity in children 4 years later (+340%, OR 4.4), as did loud snoring (+350%, OR 4.5). The top 25% of snorers had a 5.3-fold increased risk of hyperactivity 4 years later (+430%). Sleepiness was associated with a 3-fold increased risk (+200%), and sleep-related breathing disorders with a 4-fold increased risk (+300%) of hyperactivity 4 years later.¹³⁷

Among children who snored occasionally or frequently, the prevalence of ADHD was doubled (+100%).¹³⁴

In contrast, a study of n = 512 snoring children and adolescents (70% of whom were overweight or obese and 35% of whom had an elevated obstructive AHI of more than 3/h) found that among the snoring children¹³⁸

• 36% exhibited hyperactivity/impulsivity
• 24% exhibited emotional dysregulation
• Surprisingly, it was not the reduced oxygen supply caused by sleep apnea that correlated with hyperactivity/impulsivity or emotional dysregulation, but rather the volume of the snoring

In a large study of children aged 6 to 12, various forms of snoring were associated with a 30% increase in scores for inattention, hyperactivity, and ADHD overall, as measured by the Korean ADHD-RS:¹³⁹

• Snoring more than half the time
• Always snores
• Loud snoring
• Heavy or loud breathing

Among children aged 5 to 7 who had not been diagnosed with ADHD and did not exhibit hyperactivity, frequent snoring was associated with¹⁴⁰

• Attention problems
• Social problems
• Symptoms of anxiety
• Symptoms of depression
• Lower cognitive scores

Children aged 6 to 10 years with habitual snoring who underwent polysomnography (PSG) showed elevated levels of, compared to controls,¹⁴¹

• Hyperactivity (ADHD Rating Scale)
• Inattention (ADHD Rating Scale)

ADHD symptoms in children aged 6 to 12 depended on the severity of their snoring:¹³⁰

• Children who snore frequently
  • 31.3% attention deficit
  • 18.2% hyperactivity/impulsivity
• children who occasionally snore
  • 16.2% attention deficit
  • 9.9% hyperactivity/impulsivity
• children who don’t snore
  • 13.9% attention deficit
  • 8.8% hyperactivity/impulsivity

Children aged 2 to 14 who had a hospital appointment showed:¹³²

• Hyperactivity: 22% among habitual snorers vs. 12% among non-snorers

The severity of snoring—but not the AHI—correlated in children aged 4 to 10 with¹⁴²

• Hyperactivity (CPRS-R)
• Inattention (CPRS-R)
• Cognitive abilities (NEPSY, DAS)
• Internalizing symptoms (CBCL)
• Externalizing symptoms (CBCL)
• Understanding instructions (NEPSY)
• The correlation between snoring and AHI was weak (rs = 0.24).

Among snoring children aged 5 to 7, an AHI of 5 or higher in the NEPSY study was associated with poorer scores in terms of¹⁴³

• Inattention
• Executive function problems

Habitual snoring in children and adolescents was associated with hyperactivity.¹³¹¹⁴⁴

A study of n = 405 children aged 4 to 9 years found clinically significant hyperactivity in 15.5% of the participants, compared with 5.3% of the controls (+188%). In addition, 11.1% were found to have a high probability of hyperactivity, compared with 4.1% in the control group (+170%).

A study found that children who snored had 43% higher rates of hyperactivity and 25% higher rates of inattention. Both measures improved significantly following an adenotonsillectomy.¹⁰¹

Habitual snoring among elementary school children was associated with:

• Hyperactivity increases¹⁴⁵ by 180%¹⁴⁶ by 140% ¹⁴⁷
• Inattention increases¹⁴⁵ by 340%¹⁴⁶ by 300%¹⁴⁷
• Increased defiant behavior¹⁴⁵
• Behavioral problems are 180% more common ¹⁴⁷
• Emotional problems are 450% more common¹⁴⁷
• Problems with peers are 870% more common ¹⁴⁷
• Daytime sleepiness is 970% more common¹⁴⁶
• UARS/OSA at 25%¹⁴⁶
• poorer academic performance¹⁴⁶
  • Mathematics + 160%
  • Natural Sciences + 230%
  • Spelling + 150%

The changes occurred 140% more frequently, regardless of intermittent hypoxia.¹⁴⁷ The behavioral problems improved when the snoring stopped.

Among adolescents, frequent snoring was associated with a 130% increased risk of ADHD.¹⁴⁸

A study using Mendelian randomization found no statistically significant association between sleep apnea or snoring and ADHD. ADHD was significantly correlated with shorter sleep duration.¹⁴⁹

Children with ADHD snored more frequently than those without the condition.^150151152

• 77.8% of children aged 6 to 14 with ADHD who underwent polysomnography snored heavily. Obstructive sleep apnea syndrome (OSAS) was found in 50.0% of them.¹⁵³
• 40% of children with ADHD sometimes snored louder than 60 dB, compared with 28% of the control group.¹⁵⁴
• 33% of children with ADHD (DSM-IV) snored, compared with 9% to 11% of those without the condition¹³⁵
• According to¹⁵⁵, 26.7% of children aged 5 to 13 with hyperkinetic syndrome snored
• 21% of all children with ADHD (average age 8.9 years) snored.¹⁵⁶

Adolescents who had been diagnosed with ADHD (DSM-IV) as children,¹⁵⁷

• and whose ADHD persisted into adolescence, 57.9% snored. Snoring was thus 3.5 times as common as among those without ADHD (+250%)
• and whose ADHD did not fully persist into adolescence (subclinical ADHD), 43.4% of them snored—2.0 times as often as those without ADHD (+100%)
• Snoring was thus 80% more common in cases of persistent ADHD than in cases of subclinical ADHD.
• 28.3% of the inspections that were not affected were suspended

ADHD at age 5 was associated with a 32% higher risk of snoring at age 14.¹⁵⁸
Among adolescents aged 10 to 17, 50.7% of people with ADHD-I and ADHD-C snored, compared to 33.2% of people without ADHD¹⁵⁹ In contrast, a small study found an increased prevalence of snoring only among people with ADHD-HI.¹⁶⁰

Even occasional snoring in children was associated with increased ADHD symptoms.¹⁶¹

After 6 months, methylphenidate improved snoring and bruxism in patients with ADHD-I.¹⁶²

6.6.2.3. Adenotonsillectomy for Snoring and Changes in ADHD Symptoms¶

In children who snore, an adenotonsillectomy improved:

• Attention/concentration by 42%¹⁶³
• verbal fluency by 92%¹⁶³
• Learning/memory by 38%¹⁶³
• executive functions by 52%¹⁶³
• general intellectual abilities by 33%¹⁶³
• Inattention by 21%¹⁶³
• Hyperactivity by 21%¹⁶³
• neurocognitive performance does not¹⁶⁴

See also under Differential Diagnosis: Primary Organic Disorders

6.6.3. Nasal turbinate constriction (+300%)¶

Hypertrophy of the inferior turbinate can cause sleep-related breathing disorders (SRBD) and ADHD symptoms.
The inferior turbinates account for up to 50% of the total resistance in the nasal airways.¹⁶⁵ Up to 20% of the population suffers from chronic nasal congestion due to turbinate hypertrophy.¹⁶⁶
Chronic hypertrophy of the turbinates—often caused by allergic rhinitis (hay fever) or chronic rhinosinusitis—can significantly impair nasal breathing even in the absence of adenotonsillar pathology.¹⁶⁷

A retrospective cohort study of n = 326 children aged 3 to 17 years (mean age 9 years, 65% boys) who underwent inferior turbinate reduction (ITR) between December 2020 and May 2023 (either as a standalone procedure or in combination with an adenotonsillectomy, septoplasty, or functional endoscopic sinus surgery) found that 32.5% of the participants exhibited ADHD-like symptoms prior to surgery. Twelve months after surgery, parents of these children reported:¹⁶⁷

• 89.6% improvement in nasal breathing
• 84.0% resolution of SBAS symptoms
• A 48.1% improvement in ADHD symptoms, which correlated significantly with an improvement in nasal breathing

Assuming an ADHD prevalence of 8% among children and assuming that ADHD symptoms are equivalent to an ADHD diagnosis, a figure of 32.5% would indicate a 300% increased risk of ADHD.

A study found a significant improvement in sleep quality, but no improvement in ADHD symptoms, following nasal septum surgery (straightening of a deviated nasal septum).¹⁶⁸

6.6.4. Enlarged pharyngeal and palatine tonsils (adenotonsillar hypertrophy) (up to +275%)¶

**Adenotonsillectomy: Surgical removal of the palatine tonsils and pharyngeal adenoids, often due to recurrent infections or enlargement that leads to breathing problems such as obstructive sleep apnea. A common standard treatment for children with moderate to severe sleep apnea syndromes. It can improve breathing problems, behavioral issues, and daytime sleepiness.
**Adenotomy: Surgical removal of only the pharyngeal tonsils (adenoids, childhood polyps)
**Tonsillectomy: Surgical removal of only the palatine tonsils (tonsils, throat tonsils)

Adenotonsillar hypertrophy is the most common cause of SBAS in children.⁵⁷¹⁶⁹
Chronic adenotonsillar hypertrophy can lead to various types of sleep-related breathing disorders, ranging from loud snoring to severe obstructive sleep apnea. Chronic adenotonsillar hypertrophy can disrupt sleep architecture, e.g., through increased arousal during sleep, increased REM sleep latency, reduced REM sleep, and decreased sleep efficiency.
or reduced sleep duration.¹⁷⁰¹⁷¹
Enlarged tonsils usually occur especially during the first few years of life and typically—though not necessarily—reduce in size during late childhood.
The loss of nasal function during breathing can contribute to chronic inflammation of the upper respiratory tract.

6.6.4.1. Prevalence of Adenotonsillar Hypertrophy¶

6.6.4.2. Adenotonsillar Hypertrophy and ADHD Symptoms¶

The prevalence of ADHD among children with adenotonsillar hypertrophy was (compared to an estimated prevalence of 8%)

• 30% (+275%)¹⁷⁶
• 30% (+275%)¹⁷⁷
• 27.1% (+238%)¹⁷⁸
• 26.8% (+235%)¹⁷⁹

In a group of n = 35 children aged 5 to 12 years with adenotonsillar hypertrophy and ADHD (DSM-IV), an adenotonsillectomy** Resulted in the following six months after surgery:¹⁸⁰

• 57.8% reduction in ADHD-C (22.9% after surgery compared to 54.3% before surgery).
• Significantly reduced inattention
• Hyperactivity significantly reduced
• significantly reduced combined ADHD symptoms

Children with ADHD aged 6 to 12 had a 2.71-fold increased risk of adenotonsillar hypertrophy.¹⁷⁵

Impaired cognitive function and behavior in children aged 6 to 12 correlated with snoring, sleep efficiency, sleep latency, and ethnicity, but not with tonsil size. Snoring correlated more strongly with these deficits than the number of apnea and hypopnea episodes per hour of sleep.¹⁸¹

6.6.4.3. Adenotonsillectomy for Adenotonsillar Hypertrophy¶

Adenotonsillectomy in Children with ADHD and Adenotonsillar Hypertrophy

• ADHD was resolved in 50% of patients 6 months after surgery. ODD remained unchanged.¹⁷⁶
• resolved ADHD in 70% of patients 6 months after adenotonsillectomy¹⁸²
• reduced (even more pronounced after 6 months than after 3 months):¹⁸³
  • Oppositional behavior
  • Inattention / cognitive symptoms
  • Hyperactivity
  • Overall ADHD symptoms
• showed improvement in children with ADHD, as well as in children without ADHD.¹⁸⁴
  • Oppositional behavior
  • Inattention / cognitive symptoms
  • Hyperactivity
  • Overall ADHD symptoms
  • In a long-term follow-up, the scores did not worsen 2.4 to 3.6 years after surgery and remained—with the exception of the ADHD total score—significantly better than the scores before surgery.¹⁸⁵
• improved ADHD symptoms to a greater extent than treatment with MPH alone without surgery, with symptoms dropping to nearly the same level as those of people without ADHD after the surgery¹⁸⁶
• significantly improved the scores of children and adolescents with SBAS and ADHD (according to DSM-IV) in ^{187188179189190}
  • Hyperactivity
  • Inattention
  • Total ADHD score

Similarly, 54% of children with enuresis no longer experienced it after the surgery.¹⁸⁸

Among 26.3% of children (ages 3 to 7) who underwent an adenotonsillectomy, sleep apnea (AHI greater than 2) was still present one year later.¹⁹¹

6.6.5. Breathing pauses during sleep (sleep apnea, OSA, OSAS) (+100%)¶

Sleep apnea (obstructive sleep apnea syndrome, OSA, OSAS) is measured using the apnea-hypopnea index (AHI). This index indicates the number of complete breathing pauses (apneas) and partial breathing disturbances (hypopneas) per hour of sleep. An AHI below 5 is considered normal; 5 to 14 indicates mild sleep apnea; 15 to 30 indicates moderate sleep apnea; and an AHI of more than 30 indicates severe sleep apnea.¹⁹²

6.6.5.1. Prevalence of OSA¶

OSA is associated with hypoxia, arousal episodes during sleep, and negative fluctuations in intrathoracic pressure. The consequences may include e⁷⁹

• Strain on the cardiovascular system.
  • peripheral vasoconstriction
  • intermittent increases in blood pressure (increased blood pressure variability)
  • increased heart rate
  • reduced heart rate variability
  • Treatment of OSA improves cardiovascular factors.⁷⁹
• Activation of the sympathetic nervous system
  • elevated urinary catecholamine levels
• increased oxidative stress
• systemic inflammation
• endothelial dysfunction
• reduced nocturnal baroreflex gain
  • with consequences of increased fluctuations in blood pressure
• subclinical abnormalities in heart structure and function that are detectable only by ECG
• Enuresis
  • improved through OSA treatment
• Growth restriction
  • Size and Weight
  • improved through OSA treatment
• Excessive daytime sleepiness
  • improved through OSA treatment
• Reduced quality of life
  • improved through OSA treatment
• ADHD (see below)
  • Hyperactivity
  • Inattention
  • cognitive limitations
  • impaired executive functions
  • improved through OSA treatment

The prevalence of insomnia in OSA ranges from 39% to 55%.¹⁹⁵

6.6.5.2. ADHD Symptoms in OSA¶

Sleep-related breathing pauses in children can cause symptoms that resemble ADHD.¹⁹⁸
It remains unclear whether sleep apnea can cause enough stress to contribute to ADHD through epigenetic changes, or whether it merely causes symptoms that resemble those of ADHD. In the latter case, people who did not previously have ADHD and who developed ADHD-like symptoms due to sleep apnea would have to see those symptoms disappear completely once the sleep apnea is resolved. To date, we are not aware of any studies on this topic.

Among children with OSA, the prevalence of ADHD was doubled (+100%).¹³⁴

Children aged 6 to 10 with OSA who had undergone polysomnography (PSG) showed elevated levels of¹⁹⁹

• Hyperactivity (ADHD Rating Scale)
• Inattention (ADHD Rating Scale)

Among 110 boys aged 6, SBAS was correlated with hyperactivity but not with inattention.²⁰⁰

Children aged 4 to 12 years with mild or moderate OSAHS diagnosed by polysomnography showed, compared to healthy controls,²⁰¹

• FIQ, VIQ, and performance IQ (PIQ) scores did not correlate with AHI, OAHI, and the lowest nocturnal SO2 value
• under 6 years old
  • significantly lower scores on the full-scale IQ (FIQ), verbal IQ (VIQ), comprehension test, and visual analysis test
  • The cumulative time with SO2 levels below 90% (p = 0.046) and the percentage of cumulative time with SO2 levels below 90% during total sleep time (p = 0.034) were significantly negatively correlated with the PIQ
• Starting at age 6, significantly lower IQ and classification test scores in children with OSAHS

Children with ADHD have a significantly higher AHI (apnea-hypopnea index). (METASTUDY, k = 16, n = 1,360)²⁰² A case study of three adults with ADHD and OSA drew attention to this issue early on.²⁰³

Children with ADHD but without OSA, aged 6 to 13, showed normal sleep patterns on polysomnography.²⁰⁴

Compared to children with OSA but without ADHD, children with both OSA and ADHD showed:²⁰⁵

• Elevated AHI values
• Increased blood oxygen saturation
• Increased IL-4
• Increased IL-12
• Elevated IL-13
• transforming growth factor (TGF)-β significantly lower
• Elevated dopamine levels (presumably peripheral)
• Norepinephrine levels significantly lower (presumably peripheral)
• Elevated serum leptin levels
• Adiponectin decreases
• Reduces resistin

6.6.5.3. Adenotonsillectomy for OSA and Changes in ADHD Symptoms¶

Children with OSA due to grade 3 and 4 adenotonsillar hypertrophy exhibited cognitive impairment (lower NESPY score). An adenotonsillectomy improved these outcomes and reduced serum cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. Lifestyle interventions were effective in cases of mild OSAS and minimal cognitive impairment and improved the outcomes of adenoidectomy prior to surgery. Among the participants, 33.5% were overweight and an additional 55.8% were obese. Tonsillar hypertrophy was grade 4 in 27.7%, grade 3 in 44.2%, grade 2 in 27.2%, and grade 1 in 0.9%. Adenoid hypertrophy was grade 0 in 5.4%, grade 1 in 5.7%, grade 2 in 41.1%, grade 3 in 36.2%, and grade 4 in 11.5%. Neither tonsillar hypertrophy nor adenoid hypertrophy correlated statistically significantly with the OSA AHI score. Severe OSA was associated with a tendency toward increased adenoid hypertrophy.²⁰⁶ Of the 181 patients with grade 3 or 4 adenotonsillar hypertrophy, 19 underwent adenoidectomy, 76 underwent tonsillectomy, and 86 underwent adenotonsillectomy. A tonsillectomy or adenotonsillectomy was required significantly more often in cases of severe OSA. Cognitive performance (NEPSY score) was significantly worse before treatment in patients with severe OSA than in those with mild OSA. At follow-up, cognitive performance improved in 76.7% of patients with mild OSA, 84.1% with moderate OSA, and 87.8% with severe OSA.
The reduced serum levels of inflammatory cytokines suggest that OSA plays a role in inflammatory processes.

In children aged 5 to 9 years with an OAI (apneas per hour of sleep) of 1 to 20 or an AHI (apneas or hypopneas per hour of sleep) of 2 to 30, adenotonsillectomy was associated with slight improvements (SMD Cohen’s d, 0.20 to 0.24) with respect to²⁰⁷

• nonverbal thinking
• Fine motor skills
• selective attention

A study of children with OSA without prolonged desaturation of blood oxygen levels found that early adenotonsillectomy, compared with a watch-and-wait approach with supportive treatment, resulted in a trend toward (SMD 0.15), but not statistically significant improvement in attention and executive function scores on the Developmental Neuropsychological Assessment. However, compared to a watch-and-wait approach, early adenotonsillectomy correlated with significantly greater improvements in:⁷⁷

• Behavior
• Quality of life
• polysomnographic findings (79% normalization compared to 46%)
• ADHD symptoms (SMD 0.28 on the parent rating and SMD 0.29 on the teacher rating of the Conners Rating Scale)

Children with OSA showed

• Before an adenotonsillectomy

  • Significantly poorer cognitive performance compared to the control group; postoperatively, there was no longer any difference in the scores.²⁰⁸

• After an adenotonsillectomy

  • A statistically insignificant trend toward higher scores on the Homework Performance Questionnaire (HPQ-P).²⁰⁹
  • Moderate improvement in executive functions²¹⁰
  • Attention moderately improved²¹⁰
  • Moderate improvement in motor skills²¹⁰
  • Moderate improvement in internalizing behaviors (parent report)²¹⁰
  • moderate improvement in externalizing behaviors (parent report)²¹⁰

Among 52 children with OSA (age 7.1; 2.5–14.9 years) (AHI 16.2; 5.0–88.0), mean BASC-t scores for all behavioral scales and composites exceeded 50 prior to adenoidectomy and tonsillectomy. Following the procedure, significant improvements were observed for:²¹¹

• Aggression
• Atypicality
• Depression
• Hyperactivity
• Somatization

Elevated levels of IL-6, IL-8, IL-17, IL-18, MIF, Hs-CRP, TNF-α, PAI-1, and leptin were found to correlate with OSA; of these, only IL-18 did not also correlate with BMI, whereas IL-23 additionally correlated with BMI.²¹²

Children aged 6 to 12 with a low AHI (1 to 4) showed no statistically significant impairments in neuropsychological functions (intelligence, verbal and nonverbal reasoning, attention, executive functions, memory, processing speed, and visuomotor skills).²¹³

6.6.5.4. Risk Factors for OSA¶

The STOP-BANG questionnaire provides a rough risk assessment for obstructive sleep apnea.

1. Do you snore loudly (louder than when you speak, or loud enough to be heard through a closed door)?
2. Do you often feel tired or sleepy during the day?
3. Has anyone ever noticed that you stop breathing while you sleep?
4. Are you currently being treated for high blood pressure, or have you been treated for it in the past?
5. BMI greater than 35 kg/m² (BMI = weight in kg / (height in m) x (height in m))
6. Are you over 50?
7. Neck circumference greater than
   • 40 cm for women
   • 43 cm for men
8. Gender: Male

If you answer “yes” to 3 of these questions, you have a 50% risk of OSA.¹²⁶
The more “yes” answers you give, the more strongly we recommend undergoing a polygraph test (using a home testing device).
Polysomnography (sleep lab) is performed only in the second step.

6.6.5.5. Treatment Options for OSA¶

There are various treatment options for OSA:¹²⁶

• Sleep Mask (Standard Treatment)
  • After 3 years, half of OSA patients stop using a sleep mask.
• Nighttime mandibular advancement splint (covered by insurance only if the mouthguard does not work)
  • Pushes the lower jaw forward
• Tongue pacemaker (not covered by insurance, expensive)
• Position sensors that prevent the patient from lying on their back
  • It seems to be just as effective as a sleep mask
• Medications (currently only in research; not yet in clinical use)
• Weight Loss
  • GIP/GLP-1 receptor agonist: 20% weight loss after 52 weeks + AHI reduced by 25 to 30²¹⁴

6.6.6. Upper Airway Resistance Syndrome (UARS)¶

While OSA is characterized by apneas (breathing pauses) and hypopneas (reduced breathing depth) that last more than 10 seconds (2 to 3 breaths) and are often accompanied by a drop in blood oxygen levels and an increase in CO2, upper airway resistance syndrome (UARS) is associated with shorter breathing pauses.⁵⁶

Boys are affected more often because testosterone leads to muscle growth. While the craniofacial skeleton develops in early childhood, testosterone-induced muscle growth—including that of the tongue and throat muscles—does not begin until puberty, within a spatial structure that has already been defined by the bone structure.
In addition to a genetic predisposition, increased nasal resistance is influenced by various environmental factors:⁵⁶

• Allergies
• Infections
• abnormal enlargement of the nasal lymphatic tissue (which, in turn, is exacerbated by allergies and infections of the respiratory tract or ears)

In newborns, the following symptoms appear:⁵⁶

• increased respiratory effort, lasting longer than four breaths, as measured by the rate of exhalation
• a sudden increase in respiratory effort accompanied by a negative peak end-expiratory effort, immediately followed by a cessation of diaphragmatic movement for two or more breaths. These are not central apneas, but rather a response to the sudden increase in respiratory effort
• an abrupt increase in respiratory rate of 4 or more breaths without an increase in respiratory effort. The increase in respiratory rate serves to compensate for the decrease in
  Tidal volume
• These events occur without a significant decrease in oxygen saturation (pulse oximeter) or oxygen tension (transcutaneous P o 2 electrode)

In infants, the following symptoms appear:⁵⁶

• more pronounced nighttime symptoms
• Possible difficulty sleeping through the night; crying upon waking at night
• Thumb-sucking can promote a change in tongue position; the combination of pressure and suction can reduce the initial resistance to inhalation, especially
  when breathing through the mouth
• less commonly, talking in one’s sleep
• Restless sleep
• Night sweats, the severity of which correlates with fluctuations in nasal resistance
• The head may be hyperextended
• Sleeps on her stomach more often, sometimes every night with her knees tucked under her stomach and her bottom raised
• breathing through the mouth, at least some of the time
• occasional snoring
• Enuresis is possible
• A long head with a narrow jaw favors UARS

Often accompanied by:

• more frequent earaches
• frequent respiratory infections
• Respiratory allergies

Behavioral problems can be a consequence of this age:⁵⁶

• Attention problems
• Hyperactivity
• rebellious behavior
• unexplained aggression toward peers
• significant shyness
• Anxiety

In school-age children and teenagers, the following symptoms appear:⁵⁶

• common:
  • Hyperactivity
  • Attention Disorders
  • Poor academic performance
  • occasional daydreaming (teacher’s report)
  • Daytime sleepiness
  • Normal weight to underweight
• possible:
  • Drowsiness
  • Difficulties with peers
  • Aggressiveness
  • mild autonomic dysfunction
    • cold hands and/or feet
    • Dizziness or lightheadedness when bending over or standing up suddenly

.

• Sleep patterns:
  • frequent snoring
  • continuous movements
  • Difficulty getting up in the morning
    • Teenagers are often hard to wake up in the morning
      • late for school / for training
      • shifted circadian rhythm (eveningness)
      • Daytime sleepiness
      • Exhaustion at the end of the day
      • Anxiety during the day
  • night sweats
  • morning headaches
  • Enuresis
  • Conversations in Sleep
  • Sleepwalking
    • especially among teenagers
    • sometimes accompanied by nightmares or sleep disturbances
  • Teeth grinding

Treatment options for children:
- Tonsillectomy
- adenoidectomy, if necessary
- Orthodontic treatment, if necessary:
- slow maxillary distraction
- maxillary and/or mandibular expansion
- Braces
- Removing wisdom teeth in cases of a narrow jaw

6.7. Gastroesophageal Reflux (+248%)¶

Gastroesophageal reflux disease (GERD) increased the risk of ADHD between the ages of 3 and 5 (HR = 3.48) (registry study, n = 631,695).²¹⁵
ADHD increases the risk of GERD.²¹⁶

It is not clear from the abstract whether the study actually deals with GERD in the children themselves. We have not yet been able to access the full text of the study.

6.8. Anorectal malformations (+200%)¶

Anorectal malformations are congenital abnormalities of the anal canal and are associated with an increased risk of ADHD, depression, and anxiety disorders.²¹⁷

• A threefold increased risk of ADHD and ASD²¹⁸
• ADHD medications are prescribed 2.26 times as often²¹⁸

6.9. Febrile seizures (+168%)¶

According to clinical and animal studies, febrile seizures have harmful effects on neurodevelopment, which can lead to ADHD, increased susceptibility to epilepsy, hippocampal sclerosis, and cognitive decline in adulthood.²¹⁹
Febrile seizures in children increased the risk of ADHD by

• 168% (91% unadjusted) (meta-analysis, k = 12, n = 958,082)²²⁰
• 66%²²¹
• 28%²²²

6.10. D-3 deficiency (+157%)¶

A meta-analysis of 10,334 children and adolescents found a 2.57-fold increased risk of ADHD in cases of vitamin D3 deficiency (between 10 and 30 mg/nl in blood plasma).²²³

Comprehensive information on vitamin D3 at Vitamin D In the article Vitamins for ADHD in the section Vitamins, Minerals, and Dietary Supplements for ADHD in the chapter Treatment

6.11. (Untreated) Type 1 diabetes (+145% to +719%)¶

People with type 1 diabetes were found to have an increased risk of ADHD:²²⁴

• 8.19-fold increased risk of ADHD (HR = 8.19)²²⁵
• A 2.45-fold increased risk of ADHD among untreated participants in a study of people with ADHD, both those treated with and those not treated with an insulin pump, in which ADHD was considered a risk factor for inconsistent diabetes management²²⁶
• 1.68 times the risk of ADHD (4.2% vs. 2.5%)²²⁷
• Among people with type 1 diabetes, 15.9% had a prior ADHD diagnosis, and an additional 31.9% met the ADHD criteria of the ASRS.²²⁸ Assuming an ADHD prevalence of 8%, this would represent a doubling (+100%). However, the participants were those who had responded to the ASRS that was sent to them, so a bias toward an inflated ADHD rate is to be expected here.
• Children with diabetes have a higher prevalence of ADHD, ASD, seizures, and depression, as well as a tendency toward lower IQ scores and poorer academic performance²²⁹

A study found no evidence of a causal link between autoimmune diseases such as type 1 diabetes and ADHD.²³⁰

In addition to regulating blood sugar levels, insulin also plays a role in the brain:²²⁹

• acts on the IR in brain astrocytes, which affects dopaminergic signaling and can thus modulate cognition and mood
• increases the number of NMDAR channels in the cell membrane through regulated exocytosis
  • NMDARs regulate the influx of calcium ions into the cell and trigger long-term potentiation (LTP), which is associated with learning and memory processes
• affects the activity of AMPA receptors in the hippocampus
  • This leads to LTD in the CA1 region, which downregulates the receptor—a process that is important for memory consolidation and flexibility
• affects brain development
  • regulates the proliferation, differentiation, and growth of neurites²³¹
• responsible for memory consolidation
• increases GABA receptors in the hippocampus
• Insulin deficiency leads to diabetic neurological complications in older adults and children
• Insulin activates phosphatidylinositol (PI)-3-kinase, which increases the externalization of DAT to the membrane surface. Chronic hypoinsulinemia, such as that seen in diabetes, appears to reduce the amount of DAT available on the cell surface.²³² This increases extracellular dopamine and, to the best of our understanding, is likely to reduce phasic dopamine, since less dopamine enters the cell to be stored in vesicles and released in response to signals.

6.12. Premenstrual Syndrome (PMS) / Premenstrual Dysphoric Disorder (PMDD) (+143%)¶

A study of 290 women with severe PMD/PMDD found increased risks for:²³³

• ADHD: 2.43 times (+143%)
• AuDSH: 3.27 times (+227%)

The risk of ASD without ADHD remained unchanged.

6.13. Dystrophinopathy (muscular dystrophy, muscle weakness) (+130%)¶

See the section below on Monogenic Causes of ADHD.

6.14. Atopic disorders (excess immunoglobulin E)¶

Atopy is a genetic predisposition to have hypersensitive (allergic) reactions to environmental substances that are otherwise harmless.

In children with low birth weight, a history of type 2 inflammatory diseases such as asthma and atopic dermatitis increased the risk of:²³⁴

• ADHD by 81%
• Learning disability by 74%
• ASS by 47%
• intellectual disability of 35%

Atopic disorders were associated not only with an increased risk of ADHD but also with the severity of ASDHS symptoms.²³⁵

6.14.1. Respiratory allergies (+83% to 108%)¶

For the percentages in the headline, the lowest and highest results were omitted because there were a sufficient number of studies.

Children with an allergy to respiratory medications had an ADHD prevalence of 12.16% compared with 7.63% among children without such an allergy. After adjusting for covariates, the increased risk was +50%.²³⁶

Allergic rhinitis increased the risk of ADHD

• 3.96 times higher (+296%, OR 3.96). (Meta-analysis, k = 2, n = 132,561)²³⁷
• 2.08 times (+108%)²³⁸
• 1.83 times higher (+83%; meta-analysis, k = 18, n = 4,289,444)²³⁹
  • Women are 1.86 times more likely than men (+86%)
  • Children up to age 8 are 1.75 times more likely to be affected than older children (+75%)
  • ASS: 1.90-fold risk (+90%)

ADHD increased the risk of allergic rhinitis

• 1.85 times higher (+85%, OR 1.84) (meta-analysis, k = 10, n = 397,799)²³⁷
• a 1.38-fold increase across all studies (+38%; meta-analysis, k = 18, n = 4,289,444)²³⁹
  • Women compared to men: an additional +86% (meta-analysis, k = 18, n = 4,289,444)²³⁹
  • Children up to age 8 compared to older children: an additional +75% (meta-analysis, k = 18, n = 4,289,444)²³⁹
  • a 1.90-fold increase in a cohort study (+90%; meta-analysis, k = 18, n = 4,289,444)²³⁹
• a 1.27-fold increase (+27%) in a genetic association study²⁴⁰

• Allergic rhinitis was found in children with ADHD (ages 6 to 12) at¹⁷⁵
  • 26.6% of those with sleep disorders
  • 13.8% of those without sleep disorders

A systematic review (k = 21 meta-analyses, n = 348,405,029) found, with highly suggestive evidence (Class II), that allergic rhinitis (hay fever) increased the risk of:²⁴¹
- for tic disorders, by 161% (OR 2.61)
- for sleep disorders, by 171% (OR 2.17)

6.14.2. Food allergies (+72%)¶

A food intolerance is a reaction of the digestive system, whereas a food allergy is a reaction of the immune system.
Food allergies are part of the atopic spectrum.²⁴²

Children with a food allergy had an ADHD prevalence of 12.66% compared with 7.99% among children without such an allergy. After adjusting for covariates, the increased risk was +72%.²³⁶

Food allergies may mediate behavioral abnormalities via the microbiota-gut-brain axis (MGBA), specifically through the gut microbiota and amino acid metabolites.²⁴³ People with food allergies exhibit different microbiome profiles compared to those without food allergies. Microbial interventions can support the restoration of gut microbiome structure, e.g.:²⁴⁴

• Nutrition
• Probiotics (live microorganisms such as bacteria and yeasts)
• Prebiotics (indigestible dietary fiber)
• Synbiotics (a combination of probiotics and prebiotics)
• Fecal transplant²⁴⁵²⁴⁶

6.14.3. Atopic eczema (+72%)¶

Eczema increased the risk of ADHD by a factor of 1.72 (+72%).²³⁸

6.14.4. Skin allergies (+65%)¶

Children with a skin allergy had an ADHD prevalence of 11.46% compared with 7.83% among children without such an allergy. After adjusting for covariates, the increased risk was +65%.²³⁶

6.14.5. Asthma (+34% to +62%)¶

While respiratory allergies affect the upper respiratory tract, allergic asthma affects the lungs.

A systematic review (k = 21 meta-analyses, n = 348,405,029) found that asthma increases the risk of ADHD by 34% (OR 1.34), based on convincing evidence (Evidence Class I).²⁴¹
Based on highly suggestive evidence (Class II), asthma increased the risk of

• Depression by 64% (OR 1.64)
• Anxiety by 95% (OR 1.95)
• tic disorders by 90% (OR 1.90),
• Suicidal thoughts: 52% (OR 1.52)
• Suicide attempts: 60% (OR 1.60)

• Asthma was found in children with ADHD (ages 6 to 12) at¹⁷⁵
  • 10.7% of those with sleep disorders
  • 5.3% of those without sleep disorders

A large study found an association between ADHD and asthma in children of +79% before and +62% after adjusting for all covariates. ADHD causally increased the risk of asthma in children by 27%.²⁴⁷
Children with bronchial asthma are more likely to have ADHD (SMD 0.29; meta-analysis, k = 7, n = 104,975).²⁴⁸

A genetic association study found no causal increase in the risk of ADHD due to asthma.²⁴⁰

6.14.6. Neurodermatitis / atopic dermatitis (+11.6% to +28%)¶

The highest and lowest values were excluded when calculating the figures in the headline.

Neurodermatitis / atopic eczema / atopic dermatitis in childhood is associated with an increased risk of ADHD.²⁴⁹

A systematic review (k = 21 meta-analyses, n = 348,405,029) found, with highly suggestive evidence (Class II), an increased risk in patients with atopic dermatitis²⁴¹

• for ADHD, by 28% (OR 1.28)
• for depression, by 60% (OR 1.60)
• for anxiety by 62% (OR 1.62)
• for suicidal thoughts, by 44% (OR 1.44)

A study conducted in Saudi Arabia among people with atopic dermatitis found a prevalence of ADHD of 20.9% among children and 18.9% among adults. Atopic dermatitis was not correlated with the severity of ADHD symptoms.²⁵⁰

A study found evidence that a predisposition to atopic dermatitis causally increases the risk of ADHD (+11.6%) and ASD (+13.1%). Conversely, a predisposition to ADHD (+11.2%) and anorexia nervosa (+10%) was associated with an increased risk of atopic dermatitis. Only the causal relationship between AD and ASD was independent of bias caused by the reverse effect.²⁵¹
In cases of urticaria, the risk of ADHD increased by 9%.²⁵²

People with ADHD had a 45% increased risk of atopic dermatitis (OR = 1.45).
People with atopic dermatitis had a 34% to 42% increased risk of ADHD (OR = 1.34; HRs = 1.42); in cases of severe atopic dermatitis, the risk of ADHD was 162% higher (OR = 2.62); by 189% in cases of multiple allergic conditions (OR = 2.89), and by 143% in cases of atopic dermatitis with concurrent sleep disorders (ORs = 2.43). (Meta-analysis, k = 49)²⁵³

In contrast, a cohort study found no significant (+2%) increase in the risk of ADHD among children with atopic dermatitis.²⁵⁴
A cohort study of n = 69,732,807 people found an increased risk of learning difficulties (OR = 1.77) and memory problems (OR = 1.69) among individuals with atopic dermatitis.
The increase in risk was unevenly distributed: Among children with neurodevelopmental disorders such as ADHD, the risk of memory or learning difficulties was 2 to 3 times higher. In contrast, among children without neurodevelopmental disorders, atopic dermatitis did not alter the risk of learning or memory difficulties.²⁵⁵

6.15. Hyperthyroidism / Overactive Thyroid (+70%)¶

A study found that the prevalence of ADHD was 1.7 times higher among children with hyperthyroidism.²⁵⁶
Children with ADHD showed

• significantly higher T4 levels (total thyroxine).²⁵⁷
• Significantly reduced FT4 (free thyroxine) and TT3 (total triiodothyronine) levels (meta-analysis, k = 12, n = 11,836)²⁵⁸, Children with ASD showed reduced FT4 and unchanged TT3.

Hyperthyroidism can cause ADHD-like symptoms, including anxiety, nervousness, irritability, and physical hyperactivity. One study found a correlation between elevated TSH levels and hyperactivity in ADHD.²⁵⁹

Hyperthyroidism can cause inattention and hyperarousal, among other cognitive deficits. Depending on the severity of hypothyroidism, the cognitive effects can range from mild impairments in memory and attention to full-blown dementia.²⁶⁰²⁶¹

The THRA gene encodes the thyroid receptor alpha (TRα1), while the TRHB gene encodes the thyroid receptor isoforms TRβ1 and TRβ2.
The pituitary hormone TSH (thyroid-stimulating hormone) stimulates the thyroid gland to produce thyroxine (T4; prohormone) and subsequently 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.
In cases of (rare, genetically determined) resistance to thyroid hormone β, this negative feedback loop—which stabilizes TH levels in the blood—is disrupted. This leads to elevated TH levels and unsuppressed—i.e., normal—TSH levels.²⁶²

One cause of hyperthyroidism is Graves’ disease. The prevalence of Graves’ disease in the United States was reported in 1972 to be between 0.02% and 0.4%, with children accounting for 5% of cases.²⁶³ Today, in countries with adequate iodine intake, the prevalence is estimated to be 2% to 3% among women and 0.2% among men. Most cases occur between the ages of 30 and 60. Other sources report that the highest incidence occurs between the ages of 11 and 15.²⁶⁴
There is evidence of an increased risk of ADHD in patients with Graves’ disease.^{265266 267} A small study reports a twofold increase in ADHD prevalence.²⁶⁸ A medical practice reports hyperactivity in 85% of the people with ADHD (n = 21), which subsided in 20 of them following treatment for hyperthyroidism.²⁶³

For information on the effects of abnormal thyroid hormone levels during pregnancy, see Prenatal Stressors as Environmental Causes of ADHD

6.16. Nutrition and Food Intolerances¶

6.16.1. High-sugar diet (+41%)¶

A diet high in refined sugar and saturated fats during childhood increased the risk of ADHD by 41%, while a healthy diet reduced the risk of ADHD by 35%. (Meta-analysis, k = 14 studies)²⁶⁹ Compared to a healthy diet, an unhealthy diet therefore increases the risk by 117%.

A study found a correlation between sugar intake at 30 months and the risk of ADHD, sleep disorders, and anxiety. No correlation was found at 12 months of age.²⁷⁰
In an Egyptian study, a child’s daily consumption of sweets was associated with a 6.82-fold increased risk of ADHD (+582%).²⁷¹ It remains unclear whether this represents a causal relationship or a consequence of altered food preferences resulting from a predisposition to the disorder.

6.16.2. Highly processed foods (up to +25%)¶

A high percentage of highly processed foods in children aged 3 to 4 increased the risk of ADHD at ages 12 to 13 by 25% (RR 1.25).²⁷²

6.16.3. Commercially packaged pasta¶

Children who consumed commercially packaged pasta three times or more per week were found to have a 57-fold increased risk of ADHD.²⁷¹
It remains unclear whether this is related to the ingredients in commercially packaged pasta in Egypt, to food preferences resulting from ADHD, or to the family’s low socioeconomic status.

6.16.4. Unpackaged flour¶

According to an Egyptian study, the use of unpackaged flour in cooking was associated with a 44-fold increased risk of ADHD.²⁷¹

6.16.5. Food Intolerances¶

A food intolerance is a reaction of the digestive system, whereas a food allergy is a reaction of the immune system.

It has been established that ADHD is not caused by any single, specific food, phosphates, or additives.

However, individual food intolerances or allergies are just as much stressors as illnesses, toxins, or psychological stress, and can therefore exacerbate the stress experienced by people with ADHD to the point that symptoms develop. This is not an observation specific to ADHD. For example, in a group of children with schizophrenia-related issues, dietary treatment of an existing gluten intolerance eliminated the schizophrenia symptoms in the affected children.²⁷³²⁷⁴ The same was observed in people with ADHD.²⁷⁵

Food additives (in this case: Sun Yellow, Carmoisine, Tartrazine, Ponceau 4R; Quinoline Yellow, Allura Red, sodium benzoate) can cause the release of histamine from circulating basophils. This process is not allergic in nature, i.e., it does not depend on immunoglobulin E. The increased release of histamine can—in individuals who carry certain gene variants encoding histamine-degrading enzymes—exacerbate ADHD symptoms.²⁷⁶

An elimination diet can be helpful in identifying rare food intolerances (which, unlike allergies, cannot be detected through blood tests). However, such a diet is very difficult to implement and adhere to, and is barely possible to follow for younger children. In particular, any potential benefits must be weighed against the sometimes serious social consequences.

In other cases, such a diet can help alleviate symptoms in people with existing food intolerances.

When assessing the effectiveness of diets (and other “desirable” treatment approaches), parents’ evaluations often far exceed what tests or teacher evaluations can confirm.

A systematic review (k = 21 meta-analyses, n = 348,405,029) found, with highly suggestive evidence (evidence class II), an increased risk of ASS by 179% in cases of food allergies (OR 2.79).²⁴¹

For more information, visit ⇒ Nutrition and Diet for ADHD.

6.17. Precocious puberty (Pubertas praecox) (+40%)¶

Among girls with precocious puberty (the onset of sexual maturation before age 8 in girls and before age 9 in boys), the prevalence of ADHD was 13.5%.²⁷⁷

6.18. Surgical procedures under general anesthesia (+25 to 39%)¶

Anesthesia in childhood is associated with an increased risk of ADHD.²⁷⁸
Children who underwent a single surgical procedure under anesthesia before the age of 5 were 37% more likely to take ADHD medication in later years.²⁷⁹ A Korean cohort study found a 41% increased risk of ADHD as a consequence of general anesthesia in early childhood. In addition, the duration of general anesthesia was correlated with an increased risk of ADHD.²⁸⁰
A study found a 37% increase in the risk of ADHD following a single instance of anesthesia during surgery before the age of 5, and a 75% increase following multiple instances.²⁸¹
A cohort study of n = 15,072 children, half of whom had received anesthetics between the ages of 0 and 3, found a 39% increased risk of ADHD.The frequency of anesthetic exposure, the duration of exposure, male gender, and surgeries involving the central nervous system were significant risk factors for future ADHD.²⁸²
Other studies have reached similar conclusions.²⁸³²⁸⁴
A meta-analysis found that general anesthesia in childhood was associated with a 25% increase in the risk of developing ADHD later in life (RR = 1.26).²⁸⁵

• 38% (RR = 1.38) due to a single general anesthesia lasting no more than 60 minutes during childhood
• 55% (RR = 1.55) due to a single general anesthesia lasting a maximum of 61 to 120 minutes or more than 120 minutes during childhood
• 61% (RR = 1.61) after multiple general anesthesias

In contrast, a cohort study in Taiwan found no increased risk of ADHD associated with anesthetics during the first 3 years of life.²⁸⁶

It remains unclear to what extent the likelihood of undergoing surgery under anesthesia is already influenced by the increased risk of accidents among people with ADHD. For more on this, see ⇒ Consequences of ADHD.

However, there is evidence that general anesthesia using fentanyl and sevoflurane in newborn mice can cause ADHD symptoms—such as ADHD-like behaviors, cognitive impairments, and fine motor skill disorders—as well as disrupt neurogenesis and alter gene expression. These effects could be reduced by prior administration of vitamin K2. Administration of K2 prior to general anesthesia led to significantly different changes in gene expression.²⁸⁷

6.19. Selective immunoglobulin A deficiency (+30%)¶

Selective immunoglobulin A deficiency was associated with a 30% higher risk of ADHD (OR 1.30) as well as an increased incidence of respiratory and gastrointestinal infections.²⁸⁸.

6.20. Inflammatory Bowel Disease (IBD) (+20%)¶

Inflammatory bowel disease (IBD) is associated with an increased risk of ADHD and higher use of stimulants.²⁸⁹
People whose IBD began in childhood had an increased risk of²⁹⁰

• ADHD: +20%
• ASS: +40%
• Psychiatric disorders overall: +60%
• Anxiety disorders: +90%
• Affective disorders: +60%
• Eating disorders: +60%
• Personality disorders: +40%
• Suicide attempts: +40%

A study found no significant increase in ADHD associated with IBD overall, but did find an increase associated with Crohn’s disease (CD) (+6.5%) and ulcerative colitis (UC) (+5%).²⁹¹

A study of individuals with childhood-onset IBD found a 25% reduced risk of MPH use. Ulcerative colitis was associated with a 37% reduced risk of MPH use and—although not statistically significant—a reduced risk of an ADHD diagnosis. The risk of depression was 50% higher in people with IBD and 73% higher in people with both IBD subtypes (Crohn’s disease and ulcerative colitis).²⁹²

Some studies suggest that IBD in the mother during pregnancy can cause inflammation in the central nervous system, which increases the risk of ADHD in her children.²⁹³

6.21. Antihistamines in Early Childhood¶

A large cohort study found that taking antihistamines (especially first-generation antihistamines) during the first years of life significantly increased the risk of developing ADHD later on. A disorder of REM sleep was cited as a possible cause, which in turn impairs brain maturation.²⁹⁴

6.22. Lack of sleep¶

Short sleep duration was associated with an increased risk of anxiety, attention-deficit/hyperactivity disorder, and emotional and psychological conditions that limit daily functioning, after adjusting for ethnicity, deprivation, age, and gender.²⁹⁵
Ethnicity and socioeconomic disadvantage in the neighborhood were independently associated with short sleep duration and snoring or noisy breathing during sleep.
Long sleep duration was independently associated with an increased risk of depression.

6.23. Acne vulgaris¶

A study found moderately elevated levels of the following in adolescents (ages 12 to 17) with acne vulgaris:²⁹⁶

• Hyperactivity
• Hyperactivity/Impulsivity
• Inattention
• Total ADHD score

For both acne vulgaris and ADHD, elevated levels of androgens in the womb are thought to be a contributing factor.

6.24. Gut-Brain Axis, Gut Bacteria, Gut Flora¶

See the section on Gut-Brain Axis

6.25. Polycystic Ovary Syndrome (PCOS)¶

Women with polycystic ovary syndrome (PCOS) appear to have an increased risk of mental disorders, primarily anxiety disorders and depression, but also ADHD.²⁹⁷
Adolescents with PCOS also showed an increased risk of ADHD.²⁹⁸

6.26. Anabolic-Androgenic Steroids (AAS)¶

Strength athletes who take anabolic-androgenic steroids are significantly more likely to have ADHD than strength athletes who do not take them.²⁹⁹

6.27. Glucose-6-phosphate dehydrogenase deficiency (G6PD)¶

Glucose-6-phosphate dehydrogenase (G6PD) deficiency increased the risk of ADHD by 16%.³⁰⁰

G6PD deficiency is an X-linked genetic disorder that affects about 4.9% of the population.
The enzyme glucose-6-phosphate dehydrogenase (G6PD) facilitates the synthesis of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), which are involved in regulating the redox balance. G6PD deficiency leads to reduced GSH levels and, consequently, increased oxidative stress.

G6PD deficiency is usually food-related (favism; a hemolytic reaction to the consumption of fava beans) and is sometimes genetic (more common in the Mediterranean region and the Middle East, and to some extent in Asia and Africa).
G6PD deficiency can cause (especially in children):

• severe hemolysis
• Hyperbilirubinemia
• Jaundice
• Hearing impairments
• Behavioral disorders
• lead to long-term neurological damage
• increased production of reactive oxygen species (ROS)
  • resulting in the activation of astrocytes and microglia, increased levels of proinflammatory chemokines and cytokines, neuroinflammation, and impaired brain development
• Imbalance in the antioxidant system
  • which leads to damage to astrocytes, neuronal death, and DNA damage
  • oxidative cell death of leukocytes, myocytes, and other immune cells.

6.28. Lipodystrophy (lack of adipose tissue)¶

A study found evidence of a significantly increased prevalence of ADHD in patients with lipodystrophy.³⁰¹

6.29. Lipid Metabolism, Fatty Acids¶

To avoid repetition, we have included this section under “Fatty Acids, Probiotics, and More for ADHD“ In the chapter “ Treatment: Medications for ADHD”, in the section “ : Vitamins, Minerals, and Dietary Supplements for ADHD”.

6.30. Gender Diversity¶

A multinational study found evidence that the frequency and severity of ADHD symptoms were particularly high among individuals with gender-specific differences.³⁰²

6.31. Mitochondrial disorder¶

Mitochondrial dysfunction or mitochondrial disorders are being discussed as a possible cause of ADHD.^{303304 305} To date, no concrete findings have emerged on this topic.

6.32. Diaphragmatic hernia¶

Among children with a congenital defect in the diaphragm (diaphragmatic hernia), 26.3%³⁰⁶ to 39%³⁰⁷ of the survivors had problems with sustained attention. 51.9% had a formal diagnosis of ADHD, a specific learning disability, or a developmental disorder.³⁰⁶
If there is a hole in the diaphragm, organs from the abdominal cavity can enter the area around the lungs and interfere with lung development and breathing.
The mechanism underlying ADHD is therefore hypoxia.

6.33. Factors Not Associated with an Increased Risk of ADHD¶

• Children with ADHD were found to have a 14% lower prevalence of microcytic anemia (OR: 0.86).³⁰⁸
• Growing up bilingual did not increase the risk of ADHD³⁰⁹
• Autoimmune diseases showed no evidence of a causal link between autoimmune diseases and ADHD. The following were examined:²³⁰
  • Lupus erythematosus
    • In contrast, a retrospective matched-cohort study (n = 11,144) that a lupus diagnosis 15 years or more after the onset of psychiatric disorders was associated with a 61% higher likelihood of such disorders, and that psychiatric disorders were associated with a 120% increased risk of lupus 10 years or more after their onset. A lupus diagnosis was associated with an increased prescription of, among other things, ADHD medications 10 years prior.³¹⁰
  • Crohn’s disease
  • Ulcerative colitis
  • Type 1 diabetes (contradictory study: see above)
  • rheumatoid arthritis
  • Psoriasis
  • Ankylosing spondylitis
  • Multiple sclerosis
• High blood pressure
  • A study found no statistically significant genetic link between high blood pressure and ADHD.³¹¹ This finding is contradicted, at least, by the primary ADHD animal model, the SHR, which develops high blood pressure with age.
• COVID-19 Genetic Testing
  • A genetic predisposition that increases susceptibility to COVID-19 showed no signs of an increased risk of ADHD. Conversely, however, ADHD and Tourette syndrome are associated with an increased risk of COVID-19 and a more severe course of the disease.³¹²
• T1-weighted/T2-weighted ratio
  • The T1w/T2w ratio is an indicator of intracortical myelin based on magnetic resonance imaging (MRI). No differences in the T1w/T2w ratio were found between the ADHD and ASD groups and the control group.³¹³
• Obesity
  • After adjusting for confounding factors, no significant causal effect of obesity on ADHD was observed³¹⁴
• Platinum- and taxane-based chemotherapy in children³¹⁵
• Congenital abdominal wall defect³¹⁶
  • ADHD risk remains unchanged
  • 3.51-fold increased risk of ASD

6.34. Factors Associated with a Reduced Risk of ADHD¶

• The parents’ immigrant status is associated with a reduced risk of ADHD³¹⁷ within the first two generations.³¹⁸
• Lyme disease was associated with a 10% reduction in ADHD prevalence³¹⁹