Pathogenesis (development of the disease)
The exact mechanism of origin of ADHD has not yet been precisely clarified. However, it is certain that it is a multifactorial genesis (emergence). Genetic factors, in particular, play a role. However, exogenous (external) factors such as pregnancy or birth complications, diseases of the CNS (central nervous system) or nicotine abuse (tobacco addiction) of the mother are also suspected as promoting factors. In addition, an unfavorable social environment also plays a role with some certainty. Pathogenetically, the affected children have a reduced binding capacity in the area of the dopamine receptors (receiving unit for signals by the neurotransmitter dopamine) in the brain. Furthermore, there are pathological changes in the noradrenergic system as well as in the structural organization of the brain, especially in the area of the prefrontal cortex (part of the frontal lobe of the cerebral cortex, which is located at the frontal side of the brain) or the basal ganglia (group of endbrain and diencephalic nuclei). A meta-analysis establishes an association between ADHD and obesity in children (odds ratio [OR]: 1.20) as well as in adults (OR: 1.55). Causality remains an open question.
Etiology (Causes)
Biographical Causes
- Genetic burden from parents (at least 20% for first-degree family members), grandparents; twin and adoption studies indicate a heritability of ADHD of 60-80%
- Cross-aggregation: younger siblings of ADHD children were also at increased risk of autism spectrum disorder (ASD) (odds ratio 6.99; 3.42-14.27); younger siblings of ASD children were almost 4-fold more likely to have ADHD (OR 3.70; 1.67-8.21)
- Genetic risk dependent on gene polymorphisms:
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genes: CLOCK
- SNP: rs1801260 in the gene CLOCK
- Allele constellation: TT (higher risk).
- Allele constellation: CC (lower risk).
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Mother:
- Overweight/obesity during pregnancy:
- BMI (body mass index/body mass index): 25-30: adjusted risk ratio 1.14 (95% confidence interval 0.78 to 1.69) (vs. normal-weight mothers)
- BMI: 30-35 on adjusted risk ratio 1.96 (1.29-2.98).
- BMI > 35 to 1.82 (1.21-2.74).
- Smoking during pregnancy (epigenetic programming) – children of pregnant women with a positive cotinine detection (degradation product of nicotine) were 9% more likely to develop ADHD later.
- Overweight/obesity during pregnancy:
- Low birth weight
- ADHD risk increases significantly by 80% at >2 standard units (SD), 36% at 1.5-2 SD, and 14% at 1-1.5 SD.
- Birth weight < 1,000 grams
- Socioeconomic factors – low socioeconomic status.
- Preterm birth (= birth of an infant before completion of the 37th week of pregnancy (SSW)) – children born in the 38th SSW have a 12% increased risk of ADHD; with each additional SSW that a child is born prematurely, the risk of ADHD increases exponentially; children born in the 33rd SSW already have a 3, 5-fold increased risk and children born in the 23rd-24th SSW have a 12-fold increased risk.
Behavioral causes
- Nutrition
- Micronutrient deficiency of unsaturated fatty acids (omega-3/omega-6 fatty acids).
- Micronutrient deficit of zinc
- Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
- Consumption of stimulants
- Psycho-social situation
- Social stresses on the child such as neglect.
Causes related to illness
- Epilepsy – recurrent (recurring) seizures.
- CNS (central nervous system; brain and spinal cord) disorders.
- Gestational diabetes mellitus (gestational diabetes).
- Brain tumors
- Hyperthyroidism (overactive thyroid gland)
- Infections during pregnancy
- Complications during pregnancy or childbirth (e.g., oxygen deprivation)
- Neurodermatitis (it is suspected that there is a relationship between the two diseases).
- Traumatic brain injury (TBI)
- CNS injuries (e.g., cerebral infarction/ischemic stroke, epilepsy/convulsive disorder).
Laboratory diagnoses – laboratory parameters that are considered independent risk factors.
- Hyperhomocysteinemia (elevated blood levels of homocysteine).
- Iron-deficiency anemia (anemia due to iron deficiency) before 31 weeks of gestation: 9.3% of anemic mothers versus 7.1% of healthy mothers (odds ratio 1.37; 1.14-1.64)
Medication
- Sedatives (especially benzodiazepines) during pregnancy.
- Valproate during pregnancy
- Prenatal (“before birth”) administration of glucocorticoids (established therapy for threatened preterm birth to promote lung maturation/prevent respiratory distress syndrome)
