Development of ADHD - Introduction

There are several developmental pathways that can alone or simultaneously cause ADHD to develop.

• 1. Pathways of ADHD development
  • 1.1. Genes as ADHD cause
  • 1.2. Environment as ADHD cause
    • 1.2.1. Early or chronic severe stress
    • 1.2.2. Diseases
    • 1.2.3. Immune system
    • 1.2.4. Other environmental factors
  • 1.3. Epigenetics (inherited environmental influences and experiences) as ADHD cause
  • 1.4. Interaction of multiple pathways in the development of ADHD
• 2. ADHD: Dopamine and norepinephrine deficiency
• 3. How significant is which pathway of ADHD development?
  • 3.1. Genetic component: approx. 76%
  • 3.2. Influence of the environment time-dependent
  • 3.3. Opportunity-risk genes increase environmental influence

1. Pathways of ADHD development¶

1.1. Genes as ADHD cause¶

ADHD can be caused by an interaction of a plurality of random genes, without the need for environmental influences. Let’s call it “genetically inherited ADHD”.

These gene variants have developed without the influence of stress. If several such gene variants come together in such a way that they have a similar influence on the course of certain processes in the brain, these influences can add up in such a way that the healthy balance of the processes is disturbed. Depending on which processes are affected (e.g., which neurotransmitters are increased or decreased in which brain regions), different disorder patterns develop. In ADHD, several gene variants, all of which act to reduce dopamine and norepinephrine in the brain, can combine to reduce this effect to such an extent that the typical ADHD symptoms develop.
Genetic causation is the most common pathway. The genetic component of ADHD is slightly stronger than that for intelligence, at around 75%, and no single gene is the cause. To date, quite a few hundred genes are known or suspected. ⇒ Candidate genes in ADHD
The 75% was determined with studies on monozygotic and dizygotic twins.¹ This 75 % thus includes the entirety of genetic transmission through a. gene variants and b. environmental influences in the preceding 2 to 4 generations, which are passed on through epigenetics. The remaining 25% are therefore only those environmental influences that affect the individuals themselves.

1.2. Environment as ADHD cause¶

Environmental factors can contribute to ADHD development. Let’s call it “acquired ADHD”.

1.2.1. Early or chronic severe stress¶

Early or chronic severe stress can permanently alter the expression of genes, i.e. their activity. This can trigger the ADHD-typical changes in neurotransmitter levels or alter the effect of neurotransmitters. Stress medicine already describes these mechanisms for depression. According to this “vulnerability-stress model,” most mental disorders arise²: Anxiety, Depression, Compulsion, Autism Spectrum Disorders, Borderline and many others.
Early severe stressors in terms of child maltreatment sets 45% of the risks of psychiatric disorders that begin in childhood.³ Early severe stressors in terms of child maltreatment may include:⁴

• Emotional abuse
• Physical abuse
• Sexual abuse
• Living with a drug addict
• Living with a mentally ill family member
• Witness violent treatment of mother
• Household member in prison
• Separation or divorce of parents
• Emotional neglect
• Physical neglect

Affected individuals who experienced 5 or more of these stressors were at increased risk of psychotropic medication prescriptions ⁵⁶

• Anxiolytics: 2.1-fold
• Antidepressants: 2.9-fold
• Antipsychotics: 10.3-fold
• Mood stabilizers: 17.3-fold

Affected individuals who experienced 6 or more of these stressors have a 20-year lower life expectancy.⁵

Early childhood stress experiences are particularly significant because the stress systems in the brain are just forming in the first years of life. Early childhood stress causes permanent damage to the physiological stress systems (HPA axis, vegetative nervous system, PFC). The second particularly dangerous phase for ADHD is middle adolescence. ADHD sufferers who experienced many severe stressors in adolescence were much more likely to retain their ADHD in adulthood than children with few stressors in adolescence.

Specific to ADHD is that there is a wide range of symptoms that are also typical of acute or chronic stress (where they are functional, i.e. serve to cope with the stressor), whereas in quite a few other mental disorders individual stress symptoms are extremely (and thus dysfunctional) pronounced.
⇒ Gene disposition plus early childhood stress as a cause of other mental disorders ⇒ Environmental factors as a cause of ADHD

Acute stress increases levels of the neurotransmitters dopamine,² norepinephrine and serotonin² and the hormones CRH, ACTH and cortisol, among others. Chronic stress decreases dopamine and norepinephrine. If stress-induced altered neurotransmitter or hormone levels repeatedly occur acutely or permanently during an (early) infantile phase in which the brain systems that work with these neurotransmitters or hormones are just growing, the altered levels cause the affected brain regions to permanently adapt to them (“calibrate”). This calibration remains for a lifetime. Brain regions that rely on these neurotransmitters or hormones are therefore particularly vulnerable to stress during their growth phases.
If a corresponding genetic disposition is added to this, prolonged stress can cause massive psychological damage in children or lay the foundations for this.
⇒ ADHD as a chronicized stress regulation disorder
⇒ Stress damage - effects of early childhood and/or prolonged stress

1.2.2. Diseases¶

Diseases can also trigger ADHD.
For example, encephalitis destroys the dopaminergic cells in the brain and can thus trigger a dopamine deficit that causes ADHD-typical symptoms. Since the symptoms are permanent, encephalitis can be considered as a possible causation of ADHD.
Further, thyroid problems can trigger symptoms similar to those of ADHD. Since these symptoms can be remedied by adjusting the thyroid hormones, they are not ADHD. The same applies to vitamin or mineral deficiencies, food intolerances and many other disorders.
⇒ Diet and nutrition for ADHD
In order to determine the cause of the symptoms and to exclude other causes of disturbance, an appropriate differential diagnosis should be made during ADHD diagnostics.
⇒ Differential diagnostics in ADHD

1.2.3. Immune system¶

Rather theoretically conceivable are diseases that stimulate the immune system to ADHD-typical behavioral changes. However, there is little evidence for this. It is more likely that diseases contribute to ADHD by activating the stress systems that mediate most ADHD symptoms, just as psychological stress does.
⇒ Immune system and behavior

1.2.4. Other environmental factors¶

A variety of studies found a significant amount of environmental factors that can promote ADHD, such as toxins or medications, especially during pregnancy or the first years of life, age and wealth of parents, living environment, and quite a few others.
⇒ Environmental factors as a cause of ADHD

1.3. Epigenetics (inherited environmental influences and experiences) as ADHD cause¶

Acquired ADHD can be passed on to one’s own descendants. In contrast to the inherited ADHD of the first variant, only the epigenetic changes in gene activity are passed on here. Animal experiments have demonstrated inheritance of such acquired gene expressions over 2 to 4 generations. Let us call it “epigenetically inherited ADHD”. This ADHD cause is particularly amenable to prevention through caring warm parenting behavior.

The epigenetic changes are easier to trigger if there is a corresponding disposition, and more difficult if there is no disposition. Without genetic disposition, ADHD is only caused (and can then be inherited) by significantly more intense early childhood stress (of traumatizing intensity: physical abuse, psychological abuse, sexual abuse). More about this under the keyword chance/risk genes.

1.4. Interaction of multiple pathways in the development of ADHD¶

A relevant variant of development is that an early childhood stress experience is added to an existing gene disposition. In this case, the genes responsible for ADHD change epigenetically in such a way that ADHD now manifests (⇒ Genetic and epigenetic causes of ADHD-introduction). Epigenetics means that (intense) experiences in life can cause changes in gene expression. These acquired changes can in turn be inherited.

2. ADHD: Dopamine and norepinephrine deficiency¶

ADHD is particularly characterized by decreased dopamine and norepinephrine levels in the brain areas dlPFC and striatum. While acute stress shows increased dopamine and norepinephrine levels in these brain areas, chronic stress, like ADHD, is typically associated with decreased dopamine and norepinephrine levels in these brain regions. Acute as well as chronic stress show almost identical symptoms to ADHD, since the stress/ADHD symptom-triggering dysfunctions of the brain regions relevant here occur at any deviation from an average dopamine or norepinephrine level.

3. How significant is which pathway of ADHD development?¶

3.1. Genetic component: approx. 76%¶

ADHD has a strong genetic component of about 76%. The heritability of ADHD is thus greater than that of intelligence. Among ADHD cases with clinical intensity, up to 90% are genetically caused.⁷ However, single genes are not causative, even though certain gene variants are more frequently involved. Hundreds of candidate genes are known. It would not be surprising if there were more than 1000. We have identified more than 150 of them at ⇒ Candidate Genes in ADHD Mentioned. Nevertheless, only 5% of the genetic heritability can be attributed to specific gene variants so far. This is probably also due to the fact that genes (in most mental disorders) only represent a disposition and do not yet state that ADHD exists.

Even in a purely genetic pathway of ADHD, there are alterations in the functioning of the HPA axis (stress axis).
⇒ Research topic: ADHD in animal models

Heritability is likely to be measured within 1 generation. Environmental causes may influence the influenced individual, as well as via epigenetics, 2-4 generations of its offspring. Therefore, we assume that the proportion of environmental causes of ADHD is higher than 24%. We estimate it to be about 40%

3.2. Influence of the environment time-dependent¶

Interestingly, the relationship of the influence of genes and environment on an existing ADHD changes over time.⁸

• Genetic influences were initially moderate and nonsignificant and became substantial and significant over time
• The environmental influences were initially substantial and significant, and became moderate and nonsignificant over time.

• The same genes
• Other emerging environmental factors

At least several of the genes relevant to ADHD are epigenetically activated only by early childhood stress in such a way that they contribute to ADHD. A warm, secure, caring attachment style of parents may reduce the risk of epigenetic activation of genes and thus the risk of ADHD. ⇒ ADHD - Prevention and Screening - What Parents Can Do

3.3. Opportunity-risk genes increase environmental influence¶

Some genes are not only risk genes, but can also become a particularly enhancing and strengthening source if called upon. (Chance-risk genes, see ⇒ Parents’ attachment style to child particularly important for chance/risk genes)

The (epi-)gene changes (inherited or developed by own traumas) are passed on by the affected persons to their children “dormant” - traumas are inheritable over several generations. In the children of the affected persons, too, only an activation of the “dormant” gene disposition leads to the development of ADHD.

Since parents have the genes they pass on with a relevant probability also as a single parent themselves, the parents (or one parent) often also suffer from ADHD. The ADHD symptoms of (untreated) affected parents then make it highly likely that their children are thereby exposed to an increased stress load and that the inherited gene disposition is thus activated.

Origin

• Genetic and epigenetic causes of ADHD - Introduction
  • Candidate genes in ADHD
  • Genes or genes + early childhood stress as a cause of other mental disorders
• Environmental factors as a cause of ADHD
• Immune system and behavior
  • The immune system
    • Elements of the immune system: cytokines and co.
  • Neurophysiological mechanisms of action on behavior through immune responses
    • Effect of individual cytokines and inflammatory markers
    • Immune responses and inflammation as ADHD causes?
    • Immune responses and inflammation in other mental disorders
  • Neurophysiological mechanisms of action on behavior by pathogens
• Is the incidence of ADHD increasing?
• ADHD - different explanatory models in the past and today