ADHD - different explanatory models in the past and today

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

ADHD cannot be explained solely by symptom-oriented descriptions or by a single neurological mode of action. Different models explain ADHD from different perspectives and complement each other.
Since ADHD is dimensional, it can be described (as a disorder) as an extreme form of a personality trait.
Older, simple models were limited to naming the visible symptoms such as hyperactivity, impulsivity and inattention. One model sees an inhibition disorder as a central feature of ADHD. Altered reward response behavior and altered motivation are also mentioned as possible explanations. The hypothesis that ADHD could have arisen as an evolutionary consequence (hunter-gatherer) is barely tenable.
Several explanatory models describe ADHD as a lack of dopamine in the brain, reduced extracellular dopamine levels and reduced or increased phasic dopamine release.
ADHD is also described as a brain developmental delay, particularly of dopaminergic brain pathways.
The human brain only matures between the ages of 23 and 25. In ADHD, the development of the prefrontal cortex is delayed or disrupted, which can lead to symptoms such as hyperactivity, inattention and impulsivity. In some people with ADHD, the brain can catch up with the developmental delay in adulthood. In adolescence, around 80% of people with ADHD still have ADHD symptoms, while in adulthood only around 50% still have symptoms, some of which then take a different form.

There are also more complex models:
The dynamic developmental theory emphasizes the role of altered dopaminergic function and explains the behavioral problems and symptoms of ADHD through the interaction of genetic predisposition and environmental influences. The dopamine transfer deficit model describes an attenuated phasic dopamine response to reward cues. The cognitive-energetic model according to Sergeant sees a lack of overall cortical activation due to dysfunction in the reticular system of the brainstem. Sonuga-Barke’s 2 or 3-cause model assumes that different control circuits in the brain are responsible for various symptoms such as inhibition disorders, reward problems and time processing disorders. Hunt’s 4-category model describes four main problems in ADHD: a disorder of selective attention, excessive arousal, behavioral disinhibition or impulsivity/hyperactivity and problems in the reward system. The reduced inhibition model states that reduced suppression of the default mode network (DMN) leads to inattention in ADHD.

Ulrich Brennecke’s hypothesis (ADxS.org) states that the brain in ADHD works permanently in a functional profile that is actually intended for severe stress. The symptoms thus induced would be functional in severe stress, but in ADHD (which is mostly genetic in origin and has no stressor to combat) they are detrimental. While stress-related symptoms go away with the stressor, in ADHD the symptoms remain permanent and often lifelong. The hypothesis suggests that ADHD medications may also be helpful in the short term for (only) severe stress.

• 1. Symptom-oriented descriptions
  • 1.1. Fidget spinner
  • 1.2. Hans-Guck-in-the-Air; Träumerle
  • 1.3. Attention/hyperactivity disorder
• 2. Principle-based explanatory models
  • 2.1. Disorder of the ability to concentrate and pay attention
  • 2.2. Stimulus filter weakness
  • 2.3. Delay in brain development / brain maturation
  • 2.4. Extreme form of a personality trait / dimensional definition
  • 2.5. Attention model (Posner, Petersen)
    • 2.5.1. Alertness/alerting/visual orientation
    • 2.5.2. Orientation/attention alignment circle
    • 2.5.3. Executive control
  • 2.6. Inhibition disorder (Barkley)
  • 2.7. Disorder of executive functions
  • 2.8. Motivational disorder / altered reward response behavior
  • 2.8. ADHD as an evolutionary consequence
    • 2.8.1. Hunter and gatherer (Hartmann)
    • 2.8.2. Speed of human development (mismatch theory / anachronism of ADHD)
    • 2.8.3. Theory of natural positive selection (Thagaard et al.)
    • 2.8.4. ADHD as a consequence of increased sexual activity
  • 2.9. ADHD as deviant functional profiles of the brain
    • 2.9.1. Posteriorization of behavior control (Dietrich)
    • 2.9.2. Unusual Management of Information and Functions (Lachenmaier)
    • 2.9.3. Variable Attention Stimulus Trait (VAST) (Hallowell, Ratey)
    • 2.9.4. ADHD symptoms as a malfunction of the stress regulation systems (Brennecke)
• 3. Cause-oriented explanatory models
  • 3.1. Nutritional consequences / food intolerances
  • 3.2. Dopamine as the cause of ADHD
    • 3.2.1. Dopamine levels too low
    • 3.2.2. Tonic and phasic dopamine
      • 3.2.2.1. The dynamic development theory
        • 3.2.2.1.1. The mesolimbic dopamine pathway
        • 3.2.2.1.2. The mesocortical dopamine pathway
        • 3.2.2.1.3. The nigrostriatal dopamine pathway
      • 3.2.2.2. Reduced tonic dopamine release increases phasic dopamine release
    • 3.2.3. Dopamine transfer deficit model (DTD; Tripp and Wickens, 2008)
    • 3.2.4. ADHD as a developmental disorder of dopaminergic brain pathways
      • 3.2.4.1. The maturation of the dopaminergic pathways
      • 3.2.4.2. Post-maturation of the brain?
  • 3.3. Dysfunction in the anterior cingulate cortex
  • 3.4. Energy deficit hypothesis
• 4. More complex neurological models
  • 4.1. Cognitive-energetic model according to Sergeant (2000)
  • 4.2. 2 Or 3 - causes model according to Sonuga-Barke (dual-pathway / triple-pathway)
  • 4.3. 3 Endophenotypes according to Castellanos and Tannock
  • 4.4. 4-Category model according to Hunt
  • 4.5. Reduced inhibition / overactivity of the Default Mode Network (DMN)
  • 4.5. Rolandic wave spikes and epileptoform EEG abnormalities

1. Symptom-oriented descriptions¶

The simplest models are based solely on the visible symptoms.

1.1. Fidget spinner¶

This term referred solely to motor hyperactivity. The term was merely a book title. ADHD encompasses much more than just hyperactivity and also occurs as ADHD-I without hyperactivity.

1.2. Hans-Guck-in-the-Air; Träumerle¶

These terms refer to the ADHD-I subtype.

1.3. Attention/hyperactivity disorder¶

This term - still abbreviated to ADHD-HI today - added the attention problems. The two terms lead to the misconception that these two symptoms characterize the problems comprehensively. The ⇒ List of symptoms according to manifestations Comprises around 20 symptom groups with over 50 symptoms.

The reduction to hyperactivity and attention also overlooks the fact that these two symptoms do not occur in all people with ADHD.¹

The fixation on these terms also meant that it was long overlooked that hyperactivity is often significantly reduced in adulthood. This is when the (probably already pre-existing but unrecognizable) inner restlessness and an urge to be constantly active come to the fore in previously hyperactive persons with ADHD. While hyperactivity and inattention are very easily recognizable for third parties (especially parents and teachers) and have therefore been the sole focus of the description for (far too) long, the less visible symptoms of emotional dysregulation and underactivation are far more stressful for the people with ADHD themselves.

2. Principle-based explanatory models¶

Further descriptions attempted to reduce ADHD to a single “defective” neuro(physio)logical principle of action.

2.1. Disorder of the ability to concentrate and pay attention¶

The most obvious description of ADHD, that the ability to concentrate and pay attention is neurologically impaired per se, is not tenable.
The technical ability to concentrate and pay attention is not impaired in people with ADHD. People with ADHD can concentrate very well - even for long periods of time (keyword: hyperfocus). However, they are not able to direct this attention and concentration in the same way as those who are not affected.

However, on closer inspection, the ability to control attention and concentration is not “defective” - it merely follows a different model. This model is that there is an acute, serious stress situation, comparable to a life-threatening situation. Attention and concentration skills, including distractibility, are optimal for this situation.
⇒ Stress benefits - The survival-promoting purpose of stress symptoms.

However, fully functional attention, concentration and attention control are so distorted by this model of the emergency state that their suitability for everyday life is limited - there is “stress without an adequate stressor”. The functional changes that occur under severe stress, e.g. in attention, are permanently applied, resulting in a serious malfunction.
What is faulty is neither the ability to concentrate and pay attention, nor the ability to direct attention. What is faulty is that they run in stress mode even though there is no adequate stressor. What is impaired is the proper activation and/or deactivation of the stress regulation systems.
⇒ ADHD as a chronic stress regulation disorder.

2.2. Stimulus filter weakness¶

In ADHD, the filter that blocks out unimportant stimuli is regularly too wide open, among other things. Stimulus filtering is particularly weak in situations with low intrinsic interest.². The cause of ADHD as a weakness in stimulus filtering is attributed to dysfunctions of the striatum³ and the thalamus.
If the stimulus filter is opened too wide, this leads to distraction on the one hand and therefore to inattention and concentration problems and on the other hand, due to the excess of stimuli absorbed, to an additional increase in the stress load and therefore to stress, which can manifest itself in hyperactivity (ADHD-HI) or in drifting away (Träumerle, ADHD-I) - or in a mixture of both.
Stimulus filter weakness is a part of ADHD, but it can occur without ADHD, so it is not the only causal pathway.

However, in addition to an impaired ability to block out irrelevant stimuli, many people with ADHD also report an increased (subjective) sensitivity to stimuli within their focused attention. This phenomenon could also be described as the proportion of high sensitivity in ADHD, whereby the as yet unvalidated construct of high sensitivity according to Aron also includes other elements.

High sensitivity can also exist without ADHD. High sensitivity is not identical to ADHD, although a certain proximity cannot be overlooked. We know a number of (in some cases extremely) highly sensitive people who have very similar reactions to people with ADHD in some respects, but whose (stress) regulation systems are fully functional, i.e. who are not subjectively overloaded. In our opinion, it is only this overload that turns the stimulus filter weakness (high sensitivity) into ADHD.

2.3. Delay in brain development / brain maturation¶

At the end of the 1990s, it was recognized that although ADHD develops in childhood, it does not necessarily disappear after puberty, but persists in 50 to 80 % of cases in adulthood, with the symptoms changing in the process. Hyperactivity decreases significantly, inner restlessness comes to the fore, attention problems and impulsivity problems decrease somewhat, etc.
⇒ ADHD in adults

ADHD is associated with a developmental delay (or permanent developmental disorder if ADHD persists into adulthood) of certain brain functions / brain areas, primarily with regard to the maturation of dopaminergic⁴ and noradrenergic pathways⁵. The fact that ADHD is attenuated / lost in a number of people with ADHD can be attributed to delayed development of individual brain functions. Some of these brain functions can still underdevelop during adolescence, so that their functionality approaches that of non-affected individuals.

However, this post-development of the brain only occurs in some of the brain regions affected, but not in others. Furthermore, even in people whose ADHD exposure in childhood has been reduced to such an extent in adulthood that there is no longer a disorder, the relevant areas of the brain are not completely “post-developed”.

It is true that the brain development of children with ADHD is already delayed in childhood. However, not all brain development delays necessarily cause ADHD symptoms or correlate with them.
While the first maximum of cortex thickness is reached at the age of 7 to 8 years in people without ADHD, this is only the case on average at 10.8 years in people with ADHD. The fact that this is not necessarily a causal cause of ADHD is conclusively shown by the fact that the brain development delay is even slightly greater in gifted children (first maximum cortex thickness on average at 11 years of age).
Since rats that grow up in enriched environments develop a thicker cortex, it is conceivable that the high sensitivity correlated with ADHD and giftedness as the equivalent of enriched perception leads to a thicker cortex (which also develops later).
In contrast, our hypothesis that the high sensitivity/stimulus filter weakness that we believe is inherent in ADHD should also be frequently present in giftedness was not confirmed by the data from the ADxS online tests.
Find out more at ⇒ Giftedness and ADHD.

If it is true that certain brain regions are dependent on dopamine for their maturation,⁶ the fact that dopamine levels are reduced in certain areas of the brain in ADHD (PFC, striatum) could possibly explain a delay in brain maturation. This would then possibly be the Consequences and not the cause of ADHD. It is possible that the genetic causes of ADHD lead to a dopamine deficiency, which causes a delay in brain development. This is consistent with the fact that early childhood stress can also impair the dopaminergic systems, which is also associated with brain developmental delays as a consequence.⁷⁸
More on this at ⇒ Early attachment disorder impairs self-organization of the right hemisphere of the brain In the article ⇒ Brain hemispheres in the chapter ⇒ Neurological aspects
There is evidence that the brains of people with ADHD continue to develop to a certain extent into adulthood, which can reduce IQ deficits.⁹

Overall, ADHD is therefore associated with delayed brain development, but cannot be (generally) reduced to this or explained monocausally. The developmental delay appears to be more a reflection of altered neurological processes.

It is fascinating that gifted people and people with ADHD are not only linked by the phenomenon of delayed brain development, but also by shared specific character traits. More on this at ⇒ Giftedness and ADHD.
More on ADHD as a brain development disorder at *⇒ Brain development disorder and ADHD

2.4. Extreme form of a personality trait / dimensional definition¶

There is barely any discussion as to whether ADHD could be defined categorically. ADHD should rather be described dimensionally.¹⁰
Categorical means that the presence of certain characteristics or symptoms determines whether ADHD exists. Categorical is: pregnant or not. Dimensional, on the other hand, means that it is not individual specific symptoms that define the presence of ADHD, but the frequency and degree to which they occur. Dimensional is: mildly or severely depressed.

ADHD is sometimes described as an extreme manifestation of a personality structure (Farmer/Hunter hypothesis).

It is possible that this personality trait is particularly successful,¹¹ because the certain candidate genes for ADHD spread far faster than would be statistically expected.¹² This ties in with the model of chance/risk genes, which is described in ⇒ How ADHD develops: genes + environment Is presented in detail.

Banaschewski concludes from the fact that ADHD is caused by the interaction of multiple gene variants with each other, possibly under additional environmental influences, that ADHD probably represents the extreme expression of a behavioral dimension.¹³

Barkley¹⁴ has collected 18 symptoms for ADHD in adults. He notes that all of these symptoms can also occur in non-affected people. The difference between ADHD and non-ADHD is the frequency of occurrence of the symptoms. While only 1 of these 18 symptoms occurs frequently on average in non-affected people, 12 of the 18 symptoms occur frequently on average in adults with ADHD. ADHD can then be defined dimensionally.

ADHD can therefore be defined dimensionally in terms of symptoms. However, this does not explain the neurological cause of the disorder, how it manifests itself and (based on this) how it can be treated.

2.5. Attention model (Posner, Petersen)¶

In 1990, Petersen and Posner described three neuronal attention systems that are disturbed in ADHD.¹⁶.
Petersen and Posner revised their presentation, which has been cited 3,500 times, in 2012.¹⁷.

The following presentation is based on Drechsler,¹⁸ supplemented by information from Review Petersen, Posner (2012)¹⁷.

2.5.1. Alertness/alerting/visual orientation¶

This is noradrenergic controlled.

Symptoms:

• Inattention
• Impaired alertness
• Difficulties with sustained attention
• Do not finish work
• Aversion to prolonged (monotonous) exertion

neuronal circuits:

• Locus coeruleus
• Right frontal
• Right posterior parietal

2.5.2. Orientation/attention alignment circle¶

Symptoms:

• Inattention
• Easily distracted
• Does not seem to be listening
• Careless mistakes

Neuronal circuits:

• Dorsal attention system (top-down)¹⁷.
  • Frontal eye fields (FEF)
  • Intraparietal sulcus
  • Superior parietal lobe
• Ventral attention system (bottom-up)¹⁷.
  • Temporoparietal junction (TPJ)
  • Ventral frontal cortex (VFC)
• Posterior parietal cortex
• Bilateral parietal cortex
• Superior colliculus
• Thalamus
• Pulvinar¹⁶.

2.5.3. Executive control¶

Symptoms:

• Hyperactive/impulsive
• Blurts out the answer
• Interrupts or disturbs others
• Can only wait with difficulty

Neuronal circuits:

• Anterior cingulate cortex (ACC)
  • Left lateral frontal
• Basal ganglia
• Medial prefrontal cortex (mPFC)

2.6. Inhibition disorder (Barkley)¶

Barkley sees ADHD as primarily affecting the control of inhibition processes (mechanisms of behavioral inhibition). Barkley defines control over inhibition processes as the ability to self-regulate.¹⁹

Barkley divides behavioral inhibition into three components:

• Suppression of dominant response tendencies
• Interruption of already started answers
• Control of interference

According to Barkley, the inhibition processes regulate the executive functions. According to Barkley, four areas are disturbed in ADHD:

• The non-verbal working memory¹⁹
  Problems with:
  • Time processing
  • Perception of time
  • Planning ahead
  • Self-awareness
• The verbal working memory¹⁹
  Problems with:
  • To give yourself instructions
  • Establish internal rules
  • Comply with rules
• Motivation, affect, arousal¹⁹
  Problems with:
  • Deferral of requirements
  • Needs control
  • Perception of the needs and perspectives of others
  • Goal-oriented action
• Reconstitution¹⁹
  Problems with:
  • Combining knowledge in new ways
  • Conclusions
  • Planning
  • Creative thinking

Barkley does not see a fundamental inability in these areas, but rather a problem in controlling the appropriate use of the basic skills available. It is not the “how” and “what” of behavior that is impaired, but rather the “where” and “when”.¹⁹

2.7. Disorder of executive functions¶

ADHD is often considered an executive dysfunction.²⁰

2.8. Motivational disorder / altered reward response behavior¶

ADHD can also be considered a motivational dysfunction characterized by attempts to escape or avoid delay. This is thought to result in particular from altered reward processes in frontostriatal circuits.²⁰
ADHD has been described as a form of reward deficiency syndrome.²¹

As early as 1971, Wender postulated that abnormalities in the reward center of the brain in ADHD reduce the ability to respond to rewards and punishments.²² On this basis, Haenlein and Caul²³ developed the hypothesis of an “increased reward threshold” in ADHD, which leads to a certain reward having a lower reward value for people with ADHD than for those without. Stimulants remedy precisely this deficit.
Multiple studies confirm that people with ADHD show the same performance in tests as people without ADHD in the following categories when rewarded appropriately

• Attention
• Inhibition

which supports the hypothesis of an increased reward threshold.
Impulsivity and, at least partially, working memory are also affected. For many other ADHD symptoms, it has apparently not yet been investigated whether they persist when an individual’s interest is stimulated by a corresponding reward.

Our explanatory model for the peculiarities of the attention system in ADHD due to a shift in motivation towards intrinsic motives supports the classification as a motivational problem.
Find out more at ⇒ Motivation problems In the chapter ⇒ Symptoms.

2.8. ADHD as an evolutionary consequence¶

In our opinion, most evolutionary theories are contradicted by the fact that ADHD has two very contrasting subtypes that barely promise an evolutionary advantage at the same time. Moreover, the subtypes are not genetically predisposed.

2.8.1. Hunter and gatherer (Hartmann)¶

According to Hartmann, people with ADHD are the successors of the hunter type, which is less compatible with the living conditions of today’s world than the gatherer type.

In our view, this hypothesis, which seems plausible at first glance, confuses externalizing behavioral phenotypes with ADHD-HI and ADHD-C and internalizing behavioral phenotypes with ADHD-I.
A person with more externalizing personality traits may be happier as a hunter than as a gatherer. However, ADHD symptoms such as inattention, impulsivity, etc. are also a hindrance to hunting and make him less successful within the group of hunters than others with just as many externalizing personality traits but without ADHD symptoms. Otherwise, if only people with ADHD-HI had an occupation that was restless enough, they would be particularly successful. However, ADHD is not a career choice problem.
Similarly, people with many internalizing personality traits may enjoy collecting more than hunting. But a person with more internalizing personality parts is also burdened by ADHD symptoms such as daydreaming, forgetfulness and distractibility as a librarian and is not encouraged by these in their job.
Professional success is certainly possible with ADHD. However, it is more helpful if the chosen profession is as close as possible to one’s true intrinsic interests than to a suitable personality phenotype. More on this in the article Motivation with ADHD.

Hartmann’s hypothesis, on the other hand, is supported by a study according to which adults with ADHD could be better pickers than non-affected people due to increased impulsivity. In a video game, n = 457 adults collected berries. The yield of a bush decreased with increasing duration; changing the bush took time. Participants with ADHD symptoms collected an average of 602 berries, test subjects without ADHD symptoms collected 521 berries. This could indicate an advantage of impulsivity in this application by promoting faster resource switching and reducing overharvesting of a bush.²⁴ Another study found an advantage from the ADHD-associated gene variant DRD4-7R in malnourished nomads, while it correlated with poorer BMI in those of the same people who had (already) settled down.²⁵ Two studies report a correlation between DRD4-7R and migrant exploratory spirit.²⁶²⁷

2.8.2. Speed of human development (mismatch theory / anachronism of ADHD)¶

These hypotheses suggest that human societies have changed so rapidly that they have outpaced the much slower evolutionary changes required to select for these traits.²⁸

2.8.3. Theory of natural positive selection (Thagaard et al.)¶

According to this theory, ADHD traits were advantageous under certain circumstances.²⁸ Hartmann’s hunter-gatherer theory is a representative of this school of thought.
Hyperactivity could have been an advantage when seeking out new opportunities or migrating to a better climate.
Impulsivity associated with reactivity and the ability to fight or flee, as well as inattention as a highly checking behavior, could likely have been adaptive under these environmental conditions.

2.8.4. ADHD as a consequence of increased sexual activity¶

Positive selection could simply have resulted from the fact that ADHD increased reproductive success, as people with ADHD have their first sexual intercourse earlier on average, have more sexual partners and become parents earlier.²⁸

2.9. ADHD as deviant functional profiles of the brain¶

By deviant functional profiles, we mean models that do not view ADHD as a direct consequence of a pathological malfunction of the brain or individual parts of it, but rather view ADHD as a consequence of a different functional mode of the brain that is not itself directly pathological, but represents (under different circumstances) healthy functioning. According to these models, what is pathological in ADHD is rather that the brain is in this other mode of functioning without the conditions or triggers being present under which the brain should be in this state in a healthy way,

2.9.1. Posteriorization of behavior control (Dietrich)¶

As early as 2010, Dietrich²⁹ described the cause of ADHD as a shift in behavioral control processes from the PFC to posterior brain regions. Dietrich describes the posteriorization process as a consequence of uncertainty.

2.9.2. Unusual Management of Information and Functions (Lachenmaier)¶

In a lecture in 2022, Winkler translated this as neurodiverse handling and coordination of perceptions, impulses, emotions and executive functions.

2.9.3. Variable Attention Stimulus Trait (VAST) (Hallowell, Ratey)¶

However, Hallowell and Ratey see VAST in ADHD 2.0 Less as an inherently functional profile that is used in inappropriate circumstances, but rather describe VAST as a trait whose pathological extreme form is ADHD. At the same time, Hallowell and Ratey differentiate between ADHD as biologically induced and VAST as environmentally induced.
In a way, this is reminiscent of Hartmann’s hunter-gatherer hypothesis.

2.9.4. ADHD symptoms as a malfunction of the stress regulation systems (Brennecke)¶

According to Ulrich Brennecke’s hypothesis, the brain in ADHD is permanently in a specific functional profile that is only healthy and sensible in cases of severe (chronic) stress. According to this hypothesis, the problem with ADHD is firstly that there is no adequate trigger for the brain to work in this state and secondly that this state is permanent, for which the functional mode is unsuitable and not intended.

This view could explain why science has such a hard time recognizing the neurophysiological causes of ADHD in the brain. If the brain of people with ADHD basically functions without an adequate stressor in the same way as healthy people without ADHD (albeit only in the emergency and exceptional situation of severe (chronic) stress), the functioning of the brain in ADHD is not per se pathological - even if the continuous operation of the brain in emergency mode, which is actually only intended for severe stress, certainly has long-term consequences.
So when science compares the brain in ADHD with that of non-affected people (outside of severe chronic stress), it naturally finds differences. The hypothesis now raises the question of the extent to which the observed changes really represent ADHD, or whether it is not merely (at least to a large extent) the consequences of the deviating functional mode of the brain that are being observed. If this were the case, there would be a risk that the conclusions drawn from the scientific findings for the practice of ADHD treatment could fail. For example, it would be unhealthy to deprive a brain of the ability to function as it does in stress emergency mode, which has its purpose.
There are barely any comparisons or studies of how the human brain functions under severe chronic stress in healthy people, because this would require deeply unethical test conditions. Stress research has to make do with short-term stressors that are not perceived as seriously threatening.

According to Ulrich Brennecke’s hypothesis, ADHD can therefore be explained as (essentially genetically determined) permanent dysregulation of the stress systems, primarily the HPA axis (stress axis). The dysregulation of the stress systems is not the cause of ADHD, but the consequences of ADHD. The symptoms of chronic stress and ADHD are mediated by the same neurotransmitter shifts: a reduction in the effect of (primarily) dopamine and noradrenaline in certain areas of the brain.

The symptoms can be triggered neurophysiologically by acute stress (high phasic DA and NE levels) or a down-regulation of tonic DA and NE levels due to chronic stress, as the function of the brain areas requires medium neurotransmitter levels and neurotransmitter levels that are too high or too low cause very similar disorders.
Stress symptoms are not a disorder in themselves, but initially a healthy and useful reaction to cope with threatening situations.
⇒ Stress benefits - the survival-promoting purpose of stress symptoms.

Insofar as it is reported that people with ADHD lose all (or at least many) symptoms when they spend several weeks in a remote mountain hut (without internet, cell phone, computer), whereby unfortunately all symptoms are immediately back when the person with ADHD participates in normal life, this would be explained conclusively according to the hypothesis that in ADHD the stress systems are activated even under normal everyday stress in a way that they are only activated in non-affected people under threatening severe stress.

Certain genes or prolonged stress in early childhood shift the relationship between mineralocorticoid receptors and glucocorticoid receptors (be it the expression or the sensitivity of the receptors), which disrupts the threshold at which the HPA axis and other stress systems switch on and off again. Changes in the release reaction of neurotransmitters and stress hormones also contribute to this. These are caused, for example, by a prolonged excessive release of certain stress neurotransmitters, hormones and peptides, which lead to a downregulation of the corresponding receptors and/or transporters.

ADHD is characterized by a dopamine and noradrenaline deficiency in the PFC and striatum. Dopamine deficiency correlates with an increase in the number of dopamine transporters,³⁰ as is also typical in ADHD. While acute stress increases DA and NE in the PFC, chronic stress can cause a reduction in DA and NE levels, depending on the stressor and age of onset.

According to Ulrich Brennecke’s hypothesis, in ADHD-HI a flattened endocrine stress response due to the associated flattened cortisol stress response leads to a deficient shutdown of the HPA axis, which would normally be shut down again by cortisol at the end of the stress response. This causes a permanent state of stress, which manifests itself in the ADHD-HI-typical (and ADHD-I-atypical) state of inability to recover.

In ADHD-I, the hypothesis is that the excessive endocrine stress response could lead to frequent overactivation (slight noradrenaline increase) and then shutdown of the PFC (strong noradrenaline increase; Consequences: thinking blocks, decision-making difficulties). The clear cortisol stress response leads to a clean shutdown of the HPA axis, which reduces noradrenaline and dopamine levels and removes the blockage of the PFC.
Presumably due to the frequent alternation between overactivation and deactivation of the PFC, there is no such continuous dopamine deficiency as in ADHD and therefore no such pronounced increase in DAT. The excessive cortisol stress response leads to a frequent alternation of activation and deactivation of the stress systems (e.g. HPA axis).

The hypothesis is further based on the fact that almost all typical ADHD symptoms have functional benefits in severe life-threatening circumstances. For example, in the case of severe chronic stress, it makes sense that extrinsic stimuli appear less interesting and motivation shifts towards covering personal interests, as this helps with survival in the event of a (life) threatening stressor.

Find out more at ⇒ ADHD as a chronic stress regulation disorder.

3. Cause-oriented explanatory models¶

Other explanations attempted to describe the causes of ADHD.

3.1. Nutritional consequences / food intolerances¶

ADHD is not categorically caused by food or supplements.

However, food intolerances as stressors can increase the intensity of ADHD or, in people with ADHD that is so weak that it is not disruptive without additional stressors (keyword: dimensional disorder), can intensify this ADHD, which is not yet present in itself, into the pathological range.
This is not a pattern unique to ADHD: eliminating food intolerances can also reduce or eliminate symptom intensity in other mental disorders.
However, at around 0.25, the Effect size of eliminating an existing food intolerance is considerably lower than that of medication (up to 1.1).

See the article ⇒ Nutrition and diet for ADHD.

3.2. Dopamine as the cause of ADHD¶

3.2.1. Dopamine levels too low¶

Neurologically, ADHD can be accurately described as a neurotransmitter disorder in certain areas of the brain, primarily dopamine deficiency in the striatum (reward/reinforcement system).

But if you take a closer look, it gets complicated again.
Dopamine deficiency is indeed the clearest cause, which subsequently explains many symptoms.
But firstly, other neurotransmitters are also imbalanced, especially noradrenaline, albeit to a lesser extent than dopamine. Serotonin, acetylcholine, GABA and other neurotransmitters are also involved to a lesser extent. It is unclear whether the imbalances of the other neurotransmitters have their own cause or whether they are a consequence of the dopamine deficiency. In addition to its own neurotransmitter functions, dopamine also plays the role of a prodrug (precursor) of (nor-)adrenaline.
If a neurotransmitter is not present in the brain in the optimal amount, signal transmission in the brain is disrupted. This applies to “too little” as well as “too much”.
The symptoms are then further dependent on which neurotransmitters are present in too much or too little quantity (or have a stronger or weaker effect, e.g. because receptors are (less) sensitive) and in which area of the brain this occurs.

Each neurotransmitter has specific brain regions in which it plays a special role.
The individual brain regions also have different functions and are networked with each other.
With these two dimensions (which neurotransmitter, which brain region), individual symptoms of ADHD can be assigned to specific brain regions.
This is important because every person with ADHD has their own mix of symptoms and symptom intensity. Understanding which symptom is triggered by which neurotransmitter in which brain region opens up opportunities for improvement in treatment.

Dopamine deficiency causes the symptoms - but is it also the cause?

The main symptoms of ADHD are predominantly caused by a lack of dopamine in the PFC and striatum. To put it simply, the effects of a reduction in dopamine receptors at the postsynapse are included in this picture.

An increase in the dopamine level in the dlPFC remedies the problems of working memory and thus the executive functions, an increase in dopamine in the striatum remedies the ADHD symptoms of more interest-driven directing of attention, including to irrelevant stimuli, motivation and hyperactivity and impulsivity.

Nevertheless, there is strong evidence that the dopamine deficiency is not the actual cause, but merely the consequence of another existing problem.

We therefore consider it conceivable that there is a superordinate instance or other mechanism that raises the (phasic) dopamine level in the striatum when there is intrinsic interest and lowers the dopamine level when there is disinterest (forced interest, extrinsic interest). According to our hypothesis, the control of this instance is impaired in people with ADHD. In the context of a (threatening) stress reaction, however, the change in control makes sense and is conducive to survival.
⇒ Stress benefits - the survival-promoting purpose of stress symptoms

3.2.2. Tonic and phasic dopamine¶

There are different models of how dopamine influences ADHD.³³
Together, they assume reduced dopamine levels in various dopaminergic control circuits, which leads to deficits in reinforcement and extinction of behaviors.

3.2.2.1. The dynamic development theory¶

The dynamic development theory³⁴ is based on the hypothesis that altered dopaminergic function plays a central role by not adequately modulating non-transaminergic (primarily glutamate and GABA) signaling. Three dopaminergic networks are impaired.

3.2.2.1.1. The mesolimbic dopamine pathway¶

Disorder in this system causes altered behavioral reinforcement and deficient behavioral extinction.
This leads to

• Delay aversion
• Hyperactivity in novel situations
• Impulsiveness
• Lack of sustained attention
• Increased behavioral variability
• Failure of the “inhibition” of reactions (“disinhibition”)

3.2.2.1.2. The mesocortical dopamine pathway¶

A problem in this system causes

• Attention deficits
  • Inadequate orientation reactions
  • Impaired saccadic eye movements (rapid involuntary gaze jumps)
  • Poorer attention reactions to a target
• Poor behavior planning
  • Poor executive functions

3.2.2.1.3. The nigrostriatal dopamine pathway¶

Functional impairments in this system cause

• Disturbed modulation of motor functions
• Lack of non-declarative habitual learning and memory.

These three impairments together lead to

• An obvious developmental delay
• Clumsiness
• Neurological “soft signs” and
• A “failure to inhibit reactions” when rapid reactions are required.

According to the dynamic development theory, hypofunctional dopamine networks play a key role in determining individual predispositions. According to this theory, behavioral problems and symptoms of ADHD result from a combination of (genetic) predisposition and environmental influences. The respective ADHD symptoms of the person with ADHD change over the course of their lifetime. Altered or inadequate learning and motor functions make optimal parenting styles and approaches particularly important. Medication can normalize the underlying dopamine dysfunction to a certain degree and reduce the increased demands (needs) of these children. The theory describes how individual predispositions interact with these conditions to produce behavioral, emotional, and cognitive effects that can become relatively stable patterns of behavior.

3.2.2.2. Reduced tonic dopamine release increases phasic dopamine release¶

This theory states that a reduced tonic release of dopamine as a feedback mechanism leads to a reduced stimulation of presynaptic autoreceptors and thus to an increased phasic release of dopamine.³⁵³⁶

Phasic dopamine increases affect and distractibility.³⁸
A similar mechanism exists in the interaction of dopamine levels between the PFC and the striatum. Stress increases the dopamine level in the PFC. Moderate increases improve the performance of the PFC, strong increases weaken it and switch off the PFC. An increased dopamine level in the mPFC causes a reduced dopamine level in the striatum. More on this at ⇒ The neurological explanation of drive and motivation problems.

3.2.3. Dopamine transfer deficit model (DTD; Tripp and Wickens, 2008)¶

The dopamine transfer deficit (DTD) theory explains ADHD by means of an attenuated phasic dopamine response to cues (predictors) of expected rewards, resulting in altered reinforcement sensitivity.³⁹⁴⁰
If healthy people repeatedly receive a reward at the same time as a predictor, the dopamine neurons begin to fire at the predictor and the reward. If the relationship between reward and predictor is clear (learned), dopamine only fires to the predictor.
In ADHD, the firing of dopamine cells is abnormal. Even when reward and predictor appeared together long enough to have been learned, people with ADHD still show too low a firing rate after the cue and an increased firing rate after the actual reward.
Less efficient learning in ADHD is also associated with a delayed response to an immediate reward. Weaker conditioning to the reward leads to faster extinction of the behavior and a weaker effect of the reinforcer on the behavior over longer periods of time. The lack of anticipatory dopamine signaling of the cue causes faster behavioral extinction when reinforcement is delayed or interrupted. This would explain some core symptoms of ADHD, including the devaluation of delayed rewards.⁴¹

3.2.4. ADHD as a developmental disorder of dopaminergic brain pathways¶

The brain consists of different areas that have developed at different times in the course of mammalian evolution. Within these brain areas, local areas can be delineated, which can be easily differentiated on the basis of metabolism, types of communication, neurotransmitter basis, specific functions and meanings as well as their communication connections with other brain areas. These 52 areas were already described by Brodmann in 1909 (Brodmann areas).

In children who suffer from ADHD, individual areas of the brain are delayed in their development. This developmental delay is triggered by the roots mentioned above. Not every developmental delay is equally relevant to the disorder. Disorder in the development of the dopaminergic pathways emanating from the nucleus accumbens (which can be triggered by early childhood stress) is a clear ADHD problem, while the (considerable) delay in the development of the first maximum of cortex thickness in ADHD corresponds quite exactly to the developmental delay in giftedness, which is more likely not to be considered a mental disorder.

The areas affected by ADHD communicate primarily via the neurotransmitters dopamine and noradrenaline (and secondarily via serotonin). It is known that the development of the dopaminergic pathways in the brain can be delayed by external stress.⁴

3.2.4.1. The maturation of the dopaminergic pathways¶

The central dopaminergic switch point in the brain is the nucleus accumbens in the striatum. It mediates between emotional and motor stimuli.

3.2.4.2. Post-maturation of the brain?¶

The human brain does not mature at birth, childhood or sexual maturity.
The PFC takes at least until the age of 23 - 25 to fully mature.⁶⁰

The fact that the PFC is involved in a number of ADHD symptoms explains why ADHD changes over the course of a lifetime and can eventually disappear or show a significantly different symptom picture in adults.
In ADHD, the development of the PFC is impaired,⁶¹ so that it matures late (symptoms disappear in adulthood) or not fully (symptoms diminish in adulthood). By adulthood, the brain of some people with ADHD can (partially) catch up with the developmental delay. More on ADHD as a brain development disorder at *⇒ Brain development disorder and ADHD

In adolescence (youth), around 80 % of people with ADHD still have the symptoms. In the remaining 20 %, the areas of the brain affected may have matured sufficiently.
In adulthood, around 50% of people with ADHD as a child still have ADHD symptoms, but in a different form.

Due to the (partial) subsequent development of the areas of the brain affected, the symptoms weaken and change. While an ADHD-HI child (with hyperactivity) cannot sit still and must be constantly on the move (lack of inhibition of the impulse to be active), this changes in adulthood to the extent that an inner restlessness remains, which no longer necessarily makes itself felt physically. The impulse to always have to do something remains. Meditation, mindfulness, keeping still without being able to do anything is very difficult for these people with ADHD (to the point of being perceived as torture). If they manage to do it anyway, it is highly effective therapy, as this breaks the symptom of inability to recover, which otherwise perpetuates the vicious circle of stress symptoms.

In principle, epigenetic changes in genes by means of methylation are possible at any age. Even short-term sports cause methylation in the muscles. However, experiences in childhood cause longer-lasting methylation than experiences in old age.⁶²

3.3. Dysfunction in the anterior cingulate cortex¶

Dysfunction in the anterior cingulate cortex can lead to anxiety, emotional instability and hyperactivation in ADHD.⁶³

3.4. Energy deficit hypothesis¶

According to the energy deficit hypothesis of ADHD, the symptoms are triggered by reduced lactate production by astrocytes in the brain. Hyperactivity is a compensatory method to utilize the lactate production of the skeletal muscles. In line with this hypothesis, an increased expression of the lactate transporter monocarboxylate transporter 1 (MCT1) at the blood-brain barrier of the hippocampus was observed in SHR.⁶⁴

4. More complex neurological models¶

4.1. Cognitive-energetic model according to Sergeant (2000)¶

The cognitive-energetic model assumes a lack of overall cortical activation due to dysfunction of the ascending reticular system of the brainstem.⁶⁵⁶⁶ It focuses on arousal, activation and readiness to exert effort.⁶⁷

• Activation: “general alertness”; tonic-physiological readiness to react
• Arousal: phasic readiness to react in anticipation of relevant stimuli
• Willingness to make an effort
• Consequences: Effects on primary increments of processing and behavior, e.g., decoding, central processing, response organization

Studies have shown that children with ADHD-HI perform worse when the event rate is slow, while their performance on exciting, challenging tasks was comparable to that of non-affected children.⁶⁸ The cause is thought to be insufficient activation of the arousal system.

It is therefore particularly important for people with ADHD (especially in school and other learning situations) to be actively addressed and motivated. Tasks should be divided into small parts. Praise/improvement must be given directly and immediately (reinforcement that does not immediately coincide with the action is ineffective).

4.2. 2 Or 3 - causes model according to Sonuga-Barke (dual-pathway / triple-pathway)¶

2 or 3 development paths⁶⁹⁷⁰⁷¹

• cognitive path
  Impairment of the mesocortical system
  dorsal striatum and dorsolateral (posterior lateral) prefrontal cortex
  Consequences: impaired executive functions, including lack of inhibition, cognitive dysregulation, behavioral dysregulation
• motivational path
  Impairment of the mesolimbic system
  ventral striatum (here primarily nucleus accumbens)
  frontal regions (incl. anterior (frontal) cingulate and orbitofrontal cortex)
  Amygdala
  Consequences: Reward problems, especially delay aversion and aversion to reward deferral.

According to Sonuga-Barke, three separate regulatory circuits are independently responsible for different disorders and symptoms of ADHD:

1. the mesocortical control loop
   disorders of inhibition and inhibition,
2. the mesolimbic control loop
   disorders of the reward system and
3. the cerebellum (small brain)
   for Disorders in time processing.

According to this model, the delay aversion typical of ADHD and inhibition problems (which are more likely to lead to hyperactivity in Consequences) are each attributable to separate, independent neurological mechanisms.⁷²⁷³⁷⁴

Delay aversion is thought to correlate with the DRD4-7R gene variant known as chance-risk, which is involved in high sensitivity as well as many disorders, including ADHD.⁷⁵

Sonuga-Barke later expanded his first model (dual-pathway) into a triple-pathway model, as in ADHD, in addition to inhibition problems and delay aversion, time processing problems are also caused by their own neurological mechanisms.

The model is based on studies according to which people with ADHD with symptoms from one of the three areas do not necessarily also have to show symptoms from one of the other areas, while twins of the (ADHD-affected) test subjects who were not affected by ADHD were also conspicuous in exactly the areas from which the symptoms of the people with ADHD arose.⁷⁶

4.3. 3 Endophenotypes according to Castellanos and Tannock¶

Source⁷⁷

• Problems in the reward system
• Problems with temporal processing
• Disorders of the working memory

According to this presentation, ADHD is characterized by a dysfunction of the prefrontal-striato-thalamic system due to smaller brain volumes in the cerebellum (hemispheric) and changes in the right prefrontal brain regions, the caudate nucleus, the pallidum and a section of the cerebellar vermis.⁷⁸⁷⁹

4.4. 4-Category model according to Hunt¶

Source⁸⁰

• Disorder of selective attention
  Cause: dopaminergic dysfunction in
  • Nucleus accumbens
  • Cortical integration regions
• Excessive arousal
  • Impact:
    • Aggressiveness
    • Impulsiveness
    • Attention deficit disorders
  • Cause: noradrenergic hyperactivity in
    • Locus coeruleus
    • Reticular activation system
• Behavioral disinhibition or impulsivity/hyperactivity
  Cause: serotonergic-dopaminergic dysfunction in
  • PFC
  • Subcortical regions
• Problems in the reward system
  • Disturbed affect regulation
  • Anhedonia

4.5. Reduced inhibition / overactivity of the Default Mode Network (DMN)¶

Source⁸¹

• The Default Mode Network (DMN) is a network that encompasses several brain areas⁸²
  • Ventrolateral and ventromedial PFC
  • Posterior cingulate cortex (PCC)
  • Cuneus
  • Inferior parietal lobe⁸³
• A reduced negative correlation between DMN and task-active networks was observed in ADHD.⁸⁴⁸⁵⁸⁶
  It has been suggested that inattention in ADHD results from inadequate suppression of the DMN (daydreaming).⁸⁷
• A meta-analysis of 55 task-based fMRI studies on ADHD suggested as the most consistent finding that in ADHD there is excessive activity in the DMN and reduced activity in the task-positive frontoparietal and ventral attention networks during cognitive tasks.⁸⁸
• Reduced activity in the DMN causes slower and more variable responses⁸⁹ which indicates increased neural noise.
• Methylphenidate increases the inhibition of DMN.⁹⁰

4.5. Rolandic wave spikes and epileptoform EEG abnormalities¶

Rolandic spikes (sharp waves) were found in 1.7% of all people with ADHD.⁹¹ Rolandic wave spikes in ADHD are also reported by Duane.⁹²

Epileptiform EEG abnormalities were found in 5.4% of all people with ADHD without epilepsy findings and were significantly correlated with female gender and ADHD-I subtype.⁹¹