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What ADHD has to do with stress

What ADHD has to do with stress

ADHD has many different causes, some of which are alternative and some of which are cumulative.
One of these causes, and one of the mechanisms by which ADHD works, is a disorder of the stress systems. ADHD could be considered a chronic stress regulation disorder, but this would only represent one aspect of ADHD and would only cover a small number of ADHD cases.
By discussing the role of the stress systems, in particular the HPA axis, in the development and mediation of ADHD symptoms, we are in no way questioning the current specialist literature on ADHD. We see our considerations as supplementary illumination of a single aspect. In particular, we do not derive any “alternative healing methods” from this.

“It is of great importance to understand the extent to which the HPA axis plays a role in the pathogenesis of ADHD-HI, as it affects pathways in the body that are often aberrant in ADHD-HI patients, such as: circadian rhythm, sleep and emotions.”1

“Animal and human studies have shown that prenatal maternal stress affects the brain and behavior of the offspring. Stressful life events, exposure to a natural disaster, and symptoms of maternal anxiety and depression increase the risk that the child will have a range of emotional, behavioral and/or cognitive problems later in life. These include depression, anxiety, attention deficit hyperactivity disorder (ADHD) and/or behavioral problems. … Studies on the biological correlates and mediators of these findings suggest that the HPA axis plays a role in mediating the effects of maternal stress on the fetal brain.”2

ADHD can result from many different causes. According to our hypothesis, one possibility is a disorder of the stress regulation systems and here in particular the HPA axis. There should barely be any reasonable doubt that the stress systems, in particular the HPA axis, are closely linked to the central dopaminergic and noradrenergic neurotransmitter systems that are affected in ADHD.

“The [stress] system also activates (acutely and transiently) the mesolimbic dopaminergic reward system (which connects the VTA to the nucleus accumbens) and the mesocortical dopaminergic system (which connects the ventral tegmentum to the frontal-prefrontal lobe), while receiving inhibitory input from the latter.”3 Other sources express similar views.4567

“Activation of the stress system stimulates arousal and suppresses sleep; conversely, sleep loss is associated with the inhibition of the stress system.”3

According to our understanding, ADHD symptoms are caused in the same way as (the corresponding) symptoms of severe chronic stress: by an (action) deficiency of dopamine and noradrenaline in certain brain regions, primarily the dlPFC and the striatum.8 Nevertheless, ADHD is different from chronic stress, because ADHD remains even when the stressor leaves.

ADHD can arise from several interacting factors:

  • Purely genetic through a combination of gene variants that cause certain influences in the brain (in particular a reduction in the dopamine level or the dopamine effect in the PFC and in the striatum) These factors are congenital and unchangeable.
  • Epigenetically through inherited characteristics of genes that influence their activity in such a way that they exert similar influences in the brain. For example, nicotine consumption by fathers or mothers before conception causes such epigenetic changes, which are passed on to the children over 2 to 4 generations. Nicotine consumption by the father before conception
  • Environmental influences (in particular early childhood stress = first hit, and possibly additional stress in adolescence = second hit), which epigenetically alter one’s own genes so that they permanently change the dopamine level in the same direction
    • There are indications of the effect of the second hit also with regard to the symptom severity of ASA9
  • Environmental influences that reversibly cause the same influences in the brain itself (e.g. lead, food intolerances, sleep disorders, etc.)

Of course, the abbreviation to reduced dopamine and noradrenaline levels in the PFC and striatum is a simplification. Nevertheless, these are probably the most important factors.

The following arguments lead us to assume a close connection between stress regulation and ADHD.

  • The relationship between genetic factors and environmental influences as an influence on existing ADHD can change within just a few years.10 We are considering whether this does not indicate a significantly higher influence of environmental factors than previously assumed.
  • Depending on the stressor and the age of the person with ADHD, chronic stress can have persistent influences on the brain that support the development of ADHD, e.g. dopamine and noradrenaline in the PFC and striatum can be reduced, which naturally causes identical resulting symptoms.
    • Acute stress tends to counteract the influencing factors typical of ADHD, as acute stress typically increases dopamine and noradrenaline in the PFC. This could explain why some people with ADHD can also experience acute stress, e.g. at work, as something positive, as they then “function better”.11
  • Purely genetically (i.e. not epigenetically) inherited gene variants can permanently alter the activity of the HPA axis. This is the case, for example, with the spontaneous(ly) hypertensive rat (SHR), which serves as a model animal for ADHD with hyperactivity, among other things. In this animal, ADHD symptoms can be improved by dexamethasone, which acts directly on the HPA axis in a similar way to cortisol. This proves that even gene variants that cannot be modified by environmental influences (i.e. epigenetically), which may be involved in ADHD, can affect the stress systems. In this case, stress is neither the cause nor the trigger of ADHD, but the stress systems are mediators of ADHD symptoms.
  • Neurofeedback, mindfulness training and psychotherapy are able to bring about lasting improvements in ADHD symptoms, although not a complete cure. We still know too little about which neurophysiological changes are mediated by this, but we suspect that this also occurs via changes in the stress systems of the person with ADHD. More research is needed to confirm or refute this assumption.
  • ADHD often shows an increased sensitivity to stress. See 1.5 below.
  • Depending on the subtype, there are different changes in the stress systems.
    • ADHD-I (without hyperactivity) is (like melancholic depression) very often characterized by an excessive endocrine stress response. The excessive increase in noradrenaline during stress leads to a shutdown of the PFC (blackouts, inability to make decisions), while the excessive cortisol stress response leads to a too frequent shutdown of the HPA axis and to a TH1/TH2 shift of the immune system: less inflammation, more fight against foreign bodies (allergies).
    • ADHD-HI and ADHD-C (like atypical and bipolar depression) are often characterized by an insufficiently elevated (flattened) endocrine stress response, in which a slightly elevated noradrenaline level only causes activation but not deactivation of the PFC. As cortisol downregulates the stress systems again at the end of its effect, an insufficient cortisol stress response does not trigger a sufficient deactivation of the HPA axis, so that it remains trapped in the stress duration state and causes permanent inner restlessness and inability to recover.
    • In our opinion, the different subtypes represent different stress phenotypes, i.e. typical patterns of co-occurring stress symptoms that most closely match the respective personality profile of the person with ADHD. ADHD-HI tends to externalize stress (externalized), while ADHD-I tends to internalize it (internalized).
    • In a completely low-stimulus environment (2 weeks in a mountain hut without internet and electronic devices), many (but probably not all) symptoms of ADHD disappear, but immediately return unchanged even under normal stress in normal everyday life.
    • There are probably other patterns of different stress system imbalances that have not yet been researched.
      More on this (including sources) at The subtypes of ADHD: ADHD-HI, ADHD-I, SCT and others and ⇒ The HPA axis / stress regulation axis
  • ADHD shows peculiarities in attention that are characterized by hyperfocus (task switching problems) on the one hand and distractibility (openness to stimuli) on the other. This profile of altered attention is not dysfunctional under other circumstances, but is conducive to survival: in the case of severe, (survival) threatening stress. Severe (survival) threatening stress changes attention in the direction of those things that are personally important. The ability to be motivated is reduced overall. Consequences of weaker motivational capacity for things that are not personally interesting impair attention control and attention performance. With high personal motivation or high extrinsic rewards, attention (including sustained attention!) and attention control function so well in persons with ADHD that they can no longer be reliably distinguished from those of non-affected people in tests.
    ADHD is not pathological because attention is altered in this way, but because it is altered in this way without an adequate stressor being present.
  • In our opinion, all ADHD symptoms are stress symptoms. ADHD symptoms are stress symptoms Conversely, not all stress symptoms are ADHD symptoms.
    This does not mean that ADHD symptoms have to be triggered by acute stress. In ADHD in particular, they typically are not. As explained earlier, acute stress causes an increase in phasic DA and NE in the PFC and striatum, while ADHD and certain chronic stresses cause a decrease in phasic and tonic DA and NE in the PFC and striatum. Nevertheless, the symptoms caused by these conditions are almost the same. This is because both too high and too low neurotransmitter levels in these brain regions cause almost identical or at least very similar symptoms: the signals that these neurotransmitters should convey are altered. This change occurs when neurotransmitter levels are not optimal, i.e. when they are too high or too low. If the symptoms are mediated by the neurotransmitter changes in the PFC and striatum that are typical during stress, it is conceivable that there is an instance that initiates these changes during stress. In the absence of an adequate acute stressor in ADHD, it would be conceivable that this instance mediates stress in ADHD without being appropriate.
    We have mentioned the Spontaneous(ly) hypertensive rat (SHR). Their genes (clearly defined and not epigenetically altered by environmental influences in the direction of stress sensitivity) are associated with changes in the HPA axis that mediate ADHD symptoms. The ADHD symptoms (but also the high blood pressure) can be remedied in SHR by dexamethasone, which, as a selective glucocorticoid receptor agonist, switches off the HPA axis.
    Furthermore, stress symptoms are not an end in themselves. They have a benefit. We call this the stress benefit. Stress benefit is the advantage that an individual has in an actual life-threatening situation if they react in the way that the stress symptom conveys.
    • For example, the DRD4-7R gene variant frequently involved in ADHD is only 40,000 to 50,000 years old, which causes a much less sensitive D4 dopamine receptor (which has an inhibitory effect, so that the inhibition of the brain region is reduced in DRD4-7R). DRD4-7R is now much more common than a normal hereditary distribution would suggest. Evolutionary biology concludes from this that it must be an unusually successful gene. From this, one could conclude that the traits conferred by DRD4-7R are advantageous. However, these benefits might depend on the circumstances: during acute stress (high DA), the inhibition of the brain region in question is increased due to a higher inhibitory effect of D4 receptors. In chronic stress (low DA), inhibition is reduced. Over the last 50,000 years, individuals with this change appear to have survived more successfully. Whether this is still true for the last 5,000 to 10,000 years since sedentarization and especially for the last hundreds of years since industrialization and office work remains to be seen.
  • A study of 2,307 subjects found correlations between ADHD and neurophysiological biomarkers of stress.12
  • Meta-analyses of childhood biochemical studies found a significant correlation of ADHD with peripheral biomarkers associated with monoaminergic pathways and the HPA axis.13

While ADHD could (according to our hypothesis - also) be a stress regulation disorder, not every stress regulation disorder is ADHD. Stress systems are also hyper-responsive in other mental disorders, such as depression or PTSD. PTSD, for example, is characterized by increased norepinephrine levels in the PFC, while norepinephrine is decreased in the PFC in ADHD. In epilepsy, stress increases the likelihood of seizures.1415
ADHD shows a very general activation/deactivation of the stress systems, whereby all ADHD symptoms would still be functional stress symptoms if they were the reaction to an adequate stressor (which does not exist in ADHD). In contrast, in the case of depression, anxiety or Compulsions, for example, the respective stress symptoms have become dysfunctional.

To illustrate that all ADHD symptoms are stress symptoms:
ADHD symptoms are stress symptoms

The connection becomes clear when you consider the benefits of stress symptoms. Stress is a very old control instrument of the human organism. In the development of Homo sapiens16 - which is 100,000 to 300,000 years old, according to some accounts - as with hominids, which have existed for several million years, a wide variety of mechanisms have evolved to protect individuals from situations that threaten their survival: the stress systems we are talking about.
Homo sapiens lived as nomads for at least 97% of his time, until 10,000 years ago. The urban way of life only began between 2000 and 3000 years ago. Our stress systems have not yet been able to adapt optimally to the recent developments of city life and office jobs and are still acting today by causing symptoms that were optimized for living conditions when Homo sapiens was not yet sedentary.
In terms of hominid time, our stress systems could have used just 1/500 of their time to adapt to sedentarization. Converted to 24 hours (1440 minutes), that would be around 2 minutes and 50 seconds.

Our stress systems have the task of supporting us in our fight for survival.
If you look at the benefits of the individual stress reactions,
Stress benefits - the survival-promoting purpose of stress symptoms It is easy to understand that all ADHD symptoms are functional (useful) stress symptoms.
ADHD symptoms are stress symptoms

It would be helpful for the diagnosis of ADHD if at least individual ADHD symptoms were not also symptoms of (massive) stress. Then ADHD could be differentiated from a “mere” acute stress situation without a chronic malfunction of the stress regulation systems on the basis of these specific symptoms. Unfortunately, no such ADHD symptoms have yet been identified, which is why ADHD in children is so difficult to distinguish from severe stress. This is easier in adults, as it is easier to determine whether a stressful situation is currently occurring and whether the symptoms have been present since childhood or adolescence. Children are usually unaware of any other life circumstances and are therefore unable to put even severely stressful circumstances into perspective.
The core symptoms of hyperactivity/impulsivity and attention problems typical of ADHD in particular are classic symptoms of severe stress and, on closer inspection, are very useful and helpful in combating an actual threat.
ADHD is characterized by symptoms that occur without an adequate stressor.

1. ADHD symptoms as chronic dysregulation of the stress systems

ADHD is usually caused by a combination of several components:

  • Strong genetic imprinting and/or
  • Genetic disposition plus early childhood stress experience.

1.1. Gene disposition

ADHD has a strong genetic component of 70 to 80 %. The heritability of ADHD is therefore greater than that of intelligence. Nevertheless, only 5% of genetic heritability can be attributed to specific gene variants.
Genetic and epigenetic causes of ADHD.
This could also be due to the fact that only some of the people with ADHD have a purely genetic cause, while others only have a genetic disposition that must first be manifested by additional environmental influences.

1.2. Early childhood stress experience

If an early childhood stress experience is added to an existing genetic predisposition, the ADHD gene candidates can change epigenetically in such a way that ADHD now manifests itself.
How ADHD develops: genes or genes + environment.
Epigenetics means that (intensive) experiences in life cause changes in gene expression: the genes then have a stronger or weaker effect on the mechanisms they control. These acquired changes can in turn be passed on. How ADHD develops: genes + environment - Epigenetics chapter

Early childhood stress can cause permanent damage to neurotransmitter systems (e.g. the dopaminergic system) and the physiological stress systems (HPA axis, autonomic nervous system). Long-lasting or particularly intense short-term (traumatizing) stress also causes serious damage to the stress systems. Early childhood stress experiences are more significant for ADHD because the stress systems are only just emerging during this time. Stress damage - effects of early childhood and/or long-term stress

Finally, prolonged cortisolergic stress leads to neurological damage to the stress regulation systems, e.g. the hypothalamic-pituitary-adrenal axis (HPA axis, stress axis).
The HPA axis / stress regulation axis
Cortisol is activating in the short term, but neurotoxic in the long term. If cortisolergic stress persists for too long, various neurological maladaptations occur.
Stress damage - effects of early childhood and/or long-term stress

The etiology (gene disposition plus an activating early childhood stress experience) is not unique to ADHD, but is reported for almost all mental disorders. Gene disposition and early childhood stress as a cause of other mental disorders Specific to ADHD, however, is the general overreactivity of the stress regulation systems.

ADHD symptoms such as hyperactivity and aggressiveness are also described as a Moro reflex persisting from infancy as a consequence of early childhood disorders in the development of the central nervous system.17 The different names should not change the etiology.

These maladaptations lead to the specific Consequences of ADHD-HI and ADHD-C on the one hand and ADHD-I subtype on the other, as described at the beginning and in more detail in the articles mentioned there.

1.3. Maladaptation of the neurotransmitter and hormone systems; downregulation, upregulation

Stress symptoms are mediated by stress hormones, primarily CRH, ACTH and cortisol. The HPA axis, which releases these stress hormones, is activated by a massive increase in neurotransmitters in the brain, primarily dopamine and noradrenaline, mediated by the limbic system.
The causes of individual symptoms must be distinguished from the activation of the HPA axis.
Stress symptoms can be mediated by any deviation of a neurotransmitter or hormone level from the optimum level for signal transmission - i.e. by an upward deviation as well as a downward deviation (Yerkes-Dodson law).181920

1.3.1. How stress normally arises

The mechanisms by which acute stress is mediated in non-affected people are:

  • The phasic noradrenaline and dopamine levels2122 in the PFC increase.
    This has the effect that
    • The dopamine level in the striatum is reduced23
    • The HPA stress axis is activated,
    • Which causes the stress hormones CRH, ACTH and cortisol to rise,
    • Which together trigger the stress symptoms.
  • Cortisol - the last hormone to be released - ends the stress response of the HPA axis. Cortisol reduces the dopamine level and increases the noradrenaline level in the locus coeruleus, in the PFC and in the striatum.24 The widely known reduction in dopamine levels in the striatum in ADHD is therefore also a consequence of stress.

1.3.2. What distinguishes ADHD from general stress

ADHD is not a consequence of acute stress, but of chronic stress. ADHD is characterized by

  • Dysregulated stress regulation systems that have impaired the dopaminergic and noradrenergic neurotransmitter systems due to early and prolonged stress exposure, e.g. by down- or upregulation of the receptor systems.
    More on this at Damage mechanisms of prolonged stress: downregulation / upregulation (in: Stress damage caused by early childhood and/or prolonged stress)
    • In ADHD, too many dopamine transporters (especially in the striatum) are probably formed. This can either be the result of genetic imprinting (the DAT1 10/10 gene variant associated with ADHD forms more dopamine transporters)25 or could possibly be the result of upregulation due to long-lasting reduced tonic dopamine levels in the striatum: dopamine deficiency correlates with an increase in the number of dopamine transporters.26
      The stress hormone cortisol triggers a reduced dopamine level in the striatum.24 Prolonged stress can lead to permanently reduced dopamine levels in the striatum and subsequently to the upregulation of the DAT described above.
    • In ADHD-HI (with hyperactivity), the dopamine receptors in the cingulate cortex appear to be downregulated.27 Downregulation could indicate an oversupply of dopamine in the cingulate cortex. However, ADHD is characterized by a permanently reduced dopamine level in the PFC. At best, it is conceivable that the receptor downregulation was triggered by earlier chronic stress, which was still associated with increased dopamine levels. Similar changes occur in the tonic (basal) cortisol levels during chronic stress.
  • A general, non-specific hyperexcitability

Consequences are that the stress systems in ADHD are dysregulated even without a specific stressor - be it that they start up too quickly and react too intensively (ADHD-I) or no longer switch off (ADHD-HI), see above.

Short-term stress (here: last month) has no effect on ADHD.28

1.4. The human stress system

The various stress systems in humans (amygdala, central nervous system, autonomic nervous system, HPA axis) are described in detail at The human stress systems.

1.5. Subjective stress response increased in ADHD

In addition to the biological / neurological changes in the various stress systems of people with ADHD, the subjective perception intensity of the stress reaction differs significantly and reproducibly. The same increase in cortisol leads to a stronger perception of stress in people with ADHD than in those not affected.2930
Persons with ADHD have a stronger psychophysiological response to the same stress as people without ADHD, e.g. greater test anxiety.3132
This is particularly interesting in view of the fact that in healthy people the cortisol and ACTH stress response correlates only moderately with the subjective perception of stress - a meta-analysis found a correlation of 0.3 to 0.5 in only 25% of 49 studies. Two thirds of the studies found a correlation between the cortisol stress response or ACTH stress response and the subjective perception of stress.33
The subjective experience of stress seems to correlate more with the physiological (cortisol) stress response during the acute stress situation itself than with that before or after the acute stress.34

People with ADHD show a maladaptive response to stress. ADHD severity correlates with stronger stress transference and higher negative affect. Stress transference and mean levels of negative affect mediate the relationship between ADHD-HI traits and internalizing problems.35

2. Stress biomarkers of ADHD

In a study, various immune system biomarkers of unmedicated people with ADHD were compared with those of non-affected people.36 The indications of changes found in various biomarkers compared to non-affected persons are shown below in brackets. Unfortunately, the study does not differentiate between subtypes. We assume that the results are likely to differ greatly between the subtypes.

  • Erythrocyte glutathione (GSH) (INCREASED)
  • Plasmalipid-soluble antioxidants
    • Retinol
    • Α-Tocopherol
    • Γ-Tocopherol
    • Retinyl palmitate (INCREASED)
    • Β-Carotene
    • Coenzyme Q10
  • Plasma malondialdehyde (MDA) (INCREASED in plasma)
  • Cytokines in the blood
    • IL-
    • IL-5 (REDUCED)
    • IL-6
    • IL-8
    • IL-10
    • Tumor necrosis factor (TNF)
    • Interferon (INF) -γ
  • Immunoglobulins
    • IgM
  • 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in urine (INCREASED)

Another study found in adult people with ADHD:37

  • Total thiol value reduced
  • Native thiol value reduced
  • Disulfide levels increased
  • 8-OHdG values increased
    • 8-OHdG is considered a marker for DNA damage

3. ADHD symptoms are stress symptoms

If you compare the list of common stress symptoms with the typical symptoms of ADHD, you will find that almost all typical symptoms of ADHD are also typical stress reactions. In contrast, not all stress symptoms that exist are also ADHD symptoms. ADHD symptoms are stress symptoms Although ADHD has a very wide range of symptoms, the focus is on emotional, cognitive and motor stress symptoms. ADHD manifests itself remarkably little in somatic (physical) stress symptoms.
Conversely, it can also be said that uncontrollable (cortisolergic) stress triggers symptoms that are identical to ADHD symptoms.

This explains, for example, why children who are bullied (e.g. unrecognized gifted children if they are unable to compensate for their “being different” due to poor social skills) are initially barely distinguishable from people with ADHD: it is precisely this self-esteem-threatening stress that causes almost identical symptoms via the HPA axis. A misunderstood “not belonging” and “being different” threatens self-esteem much more than the boredom that often exists for unrecognized gifted people, on the one hand due to underchallenge and on the other hand because gifted people (just like people with ADHD) are much more difficult to motivate extrinsically.

This leads to the question: if all ADHD symptoms are also triggered by stress - then what is ADHD? Does ADHD even exist or do the people with ADHD “just” have too much stress?

The answer is:

  • Stress symptoms are triggered by deviations in neurotransmitter levels from the optimal, moderate mean value. During acute stress, for example, the phasic dopamine and noradrenaline levels in the PFC are elevated. This causes dysfunction, e.g. of the working memory in the dlPFC.
    Chronic stress causes long-term dysregulation of the tonic Neurotransmitter systems, which - depending on the stressor and the person with ADHD - can be permanently increased or permanently decreased. Depending on which neurotransmitters in which brain region experience long-term up- or downregulation, there are different risks for different mental disorders. ADHD is the consequence of a permanent reduction of dopamine and noradrenaline in the PFC and striatum. Genes that remain unaffected by environmental influences have a compensatory or reinforcing effect here (such as DRD4-7R, which makes dopamine D4 receptors less sensitive, so that they require three times as much dopamine as other DRD4 gene variants). If a person with DRD4-7R were to suffer upregulation of dopamine and noradrenaline in the PFC, this would not be as severe as in someone suffering downregulation due to DRD4-7R.
    The symptoms of dysfunctional working memory (disorganization, impaired executive functions) are caused neurophysiologically in ADHD by reduced dopamine and noradrenaline levels in the dlPFC, and in acute stress by excessive dopamine and noradrenaline levels. Excessive noradrenaline levels cause the PFC to switch off, whereas flattened dopamine levels do not - the PFC remains in continuous operation even during stress. This explains the different symptoms of ADHD-HI and ADHD-I. SCT, which according to its symptomatology could be particularly affected by PFC deactivation, should, if our hypothesis is correct, correlate with particularly high noradrenaline levels in the PFC. This could explain why stimulants have a worse effect in SCT - these increase dopamine and noradrenaline in the PFC.
  • People who develop symptoms that seem like ADHD symptoms due to acute or chronic stress do not necessarily have ADHD. If the symptoms disappear again after the overload has ceased, there is no ADHD. In the case of ADHD, quite “normal” life circumstances without any particular stress are enough to cause massive stress symptoms.38
    The former are purely stress symptoms due to acute overload, the latter are a chronic overreaction of the stress regulation system - that is ADHD.
    Stress goes with the stressor - ADHD stays, even without an adequate stressor.
    In order to distinguish ADHD from acute stress, the diagnosis of ADHD is based on the occurrence of symptoms in various areas of life and their persistence since childhood or adolescence. A small percentage of people with ADHD (approx. 1%) only develop symptoms for the first time after the age of 16 (late onset).39

In the event of prolonged stress in early childhood, the body is subject to prolonged elevated CRH and cortisol levels. Stress hormones such as cortisol are neurotoxic, i.e. too much stress for too long damages the nervous system. One of the consequences of damage to the HPA axis caused by early stress is a change in the cortisol receptors (down/upregulation) Damage mechanisms of prolonged stress: downregulation / upregulation (in: Stress damage caused by early and/or prolonged stress)

CRH and cortisol are there to trigger fight/flight/freeze reactions and, unlike adrenaline, are only released in response to highly aversive or novel stimuli. While adrenaline cannot cross the blood-brain barrier, cortisol is able to do so. Adrenaline is released more quickly and degraded more rapidly than cortisol.40

Consequences of this are that the body reacts to even small amounts of stress hormones (e.g. CRH or cortisol) with stress. This is likely to be the central cause of ADHD.

As mentioned earlier, the fact that all ADHD symptoms are stress symptoms becomes vividly tangible when you look at the benefits of stress symptoms.
Stress benefits - the survival-promoting purpose of stress symptoms

ADHD has - very generalized - the following interactions with stress:

  • Massive stress in childhood (cause of development)
    • Activates a possible genetic disposition for ADHD
    • Leads to undesirable developments in the stress systems such as
      • Reduced stress threshold
      • Downregulation of the receptors (cortisol, CRH)
      • Non-specific arousal (noradrenaline)
      • Downregulation of dopamine receptors in the striatum
  • This manifests a chronic malreactivity of the stress systems
  • Consequences: People with ADHD are under constant stress even without an acute stressor
  • People with ADHD perceive stress with the same cortisol level more intensely than people without ADHD (see 1.5 above)
  • Consequences of stress are stress symptoms
  • ADHD symptoms are general (functional) stress symptoms

4. High confusability of ADHD

The fact that all ADHD symptoms are stress symptoms also explains why ADHD is so easily misdiagnosed and occasionally even doubted. Sometimes acute stress is mistaken for ADHD, sometimes vice versa. Supposed people with ADHD who suddenly lose their symptoms because external circumstances change and there is no acute stress do not have ADHD. This does not mean that all other people with the same symptoms only have acute stress and no ADHD. There are people who suffer from acute stress and there are people who suffer from ADHD.
While the stress symptoms of people without ADHD disappear again when the acute stress trigger is removed, allowing them to return to a healthy resilience, the stress regulation system of people with ADHD is permanently damaged. They develop the stress symptoms typical of ADHD (and possibly also other symptoms) even if there is no situation that could justify such stress symptoms, i.e. if there is no adequate stressor.

Careful diagnosis is therefore extremely important and must not be limited to querying (currently existing) symptoms, but must carefully examine the current life circumstances and the development prior to their occurrence.
These correlations further make it clear that all psychological test diagnostics will never be able to prove the existence of ADHD, because by their very nature tests can only determine the existence of symptoms as a snapshot, but this does not prove any difference between acute stress and ADHD.
It is possible that ADHD could be differentiated subtype-specifically from acute stress using the dexamethasone/ACTH/CRH test or other measurable endocrine stress responses.

ADHD therefore has a special position within the mental disorders.

  • Difficult diagnosis. ADHD is particularly often confused and (under- and over-) misdiagnosed due to its rather general stress symptoms - precisely because ADHD does not have a particularly peculiar and specific symptom that facilitates a clear diagnosis.
  • Easy treatment. No other mental Disorder is so well treatable (acutely with medication and long-term therapeutically).

5. ADHD and stress: a self-reinforcing system

We see the high correlation between ADHD symptoms and low self-esteem or depressive symptoms as an indication that dysfunctional stress regulation systems, once manifested in ADHD due to genetic disposition and triggering unfavorable circumstances, subsequently form a self-reinforcing system. The unpleasant symptoms of ADHD reinforce the stress, which causes additional stress symptoms that may be congruent with the ADHD symptoms. The result is a downward spiral of stress and the ADHD symptoms that respond to it, causing further stress. This mechanism has been described several times, both for mental disorders in general41 and for ADHD in particular,42 including a large cohort study in Sweden.43

Furthermore, the symptom of inability to relax is particularly prevalent in ADHD-HI and ADHD-C. Inability to relax is a functional stress symptom: it is conducive to survival not to indulge in pleasure and relaxation as long as there is a danger to survival. It is also an original ADHD symptom of the ADHD-HI and mixed type.
This is the reason why mindfulness techniques (e.g. yoga, meditation, ChiGong etc.) are perceived as extremely aversive, especially by people with ADHD-HI. This deprives people with ADHD of the opportunity to reduce stress through relaxation and mindfulness techniques.
The same applies to the symptom of dysphoria when inactive. This symptom is also aimed at ensuring that the person concerned remains active in order to combat the stressor. However, if, as with ADHD, there is no adequate stressor, the stress symptom is meaningless.

There is a bidirectional relationship between negative life events and mental illness.
Pronounced ADHD causes further negative life events.

The strongest correlations with negative life events are

  • Severity of the ADHD-HI manifestation
  • Female gender
  • Low socio-economic status and
  • Comorbid emotional disorders

The severity of ADHD-HI correlates more strongly with recent negative life events than with the severity of other comorbid disorders.4445
A study of stress exposure in children with ADHD found that severe stress exposure in childhood and adolescence was associated with severe ADHD-HI or ADHD-I progression into adulthood, while children with low stress exposure often showed remitting ADHD (ADHD-HI as well as ADHD-I).46 A Swedish cohort study confirms this.43
Stressors in adolescence that predicted persistent ADHD were cited as:47

  • Chronic diseases
  • Disabilities of the child
  • Disabilities of another immediate family member
  • High work pressure at school
  • Problems at home
  • Neighborhood problems
  • Unemployment
  • Financial difficulties
  • Fewer friends than the child would like to have
  • Bullying
  • Ongoing conflicts with family members
  • Ongoing conflicts with a person outside the family
  • Family members with ongoing conflicts

6. The difference: stress goes with the stressor, ADHD stays

Stress has the “advantage” over ADHD that it can also end. In healthy people, the symptoms of stress disappear when the stress ends.
You can also apparently “get rid of” ADHD by withdrawing to a completely stimulus-free environment. People with ADHD lose their symptoms after spending several weeks in a secluded mountain hut (without a cell phone or the internet).
The difference becomes apparent when both return to a normal living environment that does not contain any particular stress triggers. The person without ADHD will continue to feel well, while the person with ADHD will immediately develop the old symptoms.

7. ADHD comorbidities as dysfunctional stress symptoms

The most common comorbidities of ADHD are

  • Anxiety / panic states
  • Depression
  • Compulsions
  • Addiction

All of these phenomena are also typical stress symptoms in their basic forms.
However, it is already clear here that even if dysphoria during inactivity is a helpful stress reaction (when there is an actual threat), it is obvious that there is far more to depression, obsessive-compulsive disorder and anxiety than a momentary, acute state of stress. In such disorders, individual, specific stress symptoms have gotten out of control (become dysfunctional), whereas in ADHD the balance between the stress symptoms (in the sense of a “healthy” stress reaction under the assumption of an existing danger) is still largely maintained. In ADHD, the condition is disturbed (that stress exists although no corresponding stressor is present), while the stress response itself works physiologically largely correctly.
Acute cortisolergic stress can cause the stress symptoms that correspond to those of ADHD, but not readily symptoms of major depression or severe obsessive-compulsive behavior.
However, it has been proven that depression can be caused by long-term stress - and that depressives are in a state of increased long-term stress.48 Early childhood stress in conjunction with the genetic disposition relevant to depression leads to a high susceptibility to depression.
How ADHD develops: genes + environment

Up to this point, the triggering cause and ongoing effects of depression and ADHD have been the same. In depression, a lack of serotonin, a hormone that serves to reduce stress, maintains the increased permanent state of stress.48 In ADHD, the dopamine balance is primarily altered, followed by the noradrenaline balance and, albeit to a lesser extent, the acetylcholine balance and the serotonin balance (keyword: dysphoria during inactivity).
Stress also inhibits the melatonin balance, which normally counteracts states of stress.

8. Correlation of stress sensitivity and ADHD in animal models

The Spontaneous(ly) hypertensive rat (SHR) is a genetically selected rat that is an animal model for ADHD-HI and hypertension.
The animals have genes that cause them to develop high blood pressure at the age of 15 months (without early childhood stress experience). At the same time, they are considered a scientific animal model for ADHD-HI (with hyperactivity) in ADHD research.49
With increasing age and parallel to increasing high blood pressure, an increasing sensitivity of the HPA axis to stress is observed in animals.50
The ADHD symptoms as well as the high blood pressure in SHR can be remedied by targeted treatment of the HPA axis with dexamethasone.

Unfortunately, it can be assumed that the mechanisms for eliminating ADHD in SHR only work reliably in the (fixed) genetic constellation that is present in SHR. This treatment method is therefore - also from a scientific perspective - not transferable 1:1 to the treatment of other genetic constellations or to all people with ADHD. However, it could be applicable to those whose ADHD symptoms are caused by precisely this neurophysiological pathway.

Spontaneous hypertensive rat (SHR)

  1. Bull-Larsen, Mohajeri (2020): The Potential Influence of the Bacterial Microbiome on the Development and Progression of ADHD. Nutrients. 2019 Nov 17;11(11):2805. doi: 10.3390/nu11112805. PMID: 31744191; PMCID: PMC6893446. REVIEW

  2. Lautarescu, Craig, Glover (2020): Prenatal stress: Effects on fetal and child brain development. Int Rev Neurobiol. 2020;150:17-40. doi: 10.1016/bs.irn.2019.11.002. PMID: 32204831. REVIEW

  3. Chrousos (2009): Stress and disorders of the stress system. Nat Rev Endocrinol. 2009 Jul;5(7):374-81. doi: 10.1038/nrendo.2009.106. PMID: 19488073. REVIEW

  4. Morgan, LeDoux (1995): Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci. 1995 Aug;109(4):681-8. doi: 10.1037//0735-7044.109.4.681. PMID: 7576212.

  5. Sullivan, Gratton (1999): Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and autonomic stress responses in rats. J Neurosci. 1999 Apr 1;19(7):2834-40. doi: 10.1523/JNEUROSCI.19-07-02834.1999. PMID: 10087094; PMCID: PMC6786056.

  6. Fuster (2001): The prefrontal cortex–an update: time is of the essence. Neuron. 2001 May;30(2):319-33. doi: 10.1016/s0896-6273(01)00285-9. PMID: 11394996 REVIEW

  7. Kalivas, Volkow (2005): The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005 Aug;162(8):1403-13. doi: 10.1176/appi.ajp.162.8.1403. PMID: 16055761. REVIEW

  8. Baik (2020): Stress and the dopaminergic reward system. Exp Mol Med. 2020 Dec;52(12):1879-1890. doi: 10.1038/s12276-020-00532-4. PMID: 33257725; PMCID: PMC8080624. REVIEW

  9. Waizbard-Bartov E, Ferrer E, Heath B, Andrews DS, Rogers S, Kerns CM, Wu Nordahl C, Solomon M, Amaral DG (2023): Changes in the severity of autism symptom domains are related to mental health challenges during middle childhood. Autism. 2023 Sep 10:13623613231195108. doi: 10.1177/13623613231195108. PMID: 37691349.

  10. Zheng, Pingault, Unger, Rijsdijk (2019): Genetic and environmental influences on attention-deficit/hyperactivity disorder symptoms in Chinese adolescents: a longitudinal twin study. Eur Child Adolesc Psychiatry. 2019 May 20. doi: 10.1007/s00787-019-01346-0.

  11. Öster, Ramklint, Meyer, Isaksson (2019): How do adolescents with ADHD perceive and experience stress? An interview study. Nord J Psychiatry. 2019 Oct 15:1-8. doi: 10.1080/08039488.2019.1677771.

  12. Vogel, Bijlenga, Verduijn, Bron, Beekman, Kooij, Penninx (2018): Attention-deficit/hyperactivity disorder symptoms and stress-related biomarkers. Psychoneuroendocrinology. 2017 May;79:31-39. doi: 10.1016/j.psyneuen.2017.02.009.

  13. Scassellati, Bonvicini, Faraone, Gennarelli (2012): Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry. 2012 Oct;51(10):1003-1019.e20. doi: 10.1016/j.jaac.2012.08.015. PMID: 23021477. METASTUDIE


  15. Himmer: Tamme passt auf. Süddeutsche Zeitung 24.05.19

  16. Richter, Grün, Joannes-Boyau, Steele, Amani, Rué, Fernandes, Raynal, Geraads, Ben-Ncer, Hublin, McPherron (2017): The age of the hominin fossils from Jebel Irhoud, Morocco, and the origins of the Middle Stone Age. In: Nature. 546, Nr. 7657, 2017, ISSN 0028-0836, S. 293–296. doi:10.1038/nature22335.

  17. Lauff (2009): Neurophysiologische Ursachen aggressiven Verhaltens; in: Friedrich (2009): Umgang mit Konflikten und Gewalt an der Schnittstelle zwischen Psychologie, Pädagogik und Sozialer Arbeit, Lulu, Seite 115 ff

  18. Yerkes-Dodson-Gesetz

  19. Cools, Aarts, Mehta in Kapur (Herausgeber): The Paradoxical Brain (2011): Paradoxical effects of drugs on cognitive function: the neuropsychopharmacology of the dopamine and other neurotransmitter systems; Seite 397, 401

  20. Krause, Krause (2014): ADHS im Erwachsenenalter; Schattauer, Seite 255

  21. Gresch, Sved, Zigmond, Finlay (1994): Stress-induced sensitization of dopamine and norepinephrine efflux in medial prefrontal cortex of the rat. J Neurochem. 1994 Aug;63(2):575-83.

  22. Morrow, Redmond, Roth, Elsworth (2000): The predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat. Brain Res. 2000 May 2;864(1):146-51.

  23. Ferenczi, Zalocusky, Liston, Grosenick, Warden, Amatya, Katovich, Mehta, Patenaude, Ramakrishnan, Kalanithi, Etkin, Knutson, Glover, Deisseroth (2016): Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698

  24. Park, Jung, Park, Yang, Kim (2018): Melatonin inhibits attention-deficit/hyperactivity disorder caused by atopic dermatitis-induced psychological stress in an NC/Nga atopic-like mouse model Sci Rep. 2018; 8: 14981. doi: 10.1038/s41598-018-33317-x; PMCID: PMC6175954 PMID: 30297827

  25. Cornish, Manly, Savage, Swanson, Morisano, Butler, Grant, Cross, Bentley, Hollis (2005): Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample. Mol Psychiatry. 2005 Jul;10(7):686-98.

  26. Brake, Sullivan, Gratton (2000): Perinatal Distress Leads to Lateralized Medial Prefrontal Cortical Dopamine Hypofunction in Adult Rats; Journal of Neuroscience 15 July 2000, 20 (14) 5538-5543

  27. Satoh, Suzuki, Saitow (2018): Downregulation of Dopamine D1-like Receptor Pathways of GABAergic Interneurons in the Anterior Cingulate Cortex of Spontaneously Hypertensive Rats. Neuroscience. 2018 Oct 28. pii: S0306-4522(18)30709-7. doi: 10.1016/j.neuroscience.2018.10.039.

  28. Garcia, Rouchy, Galéra, Tzourio, Michel (2019): The relation between ADHD symptoms, perceived stress and binge drinking in college students. Psychiatry Res. 2019 Nov 15:112689. doi: 10.1016/j.psychres.2019.112689.

  29. Corominas-Roso, Palomar, Ferrer, Real, Nogueira, Corrales, Casas, Ramos-Quiroga (2015): Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.Int J Neuropsychopharmacol. 2015 Mar 17;18(9). pii: pyv027. doi: 10.1093/ijnp/pyv027, n = 121

  30. Isaksson, Nilsson, Lindblad (2015): The Pressure-Activation-Stress scale in relation to ADHD and cortisol. Eur Child Adolesc Psychiatry. 2015 Feb;24(2):153-61. doi: 10.1007/s00787-014-0544-9. n = 248

  31. Raz, Leykin (2015): Psychological and cortisol reactivity to experimentally induced stress in adults with ADHD; Psychoneuroendocrinology. 2015 Oct;60:7-17. doi: 10.1016/j.psyneuen.2015.05.008.

  32. Palma, Natale, Calil (2015): A four-year follow-up controlled study of stress response and symptom persistence in Brazilian children and adolescents with attention deficit disorder and hyperactivity (ADHD); Psychiatry Res. 2015 Dec 15;230(2):227-32. doi: 10.1016/j.psychres.2015.08.044.

  33. Campbell, Ehlert (2012): Acute psychosocial stress: does the emotional stress response correspond with physiological responses? Psychoneuroendocrinology. 2012 Aug;37(8):1111-34. doi: 10.1016/j.psyneuen.2011.12.010. METASTUDIE

  34. Hellhammer, Schubert (2011): The physiological response to Trier Social Stress Test relates to subjective measures of stress during but not before or after the test, Psychoneuroendocrinology, Volume 37, Issue 1, 2012, Pages 119-124, ISSN 0306-4530,

  35. Speyer, Brown, Ribeaud, Eisner, Murray (2022): The role of moment-to-moment dynamics of perceived stress and negative affect in co-occurring ADHD and internalising symptoms. J Autism Dev Disord. 2022 Jun 8. doi: 10.1007/s10803-022-05624-w. PMID: 35674983. n = 262

  36. Verlaet, Breynaert, Ceulemans, De Bruyne, Fransen, Pieters, Savelkoul, Hermans (2018): Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case-control comparison. Eur Child Adolesc Psychiatry. 2018 Oct 22. doi: 10.1007/s00787-018-1239-4.

  37. Kurhan, Alp (2021): Dynamic Thiol/Disulfide Homeostasis and Oxidative DNA Damage in Adult Attention Deficit Hyperactivity Disorder. Clin Psychopharmacol Neurosci. 2021 Nov 30;19(4):731-738. doi: 10.9758/cpn.2021.19.4.731. PMID: 34690128; PMCID: PMC8553522. n = 82

  38. Combs, Canu, Broman-Fulks, Rocheleau, Nieman (2015): Perceived stress and ADHD symptoms in adults. J Atten Disord. 2015 May;19(5):425-34. doi: 10.1177/1087054712459558. Epub 2012 Oct 3. n = 983

  39. Kieling, Kieling, Rohde, Frick, Moffitt, Nigg, Tannock, Castellanos (2010): Am J Psychiatry. 2010 Jan;167(1):14-6. doi: 10.1176/appi.ajp.2009.09060796.

  40. Krohne (2016): Stress und Stressbewältigung bei Operationen, Springer, Seite 15

  41. Grant, Compas, Thurm, McMahon, Gipson (2004): Stressors and Child and Adolescent Psychopathology: Measurement Issues and Prospective Effects, Journal of Clinical Child & Adolescent Psychology, 33:2, 412-425, DOI: 10.1207/s15374424jccp3302_23

  42. Biederman, Milberger, Faraone, Kiely, Guite, Mick, Ablon, Warburton, Reed, Davis (1995): Impact of adversity on functioning and comorbidity in children with attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995 Nov;34(11):1495-503.

  43. Björkenstam, Björkenstam, Jablonska, Kosidou (2018): Cumulative exposure to childhood adversity, and treated attention deficit/hyperactivity disorder: a cohort study of 543 650 adolescents and young adults in Sweden. Psychol Med. 2018 Feb;48(3):498-507. doi: 10.1017/S0033291717001933.

  44. Garcia, Bau, Silva, Callegari-Jacques, Salgado, Fischer, Victor Sousa, Karam, Rohde, Belmonte-de-Abreu, Grevet (2010): The burdened life of adults with ADHD: Impairment beyond comorbidity. European Psychiatry, Eur Psychiatry. 2012 Jul;27(5):309-13. doi: 10.1016/j.eurpsy.2010.08.002.

  45. Schmidt, Petermann: ADHS über die Lebensspanne – Symptome und neue diagnostische Ansätze, Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 59 (3), 2011, 227–238, Seite 230.

  46. Hartman, Rommelse, van der Klugt, Wanders, Timmerman (2019): Stress Exposure and the Course of ADHD from Childhood to Young Adulthood: Comorbid Severe Emotion Dysregulation or Mood and Anxiety Problems. J Clin Med. 2019 Nov 1;8(11). pii: E1824. doi: 10.3390/jcm8111824. n = 609

  47. Hartman, Rommelse, van der Klugt, Wanders, Timmerman (2019): Stress Exposure and the Course of ADHD from Childhood to Young Adulthood: Comorbid Severe Emotion Dysregulation or Mood and Anxiety Problems. J Clin Med. 2019 Nov 1;8(11). pii: E1824. doi: 10.3390/jcm8111824. n = 609


  49. Sagvolden, Metzger, Schiorbeck, Rugland, Spinnangr, Sagvolden (1992): The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants; Behavioral and Neural Biology, Volume 58, Issue 2, September 1992, Pages 103-112;

  50. Iams, McMurtry, Wexler (1979): Aldosterone, Deoxycorticosterone, Corticosterone, and Prolactin Changes during the Lifespan of Chronically and Spontaneously Hypertensive Rats; Endocrinology, Volume 104, Issue 5, 1 May 1979, Pages 1357–1363,