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Stress theories and stress phenotypes: a possible explanation of ADHD subtypes

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Stress theories and stress phenotypes: a possible explanation of ADHD subtypes

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

We support the hypothesis that the symptoms of different ADHD subtypes (in particular the two poles ADHD-HI and ADHD-C (with hyperactivity and impulsivity = externalizing) and ADHD-I (without hyperactivity = internalizing)) can be described or explained as phenotypically different stress reactions.

Mammals and humans react to stress with different patterns that vary randomly within a population. On the one hand, there are individuals that react to stress with aggression or attack (fight type), while others tend to react with flight or “playing dead” (flight type). Another reaction pattern could be the “freeze” pattern. These different stress responses have developed over the course of evolution and have enabled populations to respond better to different challenges and survive.
Grey’s BIS/BAS/FFFS system describes different stress response patterns in mammals and humans. The BAS type reacts to stress with attack, the FFFS type with flight or “playing dead” and the BIS system is responsible for balancing BAS and FFFS.

This leads to the hypothesis that the expression of the different ADHD presentation forms (subtypes) is also based on different stress response patterns. People with ADHD-HI and ADHD-C show a tendency towards an extroverted stress response, while people with ADHD-I tend to react more introverted.
Accordingly, there is a correlation between certain personality traits and the different stress response patterns and ADHD subtypes. The Type A personality is associated with the ADHD-HI and ADHD-C subtypes, while the Type C personality is associated with the ADHD-I subtype.

There are also typical differences in the cortisol response to stress in healthy people. One group shows an increased cortisol response, while the other group shows a flattened response. People with a flattened cortisol stress response were more likely to have externalizing stress symptoms, aggression, violence, a lack of empathy and a low sense of punishment. They also showed higher cognitive intelligence, higher extraversion and higher neuroticism.
An increased cortisol stress response, on the other hand, correlates with internalizing disorders such as anxiety or (melancholic) depression

Differences in the cortisol response were also observed in other mental disorders. In depression, forms of presentation were found with an elevated (melancholic depression) as well as a flattened cortisol stress response (agitated depression). In post-traumatic stress disorder, phenotypically different stress reactions to the same trauma were observed.

1. Typical stress response patterns in mammals and humans

Mammals react to stress with different patterns that are randomly distributed within a population.
According to the Fight/Flight Stress Response Model (Fight/Flight System, FFS) of Cannon, 1932 (later also Gray), part of the population tends to react to stress with aggression or attack (fight), i.e. an outwardly directed (extroverted) reaction.
The other part of the population tends to react to stress by running away (flight) or “pretending not to be there” (freeze), i.e. with an inward-looking (introverted) reaction.

A detailed description of the BIS/BAS/FFFS system can be found at ⇒ Neurophysiological correlates of BIS/BAS In the section*⇒ The human stress system - the basics of stress* in the chapter ⇒ Stress.

2. Stress reaction patterns based on the BIS/BAS/FFFS system according to Grey

Mammals do not react uniformly to stress.
According to the fight/flight stress model (by Connor (1932) and later Gray, who combined it with the BIS/BAS model, → RST from 1990, revised 2000), there are 2 to 3 main groups of stress reactions:

The Fight type (BAS) reacts to stress by attacking.
The flight/freeze type reacts to stress by fleeing or playing dead.
According to the revised Reinforcement Sensitivity Theory (RST) by Gray (2000), the BIS system no longer reacts to external stimuli, but only becomes active when the BAS and the FFFS system have both been activated. The BIS system is responsible for weighing up the BAS and FFFS.

Benefits of different stress phenotypes

These reaction models are very deeply rooted. The probability of survival of a “stone-age” group of Homo sapiens has always been higher if the group had members with different stress phenotypes. Modern industrial psychology knows that groups with different characters are more successful than homogeneous groups.

Examples

Quite banal: if all members of a group were night owls or early risers - how well would the primeval group have been protected from enemies if all group members slept at the same time?
Similarly, what is the likelihood that at least individual group members would have survived if an entirely new challenge had arisen in which either deliberate or spontaneous action was the optimal survival strategy?
In other words, it would run counter to the basic idea of evolution that groups with a homogeneous character structure survive better than others.

The different stress response phenotypes are also recognizable in other organisms, e.g. in guppies.1
Consequences, it seems conclusive to us that the expression of the individual as a Fight or Flight type is a purely random variable that ensured that a population had enough members of both types.
If “freeze” is added as an independent stress response phenotype (which could perhaps explain the phenomenon of SCT / CDS), there would be three stress phenotypes.

Put another way: Groups in which a single type became genetically dominant were less likely to survive, so we are descendants of those who passed on this trait with a high random distribution.

Similar: Farmer/Hunter hypothesis

In the Hunter/Farmer hypothesis, people with ADHD-HI subtype are phenotypically regarded as hunters and people with ADHD-I subtype are phenotypically regarded as farmers, with the ADHD symptoms of each subtype taking an (unhealthy) extreme form of the two poles. A representation as extreme poles is conclusive.
Sometimes, however, an idealization or strangely justified “superiority” of ADHD is derived from the Hunter/Farmer hypothesis - we expressly do not share this view. People with ADHD may be different from people without ADHD, which may have disadvantages in some constellations and advantages in others - but superiority cannot be derived from this. If one realizes that the standards of what is “right” and what is “wrong”, i.e. what is “sick” and what is “healthy”, are always defined by the majority and that in the case of a particularity, the majority is by definition not affected by the particularity of minorities, this relativizes the evaluation of a designation considerably anyway.

Our observation is that professional / entrepreneurial self-employment is the domain of the type A personality and the ADHD-HI / mixed type. According to our (purely subjective) impression, type C personalities and people of the ADHD-I subtype are less or less successful as self-employed persons. This is particularly true for people with ADHD who, in our experience, are not advised to become self-employed.
Independence requires the ability to make quick decisions. While hasty or even ill-considered, impulsive decisions may be detrimental to self-employment, difficulties in making decisions appear to be an even greater obstacle.
Conversely, according to our (purely subjective) impression, activities that require a great deal of empathy and persistence, such as therapeutic professions, seem to be a strength of the more introverted types.

A detailed description of the BIS/BAS/FFFS system can be found at
⇒ The BIS-/BAS-/Fight-Flight-Freeze-System.

2.1. ADHD subtypes as BIS/BAS/FFFS types

We understand the ADHD-HI subtype to be an ADHD person with ADHD who responds to stress with action and extroversion (fight, BAS, extroverted), while the ADHD-I subtype is an ADHD person with ADHD who responds to stress by fleeing or playing dead (flight/freeze, introverted). Research confirms that the personal tendency to act out stress through externalizing reactions correlates with high BAS, while the personal tendency to internalize stress correlates with high flight/freeze. (According to the definition of the “old” RST by Gray before 2000, this would still be the BIS).2.

Several years after the first thoughts on this side about a connection between the BIS/BAS system and the ADHD subtypes, we came across a meta-analysis on cortisol and ADHD that had already discussed this idea.3

2.1.1. ADHD-HI/ADHD-C (with hyperactivity): high BAS

The ADHD-HI subtype (with hyperactivity) develops in people with ADHD with the stress response pattern Fight (aggression and attack). ADHD-C would then be a weakened form of the ADHD-HI subtype (with partially delayed brain development).

Symptomatic:

  • Stress is externalized, acted out
  • Frequent aggressive behavior
  • Frequent impulsive behavior
  • Frequent motor hyperactivity
  • More conflicts with peers
  • Attention problem: easily distracted

The description of the mixed type as a relative of the ADHD-HI subtype is supported by the fact that in both the cortisol levels to acute stressors fall and remain well below the levels of non-affected individuals, while in the ADHD-I subtype the cortisol response to acute stressors rises above the level of non-affected individuals.
⇒ The HPA axis / stress regulation axis

2.1.2. ADHD-I subtype (without hyperactivity): high FFFS

The ADHD-I subtype (without hyperactivity) is formed in people with ADHD who tend to have a high FFFS (according to the old RST: BIS) and the stress reaction pattern Flight (flight or playing dead, whereby playing dead is probably only the precursor to flight on discovery; playing dead is associated with very high internal tension).

Symptomatic:

  • Stress is internalized, lived out inwardly
  • Less aggressive behavior
  • Less impulsive behavior
  • Significantly fewer conflicts with peers
  • Attention problem: easily bored

The internal pressure (or stress) that triggers the reactions is the same for both types. However, the different ways of dealing with the inner pressure lead to different symptoms.
According to this view, the different symptoms of ADHD-HI and ADHD-I are fundamentally based on the method of coping with stress used by the person with ADHD.

2.1.3. SCT / Sluggish: Dysfunctional FFFS?

According to this view, the new RST could explain the phenomenon of SCT (“sluggish cognitive tempo”) as a “switched off” BIS (due to particularly high levels of noradrenaline and dopamine4?), which is therefore particularly inhibited in its decision-making. This could explain why people with ADHD can have above-average intelligence and yet be massively impaired in their decision-making.

According to this hypothesis, in SCT the BIS system, which (according to the new RST) primarily has weighing tasks with simultaneously activated BAS and FFS, is also switched off by excessive noradrenaline and dopamine levels (which deactivate the PFC).

3. Stress response patterns explain ADHD presentation forms

Family and twin studies have proven hereditary causes for character traits such as extraversion / introversion / neuroticism / harm avoidance as well as personality traits such as affective instability or social avoidance.5
Similarly, Huber6 and Trappmann-Korr7 describe a connection between ADHD presentation forms and personal character traits of the persons with ADHD.
Similarly, a study that distinguished comorbidities in ADHD by presentation found that hyperactivity/impulsivity (ADHD-HI) correlated closely with externalizing comorbidities, and predominant inattention (ADHD-I) clustered with internalizing comorbidities such as dysthymia and anxiety disorders including Generalized Anxiety Disorder.8

Diamond9 described SCT as a subset of ADHD-I, which seemed plausible in the context of our differentiation matrix according to stress reaction types, but has since been refuted: SCT is now regarded as an independent disorder, even though it very often occurs comorbidly with ADHD.

We assume that the classic ADHD presentation form poles ADHD-HI (with hyperactivity) and ADHD-I (without hyperactivity) represent different stress phenotypes that show different stress reaction patterns to one and the same cause (ADHD). ADHD-HI tends to react to stress in an externalizing way, while ADHD-I tends to absorb stress in an internalizing way.
Interestingly, it is more frequently reported that it is possible to switch between ADHD presentation forms over a number of years.

Find out more at ⇒ The subtypes of ADHD: ADHD-HI, ADHD-I, SCT and others

Note:
Gray’s BIS / BAS system, Connor and Gray’s FFFS system and the distinction between the ADHD-HI and ADHD-I subtypes are recognized standard models. The explanation of the ADHD-HI and ADHD-I subtypes as stress phenotypes is a hypothesis developed by us.

4. Stress response patterns in healthy people

Even in healthy people, there are typical differences in the cortisol response to stress in that one group reacts with an increased cortisol response and one group with a flattened cortisol response, regardless of the type of stressor. See 4.4 for sources.

According to this view, this stress phenotype determines which ADHD subtype a person with ADHD develops. The stress phenotype based on healthy people ultimately only uses different terms instead of the ADHD subtypes commonly used for people with ADHD.

One study found that temperament could explain about 20% of ADHD-HI symptomatology.10 Unfortunately, the study did not differentiate between ADHD-HI and ADHD-I and apparently only examined the ADHD-HI subtype. Nevertheless, we believe that we can interpret the result as tending to confirm a correlation between character traits and ADHD-HI subtype symptoms.

4.1. Personality types

Friedman and Rosenman initially categorized personality types into Type A and Type B only. Type C and type D were only added later.

4.1.1. Type A personality

4.1.1.1. Personality traits of the type A personality

Type A personality occurs more frequently:

  • Male1112
  • Anger (which correlates with high blood pressure)111213
  • Hostility11121415
  • Distrust1112
  • Stronger development of competitive thinking and struggle against existing or perceived obstacles, competitive drive111213
  • Stress response is increasingly based on the sympathetic nervous system1112
  • Intensive and durable drive13
  • Impatience13
  • Restlessness13
  • Ambition13
  • More frequent injuries16
  • Hyperactive tendencies17
  • Tendency to interrupt or finish a sentence in conversation18
  • Tendencies towards impulsiveness18
  • Tendencies towards constant vigilance18
  • Unsatisfactory interpersonal relationships due to
    • More frequent self-centeredness
    • Bad listening
    • Assumption of own superiority
    • A lot of anger, frustration or hostility if your wishes are not respected or your goals are not achieved19
  • Frequently occurring abnormalities of fat metabolism (hypertriglyceridemia) can be eliminated in the type A personality by ACTH administration, but not by cortisol administration.20
    The described ACTH effect is consistent with the current understanding of an underreactivity of the HPA axis in type A.
  • The majority of patients have an increased insulin response to glucose (hyperinsulinemia),20 which is not caused by hypertriglyceridemia, but could be related to it.
  • It is assumed that the HPA stress response in type A is primarily mediated by CRH.21.
    This could indicate a pituitary weakness (and consequently a weak adrenal response) in type A and ADHD-HI, possibly due to downregulation of the CRH receptors in the pituitary gland as a result of prolonged stress-induced CRH release. However, this is contradicted by the fact that a flattened cortisol stress response to ACTH administration also occurs (albeit in healthy type A people) (see 4.1.1.2.).
  • The lower the social contacts and social support, the higher the resting pulse rate and the (basal = stressor-independent) urine adrenaline level in type A.22

A study of 58 sports students found no significant traits in type A personalities.23 In our opinion, this could possibly be due to the fact that sports training increases stress resistance and therefore levels out differences.

4.1.1.2. Flattened cortisol stress response of the type A personality

A flattened cortisol stress response is believed to be a phenotypic biomarker of type A personality.

  • Type A correlates with a flattened cortisol stress response.24
  • Type A reacts to ACTH injection with a flattened cortisol response. 40 % showed no cortisol response at all or a reduced cortisol response.25
  • The basal ACTH level is elevated in healthy type A personalities compared to healthy type B personalities.26
  • The ACTH awakening response is also increased.25

The elevated basal ACTH levels may be related to the flattened cortisol response in such a way that the sustained ACTH elevation has caused a downregulation of the ACTH receptors, which is why the cortisol response is reduced.25

  • The growth hormone is reduced basally25
  • The growth hormone response to an infusion of vasopressin is reduced25
  • An infusion of human growth hormone reduces serum cholesterol levels.25 Hypercholesterolemia is induced by changes in the hypothalamus.
4.1.1.3. ADHD-HI/ADHD-C as Type A personality
  • The typical characteristics of the Type A personality coincide with those of the ADHD-HI/mixed type
  • Persons with ADHD-HI (hyperactive, type A personality, active-coping) often react to a stressor with a flattened cortisol response compared to people with ADHD (⇒ The HPA axis / stress regulation axis) and a reduced adrenaline/noradrenaline response (⇒ The autonomic nervous system)

4.1.2. Type B personality: the balanced ones

  • Type B personalities are less prone to stress and have a balanced sympathetic/parasympathetic relationship.11

4.1.3. Type C personality

4.1.3.1. Personality traits of the type C personality

Type C personality occurs more frequently:

  • Insecurity and anxiety are characteristics attributed to the type C personality.14
  • A higher sense of shame and a lower body image correlate with a higher cortisol stress response.27
  • The type C personality is described as somewhat more anxious.11 We consider the attribution of aggressiveness mentioned there to be questionable.
4.1.3.2. Excessive cortisol stress response in type C personality
  • Type C reacts to ACTH administration with an excessive cortisol response.25 Friedman only contrasted type A with type B, which deviates from the three-stage distinction used here (A and C as opposite extremes, B as a balanced middle).
  • Although there are no other publications that have directly measured a pronounced cortisol stress response in type C personality, we have little doubt that an excessive cortisol response is likely to be a phenotypic biomarker of type C personality.
  • It is also assumed that the stress response is primarily mediated by vasopressin.28
  • After subjects had completed the TSST several times in succession, only a third showed an increased cortisol stress response (habituation effect). This third with elevated cortisol levels were more insecure, less extroverted and tended to be more neurotic in personality questionnaires.29
4.1.3.3. ADHD-I as type C personality
  • People with ADHD-I (inattentive without hyperactivity, type-C personality, passive-coping type) very often react with an increased cortisol response compared to non-affected people (⇒ The HPA axis / stress regulation axis) and increased adrenaline/noradrenaline response (⇒ The autonomic nervous system).
  • People with ADHD-I are more likely to have a shutdown of the PFC due to high noradrenergic levels because of the high endocrine stress response initiated by a high noradrenergic response. Since the PFC (in addition to the hippocampus) is able to control cortisol release,30 a blockade of the PFC could lead to an uncontrolled cortisol stress response.

Although a meta-analysis found no correlation between ADHD and cortisol stress responses,31 this is probably due to the fact that only one of the studies included differentiated between subtypes and the meta-analysis therefore looked at ADHD as a whole.

4.2. Cortisol stress responses and personality traits in healthy people

First of all, it should be noted that high or low cortisol responses already correlate with gender and general personality traits. However, the correlation between the cortisol response and the orientation of the stress phenotype is significantly more influential.

4.2.1. Personality traits with a high cortisol stress response

High cortisol responses to acute stressors are associated with personality traits:

  • Perfectionism32, n= 24))
  • High emotional intelligence32, n= 24))
  • High self-esteem32, n= 24))
  • Social dominance3334
  • Openness35; different:36
  • Compatibility36
  • Heat (for men)35

4.2.2. Personality traits with low cortisol stress response

Personality traits correlate with a flattened cortisol response:

  • Strongly externalizing stress symptoms37 with lower anxiety symptoms at the same time 38
  • Externalizing comorbidities39
  • Personality traits generally associated with psychopathy35 such as reduced anxiety40
  • Aggression41424344
  • Violence45
  • Indifferent / attenuated emotions (callous-unemotional traits: lack of empathy, superficial affect)464748
  • Insensitivity to penalties40
  • Higher cognitive/logical intelligence49
  • Higher extraversion,50 while another study found a flattened cortisol stress response with low extraversion in men35
  • High neuroticism.513652 Another study only found this in women. Neuroticism was associated with high morning cortisol levels in another study.3553
    The flattened cortisol stress response in neuroticism is explained by one publication as meaning that individuals with higher neuroticism would experience higher levels of chronic stress, with chronic prolonged stress experience leading to downregulation of both the autonomic nervous system and the HPA axis.36 It is true that chronic stress can trigger downregulation.525455 However, it is doubtful that the personality trait neuroticism alone triggers such high and chronic stress.
  • Higher novelty seeking5657
  • Higher anxiety in healthy people was surprisingly associated with low cortisol, ACTH, adrenaline, noradrenaline and prolactin levels during psychosocial stress in a study with a small number of subjects.58

More on typical character traits in relation to excessive or flattened cortisol stress response at ⇒ Stress response phenotypes in humans.

Generally, healthy men show a higher cortisol response to stressors such as the TSST than healthy women. Healthy people with a higher social affinity have a lower cortisol response to the TSST. A higher stress resilience with social affinity is assumed to be the cause.34
A study of 120 healthy volunteers found different cortisol stress responses in healthy adult men.59
Some of the test subjects reacted to stress with an increase in cortisol, while the others showed a decrease in cortisol (flattened cortisol stress response). Another study came to the same conclusion.60

Second graders showed increased cortisol levels on exam days and simultaneously decreased adrenaline and noradrenaline levels. The individual differences in secreted hormones were significantly related to personality variables observed in the classroom as well as the effects of academic stress:61

  • Social approach behavior correlated with higher cortisol and adrenaline levels
  • Fidgeting correlated with low adrenaline levels.
  • Aggressiveness correlated with high noradrenaline levels.
  • Inattention correlated with low noradrenaline levels.

Novelty-seeking correlates with low basal cortisol levels and cortisol stress responses to the dexamethasone/CRH test and the TSST in healthy adults; low novelty-seeking correlates with high levels. There is no correlation with ACTH.62 Harm avoidance and reward dependence, on the other hand, did not correlate with cortisol levels in healthy adults,63 but with internalizing symptoms57 typical of ADHD-I.

Another study of 79 healthy women also showed a distribution into three groups with low, moderate and high cortisol stress responses, even with prolonged stress induction. The lower and higher cortisol stress responses were correlated with more unbalanced and negative emotions such as sadness and increased inner tension.64
In the healthy women studied, a reduced cortisol stress response correlated with hostility and negative emotions, while an increased cortisol stress response correlated with increased sadness and inner tension.64

The latter fully corresponds to the picture of stress phenotypes that we have postulated:
Increased as well as flattened cortisol stress responses are

  • A sign of an imbalance in the stress systems and
  • Correlates with different stress phenotypes:
    • The externalizing stress phenotype with a flattened cortisol stress response (ADHD-HI, atypical depression, bipolar, aggression disorders) tends towards more hostility and negative affects
    • The internalizing stress phenotype with an excessive cortisol stress response (ADHD-I, melancholic / psychotic depression) shows more sadness and inner tension

In our understanding, this also means that the different cortisol stress responses in ADHD-I (and possibly SCT) (increased cortisol stress response) and ADHD-HI (flattened cortisol stress response) are initially patterns of a stress phenotype and not necessarily an expression of a pathological imbalance of the cortisol system or the HPA axis.
We suspect that a more intense imbalance in the stress systems is associated with a more intense increase or flattening of cortisol stress responses and correlates with an increased likelihood of mental disorders. Unfortunately, there are no studies on this yet.

It is also fitting that in depression the result of the dexamethasone/CRH test, which measures the cortisol stress response, is an indicator of the presence of depression on the one hand and, after the depressive symptoms have subsided, an indicator of the likelihood of a relapse on the other. This could be interpreted to mean that the cortisol stress response is an indicator of disease vulnerability and not an exclusive indicator of the Disorder itself.

This could be consistent with the fact that a meta-analysis of 49 studies found a correlation between the cortisol and ACTH stress response and the subjective perception of stress in only around 1/4 of the studies, and a correlation between the cortisol or ACTH stress response in 2/3. The correlation between the stress response of cortisol (as well as ACTH) and the subjective perception of stress was not dominant at 0.3 to 0.5.65

Stress phenotypes have also been identified in animals. Animals with an active response to environmental threats show lower CRH and cortisol stress responses than animals with a passive response.66 On the other hand, mice with CRH overexpression throughout the central nervous system (but not CRH overexpression in specific forebrain regions) show increased active stress scoping.67

4.2.3. Cortisol stress responses, basal cortisol levels and personality traits

A study examined the correlation of personality traits with low/high cortisol stress response and low/high basal cortisol levels in healthy long-term unemployed people.24 The following personality traits correlated with the different groups:

4.2.3.1. Low cortisol stress response
4.2.3.1.1. Low basal cortisol level

Were significantly increased:

  • Somatic anxiety
  • Muscle tension
  • Irritability
  • Depression (according to the Beck Depression Inventory)

Was significantly reduced:

  • The perceived control (mastery)
4.2.3.1.2. High basal cortisol level
  • Type A behavior increased
  • Monotony avoidance increased
  • Perceived control (mastery) higher
  • Depression reduced
4.2.3.3. High cortisol stress response
4.2.3.3.1. Low basal cortisol level
  • High depression
  • Low perceived control (mastery)
4.2.3.3.2. Low basal cortisol level
  • Type A behavior lowest

The comparison shows that the cortisol stress response has a significantly greater influence on personality traits than the basal cortisol level.

4.3. Stress phenotype as affective style

We suspect that what we refer to as stress phenotype is referred to by others as affective style.
According to Davidson68, affective styles are determined, among other things, by the brain regions

  • DlPFC
  • Ventromedial PFC (vmPFC)
  • Orbitofrontal cortex (OFC)
  • Amygdala
  • Hippocampus
  • ACC
  • Insular cortex

regulated.

4.4. Externalizing / internalizing behaviour and changes in grey matter

Internalization and externalization are associated with opposing grey matter changes in similar cortical and subcortical areas {{Adams RA, Zor C, Mihalik A, Tsirlis K, Brudfors M, Chapman J, Ashburner J, Paulus MP, Mourão-Miranda J (2024): Voxel-wise multivariate analysis of brain-psychosocial associations in adolescents reveals six latent dimensions of cognition and psychopathology. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Apr 6:S2451-9022(24)00085-5. doi: 10.1016/j.bpsc.2024.03.006. PMID: 38588854.}
The density of gray matter in the individual voxels revealed stronger correlations between brain and psychosocial situation than the parcellation of the brain.
ADHD was related to increased and internalization was related to decreased gray matter density in dopaminergic and serotonergic midbrain areas, while oppositional symptoms were related to increased gray matter in a noradrenergic nucleus.
Internalization symptoms were associated with increased and oppositional symptoms with decreased gray matter density in the insula, cingulate and auditory cortex.
Striatal regions played an important role, with reduced gray matter in the caudate nucleus in ADHD and reduced gray matter in the putamen in oppositional/behavioral problems.

5. ADHD-HI/ADHD-C and ADHD-I as stress phenotypes

5.1. No genetic differentiation of the subtypes

Although ADHD is strongly genetically predisposed, there is no genetic correlation with kin subtypes. In other words, ADHD is heritable and dependent on genetic factors, but the subtype is not heritable and therefore arguably does not depend on (ADHD-specific) heritable genetic factors.69

5.2. Stress response phenotypes in animals

While ADHD-HI/ADHD-C tend to externalize stress, stress tends to be internalized by people with ADHD-I.
These different reaction patterns are not limited to humans.

Two different stress phenotypes were detected in rats across different populations:70

  • The acting-coping type shows an increased adrenaline and noradrenaline response to a stressor. This group showed a more active defense and flight readiness and a more inflexible behavioral stereotype as well as increased blood pressure and pulse.
  • The passive-coping type shows a lower adrenaline and noradrenaline response to a stressor. Typical stress symptoms here were freezing/deadlocking, a lower readiness to defend and flee with a simultaneously higher flexibility of the behavioral response and a lower pulse rate.

Stress alters brain functions

Put simply, the high levels of stress hormones released during high stress, particularly noradrenaline and dopamine, reduce the activity of the PFC. While low DA and NE increases due to mild stress usually increase cognitive performance, high DA and NE levels cause developmentally younger brain regions, especially the frontal cortex, to shut down.4 Stress impairs prefrontal cortical function.71 The increased noradrenaline level during acute stress therefore disrupts the function of the prefrontal cortex7273 74

This mechanism made perfect sense for our ancestors, who usually had to fight or flee when faced with existential stress, as the slow thinking of the PFC costs too much time in the race to be at least the second slowest. We are the descendants of the more successful of our ancestors, i.e. those who (metaphorically speaking) managed to run away faster than at least one other person and were therefore spared by the lion, or were able to fight a little better than the respective opponent. In today’s existential stress situations - e.g. divorce or insolvency - this reaction is more of a hindrance. Today, cognitively complex performances are still required in such stressful situations.

If this model is now applied to people with ADHD, who by definition are particularly sensitive to stress, the various ADHD symptoms can be explained as individual phenotypes caused by different stress hormone and neurotransmitter responses to a stressor, thereby determining which regions of the brain are altered or impaired by the stress load and how.

5.3. Stress response phenotypes in humans

Even in healthy people, there are typical differences in the cortisol response to stress in that one group reacts with an increased cortisol response and one group with a flattened cortisol response, irrespective of the type of stressor.5960

5. Stress phenotypes in other mental disorders

Depression is also known to have different symptoms depending on the cortisol response to an acute stressor.

5.1. Depression

  • Melancholic depression and even more so psychotic depression are characterized by an excessive cortisol stress response, which is also common in the ADHD-I subtype.
    ⇒ Melancholic and atypical depression
  • Atypical depression is characterized by a flattened cortisol stress response, which is also common in ADHD-HI/ADHD-C.75
    ⇒ Melancholic and atypical depression
  • In bipolar depression, a flattened cortisol stress response is predominantly found, as well as a normal cortisol stress response, but never an excessive cortisol stress response.
    In addition, the amylase stress response is excessive.
    ⇒ Bipolar depression in the article Cortisol in other disorders

5.2. Post-traumatic stress disorder (PTSD)

  • In post-traumatic stress disorder, phenotypically different stress reactions to one and the same traumatization are reported.76

More on the different cortisol stress responses in ADHD-HI and ADHD-I:
⇒ Cortisol and other stress hormones in ADHD
More on the cortisol stress responses in various other mental disorders: ⇒ Cortisol in other disorders Cortisol in other disorders. We have not yet encountered a mental disorder with a typically normal, moderate cortisol stress response. However, not every person with ADHD has an increased or decreased stress response. A normal cortisol stress response can occur in ADHD-HI or atypical depression, although the flattened cortisol stress response may be more common in both.

More about the subtypes of ADHD:
⇒ The subtypes of ADHD: ADHD-HI, ADHD-I, SCT and others

6. Temperament and character as symptom predictors

An interesting study on the prediction of symptom severity using AI / machine learning came to the surprising conclusion that the results of the “Temperament and Character Inventory Scale” (TCI) have a particularly high influence on the prediction of symptom variance of77

  • Mood
  • Anxiety
  • Anhedonia

  1. Guppys zeigen unterschiedliche Reaktionen auf Stress ↥

  2. Hundt, Kimbrel, Mitchell, Nelson-Gray (2007): High BAS, but not low BIS, predicts externalizing symptoms in adults; Psychology Department, University of North Carolina at Greensboro, 296 Eberhart Building, P.O. Box 26170, Greensboro, NC 27402-6170, USA ↥

  3. Corominas, Ramos-Quiroga, Ferrer, Sáez-Francàs, Palomar, Bosch, Casas (2012): Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits, ADHD Attention Deficit and Hyperactivity Disorders; June 2012, Volume 4, Issue 2, pp 63–75 ↥

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