Stress theories and stress phenotypes: a possible explanation of ADHD subtypes.
We hypothesize that the different ADHD subtypes (especially the two poles ADHD-HI and ADHD-C (with hyperactivity) and ADHD-I (without hyperactivity)) can be described or explained as phenotypically different stress responses.
- 1. Typical stress response patterns in mammals and humans
- 2. Stress reaction patterns based on the BIS/BAS/FFFS system according to Grey
- 3. Stress response patterns explain ADHD subtypes
4. Stress response patterns in healthy people
4.1. Personality types
- 4.1.1. Type A personality
- 4.1.2. Type B personality: the balanced ones
- 4.1.3. Type C personality
4.2. Cortisol stress responses and personality traits in healthy individuals
- 4.2.1. Personality traits in high cortisol stress response
- 4.2.2. Personality traits in low cortisol stress response
- 4.2.3. Cortisol stress responses, basal cortisol levels, and personality traits
- 4.3. Stress phenotyping as affective style
- 4.1. Personality types
- 5. ADHD-HI/ADHD-C and ADHD-I as stress phenotypes
- 5. Stress phenotypes in other mental disorders
- 6. Temperament and character as symptom predictors
1. Typical stress response patterns in mammals and humans
Mammals respond to stress with different patterns that are randomly distributed within a population.
According to the Fight/Flight stress response model (Fight/Flight System, FFS) by Cannon, 1932 (later also Gray), a part of the population tends to react to stress with aggression or attack (Fight), i.e. an outward (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 (introverted) reaction.
For a detailed account of the BIS/BAS/FFS system, see ⇒ Neurophysiological correlates of BIS/BAS In the section⇒ The stress systems of humans-basics of stress in the chapter ⇒ Stress.
2. Stress reaction patterns based on the BIS/BAS/FFFS system according to Grey
Mammalian responses to stress are not uniform.
According to the fight/flight stress model (by Connor (1932) and later Gray, who combined it with the BIS/BAS model → RST of 1990, revised 2000), there are 2 to 3 main groups of stress responses:
The BAS type reacts to stress with attack.
The FFFS type reacts to stress by running away or playing dead.
According to Gray’s (2000) revised Reinforcement Sensitivity Theory (RST), the BIS system no longer responds to stimuli from the outside, but only becomes active when the BAS and FFFS systems have both been activated. The BIS system is responsible for the trade-off between BAS and FFFS.
Benefits of different stress phenotypes
These reaction models are very deeply rooted. The survival probability 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.
Quite banally: 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?
Likewise, what is the likelihood that at least individual group members would have survived if an entirely new challenge arose 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 homogeneous character structure survive better than others.
The different stress response phenotypes are also evident in other creatures, e.g., guppies.1
Subsequently, it seems conclusive to us that the expression of the single individual as fight or flight type is a purely random variable that ensured that a population had enough members of the two types.
If we add “freeze” as an independent stress response phenotype (which after all could plausibly explain the phenomenon of sluggish thinking), there would be three stress phenotypes.
Put another way: Groups in which a single type has become genetically dominant have had less probability of survival, so that we are descendants of those who have passed on this trait with a high random distribution.
Similar: Farmer/Hunter hypothesis
In the Hunter/Farmer hypothesis picture, ADHD-HI subtype sufferers are phenotypically viewed as Hunter (hunters) and ADHD-I subtype sufferers are phenotypically viewed as Farmer (sedentary), with the ADHD symptoms of each subtype occupying an (unhealthy) extreme form of the two poles. Representation as extreme poles is conclusive.
Sometimes, however, an idealization or strangely justified “superiority” of ADHD is derived from the Hunter/Farmer hypothesis - we explicitly do not share this view. ADHD sufferers may be different from non-affected people, which may have disadvantages in some constellations and advantages in others - but a 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 valuation 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. Type C personalities and people of the ADHD-I subtype are, according to our (purely subjective) impression, less or less successful as self-employed persons. This is especially true for SCT sufferers, who, according to our experience, are rather advised not to become self-employed.
Independence necessarily requires the ability to make quick decisions. While hasty or even ill-considered impulsive decisions may be disadvantageous for independence, decision-making difficulties seem to be an even greater stumbling block.
Conversely, according to our (purely subjective) impression, activities that require great empathy and patience, such as therapeutic professions, seem to be a strength of the more introverted types.
A detailed description of the BIS/BAS/FFS system can be found under
⇒ 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 sufferer who responds to stress with action and extroversion (fight, BAS, extroverted), whereas the ADHD-I subtype is an ADHD sufferer who responds to stress with flight or play 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 Gray’s “old” RST definition 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 ADHD subtypes, we encountered 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) forms in ADHD sufferers with the stress response pattern Fight (aggression and attack). ADHD-C would then be a weakened form of the ADHD-HI subtype (with partially caught-up brain development).
- Stress is externalized, acted out externally
- More frequent aggressive behavior
- More frequent impulsive behavior
- More frequent motor hyperactivity
- More conflicts with peers
- Attention problem: easily distracted
Supporting the description of the mixed type as a relative of the ADHD-HI subtype is the fact that in both, cortisol levels to acute stressors fall and remain well below those of unaffected individuals, whereas in the ADHD-I subtype, the cortisol response to acute stressors rises above that of unaffected 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 ADHD sufferers with a tendency to 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 upon detection; playing dead is associated with very high internal tension).
- Stress is internalized, acted out inwardly
- Less aggressive behavior
- Less impulsive behavior
- Significantly fewer conflicts with peers
- Attention problem: easily bored
The inner pressure (or stress) that triggers the reactions is the same for both types. However, the different way of dealing with the inner pressure leads to different symptoms.
According to this view, the different symptoms of ADHD-HI and ADHD-I are basically based in the method of coping with stress of the affected persons.
2.1.3. SCT / Sluggish: Dysfunctional FFFS?
According to this view, the new RST could explain the phenomenon SCT (“sluggish cognitive tempo”) as a “switched off” BIS (due to particularly high norepinephrine and dopamine levels4?), which is thus particularly strongly inhibited in its decision making. This could explain why SCT sufferers can have above-average intelligence and yet be massively impaired in their decision-making.
According to this side hypothesis, in SCT, the BIS system, which (according to the new RST) has mainly deliberative tasks in the presence of simultaneously activated BAS and FFS, is also turned off by too high levels of norepinephrine and dopamine (which deactivate the PFC).
3. Stress response patterns explain ADHD subtypes
For character traits such as extraversion / introversion / neuroticism / harm avoidance as well as personality traits such as affective lability or social avoidance, family and twin studies have demonstrated hereditary causes.5
Comparably Huber6 and Trappmann-Korr7 describe a connection between ADHD subtypes and personal character traits of the affected persons.
Similarly, a study that distinguished comorbidities in ADHD by subtype found that hyperactivity/impulsivity (ADHD-HI) closely correlated 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 by stress response type, but is now considered refuted: SCT is now considered a disorder in its own right, even though it is very often comorbid along with ADHD.
We assume that the classical ADHD subtype poles ADHD-HI (with hyperactivity) and ADHD-I (without hyperactivity) represent different stress phenotypes, which show different stress reaction patterns to one and the same cause (ADHD). ADHD-HI tends to externalize stress, while ADHD-I tends to internalize stress.
See more at ⇒ The subtypes of ADHD: ADHD-HI, ADHD-I, SCT, and others
Gray’s BIS / BAS system, Connor and Gray’s FFFS system, and the distinction between the ADHD-HI and ADHD-I subtypes are accepted standard models. The explanation of the subtypes ADHD-HI and ADHD-I 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 to the extent that one group reacts with an increased cortisol response and one group reacts with a flattened cortisol response, although this is independent of the type of stressor. Sources for this under 4.4.
According to this view, this stress phenotype determines which ADHD subtype an ADHD sufferer develops. The stress phenotype, which is based on healthy people, ultimately uses only other terms instead of the ADHD subtypes commonly used for ADHD sufferers.
One study found that temperament could explain about 20% of ADHD-HI symptomatology.10 Unfortunately, the study did not distinguish between ADHD-HI and ADHD-I and apparently examined ADHD-HI subtype alone. Nevertheless, we think we can interpret the result as a tendential confirmation of a correlation between character traits and ADHD-HI subtype symptomatology.
4.1. Personality types
4.1.1. Type A personality
188.8.131.52. Type A Personality Traits
In the Type A personality occurs more frequently:
- Anger (which correlates with high blood pressure)111213
- Stronger expression of competitive thinking and struggle against existing or perceived obstacles, competitive drive111213
- Stress response relies more on the sympathetic nervous system1112
- Intense and lasting drive13
- More frequent injuries16
- Hyperactive tendencies17
- Tendency to interrupt or finish a sentence in conversation18
- Tendencies to impulsivity18
- Tendencies to persistent vigilance18
- Unsatisfactory interpersonal relationships due to
- More frequent egocentricity
- Poor listening
- Assumption of own superiority
- A lot of anger, frustration or hostility when one’s wishes are not respected or one’s goals are not achieved19
- More common abnormalities of lipid 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 present understanding of underreactivity of the HPA axis in type-A.
- Majority have an increased insulin response to glucose (hyperinsulinemia),20 which, although not caused by hypertriglyceridemia, may be related to it.
- The HPA stress response in type A is thought to be mediated primarily by CRH.21.
This could indicate a pituitary weakness (and consequently a weak adrenal response) in type A and ADHD-HI, possibly due to a downregulation of CRH receptors in the pituitary due to prolonged stress-induced CRH release. However, this is contradicted by the fact that (however: in healthy type A humans) a flattened cortisol stress response also occurs after ACTH administration (see 184.108.40.206.).
- The lower the social contacts and social support, the higher the resting pulse 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.
220.127.116.11. Flattened cortisol stress response of type A personality
A flattened cortisol stress response is believed by this side to be a phenotypic biomarker of type A personality.
- Type A correlates with a flattened cortisol stress response.24
- Type A responded to ACTH injection with a flattened cortisol response. 40% showed no cortisol response at all or a depressed cortisol response.25
- Basal ACTH levels are elevated in healthy type A personalities compared to healthy type B personalities.26
- Likewise, the ACTH awakening response is 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 downregulation of ACTH receptors, and therefore the cortisol response is reduced.25
- Growth hormone is decreased basally25
- Growth hormone response to an infusion of vasopressin is decreased25
- Infusion of human growth hormone reduces serum cholesterol levels.25 Hypercholesterolemia is induced by changes in the hypothalamus.
18.104.22.168. ADHD-HI/ADHD-C as a Type A Personality
- The typical characteristics of the Type A personality coincide with those of the ADHD-HI/mixed type
- ADHD-HI sufferers (hyperactive, type A personality, active-coping), often respond to a stressor with a flattened cortisol response compared with nonaffected individuals (⇒ The HPA axis/stress regulatory axis) and a decreased epinephrine/norepinephrine response (⇒ The autonomic nervous system)
4.1.2. Type B personality: the balanced ones
- The type B personality is less stress-prone and has a balanced sympathetic/parasympathetic nervous system.11
4.1.3. Type C personality
22.214.171.124. Type C personality traits
In the Type C personality occurs more frequently:
- Insecurity and anxiety are defining characteristics attributed to the Type C personality.14
- A higher sense of shame and 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.
126.96.36.199. Excessive cortisol stress response in type C personality
- Type C reacts to ACTH administration with an excessive cortisol response.25 Friedman contrasted type A only with type B, which deviates from the 3-level distinction used here (A and C as opposite-pole 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 nevertheless have little doubt that an exaggerated cortisol response is likely to represent a phenotypic biomarker of type C personality.
- In addition, it is assumed that the stress response here is primarily mediated by vasopressin.28
- After subjects completed the TSST several times in a row, only one third showed an elevated cortisol stress response (habituation effect). This third with elevated cortisol levels were more self-confident, less extroverted and tended to be more neurotic in personality questionnaires.29
188.8.131.52. ADHD-I as type C personality
- ADHD-I sufferers (inattentive without hyperactivity, type C personality, passive-coping type) very often react with an increased cortisol response compared with nonaffected individuals (⇒ The HPA axis/stress regulatory axis) and increased epinephrine/norepinephrine response (⇒ The autonomic nervous system).
- ADHD-I sufferers are more likely to have the PFC shut down by high levels of norepinephrine due to the high endocrine stress response initiated by a high noradrenergic response. Because the PFC (in addition to the hippocampus) is able to control cortisol release,30 blockade of the PFC could lead to an uncontrolled cortisol stress response.
Although one meta-study found no correlation between ADHD and cortisol stress responses,31 this may be because only one of the included studies differentiated by subtype and the meta-study therefore looked at the ADHD population as a whole.
4.2. Cortisol stress responses and personality traits in healthy individuals
First, it should be noted that high or low cortisol responses already correlate with gender and with general personality traits. Significantly more formative, however, is the correlation of cortisol response and the orientation of the stress phenotype.
4.2.1. Personality traits in high cortisol stress response
Personality traits are associated with high cortisol responses to acute stressors:
- Perfectionism32, n= 24))
- High emotional intelligence32, n= 24))
- High self-esteem32, n= 24))
- Social dominance3334
- Openness35; different:36
- Heat (for men)35
4.2.2. Personality traits in low cortisol stress response
Correlated with flattened cortisol response as personality traits
- A strong externalizing stress symptomatology37 with at the same time lower anxiety symptomatology 38
- Externalizing comorbidities39
- Personality traits commonly associated with psychopathy35 such as decreased anxiety40
- Indifferent / attenuated emotions (callous-unemotional traits: lack of empathy, superficial affect)464748
- Insensitivity to punishment40
- 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 found this only 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 to mean that individuals with higher neuroticism would experience higher levels of chronic stress, with chronic prolonged stressful 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 should be doubted 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, epinephrine, norepinephrine, and prolactin levels during psychosocial stress in a small-subject study.58
For more on typical character traits in relation to exaggerated or blunted cortisol stress responses, see ⇒ Stress response phenotypes in humans.
In general, healthy men show a higher cortisol response to stressors such as the TSST than healthy women. Healthy individuals with greater social affinity have reduced cortisol responses to the TSST. The cause is thought to be higher stress resilience with social affinity.34
A study of 120 healthy subjects found different cortisol stress responses in healthy adult men.59
One part of the subjects reacted to stress with an increase in cortisol, the other part with a decrease in cortisol (flattened cortisol stress response). Another study came to the same conclusion.60
Second graders showed elevated levels of cortisol on exam days and concomitant decreased levels of epinephrine and norepinephrine. Individual differences in secreted hormones were significantly related to personality variables observed in the classroom and to the effects of academic stress:61
- Social approach behavior correlated with higher cortisol and adrenaline levels
- Fidgetiness correlated with low adrenaline.
- Aggressiveness correlated with high levels of norepinephrine.
- Inattention correlated with low norepinephrine 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 In contrast, risk aversion (harm avoidance) and reward dependence did not correlate with cortisol levels in healthy adults,63 but did correlate with internalizing symptoms57 typical of ADHD-I.
Another study of 79 healthy women similarly 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 affect, such as sadness and increased internal tension.64
In the healthy women studied, a decreased cortisol stress response correlated with hostility and negative affect, and an increased cortisol stress response correlated with increased sadness and inner tension.64
The latter is completely consistent with our postulated picture of stress phenotypes:
Increased as well as flattened cortisol stress responses are
- A sign of an imbalance in the stress systems and
- Correlated with different stress phenotypes:
- The externalizing stress phenotype with flattened cortisol stress response (ADHD-HI, atypical depression, bipolar, aggression disorders) tends to have more hostility and negative affect
- The internalizing stress phenotype with an excessive cortisol stress response (ADHD-I, melancholic / psychotic depression) shows more sadness and inner tension
According to our understanding, this further 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 yet necessarily an expression of a pathological imbalance of the cortisol system or the HPA axis.
We hypothesize that the more intense skewing of stress systems is associated with more intense elevation or flattening of cortisol stress responses and correlates with increased likelihood of mental disorders. Unfortunately, there are no studies on this yet.
It also fits that in depression the result of the dexamethasone/CRH test, which measures the cortisol stress response, is on the one hand an indicator for the presence of depression and on the other hand, after the depressive symptoms have subsided, an indicator for the probability of a relapse. This could be interpreted to mean that the cortisol stress response is an indicator of disease vulnerability rather than an exclusive indicator of the disorder itself.
It could fit to this that a meta examination of 49 studies found a correlation of the cortisol and ACTH stress response with the subjective stress perception only in about 1/4 of the studies, in 2/3 a correlation of cortisol or ACTH stress response. The correlation between cortisol (as well as ACTH) stress response and subjective stress perception was not dominant, ranging from 0.3 to 0.5.65
Stress phenotypes have also been identified in animals. Animals with active responses to environmental threats have lower CRH and cortisol stress responses than animals with passive responses.66 On the other hand, mice with CRH overexpression throughout the central nervous system (but not with CRH overexpression in specific forebrain regions) show increased active stress scoping.67
4.2.3. Cortisol stress responses, basal cortisol levels, and personality traits
One study examined the correlation of personality traits with low/high cortisol stress response and low/high basal cortisol levels in healthy long-term unemployed individuals.24 The following personality traits correlated with the different groups:
184.108.40.206. Low cortisol stress response
220.127.116.11.1. Low basal cortisol level
Significantly elevated were:
- Somatic anxiety
- Muscle tension
- Irritability (Irritability)
- Depression (according to Beck’s Depression Inventory)
- The perceived control (mastery)
18.104.22.168.2. High basal cortisol level
- Type A behavior increased
- Monotony avoidance increased
- Perceived control (mastery) higher
- Depression reduced
22.214.171.124. High cortisol stress response
126.96.36.199.1. Low basal cortisol level
- High depression
- Low perceived control (mastery)
188.8.131.52.2. 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 basal cortisol levels.
4.3. Stress phenotyping as affective style
We suspect that what we refer to as stress phenotypy is referred to by others as affective style.
According to Davidson68, affective styles are determined, among other things, by brain regions
- Ventromedial PFC (vmPFC)
- Orbitofrontal cortex (OFC)
- Anterior cingulate cortex (ACC)
- Insular cortex
5. ADHD-HI/ADHD-C and ADHD-I as stress phenotypes
5.1. No genetic distinctions of the subtypes
Although ADHD is strongly genetically predisposed, there is no genetic correlation with relatives’ subtypes. In other words, ADHD is heritable and depends on genetic factors, but the subtype is not heritable and therefore probably 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, ADHD-I sufferers tend to internalize stress.
These different response patterns are not limited to humans.
Two different stress phenotypes have been demonstrated 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 readiness to defend and escape 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/deadlining, a lower readiness to defend and flee with simultaneously higher flexibility of the behavioral response, and a lower pulse rate.
Stress alters brain functions
In simplified terms, the stress hormones released in high amounts during high stress, especially norepinephrine and dopamine, reduce the activity of the PFC. Whereas low DA and NE increases due to mild stress usually enhance 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 Thus, norepinephrine levels, which are elevated during acute stress, disrupt prefrontal cortex function7273 74
This mechanism made sense to our ancestors, who mostly had to fight or flight when faced with existential stress, because 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. of those who (figuratively generalized) managed to run away faster than at least one other and were therefore spared by the lion, or could fight somewhat better than the respective opponent. In today’s existential stress situations - e.g. a divorce or insolvency - this reaction is rather a hindrance. Today, especially in such stressful situations, cognitively complex performances still have to be made.
If this model is now applied to ADHD sufferers, 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 brain regions are altered or impaired as a result of the stress load and how.
5.3. Stress response phenotypes in humans
Even in healthy individuals, typical differences in the cortisol response to stress exist to the extent that one group responds with an elevated cortisol response and one group responds with a flattened cortisol response, although this is independent 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.
- Melancholic (endogenous) depression, and even more so psychotic depression, is characterized by an exaggerated cortisol stress response, as is 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 found quite predominantly, otherwise a normal cortisol stress response, but never an exaggerated 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 responses to 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
For more on cortisol stress responses in several other mental disorders: ⇒ Cortisol in other disorders. We have not yet encountered a mental disorder with a typically normal, moderate cortisol stress response. However, not every affected individual has an elevated or depressed stress response. A normal cortisol stress response may occur in ADHD-HI or atypical depression, although the flattened cortisol stress response may be more common in both.
More about the subtypes in ADHD:
⇒ The subtypes of ADHD: ADHD-HI, ADHD-I, SCT, and others
6. Temperament and character as symptom predictors
An interesting study on predicting 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 impact on predicting symptom variance of77
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 ↥
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 ↥
Ramos, Arnsten (2007): Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther. 2007 Mar; 113(3):523-36., Kapitel 6 ↥ ↥
Costa und McCrae (1990), Cloninger et al (1993), Jang et al (2001); alle zitiert von Foelsch, Schlüter-Müller, Odom, Arena, Borzutzky, Schmeck: Theoretische Grundlagen, Seite 18, in: Behandlung von Jugendlichen mit Identitätsstörungen (AIT); pp 17-40; Date: 13 November 2013 ↥
Huber, ADHS und Hochsensibilität / Hochsensitivität, Seite 29 ↥
Ohnishi, Kobayashi, Yajima, Koyama, Noguchi (2020): Psychiatric Comorbidities in Adult Attention-deficit/Hyperactivity Disorder: Prevalence and Patterns in the Routine Clinical Setting. Innov Clin Neurosci. 2019 Sep 1;16(9-10):11-16. PMID: 32082943; PMCID: PMC7009330. ↥
Diamond: Attention-deficit disorder (attention-deficit/hyperactivity disorder without hyperactivity): A neurobiologically and behaviorally distinct disorder from attention-deficit (with hyperactivity), Development and Psychopathology 17 (2005), 807–825, Seite 810 ↥
Chauhan, Shah, Padhy, Malhotra (2019): Relation between temperament dimensions and attention-deficit/hyperactivity disorder symptoms. Ind Psychiatry J. 2019 Jan-Jun;28(1):58-62. doi: 10.4103/ipj.ipj_74_19. ↥
Rensing, Koch, Rippe, Rippe (2006): Mensch im Stress; Psyche, Körper Moleküle; Elsevier (jetzt Springer), Seite 309 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Rozanski, Blumenthal, Kaplan (1999): Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy; Circulation. 1999 Apr 27;99(16):2192-217 ↥ ↥ ↥ ↥ ↥ ↥
FRIEDMAN, ROSENMAN (1959): Association of specific overt behavior pattern with blood and cardiovascular findings; blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. J Am Med Assoc. 1959 Mar 21;169(12):1286-96. ↥ ↥ ↥ ↥ ↥ ↥
FRIEDMAN, ROSENMAN (1959): Association of specific overt behavior pattern with blood and cardiovascular findings; blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. J Am Med Assoc. 1959 Mar 21;169(12):1286-96. ↥ ↥
mit ergänzendem Abstract: FRIEDMAN, ROSENMAN (1959): Association of specific overt behavior pattern with blood and cardiovascular findings; blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. J Am Med Assoc. 1959 Mar 21;169(12):1286-96. ↥
Schafer, McKenna (1985): Type A behaviour, stress, injury and illness in adult runners. Stress Med., 1: 245-254. doi:10.1002/smi.2460010404; n = 572 ↥
Rosch, PJ, Stress And Cardiovascular Disease. Comp Ther; 9:6-13 , 1983; nicht verifizierbar; zitiert nach SEPARATING FACT FROM FICTION – an Interview with Ray H. Rosenman, M.D. by Paul J. Rosch (2004). SECTION 3: Recognizing And Rating Type A Traits. An abridged and edited version of this interview (without references) appeared in the June 2004 issue of Health and Stress,the Newsletter of The American Institute of Stress ↥
Rosch, PJ, Stress And Cardiovascular Disease. Comp Ther; 9:6-13 , 1983; nicht verifizierbar; zitiert nach SEPARATING FACT FROM FICTION – an Interview with Ray H. Rosenman, M.D. by Paul J. Rosch (2004). SECTION 3: Recognizing And Rating Type A Traits. An abridged and edited version of this interview (without references) appeared in the June 2004 issue of Health and Stress,the Newsletter of The American Institute of Stress ↥ ↥ ↥
Rosch (1983): Stress And Cardiovascular Disease. Comp Ther; 9:6-13 , 1983; nicht verifizierbar; zitiert nach SEPARATING FACT FROM FICTION – an Interview with Ray H. Rosenman, M.D. by Paul J. Rosch (2004). SECTION 3: Recognizing And Rating Type A Traits. An abridged and edited version of this interview (without references) appeared in the June 2004 issue of Health and Stress,the Newsletter of The American Institute of Stress ↥
Friedman (1977): Type A behavior pattern: some of its pathophysiological components. Bull N Y Acad Med. 1977; 53(7):593-604. ↥ ↥
Bohus, Kohlhaas (1993): Stress and the cardiovascular system: central and peripheral physiologic mechanisms. In: Stanford, Salmon (1993): Stress. From Synapse to Syndrome, Academic Press, S. 75 – 117, zitiert nach Rensing, Koch, Rippe, Rippe (2006): Mensch im Stress; Psyche, Körper Moleküle; Elsevier (jetzt Springer), Seite 309, 310 ↥
Rensing, Koch, Rippe, Rippe (2006): Mensch im Stress; Psyche, Körper Moleküle; Elsevier (jetzt Springer), Seite 312 ↥
Myrtek, Greenlee (1984): Psychophysiology of type A behavior pattern: a critical analysis. J Psychosom Res. 1984;28(6):455-66. n = 56 ↥
Grossi, Ahs, Lundberg (1998): Psychological correlates of salivary cortisol secretion among unemployed men and women. Integr Physiol Behav Sci. 1998 Jul-Sep;33(3):249-63., n = 59 ↥ ↥
Friedman (1977): Type A behavior pattern: some of its pathophysiological components. Bull N Y Acad Med. 1977; 53(7):593-604., Seite 599 ↥ ↥ ↥ ↥ ↥ ↥ ↥
Friedman, Byers, Rosenman (1972): Plasma ACTH and Cortisol Concentration of Coronary-Prone Subjects. Proceedings of the Society for Experimental Biology and Medicine, 140(2), 681–684. https://doi.org/10.3181/00379727-140-36530 ↥
Lupis, Sabik, Wolf (2015): Role of shame and body esteem in cortisol stress responses; J Behav Med. 2016 Apr; 39(2): 262–275. doi: 10.1007/s10865-015-9695-5, PMCID: PMC5125296, NIHMSID: NIHMS831105, PMID: 26577952 ↥
Bohus, Kohlhaas (1993): Stress and the cardiovascular system: central and peripheral physiologic mechanisms. In: Stanford, Salmon (1993): Stress. From Synopse to syndrome, Academic Press, S. 75 – 117, zitiert nach Rensing, Koch, Rippe, Rippe (2006): Mensch im Stress; Psyche, Körper Moleküle; Elsevier (jetzt Springer), Seite 309, 310 ↥
Kirschbaum, Prüssner, Stone, Federenko, Gaab, Lintz, Schommer, Hellhammer (1995): Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men“, Psychosomatic Medicine 57 (1995), 468-474. ↥
Arnsten (2009): Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009 Jun;10(6):410-22. doi: 10.1038/nrn2648. ↥
Kamradt, Momany, Nikolas (2018): A meta-analytic review of the association between cortisol reactivity in response to a stressor and attention-deficit hyperactivity disorder. Atten Defic Hyperact Disord. 2018;10(2):99-111. doi:10.1007/s12402-017-0238-5 ↥
[Kirschbaum, Prüssner, Stone, Federenko, Gaab, Lintz, Schommer, Hellhammer (1995): Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men. Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men. Psychosom Med. 1995 Sep-Oct; 57(5):468-74.](https://www.ncbi.nlm.nih.gov/pubmed/8552738 ↥ ↥ ↥
Pruessner, Gaab, Hellhammer, Lintz, Schommer, Kirschbaum (1997): Increasing correlations between personality traits and cortisol stress responses obtained by data aggregation. Psychoneuroendocrinology. 1997 Nov; 22(8):615-25., n = 20 ↥
Childs, White, de Wit (2014): Personality traits modulate emotional and physiological responses to stress; Behav Pharmacol. 2014 Sep; 25(5 0 6): 493–502; doi: 10.1097/FBP.0000000000000064; PMCID: PMC4119514; NIHMSID: NIHMS603933 ↥ ↥
Oswald, Zandi, Nestadt, Potash, Kalaydjian, Wand (2006): Relationship between cortisol responses to stress and personality. Neuropsychopharmacology. 2006 Jul; 31(7):1583-91., n = 68 ↥ ↥ ↥ ↥ ↥
Xin, Wu, Yao, Guan, Aleman, Luo (2017): The relationship between personality and the response to acute psychological stress, Sci Rep. 2017; 7: 16906. doi: 10.1038/s41598-017-17053-2, n = 54 ↥ ↥ ↥ ↥
Shirtcliff, Granger, Booth, Johnson (2005): Low salivary cortisol levels and externalizing behavior problems in youth. Dev Psychopathol 2005;17(1):167–84. ↥
Van Goozen, Matthys, Cohen-Kettenis, Gispen-de Wied, Wiegant, Van Engeland (1998): Salivary cortisol and cardiovascular activity during stress in oppositional-defiant disorder boys and normal controls. Biological Psychiatry, 43, 531–539. ↥
Freitag, Hänig, Palmason, Meyer, Wüst, Seitz (2009): Cortisol awakening response in healthy children and children with ADHD: impact of comorbid disorders and psychosocial risk factors. Psychoneuroendocrinology 2009;34(7):1019–28. ↥
van Honk, Schutter, Hermans, Putman (2003): Low cortisol levels and the balance between punishment sensitivity and reward dependency. Neuroreport 2003;14 (15):1993–6. ↥ ↥
McBurnett, Lahey, Rathouz, Loeber (2000): Lowsalivary cortisol and persistent aggression in boys referred for disruptive behavior. Arch Gen Psychiatry 2000;57(1):38–43. ↥
Yang, Shin, Noh, Stein (2007): Cortisol is inversely correlated with aggression for those boys with attention deficit hyperactivity disorder who retain their reactivity to stress. Psychiatry Res 2007;153(1):55–60. ↥
Murray-Close, Ostrov (2009): A longitudinal study of forms and functions of aggressive behavior in early childhood. Child Dev 2009;80(3):828–42. ↥
King, Barkley, Barrett (1998): Attention-deficit hyperactivity disorder and the stress response. Biol Psychiatry 1998;44(1):72–4. ↥
Henry (1997): Psychological and physiological responses to stress: the right hemisphere and the hypothalamo-pituitary-adrenal axis, an inquiry into problems of human bonding. Acta Physiol Scand Suppl. 1997;640:10-25. PMID: 9401599. REVIEW ↥
Stadler, Kroeger, Weyers, Grasmann, Horschinek, Freitag, Clement (2011): Cortisol reactivity in boys with attention-deficit/hyperactivity disorder and disruptive behavior problems: the impact of callous unemotional traits. Psychiatry Res 2011; 187(1):204–9. ↥
Hawes, Brennan, Dadds (2009): Cortisol, callous-unemotional traits, and pathways to antisocial behavior. Curr Opin Psychiatry 2009;22(4):357–62. ↥
Loney, Butler, Lima, Counts, Eckel (2006): The relation between salivary cortisol, callous-unemotional traits, and conduct problems in an adolescent non-referred sample. J Child Psychol Psychiatry 2006;47(1):30–6. n = 106 ↥
Mikolajczak, Roy, Luminet, Fillée, de Timary (2007): The moderating impact of emotional intelligence on free cortisol responses to stress. Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):1000-12. ↥
Xin, Wu, Yao, Guan, Aleman, Luo (2017): The relationship between personality and the response to acute psychological stress, Sci Rep. 2017; 7: 16906. doi: 10.1038/s41598-017-17053-2 ↥
McCleery, Goodwin (2001): High and low neuroticism predict different cortisol responses to the combined dexamethasone–CRH test. Biol Psychiatry. 2001 Mar 1;49(5):410-5., n = 258 ↥
Bibbey, Carroll, Roseboom, Phillips, de Rooij (2013): Personality and physiological reactions to acute psychological stress. Int J Psychophysiol. 2013 Oct;90(1):28-36. doi: 10.1016/j.ijpsycho.2012.10.018. n = 352 ↥ ↥
Portella, Harmer, Flint, Cowen, Goodwin (2005): Enhanced early morning salivary cortisol in neuroticism. Am J Psychiatry. 2005 Apr;162(4):807-9. ↥
Booij, Bouma, de Jonge, Ormel, Oldehinkel (2013): Chronicity of depressive problems and the cortisol response to psychosocial stress in adolescents: the TRAILS study. Psychoneuroendocrinology. 2013 May;38(5):659-66. doi: 10.1016/j.psyneuen.2012.08.004. ↥
Dallman (1993): Stress update Adaptation of the hypothalamic-pituitary-adrenal axis to chronic stress. Trends Endocrinol Metab. 1993 Mar;4(2):62-9. ↥
Tyrka, Wier, Anderson, Wilkinson, Price, Carpenter (2007): Temperament and response to the Trier Social Stress Test. Acta Psychiatr Scand. 2007 May; 115(5):395-402. ↥
Kang, Kwack (2019): Temperament and Character Profiles Associated with Internalizing and Externalizing Problems in Children with Attention Deficit Hyperactivity Disorder. Psychiatry Investig. 2019 Mar;16(3):206-212. doi: 10.30773/pi.2019.01.10.1. ↥ ↥
Jezova, Makatsori, Duncko, Moncek, Jakubek (2004): High trait anxiety in healthy subjects is associated with low neuroendocrine activity during psychosocial stress. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Dec;28(8):1331-6., n = 27 ↥
Henckens, Klumpers, Everaerd, Kooijman, van Wingen, Fernández (2016): Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress, Social Cognitive and Affective Neuroscience, Volume 11, Issue 4, 1 April 2016, Pages 663–673, https://doi.org/10.1093/scan/nsv149 ↥ ↥
Isaksson (2012): Cortisolreaktion und Gedächtnisleistung nach unterschiedlichen Stressoren (Lernstress und Public Speaking) bei gesunden Probanden; Dissertation, Seite 58 ↥ ↥
Tennes, Kreye, Avitable, Wells (1986): Behavioral correlates of excreted catecholamines and cortisol in second grade children. J Am Acad Child Psychiatry 25:764–770 ↥
Tyrka, Wier, Anderson, Wilkinson, Price, Carpenter (2007): Temperament and response to the Trier Social Stress Test. Acta Psychiatr Scand. 2007 May;115(5):395-402. ↥
Tyrka, Mello, Mello, Gagne, Grover, Anderson, Price, Carpenter (2006): Temperament and hypothalamic-pituitary-adrenal axis function in healthy adults. Psychoneuroendocrinology. 2006 Oct;31(9):1036-45 ↥
Admon, Treadway, Valeri, Mehta, Douglas, Pizzagalli (2017): Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females. J Neurosci. 2017;37(33):7994-8002. ↥ ↥
Campbell, Ehlert (2011): 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. ↥
Feder, Nestler, Charney (2009): Psychobiology and molecular genetics of resilience. Nat Rev Neurosci. 2009;10(6):446-57. ↥
Lu, Steiner, Whittle, Vogl, Walser, Ableitner, Refojo, Ekker, Rubenstein, Stalla, Singewald, Holsboer, Wotjak, Wurst, Deussing (2008): Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone effects on stress-coping behavior. Mol Psychiatry. 2008 Nov;13(11):1028-42. doi: 10.1038/mp.2008.51. ↥
Davidson (2000): Affective style, psychopathology, and resilience: brain mechanisms and plasticity. Am Psychol. 2000 Nov;55(11):1196-214. ↥
Smidt, Heiser, Dempfle, Konrad, Hemminger, Kathöfer, Halbach, Strub, Grabarkiewicz, Kiefl, Linder, Knölker, Warnke, Remschmidt, Herpertz-Dahlmann, Hebebrand (2003): Formalgenetische Befunde zur Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung; Fortschr Neurol Psychiatr 2003; 71(7): 366-377; DOI: 10.1055/s-2003-40561 ↥
Rensing, Koch, Rippe, Rippe (2006): Mensch im Stress; Psyche, Körper Moleküle, Seite 309 ↥
Arnsten (2000): Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanisms. Prog Brain Res. 2000;126:183-92. ↥
Birnbaum, S. G., Gobeske, K. T., Auerbach, J., Taylor, J. R. & Arnsten, A. F. T. (1999): A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in prefrontal cortex. Biol. Psychiatry 46, 1266–1274. ↥
Ramos, Colgan, Nou, Ovadia, Wilson, Arnsten (2005). The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys. Biol. Psychiatry 58, 894–900. ↥
Für starke Stimulation des D1-Dopaminrezeptors: Zahrt, Taylor, Mathew, Arnsten (1997): Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci. 1997 Nov 1;17(21):8528-35. ↥
Gold, Chrousos (2002): Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry. 2002;7(3):254-75. ↥
Lanius (2003) zitiert nach Egle, Joraschky, Lampe, Seiffge-Krenke, Cierpka (2016): Sexueller Missbrauch, Misshandlung, Vernachlässigung – Erkennung, Therapie und Prävention der Folgen früher Stresserfahrungen; 4. Aufl., Schattauer, S. 72 ↥
Mellem, Liu, Gonzalez, Kollada, Martin, Ahammad (2019): Machine Learning Models Identify Multimodal Measurements Highly Predictive of Transdiagnostic Symptom Severity for Mood, Anhedonia, and Anxiety. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jul 30. pii: S2451-9022(19)30200-9. doi: 10.1016/j.bpsc.2019.07.007. ↥