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A thorough diagnosis of ADHD always requires a careful differential diagnosis to rule out other disorders with similar symptoms.
The prevalence of mental disorders overall is quite high in Germany at 33.3% within one year (EU: 38.8%).
Important factors that should be considered in the differential diagnosis of ADHD are, for example, acute stress reactions, unrecognized giftedness or underachievement, organic primary disorders such as sleep disorders or post-commotional syndromes or medication side effects.
Mental and psychiatric disorders whose symptoms can resemble ADHD include anxiety disorders, affective disorders, autism spectrum disorders (ASD) and borderline personality disorder (BPD).
The percentages in brackets after the headings indicate the population prevalence, i.e. they are independent of ADHD.
Differential diagnosis means making sure that the symptoms are not (also) caused by other causes or disorders and consequently require different treatment.
In the differential diagnosis, it is also important to note which disorders are typical comorbidities of ADHD. For example, depression can also cause (certain) symptoms of ADHD. Depression often occurs comorbidly with ADHD.
If a disorder is a typical comorbidity of ADHD, and if the burden of the comorbid disorder is not extremely debilitating, an experienced therapist will initially focus treatment on the ADHD itself, as successful treatment of the ADHD can often also reduce or completely remit (disappear) the comorbid disorders. In addition, one in three cases of treatment-resistant depression is actually the mere consequence of unrecognized ADHD (overload depression).
Depression, for example, can be treated with various medications. Some antidepressants are also effective (in lower doses) for ADHD. Stimulants such as methylphenidate or amphetamines are also used to treat depression. Others (SSRIs) can exacerbate ADHD-I symptoms in particular. The effect of antidepressants effective in ADHD at a dosage typical of ADHD should therefore be considered before massive treatment of ADHD comorbid depression with conventional antidepressants.
When diagnosing depression, the typical ADHD symptomatology of dysphoria during inactivity must be taken into account, which is not depression but an original ADHD symptom. ⇒ Depression and dysphoria in ADHD
One study attempted to assign 238 people with ADHD, ASD and OCD who showed different symptoms or were healthy controls to homogeneous disorder groups based on cortex thickness in 76 cortex regions. This was done using machine learning (weak AI). No homogeneous groups could be formed.1
This suggests that the individual differences between people with ADHD are greater than the similarities.
1.3. Comorbidity: the difference to differential diagnosis¶
While differential diagnosis means checking whether the symptoms that (here:) point to ADHD might not actually be caused by another problem, i.e. that there is no ADHD, comorbidity means that someone who suffers from one disorder (here: ADHD) is also (additionally) affected by another disorder.
Comorbidity with ADHD therefore means that (here:) ADHD has been clearly identified and other problems exist in addition to ADHD.
Many disorders have very typical comorbidities - including ADHD, so it is always necessary to check these as part of a proper medical history. ⇒ ADHD - comorbidity
Most comorbidities typical of ADHD may have gene variants in common with ADHD or the common cause of early childhood stress exposure that meets a gene predisposition specific to the respective (co-)morbidity. ⇒How ADHD develops: genes + environment
33.3% of all Germans and 38.8% of all EU citizens suffer from a mental disorder (within 12 months). Men and women are affected in roughly equal numbers, but with different types of disorder. The age group of 18 to 34 years is most frequently affected.2
Of these 33.3%, 1/3 (i.e. a total of 11.1% of all Germans) suffer from more than one Disorder. In these cases, there is an overt comorbidity of several disorders from different diagnostic groups. The comorbidity with regard to different individual diagnoses from the same group is significantly higher again.
Comorbidities increase with age.2
For comparison with the prevalence values (frequency of occurrence) given below: ADHD has a prevalence of
Children and young people together 5.29 %
according to an international long-term meta-analysis of 102 international studies with n = 171,000 subjects3
This would make the lifetime prevalence of ADHD roughly equivalent to that of diabetes.6
Friedmann reports that the lifetime prevalence of ADHD in the US has risen from 7.8% in 2003 to 11% in 2011.5
This is not due to an increase in ADHD, but to the fact that ADHD is now better recognized and more reliably diagnosed.
An acute and subjectively threatening stress situation can cause the entire ADHD symptomatology in otherwise healthy people.
All ADHD symptoms are stress symptoms. Therefore, all symptoms can be triggered by “normal” severe stress, i.e. by a situationally appropriate but strong perception of stress in healthy people.
When the stressful situation ends, the symptoms cease completely in healthy people.
However, if ADHD exists, the stress regulation system is permanently damaged due to genetic causes or a combination of a genetic disposition and too long, too intense (usually early childhood) stress exposure (⇒Development of ADHD), so that the stress symptoms persist from then on even in the slightest (or no) stressful situations and the stress systems can overreact to minor stressful situations (ADHD-HI) or the stress systems ramp up and shut down again too early (ADHD-I). ⇒ ADHD as a chronic stress regulation disorder.
The first step in a differential diagnosis is therefore to determine whether there are acute circumstances that are so stressful that they can cause the symptoms, for example:
Prevalence of giftedness: IQ 120 and above: 8.98%, IQ 130 and above: 2.28%
Giftedness is not a Disorder. Nevertheless, symptoms can arise from unrecognized giftedness that are almost identical in nature and composition to ADHD symptoms.
2.1.2.1. Stress reaction of unrecognized gifted people as outsiders¶
Gifted children have different interests, think “differently”, have different values and react differently. The lower the social skills with which people with ADHD can overcome their differences, the stranger other children find them. This can trigger negative reactions and even bullying. But even without bullying, the “feeling different” and “not belonging” (which is not only similar, but identical to that of people with ADHD) and the lack of friends can increase stress to such an extent that the stress symptoms typical of ADHD can develop.
People with ADHD are then fidgety, disrupt lessons, act out in class (ADHD-HI-like) or switch off internally and daydream (ADHD-I-like).
In addition to the possible stress symptoms of bullied outsiders (which may well include unrecognized gifted people due to their difference), however, there are other similarities between ADHD and giftedness that are not caused by stress.
2.1.2.2. Similarities of individual typical traits in HB and ADHD¶
Giftedness not only causes faster thinking, but often correlates with typical traits (“character traits”). Many of these traits are similar to characteristics that are often observed in people with ADHD. ⇒ Giftedness and ADHD
We had suspected that the impressive correspondence between the positive characteristics of ADHD described in the ADHD literature and the typical character traits of gifted people described in the gifted literature resulted from the fact that ADHD almost always correlates with giftedness and giftedness very often correlates with high sensitivity. We assumed that these are character traits that do not result from ADHD or giftedness itself, but that they have their actual root in the shared high sensitivity.
However, more recent data (also from the ADxS.org symptom test, n = 2000, as of July 2020) show no correlation between giftedness and high sensitivity.
Highly gifted people as well as people with ADHD are attributed from the respective specialist literature:
Primarily intrinsically motivated (extrinsically difficult to motivate through external pressure)
Ability to hyperfocus
Boredom and concentration problems with uninteresting or monotonous tasks (up to underperformance and excessive error rate)
Impatience
Tendency to interrupt others
Rejection of authority (authority is only recognized on the basis of competence, not rank)
For some: difficulty in making decisions (too many options and facts to consider); mainly in people who internalize their stress reactions, less in people who externalize stress
Smalltalk version
Diplomacy deficit
Aversion to crowds
High importance of truth, equality, justice
Often being perceived as weird or strange by others.
These traits (which of course do not occur in every case of HB, but are common in HBs) should therefore be examined closely for their cause during diagnosis.
Unrecognized giftedness is not easy to spot. Not all gifted people have special abilities. Many gifted people even emphatically reject such a classification for themselves because they do not perceive themselves in this way. It is important to note the difference between giftedness = disposition and ability = realization of giftedness. Many gifted people need suitable support in order to develop their abilities. In addition, not all giftedness lies in areas relevant to school. Mathematical geniuses or the variant of the gifted person with a thirst for knowledge are naturally easily recognized as gifted.91011
Of course, being gifted is not a compelling reason for feeling like an outsider and/or for developing ADHD-like symptoms. It usually affects those who are unable to compensate for their otherness with sufficient social skills.
All the prevalence rates mentioned are merely a rough guide to make the probability of possible comorbidity visible. And, of course, not every child with ADHD is gifted.
Giftedness and its Consequences for learning-performance behavior and reactive behavioral disorders (when over/underchallenged) can act like ADHD. ADHD occurs more frequently with giftedness.11 Prevalence of giftedness: IQ 80 and below: 8.98%, IQ 70 and below: 2.28%
In the case of an existing intellectual disability, the DSM-V criteria appear to be only partially suitable for diagnosing ADHD. In particular, the main symptoms of the DSM-V in underachievers can also result from the underachievement itself. One study was able to correctly diagnose only 46% of people with ADHD using the DSM-V. Additional criteria - which the authors do not mention - are said to have increased the diagnostic accuracy of ADHD among the gifted to 82%.12
One study found that the Verbal Fluency Task showed lower phonological and semantic fluency in underachievers than in people with ADHD and lower semantic fluency than in dyslexics.13
A still age-appropriate high activity level, especially in younger children, can show a symptom picture similar to ADHD.1411
A (very) high level of activity in (very) young children can be age-related. This declines as the brain develops (which fits the description of ADHD as a developmental delay of the brain when the activity level is significantly above the usual age-appropriate level). Some children also simply need more time than others in certain developmental phases. This is not a Disorder, but an individual characteristic that everyone has. Warm attention and persistent encouragement, combined with plenty of opportunity to act out the urge to move are the most sensible responses here.
Sorted by prevalence (frequency of occurrence) in descending order. The prevalence indicates the frequency of the Disorder itself, not the frequency or probability of ADHD in this case. For example, the prevalence of deficiency symptoms is quite high, but the influence of their elimination on ADHD symptoms is not significant.
2.3.1. Consequences of sleep disorders (sleep disorders: children 47.1 %; adults: 0.6 to 7.8 %)¶
The annual prevalence of sleep disorders in Germany in 2008 was 0.6 % (15 to 19 years) to 6.6 % (60 years and over) for men and 0.8 % (15 to 19 years) to 7.8 % (60 years and over) for women.15
Sleep problems with ADHD are extremely common:
70 - 80 % of people with ADHD suffer from sleep problems
20 - 30 % of people with ADHD suffer from sleep problems
A Chinese study of 23,791 schoolchildren found that 68.7% of children with ADHD had poor sleep quality, compared to 47.1% of children without ADHD16
When it comes to sleep problems and ADHD, it is difficult to separate cause and effect. ADHD very often causes sleep disorders and sleep disorders often cause ADHD-like symptoms.
In the case of an ADHD diagnosis, comorbid sleep disorders should always be treated with special priority. In addition, when taking medication for sleep problems, their possible negative effect on ADHD symptoms must be taken into account, just as medication for ADHD must be checked to ensure that it does not exacerbate sleep problems. More on the treatment of sleep problems with ADHD: ⇒ Treatment of sleep problems with ADHD
Vigilance disorders with impaired sleep-wake regulation1718
Consequences of sleep apnea syndrome11
“Obstructive sleep apnoea syndrome (OSAS) is the most common sleep-related breathing disorder. The prevalence is around 4% in men and around 2% in women. Obstructive sleep apnea (OSA) is even more common and reaches strikingly high figures, particularly when subgroups are considered. For example, there is a prevalence of around 36% in patients with diabetes mellitus or arterial hypertension, a prevalence of 50% in obese patients and a prevalence of 83% in patients with refractory arterial hypertension. It is estimated that 80 % of male and 90 % of female patients with sleep apnoea syndrome are undiagnosed and therefore untreated.”19
Breathing interruptions in children’s sleep can trigger cognitive stress, causing symptoms that resemble ADHD.20
ADHD symptoms that are atypical of sleep problems:
Inner restlessness (typical in atypical depression, less so in melancholic depression)
Impulsiveness
High flow of speech (logorrhea, polyphrasia)
Chasing thoughts, circling thoughts
Rapid mood swings
Dysphoria with inactivity
Symptoms of sleep problems that are atypical for ADHD:
Drowsiness
(Day) tiredness
2.3.2. Post-concussion syndrome (Consequences of a concussion) (11 to 80 %)¶
Another name: post-concussion syndrome
Prevalence: probably in 1 / 10 patients with mild traumatic brain injury25
A concussion is the mildest form of traumatic brain injury. In the USA, an incidence of 1.15 % is assumed for concussion (3.8 million / 331 million). This would put the incidence of postconcussion syndrome at around 0.115% per year.
The prevalence is between 11 and 80 %.26
In uninjured adolescent athletes, ADHD appears to mimic postcommotional syndrome. Persons with ADHD report more symptoms of postconcussion syndrome than non-affected people.27 Another study reports prolonged times to recovery from concussion in ADHD.28
One study found no clustering of ADHD in 12-/13-year-old athletes with a concussion.29
Prevalence of D3 deficiency:3031
* 30.2 % inadequately supplied
* 38.4 % sufficiently supplied
* 31.4 % in need of improvement or oversupplied
A vitamin D3 deficiency also appears to be very common in ADHD.32 D3 supplementation is recommended, especially in the fall/winter.
D3 requires fat for absorption, i.e. ingestion requires that the preparations contain fat or that food is consumed at the same time. A glass of milk should suffice for this.
in children under five years of age (Disease Control Priorities in Developing Countries 2006).
East Asia/Pacific: 7 %
Eastern Europe and Central Asia: 10%
Latin America and the Caribbean: 33 %
Middle East and North Africa: 46 %
Sub-Saharan Africa: 50 %
South Asia: 79 %
Zinc deficiency manifests itself in a lack of T and B lymphocytes, among other things
Zinc deficiency often goes hand in hand with vitamin A deficiency
Zinc is involved in the Ada repair protein. This repairs (demethylates) methylated phosphate linkers in the DNA by transferring the methyl group to the cysteinate-S36
The prevalence of iron deficiency is difficult to determine because there is little reliable epidemiologic data on the subject, and it is also related to various related pathologic entities such as anemia, iron deficiency anemia, and isolated iron deficiency without anemia.
This could be particularly harmful in infants and young adults with changes in the mesolimbic signaling pathway [30]. Iron is involved in dopaminergic signaling pathways and dopaminergic neurotransmission.
Iron deficiency in the substantia nigra could result in reduced tyrosine hydroxylase activity and thus impaired dopamine synthesis.
The SERT influences dopaminergic signaling
through its modulation of intracerebral iron homeostasis. The SERT-dependent decrease in intracerebral iron concentration influences dopaminergic and noradrenergic neurotransmission because iron is required for the conversion of phenylalanine to L-tyrosine and L-tyrosine to L-dopa and thus co-regulates dopamine synthesis.
by the (reversible) decrease in the density of dopaminergic D2 receptors and presynaptic DAT, which ensure presynaptic reuptake.
Among adults with ADHD, the prevalence of substance abuse is 33.5% .39 The risk of substance abuse among adults with ADHD in the US is 1.7 to 7.9 times higher.40
The prevalence of substance abuse among German adults in 2019 was (12-month prevalence and lifetime prevalence)41
Cannabis: 7.1 % / 28.3 %
Cocaine / crack: 1.1 % / 4.1 %
Ecstasy: 1.1 % / 3.9 %
Amphetamines: 1,2 % / 3,8 %
Methamphetamine / crystal meth: 0.2 % / 0.8 %
Smoking (at least 20 cigarettes/day), adults:42
One study found an ADHD prevalence of 20.5% among patients hospitalized for alcohol dependence.44
If aggressive and oppositional defiant behavior and low self-esteem are present in addition to ADHD, the probability of substance abuse is significantly increased, while no more frequent substance abuse was found in adolescent people with ADHD without these additional symptoms.4546
In our opinion, substance abuse is much more likely to be a consequence of ADHD than the cause of a full ADHD symptom picture. In rarer cases, it is comorbid. Treatment with stimulants very often eliminates the addictive tendency in ADHD. Modern dosage forms of stimulant medications are barely suitable for abuse as a drug (e.g. Vyvanse: prodrug of amphetamine bound to lysine, which is only very slowly converted to the active ingredient in the intestine).
In the Continuous Performance Test, people with ADHD showed more responses to correct timing compared to those with substance abuse.47
In Berlin, 5.0% of respondents aged 15 to 64 met the criteria for alcohol dependence according to DSM-IV (men: 6.4%, women: 3.5%).48
In Germany, the prevalence of gambling addiction is 0.31% and the prevalence of problematic gambling behavior is 0.56%.49
In the case of comorbidity of ADHD and addiction, there is an increased probability that ADHD is the causal cause of the addiction and not addiction the cause of ADHD. This was shown at least for smoking, cannabis and probably also alcohol.50
One study found that increased polygenic risk scores (PRS) for ADHD also increased the likelihood of addiction by 20%. There were no differences with regard to the intensity of the addiction (use, abuse, dependence) or the type of addictive substance (alcohol, cannabis, other illegal drugs). Conversely, the ADHD-PRS explained only 0.2% of the probability of addiction compared to other risk factors.51
One study showed an ADHD prevalence of 16.7% in severe addicts compared to 2.5% in the control group.52
Even more significant was the fact that 53% of severe addicts had socially disturbed behavior in childhood or adolescence (up to 15 years), as measured by the SKID-II (control subjects with 2.5%).53 An earlier Disorder of Social Behavior (OR = 35.1) compared to childhood hyperkinetic behavior (OR = 5.7) is by far the greater risk factor for severe addiction.54
This indicates to us that addiction plays a role predominantly in ADHD-HI and less in ADHD-I.
The preference for addictive substances indicates a more frequent use of cannabis products among people with (former) hyperkinetic behavior. There appears to be no significant difference for opiates, cocaine, amphetamines, sedatives and hallucinogens.55
Although a joint occurrence of hyperkinetic and socially disturbed behavior is associated with an early first use of illegal drugs, statistically only an earlier and increased use of nicotine could be proven.56
Long-term abuse of dopaminergic drugs (cocaine, amphetamines) leads to prolonged downregulation of dopamine levels. Withdrawal symptoms then correspond to ADHD symptoms. 57 Against this background, the question arises as to whether ADHD medications (stimulants), which are known to have no intoxicating effect, could be helpful in the withdrawal of dopaminergic drugs.
People with ADHD with comorbid cocaine addiction showed a significant reduction in addictive behavior when treated with stimulants.58
Common symptoms of addiction / substance abuse and ADHD:24
Impulsiveness
(Inner) restlessness, motor hyperactivity
Concentration problems
High flow of speech (logorrhea, polyphrasia)
ADHD symptoms that are atypical for addiction / substance abuse:
Chasing thoughts, circling thoughts
Attention problems
Dysphoria with inactivity
Mood swings
Symptoms of addiction / substance abuse that are atypical for ADHD:
Substance abuse:
Excessive consumption of a substance, even if there are serious Consequences
Addiction / dependence:
Excessive consumption to the point of dependence on the drug
Very difficult to stop
2.3.7. Thyroid problems (cumulative 7 to 14 % in women, 2.75 to 3.5 % in men)¶
See also the guidelines of the ADHD Working Group of Pediatricians and Adolescent Doctors, as of 2014.11
From the age of 60, around 2% of the population are affected by hypothyroidism.17
ADHD-like symptoms can result from hypothyroidism63
Hypothyroidism becomes more common with increasing age (usually a consequence of Hashimoto’s autoimmune thyroiditis).
Hypothyroidism often develops slowly, which is why symptoms are difficult to recognize.
Healthy 4-year-old children with thyroid-stimulating hormone levels in the upper normal range have a higher risk of ADHD than children with low free thyroxine levels. Thyroid disorders are more common in women than in men. Since ADHD is further associated with thyroid hormone receptor insensitivity (see below), the role of thyroid hormones in the development and manifestation of ADHD in women and girls should be investigated in more detail.64
Hyperthyroidism does not preclude treatment with methylphenidate, but requires particular caution, especially strict monitoring of thyroid levels, pulse and blood pressure.
Hashimoto’s (Hashimoto’s lymphomatous goiter) is an autoimmune disorder that causes hypothyroidism63
The prevalence of Hashimoto’s in Germany is around 5 to 10 %. Prevalence and incidence increase with age. Women in the 3rd-5th decade of life are affected about 10 to 20 times more frequently than men.65
Other symptoms that are not typical of ADHD can be:61
Tiredness
In extreme cases: delusions / suicidal thoughts
Weight gain
Slowed heartbeat
Slowed reflexes
Decreased libido.
It is reported that adrenal insufficiency (reduced cortisol production by the adrenal gland) often leads to thyroid insufficiency. Treatment of the thyroid gland with thyroxine then increases the cortisol demand on the adrenal gland. However, if the adrenal gland is already so weakened that the increased cortisol production completely overwhelms it, a collapse of the adrenal gland can result, which further reduces cortisol production, which is why the adrenal gland should be considered and treated before thyroxine treatment.66
An attenuated cortisol stress response is often present in ADHD-HI. *⇒ Cortisol and other stress hormones in ADHD *This could be a sign of mild adrenal insufficiency. However, this is often likely to be caused by pituitary weakness due to CRH receptor downregulation. To differentiate from adrenal insufficiency, see ⇒ Hypocortisolism (adrenal cortical insufficiency) In this article.
However, adrenal collapse due to thyroxine therapy is not reported as typical in ADHD.
The β-thyroid receptors (TRβ) in the pituitary gland control the down-regulation of thyroid-stimulating hormone (TSH), which leads to reduced production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).
Thyroid hormone resistance (RTH) / thyroid hormone action deficiency (THAD) is an overall rare, hereditary syndrome, but the most common syndrome with reduced sensitivity to thyroid hormones.67
Mutations in the β gene of the thyroid receptor (Thrb, formerly just called RTH) can impair the receptors’ ability to bind T368
There is an imbalance between
the resistance of tissues that predominantly express thyroid hormone receptor β isoforms 1 and 2 and
overstimulation of tissues that mainly express the thyroid hormone receptor α isoform
In functional receptors, the mutant receptors form homo- and heterodimers that lack the ability to act on genomic response elements. The result of this dominant negative effect is that TSH is not downregulated (thyroid hormone resistance (RTH)).
THRB mutation thyroid hormone resistance has the following typical symptoms:
normal6970 or elevated levels of triiodothyronine/free thyroxine and non-suppressed thyroid-stimulating hormone6770
Restless legs correlates with ADHD symptoms.1718
Intensive sugar consumption can cause twitching in the limbs (especially in the legs) - especially in people who do not tolerate sugar well - which is similar to a mild form of restless legs and can make it difficult to fall asleep.
A lower frequency of D4.7R is suspected in restless legs, while this gene variant is more common in ADHD.74
In restless legs, treatment with L-dopa is often helpful in the short term, but can be detrimental in the long term.
Treatment with D4 agonists is also being discussed74
L-DOPA can have a protective or toxic effect
Autooxidation of L-DOPA produces toxic and reactive ROS and DAQs. In a computer model, L-DOPA showed a loss of dopaminergic neuronal terminals in the substantia nigra, which was mitigated by the simultaneous administration of glutathione. L-DOPA appears to have neurotoxic and neuroprotective effects depending on the oxygen tension. At physiological oxygen levels, L-DOPA inhibits mitochondrial functions, suppresses oxidative phosphorylation and depletes the NADH pool without causing auto-oxidation of L-DOPA and oxidative cell damage.75
2.3.9. Prenatal damage due to alcohol, FAS (0.8 to 8.2 %)¶
Prevalence: 0.8 to 8.2 % of all births, with around 10 % of all cases developing full symptoms.76 Long-term studies of children with FAS (fetal alcohol syndrome) found that 47.2 %77, 67.6 %78 or 70 %79 also had ADHD.
Around 15 to 30% of all mothers continue to drink alcohol during pregnancy.76 The risk to the unborn child is considerable.
This problem is also considered a possible cause of ADHD.80 The risk of ADHD among people with FAE/FAS was increased 10-fold.81
Differential diagnosis of FAS and ADHD
Symptoms of FAS alone (according to Wikipedia; black and lean), also with ADHD (bold):
Physical area
Growth disorders, short stature, underweight
Comparatively small head circumference (microcephaly), underdevelopment of the brain (microcephaly)
Flat-looking midface in profile with a flat upper jaw region, receding chin (micrognathia) and a short, flat nose (snub nose) with nostrils initially pointing forward (socket nose)
Narrow (upper) lip red (missing cupid’s bow) and little modulated, flat or missing central groove (philtrum) between nose and upper lip
Small teeth, increased tooth spacing
Specially shaped and low-set ears
Comparatively small eyes with narrow, partly drooping eyelids (ptosis)
Crescent-shaped skin fold at the inner corners of the eyes (epicanthus medialis)
Muscle weakness (muscle hypotonia), underdevelopment of the muscles
Weak connective tissue, lack of subcutaneous fatty tissue
Special hand furrows, flat hand line relief
Cleft palate can be caused by alcohol consumption during pregnancy
Organic area, physical malformations
Speech disorders
*(ADHD itself shows no or only mild speech disorders, but frequent comorbidity of partial performance disorders; speech disorders are rare and rather atypical in ADHD)
Eating and swallowing disorders, often lack of or excessive hunger
*(in ADHD, loss of appetite tends to be a consequence of medication; however, obesity is a more common comorbidity of ADHD)
Difficulty in understanding abstract things and logical connections
Problems with capturing terms such as soon, before, after, soon, the day after tomorrow.
Mathematical problems, e.g. estimating numbers, understanding the time and dealing with monetary values*
*(In the case of ADHD, dyscalculia as a comorbid partial performance disorder)
Seizures, epilepsy
Emotional instability, fluctuations in balance, moods and emotional expressions
Frequent long-lasting outbursts of temper
Hyperactivity
Hyperexcitability (hyperexcitability of the central nervous system)*
*(For ADHD: high sensitivity)
Over- or undersensitivity to even mild pain, temperature, touch stimuli, etc.*
*(ADHD: high sensitivity)
Under- or Overreaction to tactile stimuli*
*(ADHD: high sensitivity)
Lack of trust (e.g. going with strangers)
Increased willingness to take risks, recklessness, resulting in an increased tendency to have accidents
Aggressiveness* and destructiveness
*(not ADHD itself, but frequent comorbidity)
Above-average reaction times (ADHD not, rather above-average changing reaction times)
Inattention, easy distractibility up to sensory overload due to various environmental stimuli (lights, colors, sounds, movements, people, etc.)
Behavioral problems
Motor coordination difficulties due to developmental delays in fine and gross motor skills and poor hand-eye coordination (“clumsiness”)
Difficulties in coping with problems
FAS: the same approach over and over again without variables
ADHD: rather disorganization due to frequent forgetting of details, but also impaired learning
FAS: no learning from experience
ADHD: need a long time to learn from experience
Self-stimulating, sometimes self-injurious behavior
Impatience and spontaneity on the one hand, decision-making difficulties on the other
Dissocial and oppositional behavior* *(Not in ADHD itself, but here more often comorbid oppositional deficit behavior. Dissocial behavior in ADHD is also not very typical as a comorbidity)
Failure to recognize consequences
Difficulties integrating appropriately into social relationships and feeling comfortable in them*
*(In ADHD-HI due to inner tension and urge to move, in ADHD-HI and ADHD-I due to overstimulation, which leads to symptoms of exhaustion and overload; often also social phobia, in ADHD-I due to withdrawal and daydreaming tendencies)
Ignorance of verbal instructions, uncooperative and oppositional behavior when verbal boundaries are set (non-acceptance of “no”)
*(In the case of ADHD, it is more likely to be overheard, forgotten or passed over in enthusiasm. No systematic ignoring as with FAE).
Insensitivity or lack of understanding of non-verbal signals through gestures, facial expressions and body language of other people
Meaningful understanding of instructions, but inability to execute them appropriately*
*(ADHD is different anyway, more organizational inability due to planning, scatterbrainedness, forgetfulness than comprehensive inability)
Often anxious, worried and chronically frustrated attitude
Children with hydrocephalus have an almost threefold risk of ADHD.85
In old age, hydrocephalus often occurs comorbidly with Alzheimer’s disease and vascular dementia.
2.3.12. Histamine intolerance, histamine intolerance (1 %, of which 80 % adults)¶
The prevalence of histamine intolerance is given as 1%. However, 80% of those affected are said to be adults.86
The main physical symptoms of histamine intolerance are878889
Stuffy or runny nose (synonyms: blocked nose, runny nose, runny nose, rhinorrhea, non-allergic rhinitis, runny nose, nasal obstruction)
Sneezing, sneezing irritation
Narrowing of the airways (synonyms: Bronchoconstriction, bronchoconstriction, bronchoconstriction and bronchial obstruction): e.g. shortness of breath (breathlessness, dyspnea), asthma, bronchospasm
People with ADHD often show symptoms of ADHD, although the subtypes with hyperactivity seem to predominate.9091929394
Phenylketonuria (PKU) is a recessive disorder of phenylalanine metabolism due to mutations in the phenylalanine hydroxylase gene). PKU leads to a significant excess of phenylalanine (hyperphenylalaninemia). As phenylalanine and tyrosine pass through the blood-brain barrier via the same transporters, and these transporters have a higher affinity for phenylalanine, too little tyrosine reaches the brain if there is an excess of phenylalanine in the blood. Tyrosine is a precursor for dopamine, from which noradrenaline and adrenaline are further produced. Excess phenylalanine in the blood therefore leads to a lack of dopamine, noradrenaline and adrenaline in the brain.95In addition, excess phenylalanine causes changes in cerebral myelin and protein synthesis as well as reduced levels of serotonin in the brain.96ADHD and phenylketonuria therefore have the common feature of a dopamine deficiency 929798
Treatment with sapropterin improved ADHD symptoms in a pharma-funded study in phenylketunorie.99 A study also suggests BH4 treatment for ADHD, which is helpful for PKU98
2.3.15. Consequences of severe brain infections (cumulative 0.05% to 0.16%)¶
Brain infection with inflammatory changes caused by invading microorganisms. Encephalitis destroys the cells in the substantia nigra that produce dopamine.
The people with ADHD affected by the encephalitis epidemic from 1914 to 1917 showed typical symptoms of ADHD as the disease progressed. Children developed hyperactive motor skills, adults Parkinson’s symptoms.
The symptoms are consequences of the dopamine deficiency that characterizes ADHD. These symptoms have been reproduced in animal experiments as a result of impaired dopamine production.102
Oxygen deprivation during birth is one of the main causes of early childhood brain damage (ECBD).
In animal experiments, led to the death of dopamine-producing cells in the substantia nigra and thus to a decrease in dopamine levels of up to 70 %.103 Hypoxemia is associated with excess adenosine. Adenosine inhibits dopamine.
2.3.15.3. Bacterial infections (cumulative 0.01% in women, 0.12% in men)¶
Brain abscesses: 0.3-1.3 /100,000 per year (0.0003% to 0.0013%)
Local infection of the brain tissue. Begins as focal encephalitis (cerebral phlegmon, “cerebritis”). Gradually develops into a collection of pus with a connective tissue capsule
Syphilis (prevalence 11.5 / 100,000 (0.115 %) in men, 0.9/100,000 (0.009 %) in women)
Other names: Von Recklinghausen’s disease, Recklinghausen’s disease, neurofibromatosis Recklinghausen, peripheral neurofibromatosis
With a prevalence of around 1:3500 (0.029 %), it is one of the most common hereditary neurological diseases. Neurofibromatosis type 1 shows malformations of the skin and the central nervous system. Neurofibromatoses are nerve tumors.
Among 128 persons with ADHD (53.1 % girls), 28.9 % (37/128) were found to have ADHD, including 20 ADHD-C, 15 ADHD-I and 2 ADHD-HI.
Other comorbidities of neurofibromatosis type 1 were macrocephaly (head circumference more than 2 SDs above the age average, 37.5 %), headache (18.6 %), cognitive impairment (7.8 %), motor deficits (6.2 %) and epilepsy (4.68 %). MRI revealed T2-weighted hyperintensities in the basal ganglia and/or cerebellum (70.5 %), optic nerve gliomas (25.8 %), plexiform neurofibromas (9.3 %), Chiari malformation type 1 (6.7 %), arachnoid cysts (5 %), gliomas of the central nervous system (3.1 %).105
Diagnostic criteria - at least 2 of the following symptoms:106
Six or more café-au-lait spots (CAL) > 5 mm in diameter prepubertal and > 15 mm postpubertal.
Freckling in the armpit or groin region.
Two or more neurofibromas of any type or one plexiform neurofibroma (PNF)
Glioma of the visual pathway
Two or more iris nodules identified by slit lamp examination or two or more choroidal abnormalities (CAs) detected as irregular bright nodules by optical coherence tomography (OCT) or near infrared imaging (NIR imaging).
Specific bony lesions such as sphenoid dysplasia, anterolateral bowing of the tibia or pseudarthrosis of the long tubular bones.
A heterozygous pathogenic (= disease-causing) NF1 variant with an allele frequency of 50 % in normal tissue such as leukocytes.
2.3.17. Velocardiofacial syndrome (22q11DS) (0.01 to 0.05 %)¶
Other names: CATCH 22, Cayler cardiofacial syndrome, Di George syndrome, DiGeorge sequence, microdeletion 22q11.2, monosomy 22q11, Sedlackova syndrome, Sphrintzen syndrome, syndrome of conotruncal anomaly with facial dysmorphia, Takao syndrome
Addison’s disease: Prevalence: 4/100,000 (0.004 %).
Weaker forms are much more common.
Since the basal cortisol level is slightly reduced in ADHD (in ADHD-HI as in ADHD-I), ADHD could be described as very weak adrenal insufficiency (adrenal insufficiency).
2.3.18.2. Hypercortisolism (Cushing’s syndrome) (0.0002 to 0.0008 %)¶
Prevalence: 8/1,000,000 in men (0.0008%), 2/1,000,000 in women (0.0002%)111
ACTH-dependent form (80% of cases)
Micro- or macroadenoma of the anterior pituitary gland produces ACTH (= Cushing’s disease)
(mostly malignant) tumors outside the pituitary gland (often bronchial carcinomas) as the cause of ectopic ACTH production
ACTH-independent form (20% of cases)
Overproduction of glucocorticoids (cortisol) and mineralocorticoids by the adrenal cortex
Moyamoya is particularly common in Japan. Prevalence
Worldwide: 1 / 1,000,000 to 9 / 1,000,000 (0.0001 % to 0.0009 %)112
Japan: 1 / 30,000 to 1 / 9,500 (0.0033 % to 0.0105 %)
Incidence Japan: 1 / 280,000 to 1 / 89,000
Moyamoya is a narrowing or occlusion of cerebral arteries that leads to relative anemia (stroke and transient ischemic attack) in the brain. Many small compensatory vessels form as bypass circuits.
Moyamoya can be associated with symptoms that can be confused with ADHD.113
A hamartoma is a tumor-like, benign tissue change due to incorrectly differentiated or dispersed germinal tissue. A hypothalamic hamartoma can produce a variety of hormones and cause ADHD symptoms, conduct disorder, oppositional defiant disorder, antisocial behavior, tantrums, intellectual regression, cognitive disorders, premature puberty, obesity and epilepsy. 60% of people with ADHD develop externalizing disorders (especially in boys and epilepsy) and 30% develop internalizing disorders.115116MPH can significantly improve ADHD triggered by a hypothalamic hamartoma, as can treatment with a gonadotropin-releasing hormone (GnRH) analog.117 In severe cases, stereotactic laser surgery may be helpful.118
Other names: Bioelectric status epilepticus during sleep, CSWS, CSWS syndrome, ESES syndrome, Epileptic encephalopathy with continuous spike-wave discharges during slow-wave sleep Prevalence: unknown. Orphane Disorder (rare).122
Epilepsy with continuous spike-wave discharges during sleep (CSWS) is a rare epileptic encephalopathy in children. It is characterized by seizures, electroencephalographic patterns of status epilepticus during sleep (ESES) and cognitive developmental regression.123
ESES is associated with symptoms similar to ADHD. In one study, treatment with ACTH reduced ADHD symptoms by an average of 67%.124 Another study by the same authors found similar improvements with ACTH in ADHD and stuttering.125
2.3.26. Traumatic or space-occupying cerebral disorders / other psychoorganic syndromes with cerebral damage and/or mental retardation¶
Bachmann-Bupp syndrome (BABS) is characterized by126
pronounced alopecia
global developmental delay in the moderate to severe range
Hypotension
non-specific dysmorphic features
Behavioral problems
ASS
ADHD
Feeding problems
Hair
usually present at birth
can be sparse
may have unexpected color
falls out in large clusters in the first weeks of life
Seizures at the beginning of later childhood (rare)
Conductive hearing loss (rare)
Abnormal metabolites of polyamine metabolism (including elevated levels of N-acetylputrescine) indicates BABS.
Diagnosis by molecular genetic testing for heterozygous pathogenic de novo variants of the ODC1 gene.
Haploinsufficiency of the CAPRIN1 gene is an autosomal dominant disorder associated with loss-of-function variants in cell cycle-associated protein 1 (CAPRIN1).
The CAPRIN1 protein regulates the transport and translation of neuronal mRNAs that are crucial for synaptic plasticity, as well as mRNAs encoding proteins that are important for cell proliferation and migration in different cell types.
CAPRIN1 variants with loss of function were associated with the following symptoms:127
Myalgic encephalomyelitis / chronic fatigue syndrome is a severe neuroimmunological disease. A high degree of physical disability is a common consequence.132
Prevalence:
17 million people with ADHD worldwide
250.000 people with ADHD (including 40,000 children / adolescents) in Germany before the COVID-19 pandemic (0.31 %)
500.000 people with ADHD after the COVID-19 pandemic (0.62 %)
25 % can no longer leave the house
60 % are unable to work
ME/CFS is an independent, complex clinical picture. The symptom of fatigue, on the other hand, is a common accompanying symptom of chronic inflammatory diseases.
Symptoms of ME/CFS:
physical symptoms
severe fatigue (physical weakness)
significant restriction of the activity level- neurocognitive symptoms
Muscle twitching
Muscle cramps
massive sleep disorders
autonomic symptoms
Orthostatic intolerance.
Palpitations
Dizziness
Drowsiness
Fluctuations in blood pressure
Consequences: e.g. no longer able to stand or sit for long periods of time
immunological symptoms
strong feeling of illness
painful and swollen lymph nodes
Sore throat
Respiratory tract infections
increased susceptibility to infections
Post-exertional malaise (PEM)
pronounced and persistent intensification of all symptoms after minor physical or mental exertion
pronounced weakness
Muscle pain
flu-like symptoms
Deterioration of the general condition
typically occurs even after low levels of stress
Brushing your teeth
Showers
Cooking
walk a few steps
in severely affected people, even turning over in bed or the presence of another person in the room can trigger PEM
Pain symptoms
pronounced pain
Muscle pain
Joint pain
Headache
neurocognitive symptoms
“Brain Fog”
Concentration problems
Memory problems
Word-finding disorders
Increased sensitivity
Hypersensitivity to sensory stimuli
Very severely affected people often have to lie in darkened rooms and can only communicate in a whisper
Trigger:
Infectious diseases
Epstein-Barr virus
Influenza
SARS
COVID-19
Gonorrhea
Endometriosis and PDMS
Nutrient deficiencies (vitamins, trace elements)
Path:
unexplained
possible:
Autoimmune disease
severe disorder of the energy metabolism
Biomarkers:
none known
Diagnostics:
using established clinical criteria catalogs
Treatment:
there is currently no approved curative treatment or cure
Pacing
helps with ME/CFS as well as ADHD or ASA
Overloading is “punished more severely” with ME/CFS
Differences between ME/CFS and ADHD / ASD / depression:
ADHD: problems usually already as children, but no later than 16 to 18; ME/CFS: problems usually not yet lifelong
ME/CFS: gradual, usually undulating deterioration over years until at some point there is no energy left at all
no depressive states
no strong deterioration in sentiment
Depression: severe cognitive impairment and reduced drive; ME/CFS: cognitive impairment due to temporary or permanent “brain fog”
Ability to vibrate is preserved in ME/CFS
People with ADHD do not perceive themselves as depressed and do not appear depressed
Depression; drive is lacking and is missed; ME/CFS: drive present, energy for implementation is lacking or implementation leads to overload (sometimes only hours later)
Martin Winkler considers exhaustion in ADHD in the context of a regulation-dynamic model. He distinguishes between ADHD / neurodivergence:
Cognitive exhaustion
Consequences: Mental fatigue due to constant demands on attention and concentration, especially in inappropriate environments
reduced performance
reduced attention span
increased distractibility
Emotional exhaustion
Emotional regulation requires increased effort
Consequences: depletion of emotional resources
increased irritability
Mood swings
Feeling of being overwhelmed
Physical exhaustion
Constant tension and effort to concentrate / control impulsive behavior,
Consequences: physical exhaustion
Exhaustion due to adaptation requirements / masking
Increased cognitive / emotional resources to adapt to social norms and expectations
Consequences: specific adaptation requirement exhaustion
Benzodiazepines17134135
Benzodiazepines reduce the activity of the locus coeruleus and thus reduce the transport of noradrenaline to other parts of the brain.136Disorder of noradrenaline production in the locus coeruleus is also typical of ADHD.
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs (namely citalopram and escitalopram) are suspected of increasing the effect of dopamine reuptake transporters.137. Overactive dopamine reuptake transporters are a possible cause of the dopamine deficiency that triggers ADHD symptoms (especially in the striatum) by reabsorbing the presynaptically released dopamine before it has had a chance to exert its communication effect at the postsynapse. ⇒ ADHD - Neurotransmitters - Messenger substances
Prevalence: 22.9% of all women, 9.7% of all men within one year.211 Prevalence in girls under 18: 7.85%.138
Anxiety disorders are comorbid in 25% of people with ADHD,139 16.7% of children with ADHD and 27.2% of adults with ADHD.14 Other sources cite 15% to 35%140 and 35.6% of adults in England in 2007.141
Symptoms of anxiety disorders that are atypical of ADHD:
Fatigue
Muscle tension
Anxiety in ADHD may partially reduce impulsivity and response inhibition deficits, exacerbate working memory deficits, and appear to be qualitatively different from pure anxiety. Comorbid anxiety in ADHD appears to have divergent forms of expression:140144
Prevalence:
Lifetime: 10 % to 17 %146
under the age of 18: Girls 2.54 %, boys 1.10 %.147
Affective disorders are described in 27.9% of children with ADHD and in 57.9% of adults with ADHD14. Furthermore, a prevalence of 37.1 % for mood instability and 29.9 % for depression in adults in England in 2007 is cited.148
Depression must be distinguished from mere dysphoria during inactivity, which is a typical symptom of ADHD and does not constitute depression. Treatment with antidepressants would be inappropriate here.
Detailed information on this can be found at ⇒ Depression and dysphoria in ADHD In this chapter.
12% to 50% of children with ADHD also suffer from depression, which is five times more common than in children without ADHD.140 A study of young adult persons with ADHD reported a lifetime prevalence of ADHD of 25.9%,149 which is also around five times higher.
The lifetime prevalence of major depression is 15%150; women are affected twice as often as men, i.e. women 20%, men 10%.
In children with ADHD, emotional dysregulation occurs before comorbid depression.151152 This is not surprising, as emotional dysregulation is an original ADHD symptom, while depression can occur as a comorbid Disorder. Nevertheless, the degree of emotional dysregulation in children with ADHD appears to moderate the likelihood of later depression.153
In persons with ADHD, depression typically occurs years after the onset of ADHD symptoms.156 In this case, the underlying ADHD, which is often the cause of the depression, must be treated in addition to the existing depression. Otherwise, the depression would merely be treating a secondary symptom of ADHD.157156144
Around 34% of all treatment-resistant depression is caused by previously unrecognized ADHD.
Prevalence: 3.1 % of all women, 2.8 % of all men within one year2
Bipolar Disorder is characterized in particular by an alternation between depressive and manic symptoms. The changes can occur at different speeds. There is not always a change to a full-blown manic episode.
ADHD occurs more frequently than average in people with ADHD, but the comorbidity with ADHD is probably weaker than with other mental disorders.140 The prevalence of ADHD in people with ADHD differs according to the age at which the bipolar disorder first occurs158
Childhood: 80 to 95% have comorbid ADHD
Youth: approx. 50 % have comorbid ADHD
Adulthood: approx. 25 % have comorbid ADHD
In a reaction test study, both persons with ADHD and bipolar showed significantly increased variability of infrequent slow reactions compared to controls, while bipolar people showed significantly increased speed and variability of typical reactions in the flanker task compared to persons with ADHD and controls.159
2.5.3.2.1. Depressive episode of bipolar Disorder¶
The common and different symptoms of depressive episode of bipolar Disorder and ADHD correspond to those of depression and ADHD.
ADHD symptoms that are atypical for manic episodes:
Dysphoria only during inactivity
Symptoms of bipolar that are atypical for ADHD:
Alternation between depressive and manic phases
In ADHD, mood swings tend to be triggered (reactive) and disappear quickly when distracted, whereas bipolar manic phases tend to be more continuous and long-lasting.161
Cyclothymia (cyclothymia) is a rapid change of moods without reaching the intensity of the symptoms of Bipolar Disorder. Cyclothymia has a prevalence of 13% in the general population.
Cyclothymia has been found in 75% of all people with ADHD and is significantly increased in ADHD and depression.162
2.5.4. Circumscribed developmental disorders (partial performance disorders) according to ICD-10 (approx. 10 to 15 % (?))¶
Partial performance disorders are said to be a common comorbidity (especially in the ADHD-I subtype without hyperactivity).
Dyspraxia, on the other hand, is a purely motor development disorder that tends to be confused with ADHD-HI (without inattention).
Dyspraxia is also known as “clumsy child syndrome” or “clumsy child syndrome”.
Dyspraxia is a developmental disorder that lasts a lifetime.
Dyspraxia is very often comorbid with ADHD or ASD.
Children with dyspraxia show no deviations in intelligence.
There are different forms of dyspraxia.
2.5.4.1.1. Motor dyspraxia / circumscribed developmental disorder of motor functions (UEMF)¶
Problems with:
Motor deceleration
Balance problems
Impaired gait
Difficulty getting dressed while standing
Clumsiness in complex movements that require balance and dexterity165
Catch ball
Bounce
Jump
Climb
Cycling
Swim
Couple dance
Impaired automation of fine motor and gross motor activities
Impaired handwriting
Difficulty guiding the pen with the correct pressure
Problems adhering to the boundaries of the sheet.
Writing on the computer goes much better
Problems tying shoelaces or bows
Problems closing buttons
Difficulty eating with a knife and fork
Problems cutting out a figure cleanly
Frequent dropping of things
Problems with careful handling of glasses or crockery
Difficulties when pouring into glasses
Problems with crafting or wrapping gifts
Difficulty in acquiring new motor skills
Impaired eye-hand coordination
Frequent confusion between right and left
Problems with the Order of priority when putting on clothes
Rapid fatigue during physical activity
Sports
Hiking
Physically active play
Easily distracted during tasks
Too much information on one sheet can be confusing
Improved task performance with larger line spacing, larger font
Approximately 30% of children with dyspraxia also have a verbal developmental delay = verbal dyspraxia.167
Verbal dyspraxia is a disorder of speech motor planning. The speech organs are not impaired (tongue, vocal cords).
Problems with planning speech movements
Difficulty pronouncing the right words at the right time in the right Order of priority.
Frequent coughing or choking when eating
Sequence of sucking, swallowing and breathing made more difficult
High saliva production when switching from porridge to solid meals
Language development significantly delayed
Significantly later start to speak
Only a few “babbling sounds” at the beginning
Later often vowel language without consonants (“Oaaaa”, “Eeea”).
Often also problems with gross motor skills (see motor dyspraxia)
Stumble
Bump into each other, lots of bruises
Learning difficulties
Read
Spell
The risk factors for the development of dyspraxia are still unclear. As with ADHD, environmental influences during pregnancy and birth appear to increase the risk.
The extent to which the concept of developmental coordination disorders differs from that of circumscribed developmental disorders of motor functions and developmental coordination disorder (DCD) is unclear.
There are said to be different subtypes with six main symptom groups:
general instability / slight tremor
reduced muscle tone
increased muscle tone
Inability to perform a smooth movement or to combine individual movement elements into an overall movement
Inability to form written symbols
Difficulties with visual perception associated with the development of the eye muscles
People with ADHD are said to have ADHD in 50% of cases.
The risk of ADHD is also increased in children aged 4 to 5 years with developmental coordination disorder. However, the DSM-5 scale appears to be less effective here.168
The comorbidity of ADHD and learning disorders is reported to be between 10% and 90%.140
Learning disorders are said to correlate more frequently with ADHD-I than with ADHD-HI.169 Writing disorders are said to be twice as common as reading, arithmetic or spelling disorders in persons with ADHD.170
2.5.4.2.1. Reading and spelling disorder (dyslexia) (5 %)¶
Present in 17.6% of children with ADHD.14
Dyslexia is said to occur more frequently in ADHD-I than in ADHD-HI.171
Prevalence: 10% of all adult women and 5% of all adult men suffer from post-traumatic stress disorder.1718
60% of all men and 50% of all women have at least one potentially traumatizing experience in their lives.172
Of these suffer from PTSD:
Sleep problems are common in both ADHD and PTSD. In PTSD, these often arise in the first 2 weeks after the traumatizing event and are often characterized by persistent nightmares,174 which is also not typical for ADHD. In ADHD, on the other hand, the sleep disorders usually persist for life.
The Posttraumatic Stress Disorder subscale of the Child Behavior Checklist (PTSD-CBCL) is good at distinguishing PTSD from ADHD.175
While ADHD is associated with reduced dopamine and noradrenaline levels, PTSD is thought to be associated with excessive noradrenaline release.176 As noradrenaline (like dopamine) acts in the form of an inverted-U curve177, this could explain why some people with ADHD do not improve on ADHD medication (which increases dopamine and noradrenaline).
Relationship behavior:
k-PTBS: Often paranoid/mistrustful view of other people. No fear of being abandoned. Possibly conscious decision for a relationship178
Prevalence: 1% in primary school age (varying degrees of severity), 15% in primary school age (including mild and transient forms).179
Tic disorders are present in 9.5% of children with ADHD.14
31%180 to 55%181 of children with tic disorders also show ADHD.
Prevalence: among students in Germany 3.9% (2019) to 7.8% (2020, corona lockdown year)182
Internet addiction was differentiated into two subtypes by one study: one subtype that correlated with impulsivity and ADHD-HI and another subtype that correlated with compulsivity.183
2.5.8. Disorder of social behavior / Conduct Disorder (1.5 % to 5 %)¶
Prevalence: in primary school children approx. 1.5%, in adolescents approx. 5%.185
Oppositional defiant disorder is said to be present in 46.9% of children with ADHD and social behavior disorders in a further 18.5%.14 Comorbidity between ADHD-HI and Disorder of Social Behavior is reported in 15 to 85% of cases, depending on the study design and direction of the correlation, i.e. 4.7 times more frequently overall than in those not affected.186
Oppositional defiant behavior and other social disorders are considered by some experts to be a subtype of ADHD (rage type). We suspect that this is more of a separate disorder that has a high comorbidity with ADHD.
Differentiation from ADHD: Aggression in people with (pure) ADHD is reactive, defense motive, no intention to harm.119187 Aggression in people with ADHD often arises from a misjudgement of situations, after which they (supposedly rightly) defend themselves. People with ADHD therefore show reactive rather than proactive aggression.188
Borderline is a common misdiagnosis for severe ADHD-C or ADHD-HI.
Semmler attributes this to the fact that the most widely used borderline test, the SKID-II interview, as well as its successor, the SKID-5, ask about the dimensions of emotional instability and impulsivity in a joint construct and therefore mix them inappropriately. The SKID interviews are said to cause frequent misdiagnoses as a result. The IKP (Inventory of Clinical Personality Accentuations) separates these two dimensions and can be re-explored with the Borderline Personality Inventory (BPI) in the case of high scores.189
Borderline prevalence: 0.7 % - 2.7 %190, 1 % - 3 %191, 5 %192193 In psychiatric patients, the prevalence increases to 11 %194 to 12 %190, in hospitalized patients to 22 %190 to 50 %.194
ADHD increases the risk of a BPD diagnosis to 33.7%195. More on this at Borderline PS / Emotionally unstable PS In the article Psychiatric comorbidities in ADHD.
However, we are seeing a high number of borderline diagnoses that ultimately turn out to be ADHD, which is fully treatable with stimulants. Considering the high similarity of symptoms and the slowly developing awareness of how far-reaching symptoms and consequences ADHD can have, this is not surprising from our point of view.
75% of people with ADHD are women.
In the case of borderline, in addition to a symptom similarity to ADHD, a comorbid occurrence of ADHD is often found.190196197 One study addresses the question of whether one of the disorders (ADHD or borderline) can develop into one of the other disorders over time. Apparently, ADHD is more likely to be a preceding Disorder and Borderline is more likely to be a subsequent Disorder in adulthood. The increased number of traumatic childhood experiences in borderline was reported as a significant difference in environmental influences. This, as well as the different genetic disposition described below, argues against a regular developmental sequence between the two disorders. Nevertheless, we are aware of individual cases in which we consider a development from ADHD to a later borderline or a later addition of borderline to be a plausible explanation for the symptom pattern.198
Since borderline is associated with a genetic disposition on the MAO-A gene, which is also associated with aggression and behavioral disorders, borderline is likely to co-occur primarily with ADHD-HI and barely with ADHD-I. ADHD resembles a personality disorder in its course (early onset, persistent behavior patterns and possible continuation into adulthood).199
There are those who view ADHD-HI (with hyperactivity) and borderline as a continuum that varies in symptom intensity. One study found that ADHD and borderline are less distinguishable on the basis of individual symptoms, but differ primarily in the intensity of borderline symptoms.200 Hallowell reports on an ADHD-HI type with borderline overtones.201 We also see a conspicuous relationship, to the point of a strong confusability for laypersons, but assume that the aggressiveness associated with borderline is mediated by genes that are not typical for ADHD. As the correlating gene variants show, ADHD is characterized by a deficit of dopamine and noradrenaline in the dlPFC and striatum, while borderline is characterized by a normal dopamine level in the PFC and an excess of dopamine in the striatum (see below).
Borderline and ADHD have very similar symptoms, which are easily confused, and a high level of comorbidity. Around 50% of people with ADHD also suffer from borderline ADHD.
The “inner pressure” described in borderline (which can lead to self-harming behavior) is also known in ADHD.
Differentiation of the symptoms of ADHD and borderline:202
The previous assumption that ADHD and borderline differ in the time of onset (ADHD earlier, borderline later) is now being questioned.197
The BPFSC-11 appears to be good at differentiating borderline and ADHD.203
Significantly stronger in ADHD-HI/ADHD-C than in Borderline
High impulsivity in borderline is thought to indicate ADHD-HI comorbidity.
Other view: high aggressive impulsivity an endophenotype of BPD.207 We consider this more likely because DAT 9R, the gene suspected to be involved in aggressive-impulsive behavior in borderline, is not associated with ADHD. (see below).
One study found increased self-reported impulsivity in ADHD and borderline, but increased action impulsivity only in ADHD208
Borderline: Impulsivity only in relation to negative affects, ADHD: Impulsivity also in relation to positive affects209
Borderline: Impulsivity only under stress; ADHD: independent of stress210
Emotional dysregulation is even more pronounced in borderline than in ADHD. People with ADHD have a better use of adaptive cognitive emotional strategies than borderline sufferers.211 All emotions are perceived considerably more intensely (and with more stressful intensity) than in non-affected persons.193
Borderline behavioral dysregulation also does not occur in neutral life circumstances, but only in stressful moments.205
Mood swings:
Borderline: Anger and aggression, often caused by interactional triggers.178
ADHD: can become angry quickly. Anger is almost always short-lived and not regularly directed at interactional triggers. However, the affect can also tip over into hypomania.178
Attention deficit disorders
In ADHD often with too little arousal (lack of activation / stimulation)204
More frequent in BPD with a rise in tension as a dissociative phenomenon199
Borderline: no attention problems with boring things, ADHD: attention problems especially with boring things209
RS has so far been confirmed by most of the people with ADHD we have interviewed
Whereby this sickliness is a core symptom in borderline, i.e. much stronger than in ADHD
Often extreme jealousy (borderline)
Excitability, outbursts of anger
Stress intolerance
Stressors lead to significantly higher stress levels in borderline patients, which decrease much more slowly than in those not affected.193
Conflictual relationships (ADHD-HI) / instability in relationships (borderline)204
Social weakness, impaired social behavior
Sleep problems common
Borderline often shows a prolonged REM phase and nightmares (on average every 2nd night).174 Nightmares are atypical for ADHD.
Difficulty falling asleep, shortened sleep duration, low sleep efficiency with subjectively less restful sleep are common in borderline,174 as well as in ADHD.
Difficulty falling asleep in borderline patients is said to improve well with clonidine.174 Guanfacine could probably also be helpful.
One study found increased self-reported impulsivity in ADHD and borderline, but increased action impulsivity only in ADHD208
Slowing of reaction time212 although other studies have also found shorter reaction times in ADHD
Symptoms of Borderline that are atypical for ADHD:
Self-harming / self-injurious behavior
Impulsive behavior in response to intense negative feelings (“negative urgency”)208 is one of the most distinctive symptoms that characterize Borderline213
E.g. scratching (however, not all self-harming behavior is borderline)
Self-injury reduces the very high subjective stress load and objective amygdala activity (by increasing connectivity in frontal-limbic brain regions that dampen amygdala activity) in persons with ADHD after a stress test, while it further increases the (lower) stress load and objective amygdala activity in non-affected persons.193
Self-injuries that are unintentional or serve more as self-stimulation therefore do not point to borderline, but rather to ADHD
Thinking black and white
Shades of gray, both-and, mediating positions are difficult to perceive and hard to bear.
In discussions, people with ADHD tend to take extreme positions. For the person with ADHD, this can feel like they are always slipping off a bar of soap, either falling into one extreme or the other, but not being able to take a middle, both/and or mediating position.
In comorbid ADHD + borderline in particular are said to be more pronounced:197
Impulsivity (than with ADHD alone)
Symptoms of regulation of traits and emotions (as in borderline alone)
In children and adolescents, certain character traits increase the risk of a later borderline personality disorder:194
Affective instability
Negative affectivity
Negative emotionality
Inappropriate anger
Poor emotional control
Impulsiveness
Aggression
People with ADHD differ from those with other personality disorders primarily in their pronounced histrionic and more frequent narcissistic, bipolar/cyclothymic or aggressive characteristics. There is greater instability in relation to anger and anxiety and a greater oscillation in occurrence between depression and anxiety. Surprisingly, the level of intensity of emotion perception is not higher. Obsessive-compulsive, schizoid and anxious-avoidant manifestations, on the other hand, are rarer. These results are independent of gender.214
Dopaminergic substances (stimulants) can provoke impulsive and aggressive behavior in borderline patients.207 This indicates an excess of dopamine in borderline, which differs from the dopamine deficit in ADHD.
This is consistent with the results of studies according to which borderline correlates with the DAT1 gene variants 9/9 and 9/10, which cause lower DAT expression in the striatum, so that a higher dopamine level in the striatum can be expected due to the lower dopamine degradation caused by DAT.215 ADHD treatment with stimulants is also possible in cases of comorbid borderline209
The 9-repeat variant of the DAT1 gene causes an excess of dopamine in the synaptic cleft because the dopamine transporters then only reabsorb the dopamine insufficiently presynaptically. DAT 9R is associated with affective disorders and borderline personality disorder.216
Borderline correlates more frequently with215
DAT1 9/9 (OR = 2.67)
DAT1 9/10 (OR = 3.67)
HTR1A G/G (OR = 2.03)
The risk of borderline increases for carriers of the gene variant combinations215
DAT1 9/10 and HTR1A G, G (OR = 6.64)
DAT1 9/9 and C/G (OR = 5.42).
ADHD is not associated with DAT1 9R, but with DAT1 10/10, which causes increased DAT expression in the striatum, which is associated with increased dopamine efflux and therefore decreased dopamine levels in the striatum. This now explains why stimulants that increase dopamine and noradrenaline levels in the PFC and striatum work well in ADHD, while they can be counterproductive in borderline.
5 HTTPLR and 5-HT2c are two other candit data genes in Borderline.217
People with ADHD may have more regional μ-opioid receptors in some brain regions and fewer regional μ-opioid receptors in other brain regions. Emotional dysregulation (sadness) is said to correlate with the deviation of μ-opioid receptors compared to non-affected people.218
In BPD, antipsychotics bring about significant but small improvements in cognitive symptoms, mood instability and global functions. The effect on anger/rage is more pronounced. They have no significant effect on behavioral impulsivity, depression and anxiety.219
A study of n = 17,532 patients with BPD found with different forms of treatment:220
Prevalence: Lifetime prevalence of 1 to 3 %,221222 according to other sources 4.2 % of all women, 3.5 % of all men within one year.2
Girls under 18 years: Prevalence 0.96%, boys 0.63%.147
Olfactory disorders (disorders of the sense of smell) are common in ASD and OCD, but not in ADHD.223
Reactive aggression - as an immediate reaction to triggers
Low stress tolerance
Psychopathic type
Rare comorbidity with ADHD-HI / ADHD-C
Emotionally insensitive / hyporeactive
Active aggression - purposeful, instrumental violence
No increased arousal in case of frustration
No reduced stress tolerance
Differentiation from ADHD: Aggression in (pure) persons with ADHD is reactive, defense motive, no intention to harm 119187 Aggression in people with ADHD often arises from a misjudgment of situations, according to which they (supposedly rightly) defend themselves. We see a connection between this and rejection sensitivity as an excessive sensitivity to perceived or actual rejection/offensiveness. People with ADHD therefore show a reactive and not a proactive aggressiveness188
Persons with ADHD often recognize their sudden aggressive or verbal lapses or impulse control disorders as inappropriate with only a little distance and are usually able to excuse themselves, in contrast to people with ADHD with psychopathic personality structures.225
Common symptoms of antisocial personality disorder and ADHD:24
Impulsivity (atypical for ADHD-I)
Rapid mood swings
ADHD symptoms that are atypical of antisocial personality disorder:
Inner restlessness (typical in atypical depression, less so in melancholic depression)
Concentration problems
Attention problems
Dysphoria with inactivity
High flow of speech (logorrhea, polyphrasia)
Chasing thoughts, circling thoughts
Symptoms of antisocial personality disorder that are atypical of ADHD:
The lifetime prevalence is around 1%.60
Girls under 18 years: Prevalence 0.76%, boys 0.48%.147
Schizophrenia is highly hereditary (like ADHD approx. 80 %)226 and usually only develops after adolescence. However, it is usually preceded by precursors from childhood that do not resemble schizophrenia itself, but appear to genetically indicate schizophrenia.227
The negative symptoms of schizophrenia are based on a lack of dopamine. They are similar to ADHD symptoms.
The positive symptoms, on the other hand, are based on excessive subcortical presynaptic dopamine transmission (dopamine hypothesis). Although this is reduced by antipsychotic dopamine D2 receptor antagonists, in schizophrenia D2/D3 receptors appear to be only very slightly increased and DAT not altered at all, so that other medication approaches may be more appropriate.228
The excessive subcortical dopamine drive is likely due to changes in cortical function, specifically the reduction in cortical NMDA receptor-mediated glutamate signaling, which impairs cortical dopamine and GABA function. These cortical changes are thought to cause the cognitive impairments and negative symptoms of schizophrenia.226
Schizophrenia is also thought to be caused by a combination of genetic factors and environmental influences. Emotional trauma, social stress and hallucinogenic drugs have been identified as environmental influences for schizophrenia. ⇒ Genes + early childhood stress as a cause of other mental disorders
The COMT rs4680 involved in schizophrenia (as one of 50 or more candidate genes) enhances the degradation of dopamine and noradrenaline by forming a more active and thermally stable COMT enzyme.229 This causes higher schizotypal symptoms.
This can be reconciled with the newer dopamine hypothesis, according to which the positive symptoms of schizophrenia are not caused by a generally increased dopamine level in the frontal cortex (and in the nucleus accumbens, a part of the striatum), but by an increased activity (firing rate) of the mesolimbic system, which in turn is caused or influenced by a dopamine deficiency in the ventral tegmentum.229
Prevalence of ASA: approx. 0.9 %230
How many people with ADHD also show ADHD symptoms is an open question. A meta-analysis of 23 articles found results ranging from 2.6% to 95.5% for ASD without intellectual impairment.231 Some sources assume that around 42%232 to 50%233209 of all people with ADHD also suffer from ADHD.
One review concluded that ADHD and ASD may be a continuum.234
It is likely that ADHD and autism have common neurological/genetic roots.235
Disintegrative Disorder59 Prevalence: 0.008 % (one person with ADHD among 12500 people)230
Rett syndrome59 Prevalence: 0.006 % (one person with ADHD among 10000 to 17000 people)236230
Affects girls only
Symptoms of Rett syndrome236
Stereotypes of the hands (washing movements)
Partially autistic behavior
Dementia
Reduced head growth
Epileptic seizures (later stage)
Spasticity (later stage)
Apraxia
Muscle atrophy
Movement disorders in the area of the thorax
Social behavior and play development severely inhibited
Social interest continues to exist
Both ASD and ADHD show downregulation of neuroligin genes, which was even more pronounced in ASD.237
Differential diagnosis of ADHD:
Children with ASD had 15 or more of the 30 symptoms (average: 22 = 73%) of the Checklist for Autism Spectrum Disorder symptoms, while children with ADHD had an average of 4 symptoms (13.3%), none of them 15 or more. ADHD symptoms, on the other hand, were prevalent in children with ASD.238
Children with ADHD showed increased scores on the Social Responsiveness Scale (SRS), but these did not come close to the scores of people with ASD.239
Inattention rather due to too much detail orientation in ASD (compared to overlooking details in ADHD)209
Concentration breaks down when routines are disordered in ASD (compared to lack of routines and rapid jumping between different things in ADHD)
The unexpected is seen as an unpleasant irritation and a disorder of one’s own structure (rather than a welcome change in ADHD)
Routines due to their own need for structure (as opposed to laboriously getting used to routines so as not to lose too much structure with ADHD)
Great difficulty in social situations due to inner insecurity about how to behave correctly (as opposed to being offended by thoughtless behavior in ADHD)
Difficulty grasping social rules of the game (compared to difficulty adhering to the well-grasped social rules of the game in ADHD)
High attention to detail exceeds the time frame for activities (compared to project interruptions due to change of interest in ADHD)
Needs order for own inner structure, tends to find things in disorder (compared to not being able to maintain order due to other priorities with ADHD)
Deviation from the plan leads to irritation (compared to frequent deviations from the plan due to own spontaneity and impulsiveness)
Reduced flexibility (compared to less impaired flexibility in ADHD)
Concentration can be maintained during prolonged and repetitive tasks (compared to difficulties in maintaining concentration during monotonous boring tasks in ADHD)
Motor restlessness tends to occur in restless situations as a way of reacting (compared to motor restlessness in calm situations to stimulate ADHD)
Motor restlessness rather out of aversion to something = running away (as opposed to out of interest in something = running towards in ADHD)
Loose conversations or small talk unpopular, as own thought structures are thwarted; sometimes compensation through strict conversation (this is not present in ADHD; in our opinion, this is already present in ADHD, but weaker)
Lack of feeling for the situation and mood (present in ADHD)
Interrupting others rarely (like ADHD-I, different from ADHD-HI / ADHD-C)
Having to wait in a rather dark, completely unstimulating room is a rather pleasant idea (very unpleasant with ADHD-HI / ADHD-C; both possible with ADHD-I)
In ASD, the intracortical pathway (facilitation) appears to be unimpaired, whereas in ASD with comorbid ADHD, the intracortical pathway appears to be impaired. This could represent a biomarker to distinguish ASD from ADHD.241
In neurophysiological terms, pathogenesis is the promotion of a reflex or nerve cell activity by lowering the stimulus threshold for the transmission of the action potential of a nerve cell. Training mainly occurs with repeated excitation of the same nerve pathways or through the summation of subthreshold stimuli.242
Both ASD and ADHD showed slower orienting responses to relatively unexpected spatial target stimuli compared to controls, which was associated with higher pupil dilation amplitudes in ASD. ADHD showed shorter cue-evoked pupil dilation latencies than ASD and controls.243
Several studies have looked at differences between ASD and ADHD.
ASD, like dyslexia, shows deficits in global motion processing, unlike ADHD. ASD and dyslexia show significantly lower flicker fusion frequency than healthy controls or ADHD subjects.247
Self-soothing through repetitive behavior and routines210
Strongly differentiated need for relationships Important to be able to control the frequency and intensity of social contacts. Not resentful, but pragmatic.178
Shutdown: freezing and no longer being able to react.178
Meltdown: Openly aggressive, even with physical attacks or pushing in order to defend one’s own boundaries.178
Self-injurious behavior to relieve tension is also possible here at times178
ADHD symptoms that are atypical for ASD:
Poorer working memory typical for ADHD, less so for ASD244246
Both ADHD and ASD show structural abnormalities in the PFC, cerebellum and basal ganglia. Persons with comorbid ASD and ADHD showed no significant differences in the volumes of the PFC, cerebellum or basal ganglia. However, they showed significantly lower volumes of the left postcentral gyrus, but only children, not adolescents.249
One review compared catecholaminergic and cholinergic neuromodulation in ASD and ADHD. The authors came to the following conclusion:250
Stimulants could be a viable treatment option for a (possibly genetically defined) ASA subgroup
disorder of the cerebellum is much more common in ASD than in ADHD
in both cases, this could open up a noradrenaline- or acetylcholine-controlled treatment option
a deficit of the cortical salience network is considerable in subgroups of ASD such as ADHD
Biomarkers such as eye blink rate or pupillometric data can predict efficacy of targeted treatment of an underlying deficit using dopamine, noradrenaline or acetylcholine, in ADHD as in ASD
ASD is characterized by high levels of aggression and risk-taking behaviour. In addition, ASD is more frequently involved in child abuse than average.251 Aggression and high-risk behavior are also characteristics of the ADHD-HI subtype.
A review article found approximately doubled noradrenaline levels in the blood of those with ADHD and approximately halved noradrenaline levels in the blood of those without ADHD. In contrast, serotonin blood levels were four times higher in those with ASD and more than four times lower in those with ADHD.252
The ability to recognize irony was also impaired in children with ADHD.253
2.5.16. Fragile X syndrome (0.22% (men) to 0.66% (women))¶
Prevalence: 1/150 (0.66%) women, 1/456 (0.22%) men in the USA254
Source1117
PDD is characterized by severe deficits in social behavior and communication, as well as repetitive and stereotypical interests and behaviors. There are often comorbidities with reduced intelligence, ADHD, aggression and obsessive-compulsive disorder.255
Wilson’s disease (prevalence: 1 in 30,000 people, 0.0033%) is associated with excessive copper levels.
People with ADHD show symptoms that can be confused with ADHD256
Wilson disease is associated with an ATP7B gene defect and shows an excess of copper.
Although dopamine β-hydroxylase, which converts dopamine to noradrenaline, is dependent on copper for this, it does not appear to be involved in Wilson’s disease.
Monoamine neurotransmitter disorders are genetic defects in transporters or deficiencies in precursors, cofactors or degradation enzymes of monoamines (e.g. dopamine).257
Symptoms of a severe dopamine deficiency can include258
Symptoms of a severe serotonin deficiency can include258
Temperature problems
Sweating
Dystonia
The measurement of pterins (especially biopterin and neopterin) in urine is helpful in detecting deficiencies in precursors and specific metabolic defects:
There are (rarely) people with no or very severely reduced DAT. However, they show other symptoms that are not typical of ADHD (e.g. Parkinson’s dystonia in early childhood) and are therefore rarely misdiagnosed with ADHD and are more likely to be misdiagnosed with cerebral palsy. Many people with ADHD die as teenagers.262 An excess of extracellular dopamine leads to reduced production of dopamine (and thus reduced storage of dopamine in the vesicles) through activation of presynaptic D2 autoreceptors, as well as downregulation or desensitization of dopamine receptors, resulting in a lack of phasic dopamine and a dopamine effect deficiency.257
Predominantly milieu-related behavioral problems means, for example, lack of attention and stimulation, physical and/or emotional abuse, media abuse, intrafamilial conflicts and sibling conflicts11
In our understanding, this description corresponds to the environmental causes of most mental disorders such as ADHD, depression, anxiety disorders, borderline etc., all of which can arise when environmental causes, usually stressful experiences in the first 6 years of life, permanently manifest an existing genetic disposition by means of epigenetic change. Predominantly milieu-related behavioral abnormalities are therefore unsuitable for defining a separate disorder. ⇒ How ADHD develops: genes or genes + environment ⇒ Genes + early childhood stress as a cause of other mental disorders
ADHD is characterized in particular by problems with cognitive control, whereas oppositional defiant disorder (ODD) is characterized by a high desire for reward.155
Rehder (2006): Anorganische Chemie für Biochemiker, Skriptum zur Vorlesung im 4. Semester für den Studiengang Biochemie/Molekularbiologie an der Universität Hamburg, Seite 27 ↥
Hässler, Irmisch: Biochemische Störungen bei Kindern mit AD(H)S, Seite 88, in Steinhausen (Hrsg.) (2000): Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl., Kohlhammer ↥
Dreher: ADHS im Erwachsenenalter (Download 06.01.2020) unter Verweis auf ADDitude. Stategies and Support for ADHD & LD: 3. Your doctor diagnoses your ADHD as Bipolar Mood Disorder (BMD), Seite 5. ↥
