Absence seizure

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Absence_seizure 

 

Absence seizure
Other names	Petit mal seizures
Pronunciation	/ˈæbsəns ˈsiːʒər/ or /ɑːbˈsɑːns ˈsiːʒər/
Specialty	Neurology

Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). Absence seizure is very common in children. It affects both sides of the brain.

Epidemiology

Absence seizures affect between 0.7 and 4.6 per 100,000 in the general population and 6 to 8 per 100,000 in children younger than 15 years. Childhood absence seizures account for 10% to 17% of all absence seizures. Onset is between 4 and 10 years and peaks at 5 to 7 years. It is more common in girls than in boys.

Etiology

An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by GABRG2, GABRG3, and CACNA1A2 genes. Inheritance of these genes is involved in etiology of absence seizure. The factors that trigger an absence seizure are lack of sleep and compliance, drinking alcohol, and benzodiazepine withdrawal, and use of medication that reduces the threshold of seizure such as Isoniazid, antipsychotics.

Signs and symptoms

The clinical manifestations of absence seizures vary significantly among patients. Impairment of consciousness is the essential symptom, and may be the only clinical symptom, but this can be combined with other manifestations. The hallmark of the absence seizures is abrupt and sudden-onset impairment of consciousness, interruption of ongoing activities, a blank stare, possibly a brief upward rotation of the eyes. If the patient is speaking, speech is slowed or interrupted; if walking, they stand transfixed; if eating, the food will stop on its way to the mouth. Usually, the patient will be unresponsive when addressed. In some cases, attacks are aborted when the patient is called. The attack lasts from a few seconds to half a minute and evaporates as rapidly as it commenced. Absence seizures generally are not followed by a period of disorientation or lethargy (postictal state), in contrast to the majority of seizure disorders.

1. Absence with impairment of consciousness only as per the above description.
2. Absence with mild clonic components. Here the onset of the attack is indistinguishable from the above, but clonic components may occur in the eyelids, at the corner of the mouth, or in other muscle groups which may vary in severity from almost imperceptible movements to generalised myoclonic jerks. Objects held in the hand may be dropped.
3. Absence with atonic components. Here there may be a diminution in tone of muscles subserving posture as well as in the limbs leading to dropping of the head, occasionally slumping of the trunk, dropping of the arms, and relaxation of the grip. Rarely tone is sufficiently diminished to cause this person to fall.
4. Absence with tonic components. Here during the attack tonic muscular contraction may occur, leading to increase in muscle tone which may affect the extensor muscles or the flexor muscles symmetrically or asymmetrically. If the patient is standing, the head may be drawn backward and the trunk may arch. This may lead to retropulsion, which may cause eyelids to twitch rapidly; eyes may jerk upwards or the patients head may rock back and forth slowly, as if nodding. The head may tonically draw to one or another side.
5. Absence with automatisms. Purposeful or quasi-purposeful movements occurring in the absence of awareness during an absence attack are frequent and may range from lip licking and swallowing to clothes fumbling or aimless walking. If spoken to, the patient may grunt, and when touched or tickled may rub the site. Automatisms are quite elaborate and may consist of combinations of the above described movements or may be so simple as to be missed by casual observation.
6. Absence with autonomic components. These may be pallor, and less frequently flushing, sweating, dilatation of pupils and incontinence of urine.

Mixed forms of absence frequently occur. These seizures can happen a few times a day or in some cases, hundreds of times a day, to the point that the person cannot concentrate in school or in other situations requiring sustained, concentrated attention.

Risk factors

Typical absences are easily induced by hyperventilation in more than 90% of people with typical absences. This is a reliable test for the diagnosis of absence seizures: a patient suspected of typical absences should be asked to hyperventilate for three minutes, counting breaths. During hyperventilation, the oxygen and carbon dioxide level will become abnormal. This results in weakening of electrical signal which leads to a reduction in the seizure threshold. Intermittent photic stimulation may precipitate or facilitate absence seizures; eyelid myoclonia is a common clinical feature.

A specific mechanism difference exists in absence seizures in that T-type Ca⁺⁺ channels are believed to be involved. Ethosuximide is specific for these channels and thus it is not effective for treating other types of seizures. Valproate and gabapentin (among others) have multiple mechanisms of action including blockade of T-type Ca⁺⁺ channels, and are useful in treating multiple seizure types. Gabapentin can aggravate absence seizures.

Pathophysiology

The corticothalamic cortical circuit plays an important role in the pathophysiology of absence seizure. Some of the neurons are important in their occurrence. They are

• Cortical glutamatergic neurons
• Thalamic relay neurons
• Neurons of thalamic nucleus reticularis

Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

Diagnosis

The primary diagnostic test for absence seizures is electroencephalography (EEG). However, brain scans such as by an MRI can help rule out other diseases, such as a stroke or a brain tumor.

During EEG, hyperventilation can be used to provoke these seizures. Ambulatory EEG monitoring over 24 hours can quantify the number of seizures per day and their most likely times of occurrence.

Absence seizures are brief (usually less than 20 seconds) generalized epileptic seizures of sudden onset and termination. When someone experiences an absence seizure they are often unaware of their episode. Those most susceptible to this are children, and the first episode usually occurs between 4–12 years old. It is very rare that someone older will experience their first absence seizure. Episodes of absence seizures can often be mistaken for inattentiveness when misdiagnosed, and can occur 50–100 times a day. They can be so difficult to detect that some people may go months or years before being given a proper diagnosis. There are no known before or after effects of absence seizures.

Absence seizures have two essential components:

• Clinical - the impairment of consciousness (absence)
• EEG - the EEG shows generalized spike-and-slow wave discharges

Absence seizures are broadly divided into typical and atypical types:

• Typical absence seizures usually occur in the context of idiopathic generalised epilepsies and an EEG shows fast >2.5 Hz generalised spike-wave discharges. The prefix "typical" is to differentiate them from atypical absences rather than to characterise them as "classical" or characteristic of any particular syndrome.
• Atypical absence seizures:
  • Occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties who also have frequent seizures of other types, such as atonic, tonic and myoclonic.
  • Have slower onset and termination and changes in tone are more pronounced.
  • Have particular ictal characteristics: EEG is of slow (less than 2.5 Hz) spike and slow wave. The discharge is heterogeneous, often asymmetrical and may include irregular spike and slow wave complexes, fast and other paroxysmal activity. Background interictal EEG is usually abnormal.

Syndromes

Absence seizure syndromes are childhood absence epilepsy, epilepsy with myoclonic absences, juvenile absence epilepsy and juvenile myoclonic epilepsy. Other proposed syndromes are Jeavons syndrome (eyelid myoclonia with absences), and genetic generalised epilepsy with phantom absences.

Absence seizures are also known to occur to patients with porphyria and can be triggered by stress or other porphyrin-inducing factors.

Treatment

Treatment of patients with absence seizures only is mainly with ethosuximide or valproic acid, which are of equal efficacy controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective, controlling absences in around 50% of patients. This summary has been recently confirmed by Glauser et al. (2010), who studied the effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug dosages were incrementally increased until the child was free of seizures, the maximal allowable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. There were no significant differences between the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide. If monotherapy fails or unacceptable adverse reactions appear, replacement of one by another of the three antiepileptic drugs is the alternative. Adding small doses of lamotrigine to sodium valproate may be the best combination in resistant cases.

Although ethosuximide is effective in treating only absence seizures, valproic acid is effective in treating multiple seizure types including tonic-clonic seizure and partial seizure, suggesting it is a better choice if a patient is exhibiting multiple types of seizures. Similarly, lamotrigine treats multiple seizure types including partial seizures and generalized seizures, therefore it is also an option for patients with multiple seizure types. Clonazepam (Klonopin, Rivotril) is effective in the short term but is not generally recommended for treatment of absence seizure because of the rapid development of tolerance and high frequency of side effects. If medication is not effective in treating absence seizures, surgical treatment such as deep brain stimulation can reduce seizure episodes.

Prevention

Medication alone cannot prevent absence seizure. It need to be supplemented by life-style changes such as exercise, stress reduction, good sleep hygiene, and healthy diet. Research shows that patient with ketogenic diet have 50% reduction in seizure episodes and 34% of patients become seizure free.

Medications that should not be used

Carbamazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence. In particular, the GABA agonists vigabatrin and tiagabine are used to induce, not to treat, absence seizures and absence status epilepticus. Similarly, oxcarbazepine, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures because these medications may worsen absence seizures.

Data limitations

In the treatment of absence seizures there is often insufficient evidence for which of the available medications has the best combination of safety and efficacy for a particular patient. Nor is it easily known how long a medication must be continued before an off-medication trial should be conducted to determine whether the patient has outgrown the absence seizures, as is often the case in children. To date there have been no published results of any large, double-blind, placebo-controlled studies comparing the efficacy and safety of these or any other medications for absence seizures. A 2019 Cochrane review found that ethosuximide was the best mono-therapy for children and adolescents but noted that if absence seizures co-exist with tonic-clonic seizures then valproate should be preferred.

Autism and working memory

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Autism_and_working_memory 

 

Typical classroom activity requires much polytropic processing of stimuli

 

A monotropic way of teaching can be greatly helpful for students with autism.

 

Monotropic and polytropic learning

Autism is a neurodevelopmental disorder diagnosed as impaired social interaction and communication, and by restricted and repetitive behavior. In this article, the word autism is used for referring to the whole range of conditions on the autism spectrum, which is not uncommon.

Working memory is the system that actively holds multiple pieces of transitory information in the mind, where they can be manipulated. This system has a limited capacity. Working memory is a part of the executive functions (EF), an umbrella term for cognitive processes that regulate, control, and manage other cognitive processes, for instance planning and attention.

Research connections

A majority of the research has found that individuals with autism perform poorly on measures of executive function. A general decrease in working memory (WM) is one of the limitations, although some studies have found that working memory is not impaired in autistic children relative to controls matched for IQ. However, some evidence suggests that there may be minimal impairment in high-functioning autistic (HFA) individuals in that they have intact associative learning ability, verbal working memory, and recognition memory. In rare cases there are even instances of individuals possessing extremely good memory in constricted domains which are typically characterized as savants. Bennetto, Pennington and Rogers also suggest that WM deficits and limited EF is likely compounded by the onset of autism where early development yields hindrances in social interaction which typically (i.e. without impairment) improves both WM and EF. However, due to limited ability in interpreting social gestures and an impaired ability to process such information in a holistic and comprehensive manner, individuals with autism are subject to diminished and confounding instances of memory function and performance.

Physiological underpinnings

The physical underpinnings of the cause for differences in the working memory of autistic people has been studied. Bachevalier suggests a major dysfunction in the brain of an autistic individual resides in the neural mechanisms of the structures in the medial temporal lobe (MTL) and perhaps, more specifically the amygdaloid complex. This may have implications in their ability to encode information because of the role the MTL and especially the hippocampal areas play in information processing DeLong reinforces this by suggesting autism to affect hippocampal function. Because the hippocampus is pivotal in memory encoding and modulating memory consolidation, any impairment can drastically affect an autistic individual's ability to process (i.e. multi-modal) and retain information. Sumiyoshi, Kawakubo, Suga, Sumiyoshi and Kasai have suggested that it is possible that the attenuated neural activities in parahippocampal regions might have something to do with the abnormal organization of information of individuals within the autistic spectrum. The left parahippocampal region (including the parahippocampal gyrus) has an implied role in sorting, relating, and sending information to the hippocampus and thus any abnormal activity or dysfunction within these regions might be accountable for the degree of effectiveness autistic individuals organize information. This is in keeping with other findings that suggest unconventional activity or lack of activity within the hippocampal regions which have a role in explaining some aspects of ASD.

Further evidence suggests that there is abnormal circuitry in what Brothers calls the neural basis for social intelligence, or holistically interpreting people's expressions and intentions. The interaction between the amygdala, the orbitofrontal cortex (OFC), and the superior temporal sulcus and gyrus (STG) enables one to process social information for personal interaction. In the case of autistic individuals there seems to be a limitation in these structures such that facial expressions, body language and speech expressions (ex. sarcasm) go consciously unnoticed, it is theorized that this could have something to do with the sagittal stratum, which is sometimes referred to as the "sarcasm center". However, Frith and Hill suggest that through 'remediation' or training that attends to specific traits in expressions, social understanding can be partially improved. The possibility of training in social understanding has given hope that there is a path that can be taken to reduce the social divide that is between children with autism and children who are neurotypical.

Characteristics

Global working memory characteristics

Beversdorf finds that because autistic individuals are not as reliant on contextual information (i.e. comparing typically related schemas) to aid in memory consolidation, they are less likely to rely on semantically similar cues (ex. Doctor-Nurse vs. Doctor-Beach). Thus, an autistic individual would fare well on discriminating and recalling accurate items from false items.

Bennetto, Pennington and Rogers investigated the degree of cognitive impairment in autistic individuals with an emphasis on illuminating the latency in executive functioning. Findings suggested a hindrance in temporal order, source, free recall and working memory. However, their participants did exhibit capable short and long-term memory, cued recall and the capacity to learn new material. In sum, they suggested that there is both a general deficit in global working memory and a specific impairment in social intelligence where the former is exacerbated by the latter and vice versa.

Other evidence points towards unique mnemonic strategies used by autistic individuals wherein they rely less on semantic associative networks and are less constricted by conventional word-word associations (ex. Orange-Apple). This may be due to abnormalities in MTL regions. Thus, autistic individuals may have the capacity for more abstract but robust associations. Firth addresses this with the term "weak Central Coherence", meaning a reduced tendency for processing information in context and integration of higher-level meaning. This may explain why autistic individuals have a heightened capacity for noticing seemingly disjointed details. For example, in the Embedded Figures Test (EFT) autistic individuals exhibited a faster and heightened ability to locate the target because of their diminished reliance on global perception. In a study conducted on autistic children, it was shown that neurocognition influences word learning in autistic children. The process of syntactic development requires a child to match co-occurrences of words or parts of words (morphemes) and their meanings. This process can depend on working memory. The limited short term verbal memory paired with working memory may be the reason of language delay in children with autism. According to the result of this experiment the group with autism was able to perform the part of the test with nonlinguistic cues which depended on working memory but failed to pass short-term memory and the linguistic part of it. This explains the delay of language in autistic children and neurocognition is an important contributor to it.

Central executive or executive functioning

The symptoms associated with autism spectrum disorders are thought to be greatly impacted by a dysfunction in working memory. In examining autism through the lens of Baddeley & Hitch's model of working memory there have been conflicting results in research. Some studies have shown that individuals that fall within the spectrum have impaired executive functioning which means working memory does not function correctly. However, other studies have failed to find an effect in autistic people with a high level of functioning. Tests such as the Wisconsin Card Sorting Test have been administered to autistic individuals and the lower scores have been interpreted as indicative of a poor ability to focus on relevant information and thus a deficit within the central executive aspect of working memory. An aspect of ASD is that it might be present, to a certain extent, in first degree relatives. One study found that siblings of autistic individuals have limited ability to focus and conceptualize categories using updated information. Given these results, it is reasonable to suggest that these so-called deficits in cognitive ability are of the cognitive endophenotypes (i.e. relatives) of ASD.

Category integration

Given these findings it would appear as if autistic individuals have trouble categorizing. Studies have shown that category induction is in fact possible and can occur at the same cognitive level as non-autistic individuals, however. Given that category formation aspects such as discrimination and feature detection are enhanced among autistic individuals it is viable to state that although autistic individuals require more trials and or time to learn material, and also may employ different learning strategies than non-autistic individuals, once learned, the level of categorization displayed is on par with a non-autistic individual.

The idea that autistic individuals learn differently than those without autism can account for the delay in their ability to categorize. However, once they begin categorizing they are at an average level of cognitive ability as compared to those without autism. This, however, is only applicable to higher functioning individuals within the spectrum as those with lower IQ levels are notoriously difficult to test and measure.

In part with a different style of learning, individuals within the spectrum have also been proposed to have a weak central coherence. This theory meshes well with the general traits of individuals within the spectrum. Again though, this is explained through different learning styles. As opposed to viewing a forest as a collection of trees, those with autism see one tree, and another tree, and another tree and thus it takes an immense amount of time to process complex tasks in comparison with non-autistic people. Weak central coherence can be used to explain what is viewed as a working memory deficit in attention or inhibition, as autistic individuals possess an intense focus on single parts of a complex, multi-part concept and cannot inhibit this in order to withdraw focus and direct it on the whole rather than a singular aspect. Thus, this suggests that the decrement in working memory is partially inherited which is then exacerbated by further genetic complications leading to a diagnosis of autism.

Visual and spatial memory

Deficits in spatial working memory appear to be familial in people with autism, and probably even in their close relatives. Replication of movements by others, a task that requires spatial awareness and memory capacities, can also be difficult for autistic children and adults.

People with Asperger's Syndrome were found to have spatial working memory deficits compared with control subjects on the Executive-Golf Task, although these may be indicative of a more general deficit in non-verbal intelligence in people with ASD. Despite these results, autistic children have been found to be superior to typically developing children in certain tasks, such as map learning and cued path recall regarding a navigated real-life labyrinth. Steele et al. attempt to explain this discrepancy by advancing the theory that the performance of autistic people on spatial memory tasks degrades faster in the face of increasing task difficulty, when compared with normally developed individuals. These results suggest that working memory is related with an individual's ability to solve problems, and that autism is a hindrance in this area.

Autistic people appear to have a local bias for visual information processing, that is, a preference for processing local features (details, parts) rather than global features (the whole). One explanation for this local bias is that people with autism do not have the normal global precedence when looking at objects and scenes. Alternatively, autism could bring about limitations in the complexity of information that can be manipulated in short-term visual memory during graphic planning.

The difficulties that individuals with ASD often have in regards to facial recognition has prompted further questions. Some research has shown that the fusiform gyrus in ASD individuals acts differently from in non-ASD individuals which may explain the aforementioned troubles regarding facial recognition.

Research by Baltruschat et al. has shown that improvement in spatial working memory for autistic individuals may be possible. Adapting a behaviorist approach by using positive reinforcement could increase WM efficiency in young children with ASD.

Auditory and phonological memory

The research on phonological working memory in autism is extensive and at times conflicting. Some research has found that, in comparison with spatial memory, verbal memory and inner speech use remain relatively spared, while other studies have found limitations on the use of inner speech by autistic people. Others have found a benefit to phonological processing in autism when compared with semantic processing, and attribute the results to a similar developmental abnormality to that in savant syndrome.

In particular, Whitehouse et al. have found that autistic children, when compared with typically developing (TD) children of a similar mean verbal age and reading ability, performed better when asked to recall a set of pictures presented to them, but not as well when asked to recall a set of printed words presented interspersed with the pictures; a competing verbal task given to both sets of participants also worsened performance on control children more than it did on autistic children. They also reported that word length effects were greater for the control group. These results are contested by Williams, Happé, and Jarrold, who contend that it may be verbal IQ, rather than verbal ability, that is at issue, and Whitehouse et al.'s subjects were not matched on chronological age. Williams, Happé, and Jarrold themselves found no difference between autistic children and controls on a serial recall task where phonological similarity effects, rather than word length effects, were used as an alternate measure of inner speech use.

Joseph et al. found that a self-ordered pointing task in autistic children involving stimuli that could be remembered as words (e.g. shovel, cat) was impaired relative to comparison children, but the same task with abstract stimuli was not impaired in autistic children. In contrast, Williams et al. found that autistic children scored significantly lower than TD children on spatial memory tests. Williams et al. not only experimented with spatial memory tasks, but verbal memory as well. They discovered that in an experimental group and a control group of TD individuals, that while differences were found in spatial memory ability, no significant difference was seen between the groups regarding verbal memory. They ran their experiments with both children and adult participants. Autism is a developmental disorder, so it is possible that life experiences could alter the memory performance in adults who had grown up with autism. Williams et al. experimented with children separately to see if they had different results from their adult counterparts. They used a WRAML (Wide Range Assessment of Memory and Learning) test, a test specifically designed to test memory in children. Test results were similar across all age groups, that significant differences between TD and autistic participants are found only in spatial memory, not verbal working memory.

Gabig et al. discovered that children with autism, regarding verbal working memory and story retelling, performed worse than a control group of TD children. In three separate tasks designed to test verbal working memory, the autistic children scored well below the expected levels for their age. While results do show lower scores for autistic children, there was also information that suggested lack of vocabulary contributed to the lower scores, rather than working memory itself.

There is some evidence from an fMRI study that autistic individuals are more likely to use visual cues rather than verbal cues on some working memory tasks, based on the differentially high activation of right parietal regions over left parietal regions in an N-back working memory task with letters.

Opposing results

Some data has shown that individuals with ASD may not have WM impairments and that this supposed impairment observed is a result of testing. Nakahachi et al. argue that the vagueness of many tests measuring WM levels in people with ASD. They found that people with ASD only performed worse on WM tests if the test itself could have interfered with the completion of the test. These findings show that the type of test and the way it is presented given to individuals with ASD can strongly affect the results, therefore much caution should be taken in choosing the design of a study focusing on WM in people with ASD.

Ozonoff et al. have found similar results in their studies on working memory in individuals with ASD. Their research showed no significant difference between individuals with ASD and those without ASD in tests designed to measure various aspects of working memory. This supports the notion that Autism does not inhibit WM. Results from experiments that have shown lower WM facilities in ASD individuals may be due to the human interaction nature of these experiments as individuals with ASD exhibit low social functioning skills. Experiments utilizing computer rather than human interaction remove this problem and may head more accurate findings.

Further research by Griffith et al. also indicates that WM may not be impaired in those with autism. There may be some executive function impairments in these individuals, but not in working memory and rather in social and language skills, which can effect education early in life. Other research conducted by Griffith et al. on young autistic individuals did not measure verbal working abilities, but nonetheless found no significant difference between the executive functions in autistic and non-autistic individuals. Though there has been much research that alludes to low WM abilities in those with autism, these recent data weaken the argument that autistic individuals have little WM facilities.

Nobel disease

From Wikipedia, the free encyclopedia

Nobel disease or Nobelitis is the embracing of strange or scientifically unsound ideas by some Nobel Prize winners, usually later in life. It has been argued that the effect results, in part, from a tendency for Nobel winners to feel empowered by the award to speak on topics outside their specific area of expertise, although it is unknown whether Nobel Prize winners are more prone to this tendency than other individuals. Paul Nurse, co-winner of the 2001 Nobel Prize in Physiology or Medicine, warned later laureates against "believing you are expert in almost everything, and being prepared to express opinions about most issues with great confidence, sheltering behind the authority that the Nobel Prize can give you". Nobel disease has been described as a tongue-in-cheek term.

Implications

While it remains unclear whether Nobel winners are statistically more prone to critical thinking errors than are other scientists, the phenomenon is of interest because it provides an existence proof that being an authority in one field does not necessarily make one an authority in any other field, and, to the extent that winning a Nobel Prize serves as a proxy indicator of scientific brilliance and high general intelligence, such characteristics are not incompatible with irrationality.

Nobel disease also serves to demonstrate that, for some prize winners, being universally hailed as right appears to bolster the individual laureate's confirmation bias more than it does their skepticism. Milton Friedman, winner of the Nobel Memorial Prize in Economic Sciences in 1976, said of the Nobel disease, as it relates to his economic thinking towards an "antidote", the following:

I myself have been asked my opinion on everything from a cure for the common cold to the market value of a letter signed by John F. Kennedy. Needless to say the attention [from receiving a Nobel prize] is flattering, but also corrupting. Somehow we badly need an antidote for both the inflated attention granted a Nobel laureate in areas outside his competence and the inflated ego each of us is in danger of acquiring. My own field suggests one obvious antidote: competition through the establishment of many more awards. But a product that has been so successful is not easy to replace. Hence, I suspect that our inflated egos are safe for a good long time to come.

Winners reported as examples

Charles Richet

Charles Richet won the 1913 Nobel Prize in Physiology or Medicine for his research on anaphylaxis. He also believed in extrasensory perception, paranormal activity, dowsing, and ghosts.

Linus Pauling

Linus Pauling won the 1954 Nobel Prize in Chemistry for his work on chemical bonds. A decade before winning the prize, he was diagnosed with Bright's disease which he treated in part by ingesting vitamin supplements, which he claimed dramatically improved his condition. He later espoused taking high doses of vitamin C to reduce the likelihood and severity of experiencing the common cold. Pauling himself consumed amounts of vitamin C on a daily basis that were more than 120 times the recommended daily intake. He further argued that megadoses of vitamin C have therapeutic value for treating schizophrenia and for prolonging cancer patients' lives. These claims are not supported by the best available science.

William Shockley

William Shockley, who won the 1956 Nobel Prize in Physics for his invention of the transistor, promoted racialism and eugenics.

James Watson

James Watson was awarded the 1962 Nobel Prize in Physiology or Medicine, together with Francis Crick and Maurice Wilkins, "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material". Since at least 2000, Watson has consistently and publicly claimed that black people are inherently less intelligent than white people, and that exposure to sunlight in tropical regions and higher levels of melanin cause dark-skinned people to have a higher sex drive.

Nikolaas Tinbergen

Nikolaas Tinbergen won the 1973 Nobel Prize in Physiology or Medicine for discoveries concerning the organization and elicitation of individual and social behavior patterns in animals. During his Nobel acceptance speech, Tinbergen promoted the widely discredited "refrigerator mother" hypothesis of the causation of autism, thereby setting a "nearly unbeatable record for shortest time between receiving the Nobel Prize and saying something really stupid about a field in which the recipient had little experience." In 1985, Tinbergen coauthored a book with his wife that recommended the use of "holding therapy" for autism, a form of treatment that is empirically unsupported and that can be physically dangerous.

Brian Josephson

Brian Josephson won the Nobel Prize in Physics in 1973 for his prediction of the Josephson effect. Josephson has promoted a number of scientifically unsupported or discredited beliefs, including the homeopathic notion that water can somehow "remember" the chemical properties of substances diluted within it, the view that transcendental meditation is helpful for bringing unconscious traumatic memories into conscious awareness, and the possibility that humans can communicate with each other by telepathy.

Kary Mullis

Kary Mullis won the 1993 Nobel Prize in Chemistry for development of the polymerase chain reaction. Mullis disagreed with the accepted, and scientifically verified, view that AIDS is caused by the HIV virus.

Luc Montagnier

Luc Montagnier co-discovered the HIV in 1981, for which he won the 2008 Nobel Prize in Physiology or Medicine. In 2009, in a non-peer-reviewed paper in a journal that he had founded, Montagnier claimed that solutions containing the DNA of pathogenic bacteria and viruses could emit low frequency radio waves that induce surrounding water molecules to become arranged into "nanostructures". He suggested water could retain such properties even after the original solutions were massively diluted, to the point where the original DNA had effectively vanished, and that water could retain the "memory" of substances with which it had been in contact – claims that place his work in close alignment with the pseudoscientific tenets of homeopathy. He further claimed that DNA sequence information could be 'teleported' to a separate test tube of purified water via these radio waves. He explained this in the framework of quantum field theory. He has supported the scientifically discredited view that vaccines cause autism and has claimed that antibiotics are of therapeutic value in the treatment of autism.

Conditions comorbid to autism spectrum disorders

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Conditions_comorbid_to_autism_spectrum_disorders 

Autism spectrum disorder (ASD) is a developmental disorder that begins in early childhood, persists throughout adulthood, and affects three crucial areas of development: communication, social interaction and restricted patterns of behavior. There are many conditions comorbid to autism spectrum disorder such as fragile X syndrome and epilepsy.

In medicine and in psychiatry, comorbidity is the presence of one or more additional conditions co-occurring with the primary one, or the effect of such additional disorders. About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome, and ASD is associated with several genetic disorders, perhaps due to an overlap in genetic causes.

Distinguishing between ASDs and other diagnoses can be challenging because the traits of ASDs often overlap with symptoms of other disorders and the characteristics of ASDs make traditional diagnostic procedures difficult.

Comorbid conditions

Anxiety

Anxiety disorders are common among children and adults with ASD. Symptoms are likely affected by age, level of cognitive functioning, degree of social impairment, and ASD-specific difficulties. Many anxiety disorders, such as social anxiety disorder and generalized anxiety disorder, are not commonly diagnosed in people with ASD because such symptoms are better explained by ASD itself, and it is often difficult to tell whether symptoms such as compulsive checking are part of ASD or a co-occurring anxiety problem. The prevalence of anxiety disorders in children with ASD has been reported to be anywhere between 11% and 84%; the wide range is likely due to differences in the ways the studies were conducted.

A systematic review summarized available evidence on interventions to reduce anxiety in school children with autism spectrum disorder. Of the 24 studies reviewed, 22 used a cognitive behavioral therapy (CBT) approach. The review found that CBT was moderately to highly effective at reducing anxiety in school children with autism spectrum disorder, but that effects varied depending on whether they were reported by clinicians, parents or self-reported. Treatments involving parents and one-on-one compared to group treatments were more effective.

Brain fog

Brain fog is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long-term memory. Brain fog can be present in patients with autism spectrum disorder (ASD). Its prevalence, however, remains unknown.

Bipolar disorder

Bipolar disorder, or manic-depression, is itself often claimed to be comorbid with a number of conditions, including autism. Autism includes some symptoms commonly found in mood and anxiety disorders.

Bowel disease

Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. The most common gastrointestinal symptoms reported by proprietary tool developed and administered by Mayer, Padua, & Tillisch (2014) are abdominal pain, constipation, diarrhea and bloating, reported in at least 25 percent of participants. Carbohydrate digestion and transport is impaired in individuals with autism spectrum disorder, which is thought to be attributed to functional disturbances that cause increased intestinal permeability, deficient enzyme activity of disaccharides, increased secretin-induced pancreatico-biliary secretion, and abnormal fecal flora Clostridia taxa. Altered gastrointestinal function accompanied by pain may induce feeding issues and increase perceived negative behaviors, including self injury, in individuals with autism.

Depression

Major depressive disorder has been shown by several studies to be one of the most common comorbid conditions in those with ASD, and is thought to develop and occur more in high-functioning individuals during adolescence, when the individual develops greater insight into their differences from others. In addition, the presentation of depression in ASDs can depend on the level of cognitive functioning in the individual, with lower functioning children displaying more behavioral issues and higher functioning children displaying more traditional depressive symptoms.

Developmental coordination disorder

The initial accounts of Asperger syndrome and other diagnostic schemes include descriptions of developmental coordination disorder. Children with ASD may be delayed in acquiring motor skills that require motor dexterity, such as bicycle riding or opening a jar, and may appear awkward or "uncomfortable in their own skin". They may be poorly coordinated, or have an odd or bouncy gait or posture, poor handwriting, other hand/dexterity impairments, or problems with visual-motor integration, visual-perceptual skills, and conceptual learning. They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder, balance, tandem gait, and finger-thumb apposition.

Epilepsy

ASD is also associated with epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder. One in four autistic children develops seizures, often starting either in early childhood or adolescence. Seizures, caused by abnormal electrical activity in the brain, can produce a temporary loss of consciousness (a "blackout"), a body convulsion, unusual movements, or staring spells. Sometimes a contributing factor is a lack of sleep or a high fever. An EEG can help confirm the seizure's presence. Typically, onset of epilepsy occurs before age five or during puberty, and is more common in females and individuals who also have a comorbid intellectual disability.

Fragile X syndrome

Fragile X syndrome is the most common inherited form of intellectual disability. It was so named because one part of the X chromosome has a defective piece that appears pinched and fragile when under a microscope. Fragile X syndrome affects about two to five percent of people with ASD. If one child has Fragile X, there is a 50% chance that boys born to the same parents will have Fragile X (see Mendelian genetics). Other members of the family who may be contemplating having a child may also wish to be checked for the syndrome.

Gender dysphoria

Main article: Autism and LGBT identities § Autism and gender identity

Gender dysphoria is a diagnosis given to transgender people who experience discomfort related to their gender identity. Autistic people are more likely to experience gender dysphoria. Around 20% of gender identity clinic-assessed individuals reported characteristics of ASD.

Hypermobility spectrum disorder and Ehlers–Danlos syndromes

Studies have confirmed a link between hereditary connective tissue disorders such as Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorder (HSD) with autism, as a comorbidity and a co-occurrence within the same families.

Abnormal folate metabolism

Several lines of evidence indicate abnormalities of folate metabolism in ASD. These abnormalities can lead to a decrease in 5-methyltetrahydrofolate production, alter the production of folate metabolites and reduce folate transport across the blood-brain barrier and in neurons. The most significant abnormalities of folate metabolism associated with ASDs may be autoantibodies to the alpha folate receptor (FRα). These autoantibodies have been associated with cerebral folate deficiency. Autoantibodies can bind to FRα and greatly impair its function.

In 2013, one study reported that 60% and 44% of 93 children with ASD were positive for FRα-blocking and binding autoantibodies, respectively. This high rate of anti-FRα autoantibody positivity was confirmed by Ramaekers et al. who compared 75 children with ASD to 30 non-autistic "controls". These controls were children who had a developmental delay, but did not have ASD. FRα-blocking autoantibodies were positive in 47% of children with ASD, but only in 3% of children without ASD.

Many children with ASD and cerebral folate deficiency have marked improvements in their clinical status when taking folinic acid.

A series of five children with cerebral folate deficiency and low functioning autism with neurological deficits found a complete reduction of ASD symptoms with the use of folinic acid in a child and substantial improvements in communication in two other children.

Abnormal redox metabolism

An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorders (ASD). Glutathione synthesis and intracellular redox balance are related to folate metabolism and methylation, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct endophenotype of TSA closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Glutathione is involved in neuroprotection against oxidative stress and neuroinflammation by improving the antioxidant stress system.

In autistic children, studies have shown that glutathione metabolism can be improved. - Subcutaneously by injection of methylcobalamin. - Oral folinic acid. - A vitamin and mineral supplement that includes antioxidants, coenzyme Q10 and vitamins B. - Tetrahydrobiopterin. Interestingly, recent DBPC studies have shown that N-acetyl-1-cysteine, a glutathione precursor supplement, is effective in improving the symptoms and behaviors associated with ASD. However, glutathione was not measured in these studies.

Small, medium and large DPBC trials and open small and medium-sized clinical trials demonstrate that new treatments for children with ASD for oxidative stress are associated with improvements in baseline symptoms of ASD, sleep, gastrointestinal symptoms, hyperactivity, seizures and parental impression, sensory and motor symptoms. These new treatments include N-acetyl-l-cysteine, methylcobalamin with and without oral folinic acid, vitamin C, and a vitamin and mineral supplement that includes antioxidants, enzyme Q10, and B vitamins.

Several other treatments that have antioxidant properties, including carnosine, have also been reported to significantly improve ASD behaviors, suggesting that treatment of oxidative stress could be beneficial for children with ASD. Many antioxidants can also help improve mitochondrial function, suggesting that clinical improvements with antioxidants could occur through a reduction in oxidative stress and / or an improvement in mitochondrial function.

Some of these treatments can have frequent serious side effects (bronchospasm, etc. ...).

Neurotransmitter anomalies

Mitochondrial diseases

The central player in bioenergetics is the mitochondrion. Mitochondria produce about 90% of cellular energy, regulate cellular redox status, produce ROS, maintain Ca2+ homeostasis, synthesize and degrade high-energy biochemical intermediates, and regulate cell death through activation of the mitochondrial permeability transition pore (mtPTP). When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole organ systems begin to fail.

Mitochondrial diseases are a heterogeneous group of disorders that can affect multiple organs with varying severity. Symptoms may be acute or chronic with intermittent decompensation. Neurological manifestations include encephalopathy, stroke, cognitive regression, seizures, cardiopathies (cardiac conduction defects, hypertensive heart disease, cardiomyopathy, etc...), diabetes, visual and hearing loss, organ failure, neuropathic pain and peripheral neuropathy.

The prevalence estimates of mitochondrial disease and dysfunction across studies ranging from about 5 to 80%. This may be, in part, due to the unclear distinction between mitochondrial disease and dysfunction. Mitochondrial diseases are difficult to diagnose and have become better known and detected. Studies indicating the highest rates of mitochondrial diagnosis are usually the most recent.^[32]

Some drugs are toxic to mitochondria. These can trigger or aggravate dysfunctions or mitochondrial diseases.

• Antiepileptics :

Valproic acid (also used in various other indications) and phenytoin are the most toxic. Phenobarbital, carbamazepine, oxcarbazepine, ethosuximide, zonisamide, topiramate, gabapentin and vigabatrin are also.

• Other types of drugs :

Corticosteroids (such as cortisone), isotretinoin (Accutane) and other vitamin A derivatives, barbiturates, certain antibiotics, propofol, volatile anesthetics, non-depolarizing muscle relaxants, some local anesthetics, statins, fibrates, glitazones, beta blockers, biguanides, amiodarone, some chemotherapies, some neuroleptics, nucleoside reverse transcriptase inhibitors and various other drugs.

Neurofibromatosis type I

ASD is also associated with Neurofibromatosis type I (NF-1). NF-1 is a complex multi-system human disorder caused by the mutation of a gene on chromosome 17 that is responsible for production of a protein, called neurofibromin 1, which is needed for normal function in many human cell types. NF-1 causes tumors along the nervous system which can grow anywhere on the body. NF-1 is one of the most common genetic disorders and is not limited to any person's race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion of one copy (or allele) of the NF-1 gene is sufficient for the development of NF-1, although presentation varies widely and is often different even between relatives affected by NF-1.

Neuroinflammation and immune disorders

The role of the immune system and neuroinflammation in the development of autism is controversial. Until recently, there was scant evidence supporting immune hypotheses, but research into the role of immune response and neuroinflammation may have important clinical and therapeutic implications. The exact role of heightened immune response in the central nervous system (CNS) of patients with autism is uncertain, but may be a primary factor in triggering and sustaining many of the comorbid conditions associated with autism. Recent studies indicate the presence of heightened neuroimmune activity in both the brain tissue and the cerebrospinal fluid of patients with autism, supporting the view that heightened immune response may be an essential factor in the onset of autistic symptoms. A 2013 review also found evidence of microglial activation and increased cytokine production in postmortem brain samples from people with autism.

Neuropathies

The prevalence of peripheral neuropathies would be significantly increased in ASD. Peripheral neuropathies may be asymptomatic. Peripheral neuropathy is a common manifestation of mitochondrial diseases and polyneuropathies would be relatively common. Neuropathies could also be caused by other features of ASD.

Nonverbal learning disorder

See also: Nonverbal learning disorder

Obsessive–compulsive disorder

Obsessive–compulsive disorder is characterized by recurrent obsessive thoughts or compulsive acts. About 30% of individuals with autism spectrum disorders also have OCD.

Obsessive–compulsive personality disorder

Obsessive–compulsive personality disorder (OCPD) is a cluster c personality disorder characterized by a general pattern of excessive concern with orderliness, perfectionism, attention to details, mental and interpersonal control and a need for control over one's environment which interferes with personal flexibility, openness to experience and efficiency as well as interfering with relationships.

There are considerable similarities and overlap between Autism and OCPD, such as list-making, inflexible adherence to rules and obsessive aspects of routines, though the latter may be distinguished from OCPD especially regarding affective behaviors, bad social skills, difficulties with theory of mind and intense intellectual interests e.g. an ability to recall every aspect of a hobby. A 2009 study involving adult autistic people found that 40% of those diagnosed with Autism met the diagnostic requirements for a co-morbid OCPD diagnosis.

Psychosis and schizophrenia

See also: Schizophrenia and comorbid conditions

Childhood-onset schizophrenia is preceded by childhood autistic spectrum disorders in almost half of cases, and an increasing number of similarities are being discovered between the two disorders.

Studies have also found that the presence of psychosis in adulthood is significantly higher in those with autism spectrum disorders, especially those with PDD-NOS, than in the general population. This psychosis generally occurs in an unusual way, with most individuals with ASD experiencing a highly atypical collection of symptoms. Recent studies have also found that the core ASD symptoms also generally present in a slightly different way during the childhood of the individuals that will later become psychotic, long before the actual psychosis develops.

Schizoid personality disorder

Schizoid personality disorder (SPD) is a personality disorder characterized by a lack of interest in social relationships, a tendency towards a solitary or sheltered lifestyle, secretiveness, emotional coldness, detachment and apathy. Other associated features include stilted speech, a lack of deriving enjoyment from most, if not all, activities, feeling as though one is an "observer" rather than a participant in life, an inability to tolerate emotional expectations of others, apparent indifference when praised or criticised, a degree of asexuality and idiosyncratic moral or political beliefs. Symptoms typically start in late childhood or adolescence.

Several studies have reported an overlap, confusion or comorbidity with the autism spectrum disorder Asperger syndrome. Asperger syndrome had traditionally been called "schizoid disorder of childhood", and Eugen Bleuler coined both the terms "autism" and "schizoid" to describe withdrawal to an internal fantasy, against which any influence from outside becomes an intolerable disturbance. In a 2012 study of a sample of 54 young adults with Asperger syndrome, it was found that 26% of them also met criteria for SPD, the highest comorbidity out of any personality disorder in the sample (the other comorbidities were 19% for obsessive–compulsive personality disorder, 13% for avoidant personality disorder and one female with schizotypal personality disorder). Additionally, twice as many men with Asperger syndrome met criteria for SPD than women. While 41% of the whole sample were unemployed with no occupation, this rose to 62% for the Asperger's and SPD comorbid group. Although the cause for this comorbidity is not yet certain, genetic evidence for a spectrum between cluster A personality disorders/schizophrenia and autism spectrum disorders has been found. Tantam suggested that Asperger syndrome may confer an increased risk of developing SPD.

In the same 2012 study, it was noted that the DSM may complicate diagnosis of SPD by requiring the exclusion of a pervasive developmental disorder (PDD) before establishing a diagnosis of SPD. The study found that social interaction, stereotyped behaviours and specific interests were more severe in the individuals with Asperger syndrome also fulfilling SPD criteria, against the notion that social interaction skills are unimpaired in SPD. The authors believe that substantial subgroup of people with autism spectrum disorder or PDD have clear "schizoid traits" and correspond largely to the "loners" in Lorna Wing's classification The autism spectrum (Lancet 1997), described by Sula Wolff.

Sensory problems

Further information: Sensory processing disorder

Unusual responses to sensory stimuli are more common and prominent in individuals with autism, and sensory abnormalities are commonly recognized as diagnostic criteria in autism spectrum disorder (ASD), as reported in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V); although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders. Sensory processing disorder is comorbid with ASD, with comorbidity rates of 42–88%. With or without meeting the standards of SPD; about 90% of ASD individuals have some type of atypical sensory experiences, described as both hyper- and hypo-reactivity. The prevalence of reported "unusual sensory behaviors" that effect functioning in everyday life is also higher; ranging from 45 to 95% depending on factors such as age, IQ and the control group used.

Several studies have reported associated motor problems that include poor muscle tone, poor motor planning, and toe walking; ASD is not associated with severe motor disturbances.

Many with ASD often find it uncomfortable to sit or stand in a way which neurotypical people will find ordinary, and may stand in an awkward position, such as with both feet together, supinating, sitting cross-legged or with one foot on top of the other or simply having an awkward gait. However, despite evidently occurring more often in people with ASD, all evidence is anecdotal and unresearched at this point. It has been observed by some psychologists that there is commonality to the way in which these 'awkward' positions may manifest.

Reduced NMDA‐receptor function

Reduced NMDA receptor function has been linked to reduced social interactions, locomotor hyperactivity, self-injury, pre-impulse inhibition (PPI) deficits, and sensory hypersensitivity, among others. Results suggest that NMDA dysregulation could contribute to core ASD symptoms.

Sleep disorders

Sleep disorders are commonly reported by parents of individuals with ASDs, including late sleep onset, early morning awakening, and poor sleep maintenance; sleep disturbances are present in 53–78% of individuals with ASD. Unlike general pediatric insomnia, which has its roots in behavior, sleep disorders in individuals with ASD are comorbid with other neurobiological, medical, and psychiatric issues.

If not addressed, severe sleep disorders can exacerbate ASD behaviors such as self-injury; however, there are no Food and Drug Administration-approved pharmacological treatments for pediatric insomnia at this time.

Studies have found abnormalities in the physiology of melatonin and circadian rhythm in people with autism spectrum disorders (ASD). These physiological abnormalities include lower concentrations of melatonin or melatonin metabolites in ASDs compared to controls. Some evidence suggests that melatonin supplements improve sleep patterns in children with autism but robust, high-quality studies are overall lacking.

Tinnitus

According to one study, 35% of people who are autistic would be affected by tinnitus, which is much higher than in the general population.

Tourette syndrome

The prevalence of Tourette syndrome among individuals who are autistic is estimated to be 6.5%, higher than the 2% to 3% prevalence for the general population. Several hypotheses for this association have been advanced, including common genetic factors and dopamine, glutamate or serotonin abnormalities.

Tuberous sclerosis

Tuberous sclerosis is a rare genetic disorder that causes benign tumors to grow in the brain as well as in other vital organs. It has a consistently strong association with the autism spectrum. One to four percent of autistic people also have tuberous sclerosis. Studies have reported that between 25% and 61% of individuals with tuberous sclerosis meet the diagnostic criteria for autism with an even higher proportion showing features of a broader pervasive developmental disorder.

Vitamin deficiencies

Vitamin deficiencies are more common in autism spectrum disorders than in the general population.

• Vitamin D : Vitamin D deficiency was concerned in a German study 78% of hospitalized autistic population. 52% of the entire ASD group in the study was severely deficient, which is much higher than in the general population. Other studies also show a higher rate of vitamin D deficiencies in ASDs.
• Vitamine B12 : The researchers found that, overall, B12 levels in the brain tissue of autistic children were three times lower than those of the brain tissue of children not affected by ASD. This lower-than-normal B12 profile persisted throughout life in the brain tissues of patients with autism. These deficiencies are not visible by conventional blood sampling. As for the classic deficiency of vitamin B12, it would affect up to 40% of the population, its prevalence has not yet been studied in autism spectrum disorders. Vitamin B12 deficiency is one of the most serious.
• Vitamin B9 (folic acid) : Studies have been conducted regarding folic acid supplementation in autism in children. "The results showed that folic acid supplementation significantly improved certain symptoms of autism such as sociability, verbal / preverbal cognitive language, receptive language, and emotional expression and communication. In addition, this treatment improved the concentrations of folic acid, homocysteine and redox metabolism of standardized glutathione."
• Vitamin A : Vitamin A can induce mitochondrial dysfunction. According to a non-specific study on ASD: "Vitamin A and its derivatives, retinoids, are micronutrients necessary for the human diet in order to maintain several cellular functions of human development in adulthood as well as during aging (...) Although it is either an essential micronutrient, used in clinical applications, vitamin A has several toxic effects on the redox environment and mitochondrial function. A decline in the quality of life and an increase in the mortality rate among users of vitamin A supplements have been reported. Although the exact mechanism by which vitamin A causes its deleterious effects is not yet clear (...) Vitamin A and its derivatives, retinoids , disrupt mitochondrial function by a mechanism that is not fully understood."
• Zinc : Zinc deficiency incidence rates in children aged 0 to 3, 4 to 9 and 10 to 15 years were estimated at 43.5%, 28.1% and 3.3% for boys and at 52.5%, 28.7% and 3.5% among girls.
• Magnesium : Incidence rates of magnesium deficiency in children aged 0 to 3, 4 to 9 and 10 to 15 years were estimated at 27%, 17.1% and 4.2% for boys and at 22.9%, 12.7% and 4.3% among girls.
• Calcium : Incidence rates of calcium deficiency in children aged 0 to 3, 4 to 9 years and 10 to 15 years were estimated at 10.4%, 6.1% and 0.4% for boys and at 3.4%, 1.7% and 0.9% among girls.

It has been found that special diets that are inappropriate for children with ASD usually result in excessive amounts of certain nutrients and persistent vitamin deficiencies.

Other mental disorders

Phobias and other psychopathological disorders have often been described along with ASD but this has not been assessed systematically.

Intellectual disability

The fraction of autistic individuals who also meet criteria for intellectual disability has been reported as anywhere from 25% to 70%. This wide variation illustrates the difficulty of assessing intelligence in austistic indificiuals. For example, a 2001 British study of 26 autistic children found about 30% with intelligence in the normal range (IQ above 70), 50% with a mild to moderate intellectual disability, and about 20% with a severe to profound intellectual disability (IQ below 35). For ASD other than autism the association is much weaker: the same study reported typical levels of intelligence in about 94% of 53 children with PDD-NOS. Estimates are that 40–69% of individuals with ASD have some degree of an intellectual disability, with females more likely to be in severe range of an intellectual disability. Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25–75% of individuals with an ASD also have some degree of learning disability, although the types of learning disability vary depending on the specific strengths and weaknesses of the individual.

A 2006 review questioned the common assumption that most children with autism have an intellectual disability. It is possible that the association between an intellectual disability and autism is not because they usually have common causes, but because the presence of both makes it more likely that both will be diagnosed.

The CDC states that based on information from 11 reporting states 46% of people with autism have above 85 IQ.

Attention-deficit hyperactivity disorder

Previously, the diagnosis manual DSM-IV did not allow the co-diagnosis of ASD and attention-deficit hyperactivity disorder (ADHD). However, following years of clinical research, the most recent publication (DSM-5) in 2013 removed this prohibition of co-morbidity. Thus, individuals with autism spectrum disorder may also have a diagnosis of ADHD, with the modifiers of inattentive, hyperactive, combined-type, or not otherwise specified. Clinically significant symptoms of these two conditions commonly co-occur, and children with both sets of symptoms may respond poorly to standard ADHD treatments. Individuals with autism spectrum disorder may benefit from additional types of medications.