Autistic Disorder

Autistic Disorder (ASD), also known as Autism or Autism spectrum disorder, is defined as a particular neurodevelopmental disorder which causes impaired social interaction and communication, in a clinical profile characterized by repetitive behaviors and uneven intellectual development resulting in intellectual disability. The disorder usually appears in early childhood.

The disease is related to the following processes:  mental, congenital and has an incidence of about  2 / 100.000.

Overview

The main symptoms of ASD includes abnormal development which starts in early childhood but gradually becomes manifest only in later stages of life. The patient usually presents a clear history of impaired speech and language delay, which develops into final loss of acquired language skills [1]. ASD has different levels of severity. Epilepsy is seen is about 20-30% of the cases, while intellectual disability in 50%. In contrast to this, some patients might develop increased ability on an average level or even above it. Cognitive profile is uneven, with people showing some time cognitive strengths and some other times cognitive weakness. These core symptoms as usually combined with other coexisting conditions such as difficulty in sleeping or other mental disorders, that are frequently more difficult to manage that ASD itself [2].

Etiology

The etiology of ASD is still unclear. However, exerts have underlined the influence of a series of environmental, biological, and genetic factors. Among these, genetic factors appear to play a very important role [3], as indicated by the appearance of ASD in people with siblings and parents affected by the same condition or in those affected by genetic and chromosomal disorders such as fragile X syndrome. In any case, the weight of environmental and biological factors should not be underestimated. For instance, ASD is often reported in the children of women taking particular drugs such as valproic acid and thalidomide. Furthermore, many data suggest the existence of a critical period for the development of ASD, which can be placed immediately before, during, and after the birth of affected people [4], and a connection between ASD itself and the age of the parents of the children affected [5].

Epidemiology

According to the data collected from 11 communities being monitored by the US Center for Disease Control and Prevention (CDC), ASD and its related disorders appears to affect 14.7 in 1,000 children aged 8 years (1 in 68 people). The prevalence data coming from these communities are characterized by a marked level of variability, with a value ranging from 5.7 to 22.9 every 1,000 children aged 8 years.

Sex distribution
Age distribution

Pathophysiology

Neuronal anomalies
With the help of neuroanatomic and neuroimaging studies, it is possible to observe the presence of several abnormalities in the cellular configurations in some areas of the brain, especially the frontal and temporal lobes and the cerebellum. For instance, typical are the enlargements in the amygdale and hippocampus, combined with an abnormally high quantity of neurons in several divisions of the prefrontal cortex [6]. Furthermore, several differences in the neuroanatomy and connectivity have been underlined with the help of MRI studies. Connectivity is typically reduced or in any case atypical in the frontal brain regions, and the corpus callosum is much thinner. Interestingly enough, the severity of the symptoms appear to be correlated with regional neuroanatomic differences, like the dysfunction of frontal and temporal lobes associated with marked social and language deficits.

Many data also underline the presence of focal disruptions in the cortical architecture of the brain cortex. These irregularities occur in patches spread on the lobes and in the regions connected with social, emotional, communication, and language functions. The fact that these irregularities appear in patches has led experts to believe that ASD can be stopped, and the brain revived, if the disorder is diagnosed in time.

At a cellular level, these brain irregularities are connected with an increased level of myelination in the bilateral medial frontal cortices and a decreased one in the left temporoparietal junction. The grey matter too, the layer of the brain made of cell bodies, unmyelinated axons, dendrites, and glial cells, is severely affected, as shown by specific differences in its concentration observed in several regions of the brain. Furthermore, it is also possible to observe a marked reduction in the expression of the gamma- aminobutyric acid–B (GABAB) receptors. This occurs in the cingulated cortex, which plays a pivotal role in the evaluation of social relations, emotions, and cognitions, and fusiform gyrus, connected with the evaluation of faces and facial expressions.

Metabolic anomalies
According to experimental data, there is an association with the abnormalities in affiliate behaviors and the dysfunction of serotonin and the neuropeptides oxytocin and vasopressin, which can be also found in one third of the people affected by ASD, as well as their parents and siblings. Furthermore, it is possible to detect frequent functional anomalies also in other neurotransmitters such as acetylcholine and glutamate, or the connection between behavioral disorders and the reduced levels of biotinidase, an enzyme required to recycle the B vitamin biotin.

People affected by ASD frequently report a certain susceptibility to infection. This tendency can be explained with the recently detected decreased plasma concentration of the complement protein C4B. Furthermore, it has also been revealed a certain correlation between ASD and diet, as in those patients showing impaired metabolism for phenolic amines. Following this line, it is reasonable to believe that ASD symptoms might be aggravated by the consumption of certain foods, like dairy products, sugar, corn, chocolate, and bananas, and that gluten- and casein-free diets might help relieve the clinical profile. However, although very interesting, this association has not been confirmed by large population studies yet.

The pathogenesis and pathophysiology of ASD also appear to be correlated with oxidative stress, as suggested by a series of decrements found in the patients like reduced levels of cysteine, glutathione, and methionine, the reduced ratio of S -adenosyl-L-methionine (SAM) to S -adenosyl-L-homocysteine (SAH), and reduced ratio of glutathione. Along this line is also the presence of hyperlacticacidemia associated with mitochondrial disorders such as carnitine deficiency, which reflects a disturbed neuronal energy metabolism.

Prognosis

The prognosis of the people affected by ASD is dependent on their IQ. Worse cases need home or residential care for all their life, while the best ones might conduct a relatively normal life, holding jobs, taking responsibilities, and even marrying and having children. Furthermore, several comorbid disorders have been detected, like gastrointestinal pathological conditions whose risk appears to increase with the severity of ASD itself [7].

Presentation

As indicated before, ASD usually appears very early in life, within the first 3 or 4 years. The symptoms indicated below characterize this disorder:

  • Atypical social interaction patters (inability to cuddle and form reciprocal relationships, lack of any kind of attachment, or tendency to avoid eye gaze) [8])
  • Sameness (resistance to any kind of change, ritual performance, abnormal attachment to object that they consider familiar, repetitive behaviors in stereotyped patterns)
  • Unstable intellectual abilities
  • Tendency to injure oneself
  • Frequent loss of previously acquired skills (around 25% of the children have been reported with having lost previously acquired skills).

Another typical sign is the inability to imagine other people thoughts. This can play a pivotal role in the development of ASD, as it might directly lead to abnormal language development. Related to this is the inability of the 1 year old children to point at objects for communicative reasons, which can be explained with the incapability of the patients to realize that the persons addressed might understand what is being indicated. The child finds itself completely unable to point, and tends to indicate only by physically touching the objects using the hand of the adult as pointing tool.

Other typical signs of ASD include mild blindness and nonfocal neurologic findings, like poorly coordinated gait and stereotyped motor movements, and seizure which appears in 20-40% of the cases and especially those with IQ lower than 50.

Workup

Managing the diagnostic tools and tests necessary to detect ASD is not an easy task and might require several years of experience and extensive training. Therefore, clinicians are strongly advised to send the affected children to specialists if they do not have the necessary expertise.

Metabolic Studies
Since several metabolic disturbances have been associated with ASD, they can be used as useful clues to diagnose ASD. However, there is no specific biological marker to indicate, and blood studies cannot be considered as definitive positive response for the diagnosis of ASD.

Neuroimaging Studies
Having underlined the presence of many abnormalities in the brain, neuroimaging studies have turned out to be very useful for research. However, because of the inconsistency of their results, these cannot be used as routine diagnostic tools [9].

Electroencephalography
Electroencephalography is generally used to rule out the presence of other related disorder, such as seizure, acquired aphasia with convulsive disorder, or biotin-responsive infantile encephalopathy.

Psychophysiologic assessment
Since other methodologies have turned out to be unreliable, psychophysiologic assessment is the only available methodology which can be used as effective diagnostic tool. While children affected by ASD might frequently show auditory over selectivity, they do not tend to show typical signs which characterize childhood, like response habituation in respiratory period, electrodermal activity, and vasoconstrictive peripheral pulse amplitude response to repeatedly presented stimuli.

Polysomnography
Polysomnography is very useful in detecting treatable comorbid disorders, such as sleep disturbances including early morning awakening and fragmented sleep [10].

Treatment

The mainstays in the treatment of ASD include:

  • Behavioral therapy
  • Physical and occupational therapy (if needed)
  • Pharmaceutical therapy
  • Therapy to cope with speech and language difficultie

The treatment of ASD is undoubtedly multidisciplinary and is frequently based on approaches which are aimed at encouraging social interaction and communication in different social settings, especially at home and at school.
It is important that speech and language therapy is started very early using different tools which include signing, picture exchange [11], and communication devices like those based on the use of devices showing symbols selected by the children themselves. If children show physical and motor problems, this should be compensated with specifically planed motor therapies.

It seems that atypical antipsychotic drug might have a positive effect for relieving behavioral problems, like the ritualistic and self-injurious patters, aggressive behavior, impulsivity, and hyperactivity. As to dietary interventions, they do not appear to be effective at the current stage of our knowledge, and their use is not officially recommended.

Prevention

Since the disorder appears to be substantially genetic, no particular measure can be suggested to effectively prevent it. It is worth noting though that it has been found a certain correlation between thimerosal-containing vaccines or the measles-mumps-rubella (MMR) vaccine and the development of ASD. However, evidence supporting this correlation is inconclusive [12].

Patient Information

Autistic disorder (commonly known as autism) is a typical neurological and developmental disorder which usually starts during the first three years of life. The main clinical feature is the tendency of the children to close themselves to the rest of the world, showing little or no interest in others and having no awareness to social relationships and connections. This sign is usually followed by the tendency of repeating odd and peculiar behaviors which frequently consist in personal rites.

Causes
The cause of autistic disorder is still unknown. However, experts believe that autism might have a substantial genetic origin, as suggested by a variety of abnormalities found in the brain of people affected. It is not possible to exclude the possibility that autistic disorder is a behavioral syndrome.

Symptoms
Although with a certain degree of variability associated with each particular case, the typical symptoms of autism include:

  • Low level of interaction with other people, including parents;
  • Avoiding eye contact;
  • Incapacity to make friends;
  • Lack of interest or rejection of physical contact. This is the reason why children affected by autism are frequently described by their parents as unaffectionate;
  • Delayed speech/language development;
  • Low level of communication with others;
  • Repetitive behavior;
  • Echolalia (tendency to repeat the same words and phrases);
  • Irritability;
  • Repetitive motor movements;
  • Tendency to injure themselves.

Diagnosis
It is important to diagnose autism very early to avoid further complications and try to stop the progress of the disorder in time. This can be done with appropriately organized screening and testing campaigns.

Treatment
The mainstay in the treatment of autism is represented by behavioral and educational programs, which are aimed at improving the social interactions and the communication skills. These programs can be implemented in different settings, especially at home and at school. Drugs might be used as well, although their efficacy still remains limited and not properly defined.

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References

  1. Rogers SJ. Developmental regression in autistic spectrum disorders. Ment Retard Dev Disabil Res Rev. 2004; 10:139-143.
  2. Maskey M, Warnell F, Parr JR, et al. Emotional and behavioural problems in children with autism spectrum disorder. J Autism Dev Disord. 2013; 43:851-859.
  3. Huquet G, Ey E, Bourgeron T. The genetic landscapes of autism spectrum disorders. Annu Re Genomics Hum Genet. 2013; 14:191-213.
  4. Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics. 2011; 128(2):344-355.
  5. Durkin MS, Maenner MJ, Newschaffer CJ, et al. Advanced parental age and the risk of autism spectrum disorder. Am J Epidemiol. 2008; 168(11): 1268-1276.
  6. Courchesne E, Mouton PR, Calhoun ME, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011 Nov 9; 306(18):2001-10.
  7. Wang LW, Tancredi DJ, Thomas DW. The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr. 2011 Jun; 32(5):351-60.
  8. Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994 Oct; 24(5):659-85.
  9. Filipek PA, Accardo PJ, Ashwal S, et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology 2000 Aug; 55(4):468-79.
  10. Sahota PK, Miles JH, Wang CH. Sleep disorders in children with autism. Neurology. 1997; 48 (3):A258
  11. Dawson G, Rogers S, Munson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. 2010 Jan; 125(1):e17-23.
  12. Demicheli V, Rivetti A, Debalini MG, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2012; (2):CD004407.

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  • A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder - WK Goodman, ST Naylor, FR Volkmar - Am J Psychiatry, 1995 - AADPRT
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