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Autism Spectrum disorder

Autism spectrum disorder (ASD) is a spectrum of disorders representing a continuum of complex and multifactorial neurodevelopmental disabilities that occurs in infancy and toddler years. In 1908, Eugen Bleuler, a Swiss psychiatrist, coined the term “Autism”, which was derived from the Greek “autós”, meaning “self”. The term was used to demonstrate the phenomenon of withdrawal from reality in schizophrenia patients.  Later, in 1943, the term “Autism” was redefined by physician psychiatrist Leo Kanner to be used to describe symptoms of social isolation and linguistic disorders in children without schizophrenia or any other known psychiatric disorders.  Its prevalence has been increasing over the past two decades.  ASD is typically characterized by social-communication deficit and the presence of restricted interests along with an exhibition of repetitive and stereotyped behaviors. The disorder is affected by both genetic and environmental factors. In the 5th Edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a concept of “spectrum” ASD and its mode of diagnosis was developed. The DSM-5 combines disorders namely autistic disorder (AD), Asperger’s syndrome (AS), childhood disintegrative disorder (CDD) as well as pervasive developmental disorder-not otherwise specified (PDD-NOS) disorder from the previous edition (DSM-IV) into one general disorder ( excluding Rett syndrome). Subsequently, according to the DSM-5, the term “pervasive developmental disorder” was replaced by “autism spectrum disorder”.

 

The proposed DSM-5 autism spectrum disorder criteria provide for three severity classifications: Level 1 (“Requiring support”), Level 2 (“Requiring substantial support”), and Level 3 (“Requiring very substantial support”) based on which patients are evaluated.  Almost 75% of ASD patients suffer from comorbid psychiatric conditions, which mostly consist of attention-deficit hyperactivity disorder (ADHD), bipolar disorder, anxiety, depression, Tourette syndrome, and others.  Further, other illnesses including epilepsy, gastrointestinal symptoms, sleep problems, depression, anxiety disorders, mood disorders, aggressive and self-injurious behaviors, feeding problems, and toileting problems are additional comorbid conditions in individuals with ASD. In addition, many genetic disorders are also comorbid with ASD such as fragile X syndrome or Down’s syndrome are associated with ASD. The Autism and Developmental Disabilities Monitoring (ADDM) and CDC reported that in 2018, every 1 in 44 children have been diagnosed with ASD.


In India, although a lack of epidemiological homogenous data exists, some studies gave a rough figure. A study from a rural setup showed a pooled prevalence of 0.11% in children between 1 and 18 years; and, four studies conducted in the urban setting showed a pooled prevalence of 0.09 % in children aged between 0 and 15 years. A systematic review showed a lower prevalence of autism at 14.8 per 10,000 in Asia in comparison to the prevalence worldwide. Whereas, in India, specifically, the outcome from a nationwide prevalence study by INCLEN trust estimated that there are approximately 2 million children (age group of 2–9 years) who are suffering from autism.

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Symptoms

According to Kanner, the disease continuum includes typically the preservation of sameness, a monotonous repetition of verbal and motor behavior, inappropriate giggling, a fascination for objects, and mutism or language that did not seem intended to serve the purpose of interpersonal communication. The congenital abnormalities, lack of intellectual disabilities, and wide scatter of cognitive as well as motor abilities are characteristics of ASD.  Specifically, children diagnosed with these disorders typically exhibit broadly three domains involving:

  • lack of social interaction 

  • lack of communication 

  • the presence of repetitive/restricted behaviors 

 

The detailed symptoms include marked impairment in maintaining eye-to-eye gaze, facial expression, and body postures (non-verbal behavior). Based on DSM-5 diagnostic revised criteria, a patient diagnosed with the autistic disorder would have exhibited at least six of twelve deficits in social interaction, communication, or repetitive behaviors.  However, there could be heterogeneity in the degree of symptom severity across different disorders.

Diagnosis

As there is no laboratory-based test to detect ASD, it is one of the challenging tasks for clinicians to diagnose with the major tool being observing a child’s behavior and personal development. The early diagnosis of ASD needs to be as precise as possible to determine the right course of clinical management. The main features considered by clinicians to gauge the development of ASD in children in their early developmental stage consist of a) spoken language, b) social interaction and relationships, c) stereotyped behavior and activities, d) motor skills, and e) regulation. Reports showed that infants between 2 and 6 months may be at the onset of the disease based on early signs of aberrant behavior like the decline in social interactions, as well as alterations in sleep, feeding, and temperament. All of the foregoing may occur during the first twelve months in children at risk for ASD. Typically, the onset of symptoms is characterized by the reduction in discerning language and social interaction around 16–20 months or even occasionally by a delay of psychomotor expressions. Moreover, the presence of medical comorbidities like early-onset epilepsy, genetic/other medical conditions, and idiopathic diseases (ID) is frequently associated with ASD. If warranted by professionals, the child is evaluated using specific tests like 

  • childhood autism rating scale (CARS)

  • autism diagnostic observation schedule (ADOS) 

  • the developmental, dimensional, and diagnostic interview

  • The Autism Spectrum Disorder-Observation for Children (ASD-OC) 

  • The Autism Diagnostic Interview-Revised (ADI-R) 

  • The Asperger Syndrome (and high-functioning autism) Diagnostic Interview (ASDI) Diagnostic Interview for Social and Communication Disorders (DISCO) 

  • Autism Spectrum Disorder–Diagnosis Scale for Intellectually Disabled Adults (ASD-DA)

Management

Effective reversal of core autistic symptoms is not achieved by any drug to date. There are both pharmacological and non-pharmacological interventions, which are available for ASD.  The pharmacological interventions are psychostimulants, atypical antipsychotics, antidepressants, and α-2 adrenergic receptor agonists, hormonal therapies with oxytocin or vasopressin receptor antagonists, and cell-based therapy using hematopoietic as well as mesenchymal stem cells in ASD children improving some ASD symptoms. Antipsychotics, serotonin reuptake inhibitors, tricyclic anti-depressants, anticonvulsants, glutamate antagonists, acetylcholinesterase inhibitors, psychostimulants, adrenergic α2 receptor agonists, as well as opiate antagonists are other major pharmacological interventions for symptomatic relief. 

Currently, there is no approved drug to cure ASD. Dietary supplements are used regularly as non-pharmacological options for ASD. Vitamin B6, vitamin B12, vitamin D, and folic acid are used as supplements to alleviate health conditions in ASD patients. In addition, other dietary supplements like omega-3 polyunsaturated fatty acids (PUFAs), probiotics, and some phytochemicals like luteolin and sulforaphane as well as a casein-free diet have been beneficial to symptoms associated with ASD along with behavioral therapy, speech therapy, and care. In addition, some promising emerging interventions in the field of ASD management are transcranial magnetic stimulation (TMS), gut microbiota-based interventional therapy, and pivotal response treatment or PRT.

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