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EDITORIAL Table of Contents  
Ahead of print publication
Dr DS Raju oration award-andhra pradesh psychiatry conference 2021-2022


 Associate Professor, Department of Psychiatry, Alluri Sitarama Raju Academy of Medical Sciences, Eluru, Andhra Pradesh, India

Click here for correspondence address and email

Date of Submission20-Apr-2022
Date of Acceptance27-Apr-2022
Date of Web Publication20-Jun-2022
 


How to cite this URL:
RamanaRao GV. Dr DS Raju oration award-andhra pradesh psychiatry conference 2021-2022. Arch Ment Health [Epub ahead of print] [cited 2022 Jun 26]. Available from: https://www.amhonline.org/preprintarticle.asp?id=347820





  Introduction Top


The theme of my presentation is updating various developments that took place over time, particularly in the past 3–4 decades, which parallel my clinical practice as a psychiatrist. I would like to discuss how the etiology changed from psychological perspective to neurodevelopmental perspective, particularly the role of genetics, epigenetics, and the environmental factors. The reasons are probed for the sudden surge in the prevalence rates of autism. Newer developments in the assessment, diagnosis, and management of autism spectrum disorder (ASD) are discussed. An attempt is made to update the role of government in our country in enacting laws to provide the social benefits for persons with ASD. There is a sea change in the overall landscape of autism over the past 3–4 decades which posed several challenges. As mental health professionals, it is our duty to convert these challenges into opportunities along with other stakeholders.

Autism is a neurodevelopmental disorder manifesting with behavioral symptoms in childhood and persists throughout the lifespan of an individual. Leo Kanner, an American child psychiatrist, published a study of 11 children with “autistic disturbances of affect contact” in 1943. He attributed the child psychopathology to the parenting style, which he called as “Refrigerator Parenting.” Autism is characterized by social communication deficits with restricted repetitive behaviors, activities, and interests.

Autism is viewed broadly in neurodiversity and disability perspectives. People who believe in neurodiversity perspective are those who fall in the high functioning part of the spectrum and can be considered atypical in their communication, sensory perceptions, and behaviors. However, they claim that they think like others. “Little Professor Syndrome” is a fancy tag attached to such individuals with splinter skills such as extraordinary memory for dates and events. However, the vast majority of individuals with autism have social communication deficits and because of their intellectual deficiency, they can be potentially exploited. Their uneven intelligence with islands of brilliance amidst a vast sea of deprivation earns them the name “Idiot Savant Syndrome.” Most of them require lifelong support for living.

Changing prevalence rates

The prevalence rates started increasing steadily from 1960s to 1990s. In the 90s, the rate is 1 in 10,000 populations. It rose up to 1 in 1000 in 1980s. It was reported as 1 in 54 among 8-year-old children in 2010 Centers for Disease Control.[1] The reasons for sudden surge in the prevalence rates are several. Prominent among them are (1) increased assessment opportunities, (2) better awareness among parents and the doctors with an increase in request for service, (3) change in diagnostic criteria, and (4) diagnostic substitution: intellectual disability cases are being diagnosed as ASD due to change of diagnostic criteria.

Global burden of autism

Globally, autistic disorders accounted for more than 58 disability-adjusted life years/100,000 population. ASD accounts for substantial health loss across the life span. These facts are useful to inform public health policy-makers to plan for education, housing, and financial support (Baxter and Brugha 2015).[2]


  Changes in Classificatory Systems Top


There is a paradigm shift in the classificatory systems of neurodevelopmental disorders in Diagnostic and Statistical Manual of Mental Disorders 5th Edition and International Classification of Diseases, 11th Edition from categorical approach to dimensional approach. The umbrella term ASD was introduced, and other medical conditions were brought into the spectrum. They have an identifiable specific cause. They constitute 15% of ASD. The remaining 85% are constituted by idiopathic autism (National Institute of Health 2019).[3]


  Etiology of Autism Top


The genetic and environmental risk factors interplay with each other through epigenetic dysregulation to cause phenotype in the proband. However, the majority of other contributory factors are yet to be discovered.


  Genetic Factors Top


Autism is considered to be the highest heritable psychiatric disorder. Concordance rates for monozygotic twins are between 70% and 90% and dizygotic twins are between 0% and 30%. Family studies have supported the notion of familial aggregation of autism and of its broader phenotype.[4] Because the MZ concordance rate is <100%, nongenetic factors also play a role. Population studies supported strong heritability (40%–87%) with a modest shared environment component (0%–32%).[5]

General risk to siblings is 3%–10% and 7% if the proband is a female and 4% if he is a male. If two or more children are affected, the risk shoots up to 33%. It is 1% in the case of de novo genetic variants. If it is due to autosomal recessive inheritance, it will be 25%.

However, genetic causes can be attributed to only 10%–20% of all cases[6] or up to 40%.[7] Single gene accounts for 1% of cases such as fragile X syndrome and tuberous sclerosis. Gene linkage analysis has demonstrated that the regions of chromosomes 7, 2, 4, 15, 16, and 19 are likely to contribute genetic basis of autism. Rare genetic variants such as de novo mutations (variants that are detected for the first time in the proband are not present in the parental genome) are found to be increased in ASD in several studies. Mosaic mutations which arise in the zygote after conception affect only fewer cells and hence contribute to autism traits only instead of disorder.


  Consanguinity and Autism Top


It was estimated that 10% of the global population marry blood relatives. This practice is prevalent in South-East Asia, particularly South India. In Middle East Countries, consanguineous marriages are as high as 30%–50%, particularly among the rural and tribal populations. In consanguineous marriages, autosomal recessive genes from both parents contribute to genetic vulnerability for autism. The study of rare variants led to the study of families that are genetically isolated with shared ancestry. Usually, they are prone to consanguineous marriages.[8]


  Epigenetics Top


Epigenetic mechanisms modify gene expressions through DNA methylation, chromatin remodeling, etc. Moreover, they play a significant role in ASD etiology in combining genetic and environmental factors that regulate neurodevelopmental processes.

Genetic testing

With the advent of the Human Genome Project in 2003, the speed of research in genetics has picked up, and several tests are currently available to test persons with ASD and their families. Microarray techniques are available where gene chips or DNA chips are used to detect gene expression. They are known as transcriptomes or the set of mRNA transcripts. In whole-exome sequencing, the variants within the genome which codes for the proteins (exons) or flanks of the region which code for proteins (splice junctions). Whole-genome sequencing is the comprehensive method of analyzing the entire genome.

Genetic counseling

While interpreting genetic tests and counseling the parents, it should be individualized, participatory, and nondirective in nature. Parents should be explained the role of genetic factors along with the environmental factors. The general risk of recurrence for sibling is 5%–10%. The relevance of variant of uncertain significance (VUS) should be explained to the family members. If necessary, the parents and siblings should be tested for Sanger sequencing. If the particular VUS also exists in other family members, it carries no significance.


  Neural Basis of Autism Top


Familial and de novo variants constitute genetic load and when this is influenced by environmental factors through epigenetic mechanisms, there will be alterations in the neurodevelopmental pathways. Prominent among them is the mammalian target of rapamycin and FXMR pathways. Multiple abnormal genes act through these common pathways leading to abnormal brain development and produce an autism phenotype in the proband. It was observed that there is malfunctioning of neural migration resulting in large head size. Several areas in the brain relating to social emotional learning such as orbitofrontal and medial prefrontal cortex and superior temporal gyrus are dysfunctional in functional magnetic resonance imaging studies. Fusiform nucleus which is involved in facial recognition is also found to be under-functioning.

The finding of the excess density of dendrites of Purkinje fibers in the cerebellum is due to their compensatory hypertrophy in the absence of axonal growth deficits in ASD. Clinical genetic tests are available to test PTEN and SHANK-3 genes which regulate these mechanisms. Dysregulation of global gene expression in the central nervous system (CNS) is the another hallmark of ASD.

Variations and mutations of genes coding ion channels (Na+, K+, Cl, and Ca++ channels) are the leading risk factors for ASD. These findings have implications for the development of pharmacological treatments for autism.


  Environmental Problems Top


They could be causal if it is harmful and precedes ASD, mediating if it influences the causal chain between a genetic predisposition and ASD, moderating if it impacts the severity of autism, and protective if it decreases the risk of ASD. The possible mechanisms of how the environmental factors influence the CNS include neuroinflammation, immune activation, oxidative stress, hypoxia, and endocrine disruptions.

Fetal environment

High fetal exposure to testosterone may contribute to ASD risk. There is evidence that SNPS (ESR2, CYP 11B1, CYP 17A1, and CYP 19A1) in sex-steroid synthesis genes were associated with autism. PCOD mothers are at increased risk in the offspring.

Autism and viral infections

Rubella, cytomegalovirus, Zika virus, influenza, and SARS-COV-2 viruses are implicated. The viruses can have direct teratogenic effects and indirect effects of maternal immune activation on the developing brain. However, there are mixed reports regarding the role of viruses in the causation of ASD.

Advanced paternal age and autism risk

Advanced paternal age is associated with an increased risk for ASD. With every year, older the risk increases by two de novo mutations per year. The risk starts to increase at the paternal age of 30 years, plateaued after the age of 40 years, and further increases from the age of 50 years and higher.[9]

Medication

Autism risk was amplified in mothers using valproic acid during pregnancy.[10] There exists a significant positive association between SSRI exposure and ASD consistency across all trimesters.[11]

Smoking and alcohol

Heavy drinking can cause fetal alcohol syndrome. Mild-to-moderate alcohol consumption poses no risk for autism.[12] Studies revealed an association between smoking and increased risk for autism with intellectual disability, but not without.[13]

Nutrition

The depletion of essential nutrients in the mother is associated with adverse health outcomes for the offspring including increased autism risk.

Trace elements

Deficiency of iron, zinc, and copper poses the risk of causing ASD. Low iron intake had double the odds of having a child with ASD, especially in the presence of other autism risk factors (e.g., advanced paternal age, diabetes mellitus, hypertension, and obesity).[14] Low levels of zinc have been measured in the infant hair of individuals with ASD;[15] disruptions in fetal copper homeostasis during brain development might contribute to ASD risk with both elevated and decreased copper levels linked with autism.[16]

Vaccines

Wakefield et al.[17] claimed that MMR vaccination results in inflammatory bowel syndrome leading to autism. This study attracted worldwide attention and contributed to harmful drops in vaccination and resulted in measles outbreaks in several countries. The role of vaccines containing thiomersal was also refuted in several studies.[18]

Air pollution

Modest evidence exists for the toxicity of air pollution during the early development leading to ASD.[19]

Heavy metals

Mercury and lead are prominent ones in the etiological risk of ASD. Autistic individuals in low-income countries but not in high-income countries had increased lead and mercury concentrations in their hair.[20]

Pesticides

Proximity to organophosphorus compounds during pregnancy was associated with 60% increase in ASD risk. The risk was amplified for exposures during the third trimester. Exposure to chlorpyrifos during the second trimester increases the risk. Pyrethroid insecticide exposure immediately before conception or during the third trimester posed an increased risk of ASD and developmental delay.

Plastics

Phthalates and bisphenols used in plastics are nonpersistent organic pollutants. An association between phthalate and autism was reported.[21]

Persistent organic pollutants

Dichlorodiphenyltrichloroethane, polychlorinated biphenyls, and polybrominated diphenyl ethers are resistant to degradation and accumulate in the environment and enter the food chains, particularly animal fat and breast milk. They are associated with autism risk.[22] Organochlorine compounds during pregnancy are associated with ASD.[23]

Psychosocial factors

Intense maternal stress during pregnancy and extreme deprivation in infancy may have an adverse effect on both the mental and physical development of the child.[24],[25]

Protective factors

Folic acid may not protect against autism, but it may buffer the risks in mothers or infants who carry the gene variants by impacting the efficiency of folate metabolism and preventing the risk of neural tube alterations. Omega-3 fatty acids and probiotics might help in the neurodevelopment of the fetus when administered to mothers. However, the results are inconsistent.


  Advances in the Development of Assessment Tools Top


Screening procedures and tools

American Academy of Pediatrics recommends universal screening for developmental delays and disabilities at 9, 18, 24, and 30 months during well-child doctor visits. Autism Behavior Checklist, Childhood Autism Rating Scale-2, and Modified Checklist for Autism in Toddlers are popular screening tools.

Diagnostic scales

Indian Scale for the Assessment of Autism is used in the certification process by the issuing authorities in India. Autism Diagnostic Interview, Diagnostic Interview for Social and Communication Disorders, and Autism Diagnostic Observation Schedule are commonly used to diagnose ASD.


  Developments in Management Top


Behavioral and social treatments

Several behavioral and social treatments have evolved over time. They are found to be useful for children, especially as the part of early intervention. Applied behavioral analysis (ABA) by Lovaas is the most widely used intervention for children with autism. Early Stage Denver Model has also been popular. Social Communication, Emotional Regulation, and Transactional Support, Developmental, Individual difference, Relationship based and Relationship Development Intervention/Floor Time are some examples of developmental interventions. Intervention for communication includes Picture Exchange Communication System, social stories, and social skills training.

Naturalistic developmental behavioral interventions

They emphasize play, social intervention, communication initiation on the part of the child, and natural consequences follow as opposed to rewards of food as in the ABA model. They include pivotal response treatment, Joint Attention, Symbolic Play, and Engagement Regulation, and early social intervention.

Pharmacotherapy

Pharmacotherapy is used in children mainly to control disruptive behaviors. Risperidone and aripiprazole are most studied. They are prescribed in low doses. In young children, melatonin is used for insomnia. Comorbid disorders such as ADHD are treated with methylphenidate and other stimulants. Caution should be exercised in prescribing psychotropic medications to children with ASD as they can cause irreversible neurological side effects such as tardive dyskinesia and endocrinal side effects such as obesity.


  Developments in Social Benefits Top


Certification for autism spectrum disorder

In India, persons with autism are eligible for certain benefits from governmental agencies. Autism Certification Medical Boards should be formed in each state. Disability above 40% is eligible to claim the benefits. Certificate should be valid for 5 years for individuals below 18 years. Those above 18 years can claim a permanent disability certificate.

Indian acts and schemes

Persons with autism are eligible for reservation in higher education and government jobs as per the Rights of Persons with Disabilities Act 2016. About 5% of jobs are allocated for all listed categories including autism. Autism, cerebral palsy, and Mental Retardation and Multiple Disabilities Act exist since 1999. This act empowers such persons to have independent living with their own families and to avail of other benefits including legal benefits. There is a paradigm shift in the care of persons with intellectual disabilities from charity to rights-based.[26] Several other schemes were initiated by the Indian Government for the benefit of persons with ASD. They are Niramaya (insurance), aspiration (early intervention), Gyan Prabha (scholarship), etc.

Care of caregivers

Strong support from parents groups such as Forum for Autism, Action for Autism, and Autism Society of India help deal with caregiver distress and burnout by forming a support network of parents themselves. Some centers for assisted living for persons with autism came up in Gurgaon, Hyderabad, Bengaluru, etc., for a long stay.

Autism spectrum disorder in adulthood

About 10%–33% of adults with ASD do not use more than simple phrases and have intellectual disabilities requiring substantial support. In the USA, only 25% live there, and the remainder lives with their families. Marriage and long-term relations are still rare. In adults, co-occurring depression and severe anxiety can cause as much impairment as ASD features.


  Challenges and Opportunities Top


Magnitude of the problem

General consensus about the prevalence of ASD is 1%. To put this in perspective, this means 1.39 Cr people in India have ASD. For each one of these individuals, at least another 3 per household-parents and one sibling-will have their lives directly affected. This means 5.56 Cr (almost equal to the population of A.P.) people in India alone will have the impact due to ASD. In view of the complexity of the disorder, it poses enormous challenges to all the stakeholders such as mental health professionals, medical specialists, environmental scientist, public health administrators, policy-makers, and families of persons with autism. Following are some of the opportunities through which we and bring awareness among the public as well as plan infrastructure and train mental health professionals and workers to meet the demands of caring for individuals with ASDs.

Awareness programs

It would be prudent to take up awareness programs on related important days such as World Autism Day and World Mental Health Day.

Research and publication

There is an opportunity for research and publication in several domains, especially genetics and environmental factors that contribute to the causation of ASD. The results of ongoing multicenter studies in the field of autism genetics will pave the way in the understanding of the etiology of autism.

Training mental health workers and professionals

General psychiatrists need to be trained in Child and Adolescent Psychiatry (CAP). Some teaching institutions in India offer courses in PDF and DM in CAP. Indian Association for Child and Mental Health has started an online certificate course in child psychiatry.

Employment opportunities

Rehabilitation Council of India has introduced diploma courses in special education for ASD. These trained personnel can be employed in special schools and also integrated schools.

Rehabilitation facilities

They should be started in public and private sectors such as half homes and long stay homes for persons with ASD. The government should encourage the entrepreneurs who are coming forward to start them for the needy.

Preventive measures

The following preventive measures might help in reducing the prevalence rates of ASD.

  • Creating awareness among public and professionals about the early recognition and intervention
  • Risks of advanced parental age both maternal and paternal age should be explained to the prospective parents
  • Counseling the prospective marital partners about the risks of consanguineous marriages
  • Imparting knowledge about lifestyle modification such as regular physical exercises, yoga, meditation, and healthy dietary habits
  • Public health authorities and various governmental agencies should implement minimizing the use of plastics and pesticides
  • Organic farming should be encouraged
  • More number of wellness clinics with qualified professionals should be started both in private and public domains
  • The ill-effects of excess screen time exposure in the childhood should be emphasized to parents
  • The importance of adequate stimulation in the early childhood should be emphasized.



  Conclusion Top


Autism is no more a psychological disorder, as believed earlier, but a developmental disorder affecting the CNS and manifesting as a behavioral syndrome. With rapid strides in the genetic research, there is a hope for better understanding of the etiology in the near future. This will open up newer avenues in the management of ASD. It is the time to realize the importance of stimulating our children in the nature's lap by keeping it clean and tranquil. All the stakeholders should come together from local to global for prevention and creating better lives for persons with ASD. We should convert these challenges into opportunities so that we can see a better tomorrow for such individuals.



 
  References Top

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Correspondence Address:
Gorrela Venkata RamanaRao,
Department of Psychiatry, Alluri Sitarama Raju Academy of Medical Sciences, Eluru - 534 005, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amh.amh_61_22





 

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    -  RamanaRao GV


  Introduction
   Changes in Class...
  Etiology of Autism
  Genetic Factors
   Consanguinity an...
  Epigenetics
   Neural Basis of ...
   Environmental Pr...
   Advances in the ...
   Developments in ...
   Developments in ...
   Challenges and O...
  Conclusion
   References

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