Autism Spectrum Disorder

What A pervasive neurodevelopmental disorder that impacts how people communicate, interact with others, behave, and learn.
Its symptoms show in the first two years.
It is considered a spectrum because it varies in symptoms and severity among people.
Etiology:

Multifactorial etiology; genetic and non-genetic.
ASD is syndromic or non-syndromic
Genetic Non-Genetic
ASD is a complex genetic disorder with high heritability.
The phenotype for ASD is unclear, but Research has identified specific genes like FOXP2, RAY1/ST7, IMMP2L, and RELN at 7q22-q33 and noncoding regions (Yoon et al., 2020).
chromosomes 4, 7, 10, 16, 19, and 22 are ASD-related; Chromosome 7 is the most significant.
Mutation of Heterozygous FOXP2 causes severe speech and language disorders (Yoon et al., 2020).
Inherited and de novo copy number variations (CNVs) are critical to ASD because they affect neurodevelopment through deletion, translocation, duplication, and reversal. Zinc deficiency: Zinc influences protein formation, immunity, fetal growth and development, and gene expression. Therefore, prolonged deficiency during pregnancy causes abnormalities.
Parental age: A lower maternal age >20 has a lower risk of autism compared to 25-30. Risk increases after 35 years. Paternal age >30 increases risk, and it doubles at >55 years.
Parental viral infection: Infections like measles, rubella, influenza, pneumonia, syphilis, and mumps activate the immune system, causing neurological damage.
Others: Prenatal stress, exposure to heavy metals and toxins, maternal nutrition, and metabolic status.

Figure 1: Summary of ASD etiology and symptoms (Yoon et al., 2020).

ASD Pathology
Abnormalities in intracranial volumes and head circumference for children between 1-4 years.
Neuropathology
● Alterations in the brain structure, including the basal ganglia, lateral occipital lobe, proximate to the right parietal operculum, the medial temporal lobe, and the pericentral region among young individuals (Sauer et al., 2021).
● There are rapid increases in the left and right amygdala, which influence the child’s communication and social interaction deficits by age 5.
● Up to year two, a 7% increase in cerebrum size, with a 5% and 10% increase in total gray and white matter, respectively, is observed, followed by a period of growth arrest (Beopoulos et al., 2022).
● ASD is also characterized by synaptic dysfunction: The mTOR/PI3K pathway is particularly associated with syndromic ASD and the NRXN-NLGN-SHANK pathway (Sauer et al., 2021). The genetic and non-genetic contributors of ASD converge at the synaptic level.
Extracerebral pathology: 20-86% prevalence of gastrointestinal disturbances in ASD individuals reporting bloating, constipation, gastroesophageal reflux, diarrhea, and abdominal pain. These symptoms vary in severity among ASD individuals.
Epidemiology: One in 100 children are diagnosed with autism. Global estimates of 28.3 million ASD prevalent cases, 603,790 incident cases, and 4.3 million DALYs in 2019 (Li et al., 2021). ASD is highly prevalent in high-income North America, high-income Asia Pacific, and Western Europe.
DSM-5 ASD Criteria

Severity level
Diagnosis of ASD occurs in two phases: The first is the general developmental screening at clinical checkups followed by diagnostic evaluation by a multidisciplinary team. Caregiver input on child development is needed but assessment is based on DSM-5 criteria.
A multidisciplinary assessment is done using the Modified Checklist for Autism in Toddlers (M-CHAT-R) at 18 and 24 months. Scores can indicate the severity of ASD.
Other tools: Autism Diagnostic Interview, Autism Diagnostic Observation Schedule (ADOS), and Diagnostic Interview for Social and Communication Disorders (Subramanyam et al., 2019).
Level 1 ASD (Requires support): The Individual has noticeable impairments and has difficulty initiating interpersonal interactions. Their repetitive behaviors and rituals impact their daily lives, and they often resist change that interrupts these behaviors.
Level 2 (Requires substantial support)—The Individual has marked deficits in social communication and has limited social interactions. The individual experiences distress or frustration when repetitive behaviors are interrupted. The behaviors are obvious to observers.
Level 3 (Requires very substantial support): The Individual has severe deficits in verbal and nonverbal communication skills and minimal to no social interactions. Repetitive behaviors and preoccupations significantly disrupt functioning. The individual experiences marked frustration and stress when routines and rituals are interrupted.
Risk Factors
✔ Pre-term birth
✔ Maternal infection
✔ Having a sibling with ASD
✔ Having older parents
✔ Very low birth weight
✔ Hypoxia during birth
✔ Prenatal exposure to toxins
Management
Pharmacological Interventions Non-Pharmacological Interventions
Typical and atypical antipsychotics (aripiprazole and risperidone—FDA Approved) for hyperactivity, irritability, and stereotypy. Educational support: acronym SCERTS (Social Communication, Emotional Regulation, and Transactional Support)
Others with no strong evidence of effectiveness:
● Antidepressants- Selective Serotonin Reuptake Inhibitors
● Glutamate-modulating agents
● Stimulants
● α-2 adrenergic agonist Targeted skill-based intervention (social skills, vocational training, picture exchange communication system, and living skills)
Targeted behavioral intervention (Cognitive behavioral therapy)
Animal-assisted therapy
Psychoeducation for the Family
● For individuals on pharmacological interventions, the family should be informed of the side effects and how to manage them.
● Common side effects include drooling, increased appetite, drowsiness, and jerky movements.
● Empower families in providing care for the ASD individual by clarifying that autism is a neurodevelopmental disorder that is not caused by vaccines, poor parenting, or other beliefs.
● Help them understand it is a lifelong condition and the child will need support throughout. However, symptoms can improve with early intervention and promote autonomy.
● Offer links to resources to help parents with coping and helping manage issues like eating disorders, travelling with ASD children, and sleeping issues.
● Connect families with specialists for therapy and communities for social support.
● Assure them of the possibility of adequately living with ASD and offer contacts for any inquiries.
 
References
Beopoulos, A., Géa, M., Fasano, A., & Iris, F. (2022). Autism spectrum disorders pathogenesis: Toward a comprehensive model based on neuroanatomic and neurodevelopment considerations. Frontiers in Neuroscience, 16. https://doi.org/10.3389/fnins.2022.988735
Li, Y., Chen, Z., Li, X., Gu, M., Xia, N., Gong, C., Zhou, Z., Yasin, G., Xie, H., Wei, X., Liu, Y., Han, X., Lu, M., Xu, J., & Huang, X. (2022). Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors. Frontiers in Pediatrics, 10. https://doi.org/10.3389/fped.2022.972809
Sauer, A. K., Stanton, J., Hans, S., & Grabrucker, A. (2021). Autism spectrum disorders: etiology and pathology. In A. M. Grabrucker (Ed.), Autism spectrum disorders (pp. 1-15). Exon Publications.
Subramanyam, A., Mukherjee, A., Dave, M., & Chavda, K. (2019). Clinical practice guidelines for autism spectrum disorders. Indian Journal of Psychiatry, 61(8), 254-269. https://doi.org/10.4103/psychiatry.indianjpsychiatry_542_18
Yoon, S., Choi, J., Lee, W., & Do, J. (2020). Genetic and epigenetic etiology underlying autism spectrum disorder. Journal of Clinical Medicine, 9(4), 966. https://doi.org/10.3390/jcm9040966