Viruses and autism: A Bi-mutual cause and effect

Table 1 The possible underlying mechanisms and triggering factors for autism

Possible mechanism	Effects
Immune dysregulation and autoimmunity	Neuroinflammation, cytokine dysregulation, and inducing anti-brain antibodies
Neuroinflammation	Neuroinflammation of the Cortex: Raised reactive microglial and astrocyte numbers → excess neurons → local overconnectivity in specific brain regions, abnormal neuronal migration during early pregnancy → abnormal synaptogenesis and formation of dendritic spines and disturbed excitatory-inhibitory networks, prominent brain volume and weight volume
	Neuroinflammation of brainstem → brainstem dysfunction → sensory processing abnormalities → enhanced sympathetic excitation and parasympathetic hypofunction
	Neuroinflammation of thalamus → autonomic nervous system dysfunction
Abnormalities in mirror neuron system regions	→ Impaired activation of the imitation core circuit → social impairment
Impaired signaling patterns in the cingulate cortex	→ Severely reduced cingulate self-response → social impairments
Autonomic nervous system dysfunction	Chronic sensory hyperarousal state in children and sleep disorders
	Affects heart rate, blood pressure, and respiratory rhythm
	Impaired gastrointestinal motility, gastric acid, and intestinal enzyme secretion
Underlying triggering factors	Maternal vitamin D deficiency, use of medication such as valproic acids during pregnancy, prenatal infection, neonatal hypoxia, preterm delivery, abnormal presentation, cesarean section, fetal complications, neonatal hypoxia, respiratory distress, natal bleeding, low-birth weight, seizures at birth, neonatal jaundice, early postnatal infection, sepsis, meningitis, encephalopathy, postnatal vitamin D deficiency
Augmenting factors	Gastrointestinal abnormalities, repeated infections with gut dysbiosis, and impairment of the gut-brain axis cause immune imbalance and trigger neuroinflammation

Table 2 Important risk factors and co-morbidities that increase the risk of contracting infections in children with autism

Risk factors	Description
Immune system disorders	High rate of autoimmune diseases
	Immune dysregulation of T cell functions
	Impaired levels of immune mediators
	lower plasma IgG, and IgM
	Continuing immune dysfunction
	High rate of mitochondrial dysfunction
	Oxidative stress
	Neutrophils dysfunction
Medical co-morbidities	Genetic disorders: e.g., fragile X syndrome, Down syndrome, Duchenne muscular dystrophy, tuberous sclerosis complex, and neurofibromatosis type I
	Neurological disorders: e.g., cerebral palsy and congenital abnormalities
	Gastrointestinal disorders: Gastroesophageal reflux and inflammatory bowel disease
	Metabolic disorders: mitochondrial disorders, disorders of creatine metabolism, selected amino acid disorders, disorders of folate or vitamin B12 metabolism, and selected lysosomal storage disorders
	Allergic disorders: Such as asthma, nasal allergies, atopic diseases (IgE-mediated)
Behavioral problems	Stereotyping behavior: Affecting mouth and general hygiene
	Mouthing and pica behavior
	Faecal smearing
Feeding and nutritional disorders	Biological food intolerance
	Restrictive and selective behavior
	Sensory-based feeding problems
	Relational sphere disorders
	Medically-related feeding problems
	restrictive dietary management
	Nutritional deficiencies: e.g., Vitamin A, D, C, and zinc
Gastrointestinal dysfunctions	Gastroesophageal reflux
	Autonomic dysfunction and Impaired intestinal motility
	Gastric hypoacidity and
	Impaired digestive enzyme production
	Gut dysbiosis
	Inflammatory bowel disease
Vaccinophobia	Lack of parental education and awareness
	Anti-vaccine movement