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 |