Autism spectrum disorders pathogenesis: Toward a comprehensive model based on neuroanatomic and neurodevelopment...

Area of Science:

• Neurodevelopmental disorders
• Autism Spectrum Disorder (ASD) pathogenesis
• Cortical development and neural connectivity

Background:

• ASD is characterized by altered neural connectivity, cortical overgrowth, and amygdala changes.
• Early increases in brain volume are followed by later declines, suggesting prenatal origins.
• Dysregulation in prenatal cortical development, including neuronal migration, is implicated.

Purpose of the Study:

• To present a comprehensive model for ASD pathogenesis and progression.
• To explore the role of prenatal environmental factors in ASD development.
• To link early developmental disruptions to later clinical heterogeneity in ASD.

Main Methods:

• Review and synthesis of existing neurobiological mechanisms.
• Postulation of a model based on prenatal environmental influences (serotonin/kynurenine supply).
• Examination of critical gestational windows (GW7-GW20) and in utero RNA editing.

Main Results:

• Prenatal environmental changes during critical gestational weeks may drive ASD pathogenesis.
• Disrupted differentiation and RNA editing favor vulnerability over plasticity.
• Early developmental dysregulation leads to postnatal synaptic pruning issues and signal-over-noise deficits.

Conclusions:

• Prenatal environmental factors, particularly serotonin/kynurenine supply, are critical in ASD pathogenesis.
• In utero RNA editing alterations contribute to ASD vulnerability.
• This model explains ASD heterogeneity, including autonomic dysfunction and comorbidities.