A CRH Theory of Autism Spectrum Disorder

TL;DR

This paper proposes a comprehensive theory that attributes ASD to excessive stress-induced CRH release affecting brain development and hormone regulation, supported by diverse evidence and suggesting early detection and treatment options.

Contribution

It introduces a novel, complete etiological theory of ASD centered on CRH dysregulation, linking symptoms to hormonal and neural developmental mechanisms.

Findings

CRH overproduction impairs brain development related to social and sensory functions

Excess adrenal androgens disrupt long-term neural plasticity

Supports early biomarkers and promising pharmaceutical interventions

Abstract

This paper presents a complete theory of autism spectrum disorder (ASD), explaining its etiology, symptoms, and pathology. The core cause of ASD is excessive stress-induced postnatal release of corticotropin-releasing hormone (CRH). CRH competes with urocortins for binding to the CRH2 receptor, impairing their essential function in the utilization of glucose for growth. This results in impaired development of all brain areas depending on CRH2, including areas that are central in social development and eye gaze learning, and low-level sensory areas. Excessive CRH also induces excessive release of adrenal androgens (mainly DHEA), which impairs the long-term plasticity function of gonadal steroids. I show that these two effects can explain all of the known symptoms and properties of ASD. The theory is supported by strong diverse evidence, and points to very early detection biomarkers and preventive pharmaceutical treatments, one of which seems to be very promising.