The putative etiology and prevention of autism

Abstract

Since the initial psychological report by Leo Kanner in 1943, relatively little formal biochemical/neurological research on the cause of autism, other than peripheral searches for genomic mutations, had been carried until the end of the 20th century. As a result of studies on twin sets and the conclusion that autism was largely a hereditary defect, numerous investigations have sought various genetic faults in particular. However, such studies were able to reveal a plausible etiology for this malady in only a small percentage of instances. Key bio-molecular characteristics of this syndrome have been uncovered when the potential roles of the glia were studied in depth. Findings related to biochemical deficiencies appearing early in the newborn, such as depressed IGF-1 (insulin-like growth factor #1) in neurogenesis/myelination, are becoming emphasized in many laboratories. Progress leading to timely diagnoses and subsequent prevention of central nervous system dysconnectivity now seems plausible. The tendency for an infant to develop autism may currently be determinable and preventable before irreversible psychosocial disturbances become established. These discussions about glial function will be inter-spersed with comments about their apparent relevance to autism. The concluding portion of this presentation will be a detailed review and summation of this diagnosis and prevention proposition.

Keywords: Astrocyte; Autism; Biomarkers; Dysconnectivity; IGF-1; Microglia; Myelination; Oligodendrocyte; Polymorphism; Schwann.

Fig. 1

Maternal immunologic activation, secondary to an inflammatory process, promotes the release of IL6. The cytokine depresses IGF-1 production and release to the fetus. EY Hsiao, pH Patterson. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6.

Fig. 2

IGF-1 stimulates oligodendrocytes to supply myelin to the neo-neuron. IGF-1 enhances the velocity of the IGF1/IGFR/IRS1/PI3K/AKT/mTOR intracellular chain. In the presence of the polymorphic form of IRS-1 gene or reduced IGF-1, the rate of myelin production is reduced, myelination of new nerves is slowed, and connectivity of new circuits is inadequate to meet the needs of the developing infantile brain. As a result, permanent mis-wiring ensues, especially with long distance connections (e.g., parietal-to-frontal).