The Neuroimmunology of Autism

Alterations and maladaptations of the immune system remain some of the most controversial concepts in autism spectrum disorder (ASD). Nonetheless, intensifying evidence confirms that much of what ASD involves is related not to a static encephalopathy-based model of autism but rather to the consequences of environmental insult and complex and dynamic psychological and physiological processes involving the interdependence of the nervous, immune, and host microbiome. This narrative review provides a conceptual framework, focuses on clinical research, and is written for specialists and non-specialists. To provide access to multi- and interdisciplinary perspectives with wide-ranging cutting-edge implications for all people with ASD. Beginning with historical, epidemiological, and etiological underpinnings, we elaborate on a contemporary understanding of the immune system in the pathophysiology of ASD. Theoretical and scientific discourse on the relationship of the immune system with the nervous system and host microbiota in homeostasis/allostasis, neurodevelopment, and psychological and physiological health and disease is also provided. As a basis for conceptual advances detailing the interconnection, interdependence, and interference with or subjugation (as would be the case for autoinflammatory and autoimmune conditions) of the nervous system and host microbiota by the immune system, and the role of these interactions in the pathogenesis of ASD. This gives us a platform for not only examining the role of the immune system in the etiology, pathogenesis, and pathophysiology of ASD but also understanding social and higher-level processes of consciousness for individuals on the spectrum. Finally, taking a neuroimmunological perspective, we highlight the need for a multi-scale, holistic approach to understanding and developing future therapeutic modalities to address the core symptoms of ASD that go beyond the current reductionist and "magic-bullet" medical paradigm.