Research conducted by the late Paul Patterson (University of California) had shown that the incidence of autism increased in the population following widespread outbreaks of viral infections. Using animal models, he demonstrated that infecting a pregnant mouse with the influenza virus caused a syndrome resembling autism and schizophrenia—with all the limitations inherent in what such behavioral assessments can reveal. Patterson and his colleagues subsequently demonstrated that it is not the virus itself that is the direct intracerebral cause of the deficits—since no trace of the virus is found in the brain—but rather its peripheral effects through the inflammation it triggers, involving the release of inflammatory factors (Shi et al. 2003) (Shi, Tu, and Patterson 2005). The viral infection triggers a cascade of sequelae that ultimately lead to a pathological syndrome much later.
These findings have been validated in other experimental settings in which intrauterine inflammation—induced, for example, by administering immune-activating agents to pregnant mice—results in the same consequences. In newborn mice, difficulties with socialization, characteristic stress reactions, and paradoxical responses to antipsychotic agents such as clozapine or chlorpromazine are observed.
These results have been replicated in rhesus monkeys. The administration of inflammatory agents and early activation of the immune system produce repetitive abnormal behaviors, impaired social interactions, and other social changes similar to those seen in children with autism.
These and other studies suggest that early activation of the immune system due to infection facilitates the development of numerous diseases, including degenerative conditions such as Parkinson’s and Alzheimer’s diseases, as well as childhood and late-onset epilepsies, illustrating the importance and long-term effects of early pathological events (Knuesel et al. 2014). Clearly, the distinction between neurodevelopmental and neurodegenerative diseases should be reevaluated. It is still, as always, in the context of in utero brain maturation that we must seek the origins. Admittedly, we are far from understanding how—and, above all, why—such long time intervals sometimes elapse between the initial event and the onset of harmful manifestations, as well as the sequence of cascading processes that persistently impair maturation. Nevertheless, if we are to understand and treat brain disorders, we will need to gain a better understanding of these sequences and adopt a long-term perspective rather than relying on fixed, predetermined relationships triggered by any given pathological event. The dynamics of neural networks—which respond to any pathological event through “reactive plasticity” by forming new synaptic connections—preclude such rigid lines of reasoning.
Knuesel, Irene, Laurie Chicha, Markus Britschgi, Scott A Schobel, Michael Bodmer, Jessica A Hellings, Stephen Toovey, and P Eric. 2014. “Maternal Immune Activation and Abnormal Brain Development across CNS Disorders.” Nature Publishing Group 10 (11): 643–60. https://doi.org/10.1038/nrneurol.2014.187.
Shi, Limin, S. Hossein Fatemi, Robert W. Sidwell, and Paul H. Patterson. 2003. “Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring.” Journal of Neuroscience. https://doi.org/10.1523/jneurosci.23-01-00297.2003.
Shi, Limin, Nora Tu, and Paul H. Patterson. 2005. “Maternal Influenza Infection Is Likely to Alter Fetal Brain Development Indirectly: The Virus Is Not Detected in the Fetus.” International Journal of Developmental Neuroscience. https://doi.org/10.1016/j.ijdevneu.2004.05.005.
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