The Neurodevelopmental model of Schizophrenia

The neurodevelopmental model of schizophrenia provides a framework for understanding how OCs interact with the developing brain to increase the likelihood of schizophrenia in late adolescence and early adulthood. In normal development, connections in the brain (referred to as synaptic density) increase until an individual is approximately 2 years of age, which slowly decline during childhood, then decline steeply during late childhood and early adolescence. Many of these connections are unnecessary and will be eliminated in the mature brain.

During adolescence, a sharp increase in a process called synaptic pruning, which involves the elimination of superfluous connections, coincides with the emergence of abilities to solve abstract and complex problems. According to the neurodevelopmental model, patients with schizophrenia may have too many, too few, or unnecessary synaptic connections that are eliminated during adolescence, which results in the onset of psychotic symptomatology. According to one model, schizophrenia would occur due to an abnormally aggressive synaptic pruning process, leading to a reduction in synaptic connectivity beyond a psychosis threshold, resulting in a fragmented or disconnected brain.

This lack of neural connectivity throughout the brain reflects the challenges faced by patients with schizophrenia, with deficits in most areas, including cognitive, social, emotional, and perceptual difficulties. Moreover, this model is supported by postmortem studies that have found reduced neuropil without neuronal loss, in which decreased neuropil represents a loss of connections between neurons.

Early environmental insults, such as OCs, would fit within this neurodevelopmental model by reducing the amount of synaptic pruning necessary to cause psychotic symptomatology. This would lead to an earlier age of onset and possibly portend a worsened clinical outcome. As we have seen, this is precisely what occurs in individuals with a history of hypoxia-associated OCs, who typically have an earlier age of onset and more pronounced neuroanatomical abnormalities.

Viewing schizophrenia as a developmental disorder encourages exploration into possible early intervention and prevention strategies in individuals who are genetically susceptible. The emergence of candidate disease genes, as well as the advances in mapping out molecular pathways involved in schizophrenia, will likely pave the road to understanding and treating an incredibly serious and debilitating disorder.

{embed="ref/50"}