Impaired deviance detection is the core pathogenic mechanism of schizophrenia

Schizophrenia has long been a perplexing mental disorder. While it is recognized as a distinct nosological entity with a known polygenic origin, the principal mechanism by which multiple genes and their products interact to drive the pathological process remains unclear. In this article, we delve into the research on ketamine's effects on both healthy individuals and rodent models, focusing on deviance detection as reflected by the mismatch negativity (MMN) in EEG. We discuss the NMDA receptor dysfunction in schizophrenia, which resembles that induced by ketamine, and leads to the reduced MMN. Additionally, we explore the structural changes in the brain associated in literature with schizophrenia. We posit that the impaired deviance detection in schizophrenia leads to abnormal interaction between the parallel (predictive) and sequential (evidence-based) streams of speech processing in the brain, resulting in hallucinations, delusions, thought disorders, and impaired social functioning. The integration of numerous findings into this model provides compelling evidence that the NMDA receptor-mediated deficiency in deviance detection is a salient contributor to the manifestation of symptoms and the pathological progression of this psychiatric condition.