The Imbalanced Plasticity Hypothesis of Schizophrenia-Related Psychosis: A Predictive Perspective.

A considerable number of studies have attempted to account for the psychotic aspects of schizophrenia in terms of the influential predictive coding (PC) hypothesis. We argue that the prediction-oriented perspective on schizophrenia-related psychosis may benefit from a mechanistic model that: 1) gives due weight to the extent to which alterations in short- and long-term synaptic plasticity determine the degree and the direction of the functional disruption that occurs in psychosis; and 2) addresses the distinction between the two central syndromes of psychosis in schizophrenia: disorganization and reality-distortion. To accomplish these goals, we propose the Imbalanced Plasticity Hypothesis - IPH, and demonstrate that it: 1) accounts for commonalities and differences between disorganization and reality distortion in terms of excessive (hyper) or insufficient (hypo) neuroplasticity, respectively; 2) provides distinct predictions in the cognitive and electrophysiological domains; and 3) is able to reconcile conflicting PC-oriented accounts of psychosis.