Implications of Normal Brain Development for the Pathogenesis of Schizophrenia

TLDR

Recent research on schizophrenia has demonstrated that the brain is not, strictly speaking, normal. The study proposes that diagnostic symptoms arise from normal maturation of brain regions affected by early developmental pathology, especially the dorsolateral prefrontal cortex, and discusses implications for future research and treatment. The authors link the illness course and stress effects to normal maturation of dopaminergic systems targeting the prefrontal cortex. The study finds nonspecific histopathology in limbic, diencephalic, and prefrontal regions early in development, supporting a neurodevelopmental model where an early lesion interacts with later normal brain maturation, rather than metabolic, posttraumatic, or neurodegenerative mechanisms.

Abstract

• Recent research on schizophrenia has demonstrated that in this disorder the brain is not, strictly speaking, normal. The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made. If these findings are valid and not epiphenomena, then the pathogenesis of schizophrenia does not appear to fit either traditional metabolic, posttraumatic, or neurodegenerative models of adult mental illness. The data are more consistent with a neurodevelopmental model in which a fixed "lesion" from early in life interacts with normal brain maturational events that occur much later. Based on neuro-ontological principles and insights from animal research about normal brain development, it is proposed that the appearance of diagnostic symptoms is linked to the normal maturation of brain areas affected by the early developmental pathology, particularly the dorsolateral prefrontal cortex. The course of the illness and the importance of stress may be related to normal maturational aspects of dopaminergic neural systems, particularly those innervating prefrontal cortex. Some implications for future research and treatment are considered.