30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis

Abstract

At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it overreached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms.

Brain structure, IQ, and psychopathology in young offspring of patients with schizophrenia or bipolar disorder

“…This suggests that it is not the presence of psychopathology, but the increased familial risk for SZ that influences brain development in early life leading to a smaller ICV. Taken together, our finding of a smaller ICV in SZo than in BDo provides evidence for aberrant (possibly early) brain development in relation to SZ risk, which is in line with the neurodevelopmental model of SZ [54,55]. Future studies with larger samples may have increased statistical power to address the possible differential associations between IQ and ICV with familial risk for SZ or BD.…”

Rethinking Schizophrenia and Depression Comorbidity as One Psychiatric Disorder Entity: Evidence From Mouse Model

“…For example, the dopamine theory of schizophrenia mainly attempts to explain the therapeutic effect in alleviating positive symptoms (Howes and Kapur, 2009). The neurodevelopment hypothesis, on the other hand, attempts to clarify the brain damage in high-risk populations of schizophrenia (Pino et al, 2014;Murray et al, 2017). For depressive disorders, the neuroimmune theory largely fits the elevated immune factors in adolescent patients (Miller and Cole, 2012) and the increased levels of inflammatory factors that are synchronized with the acute stage of a depressive episode (Slavich and Irwin, 2014).…”

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

“…The causes of schizophrenia lie in both genetic and environmental factors interacting over the course of neurodevelopment and gradually progressing to the first outbreak of acute psychosis, which typically occurs when the patient reaches the early 20s. This process is captured by the “developmental risk factor model of psychosis” . The role of dopamine dysregulation in psychosis has been explored at length by other authors .…”

“…The role of dopamine dysregulation in psychosis has been explored at length by other authors . Although genetics, environmental factors and neurodevelopment play crucial roles in the causality of schizophrenia, the focus of this article is to explore the neurophysiology of discoordination in patients and animal models from neurons, ensembles and local circuits to large‐scale‐networks and cognitive‐behavioural manifestations, with aberrant neuroplasticity linking the explanatory levels.…”