Neurodevelopmental model of schizophrenia: update 2012

• Published in: Molecular psychiatry Vol. 17; no. 12; pp. 1228 - 1238
• Main Authors: Rapoport, J L, Giedd, J N, Gogtay, N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2012; Nature Publishing Group
• Subjects: 631/378/2571; 692/699/476/1799; 692/700/1421/65; Adult and adolescent clinical studies; Age Factors; Autism; Autopsy; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain; Brain - growth & development; Brain - pathology; Brain research; Child & adolescent psychiatry; Child psychology; Children; Cohort analysis; Copy number; Data processing; Development and progression; Epidemiology; Epilepsy; expert-review; Famine; Gene expression; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease - genetics; Humans; Illnesses; Immunoglobulins; Infections; Longitudinal studies; Medical examination; Medical imaging; Medical sciences; Medicine; Medicine & Public Health; Mental disorders; Methods; Models, Neurological; Neuroimaging; Neuroimaging - methods; Neuroimaging - psychology; Neurosciences; Pathology; Pharmacotherapy; Phenotyping; Placenta; Pluripotency; Pluripotent Stem Cells - pathology; Population studies; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychosis; Reviews; Risk Factors; Risk groups; Schizophrenia; Schizophrenia - etiology; Schizophrenia - genetics; Schizophrenia - pathology; Stem cells; United States; United States > US; placenta; CNV; genetics; schizophrenia; neurodevelopment; imaging; Psychosis; Placenta; Fetal membrane; Imaging; Schizophrenia; Genetics; Models; Review
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2012.23

The neurodevelopmental model of schizophrenia, which posits that the illness is the end state of abnormal neurodevelopmental processes that started years before the illness onset, is widely accepted, and has long been dominant for childhood-onset neuropsychiatric disorders. This selective review updates our 2005 review of recent studies that have impacted, or have the greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis. New studies suggest that placental pathology could be a key measure in future prenatal high-risk studies. Both common and rare genetic variants have proved surprisingly diagnostically nonspecific, and copy number variants (CNVs) associated with schizophrenia are often also associated with autism, epilepsy and intellectual deficiency. Large post-mortem gene expression studies and prospective developmental multi-modal brain imaging studies are providing critical data for future clinical and high-risk developmental brain studies. Whether there can be greater molecular specificity for phenotypic characterization is a subject of current intense study and debate, as is the possibility of neuronal phenotyping using human pluripotent-inducible stem cells. Biological nonspecificity, such as in timing or nature of early brain development, carries the possibility of new targets for broad preventive treatments.