Neurodevelopmental model of schizophrenia: update 2012
Open accessAbstract
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.
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Disruption in neuronal and microbial organization in prenatal and postnatal periods of mammalian development may lead to the onset of neurodevelopmental and other brain disorders later in life.
“disruption in the neuronal and microbial organization in prenatal and postnatal periods of mammalian development may lead to the onset of neurodevelopmental and other brain disorders later in life (9, 38–40).”
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Our current understanding of the genetic and environmental causes links schizophrenia with abnormal neurodevelopment.
“Although schizophrenia is usually diagnosed in young adults at the time of the first episode of psychosis, our current understanding of its genetic and environmental causes links this disorder with abnormal neurodevelopment 42,43 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [43]
Abnormalities in cortical maturation have been implicated in developmental, intellectual, psychiatric, and neurologic disorders.
“Given the importance of cortical structure and development on brain function, it is not surprising that abnormalities in cortical maturation have been implicated in developmental, intellectual, psychiatric, and neurologic disorders.”
From Quantifying cortical development in typically developing toddlers and young children, 1–6 years of age (2017) · cites this paper as Rapoport et al., 2012
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- Authors
- Rapoport, J. L., Giedd, J. N., & Gogtay, N.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Giedd, J N
- Venue
- Molecular Psychiatry
- Published
- 2012-04-10
- Volume
- 17
- Issue
- 12
- Pages
- 1228-1238
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3504171
- OpenAlex
- W2004469093
- Cited by
- 790
- References
- 133
- Citations by year
- 2026: 25 · 2025: 37 · 2024: 45 · 2023: 45 · 2022: 70 · 2021: 56 · 2020: 68 · 2019: 50 · 2018: 61 · 2017: 62 · 2016: 70 · 2015: 66 · 2014: 63 · 2013: 44 · 2012: 16
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, psychosis continuum, placental pathology, copy number variation, genetic variants, autism spectrum disorder, epilepsy, intellectual disability, human pluripotent stem cells, prophylaxis, early brain development
- MeSH terms
- Age Factors, Brain, Humans, Models, Neurological, Risk Factors, Schizophrenia, Genetic Predisposition to Disease, Pluripotent Stem Cells, Neuroimaging
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