The DOI matches its Crossref record; 222 of the 222 references it cites were found in a registry or an index.
The Neurodevelopmental Hypothesis of Schizophrenia, Revisited
Open accessAbstract
While multiple theories have been put forth regarding the origin of schizophrenia, by far the vast majority of evidence points to the neurodevelopmental model in which developmental insults as early as late first or early second trimester lead to the activation of pathologic neural circuits during adolescence or young adulthood leading to the emergence of positive or negative symptoms. In this report, we examine the evidence from brain pathology (enlargement of the cerebroventricular system, changes in gray and white matters, and abnormal laminar organization), genetics (changes in the normal expression of proteins that are involved in early migration of neurons and glia, cell proliferation, axonal outgrowth, synaptogenesis, and apoptosis), environmental factors (increased frequency of obstetric complications and increased rates of schizophrenic births due to prenatal viral or bacterial infections), and gene-environmental interactions (a disproportionate number of schizophrenia candidate genes are regulated by hypoxia, microdeletions and microduplications, the overrepresentation of pathogen-related genes among schizophrenia candidate genes) in support of the neurodevelopmental model. We relate the neurodevelopmental model to a number of findings about schizophrenia. Finally, we also examine alternate explanations of the origin of schizophrenia including the neurodegenerative model.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“symptoms do not manifest fully until late adolescence.1”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [1]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine
Kane, J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800330013001 · Cited by 4,156
(2024) · Pharmacological Reviews · doi:10.1124/pr · Cited by 2,680
Schizophrenia as a Complex Trait: Evidence From a Meta-analysis of Twin Studies
Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.12.1187 · Cited by 2,356
Carlsson, A., & Lindqvist, M. (1963) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1963.tb01730.x · Cited by 2,156
Apoptosis in the nervous system
Yuan, J., & Yankner, B. A. (2000) · Nature · doi:10.1038/35037739 · Cited by 1,882
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800
Meta-analysis of regional brain volumes in schizophrenia
Wright, I. C., Rabe-Hesketh, S., Woodruff, P. W. R., David, A. S., Murray, R. M., & Bullmore, E. T. (2000) · American Journal of Psychiatry · doi:10.1176/ajp.157.1.16 · Cited by 1,662
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
Research works printed but not linked: 22
- Fish, 1992, Archives of General Psychiatry, 49, 221, 10.1001/archpsyc.49.3.221 · DOI
- 2001, PNAS, 94, 4293
- Mednick, 1988, Archives of General Psychiatry, 45, 189, 10.1001/archpsyc.45.2.189 · DOI
- 1993, American journal of obstetrics and gynecology, 81, 941
- 2000, Cell and tissue research, 299, 235
- Susser, 1996, Archives of General Psychiatry, 53, 25, 10.1001/archpsyc.53.1.25 · DOI
- Hollister, 1996, Archives of General Psychiatry, 53, 19, 10.1001/archpsyc.53.1.19 · DOI
- 2007, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 144, 129
- 2000, 28, 53
- Akbarian, 1995, Archives of General Psychiatry, 52, 258, 10.1001/archpsyc.52.4.258 · DOI
- 2006, 52, 103
- 2006, Molecular psychiatry, 12, 195
- 2000, PNAS, 97, 3596, 10.1073/pnas.070042497 · DOI · Paper page
- 1997, Acta neuropathologica, 92, 217
- 2003, Biological psychiatry, 53, 1086, 10.1016/S0006-3223(03)00114-8 · DOI
- Akbarian, 1993, Archives of General Psychiatry, 50, 169, 10.1001/archpsyc.50.3.169 · DOI
- 1999, Archives of General Psychiatry, 48, 625
- 2005, 47, 567
- 2000, 28, 325
- Kane, 1988, Archives of General Psychiatry, 45, 789, 10.1001/archpsyc.45.9.789 · DOI
- 2000, OLANZAPINE ZYPREXA A NOVEL ANTIPSYCHOTIC, 2000, 25
- 1998, Schizophrenia Bulletin, 2, 425
Cited by
Sorted by citations
Owen, M. J., Sawa, A., & Mortensen, P. B. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01121-6 · Cited by 1,870
Dysconnectivity in schizophrenia: where are we now?
Pettersson-Yeo, W., Allen, P., Benetti, S., McGuire, P., & Mechelli, A. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.11.004 · Cited by 712
Early-life programming of later-life brain and behavior: a critical role for the immune system
Bilbo, S. D. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.014.2009 · Cited by 652
Prenatal Poly(I:C) Exposure and Other Developmental Immune Activation Models in Rodent Systems
Meyer, U. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.011 · Cited by 626
Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516
“Thus, circuits tend to be malleable but vulnerable during postnatal development; notably, several neurodevelopmental disorders, such as ASD and SCZ, manifest during this plasticity period [49, 50].”
Background
Metadata
- Authors
- Fatemi, S. H., & Folsom, T. D.
- Affiliations
- University of Minnesota (US)
- ORCID
- Fatemi, S. H.
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-30
- Volume
- 35
- Issue
- 3
- Pages
- 528-548
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC2669580
- OpenAlex
- W2132748057
- Cited by
- 860
- References
- 222
- Citations by year
- 2026: 23 · 2025: 46 · 2024: 47 · 2023: 42 · 2022: 39 · 2021: 48 · 2020: 45 · 2019: 40 · 2018: 43 · 2017: 48 · 2016: 61 · 2015: 53 · 2014: 55 · 2013: 76 · 2012: 66
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Schizophrenia Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD046589)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, neurodevelopmental hypothesis
- MeSH terms
- Adolescent, Adult, Animals, Brain, Disease Models, Animal, Female, Humans, Infant, Newborn, Mutation, Nerve Net, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Schizophrenia, Schizophrenic Psychology, Virus Diseases, Gene Expression, Neurodegenerative Diseases, Oligonucleotide Array Sequence Analysis, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
