Rethinking schizophrenia
Abstract
How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.
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An analysis of 22 screenings found 98 duplications in 36,676 SZ patients (0.26%) and only 12 duplications in 48,331 controls (0.025%), indicating a 10.79-fold increase in SZ risk.
“An analysis of 22 screenings in various populations found 98 duplications in 36,676 SZ patients (0.26%), with only 12 duplications in 48,331 controls (0.025%), indicating a 10.79-fold increase in risk for developing SZ [43].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [43]
Psychosis is not the onset of schizophrenia, but rather a prominent consequence of a developmental path toward schizophrenia that can be perhaps prevented through early intervention.
“According to this view, psychosis is not the onset of the disorder, but rather a prominent consequence of a developmental path toward schizophrenia that can be perhaps prevented through early intervention 44 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [44]
Schizophrenia is increasingly viewed as a neurodevelopmental disorder involving brain circuit alterations, including dysfunction of parvalbumin-positive fast-spiking GABA neurons.
“Schizophrenia is increasingly recognized as a neurodevelopmental disorder that involves alterations in brain circuits, including dysfunction of parvalbumin (PV)-positive, fast-spiking GABA neurons (1, 2).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [2]
Mis-timed developmental trajectories of brain plasticity may contribute in part to the etiology of mental illnesses involving oxidative stress, such as schizophrenia.
“Mis-timed developmental trajectories of brain plasticity may therefore contribute in part to the etiology of mental illnesses involving oxidative stress, such as schizophrenia (2, 3, 18).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [2]
Several molecular brakes relevant to schizophrenia, other than PNNs, limit critical period plasticity, including myelin signaling through NgR-PirB and dampened nicotinic receptor signaling by Lynx1.
“Several molecular brakes of relevance to schizophrenia (other than PNNs) have been identified to limit critical period plasticity, including myelin signaling through a NgR-PirB complex (2, 74, 75) or dampened nicotinic receptor signaling by Lynx1 (29, 76).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [2]
Deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition.
“Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition.”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [3]
Many diverse causes of schizophrenia and schizophrenia-like behaviours converge on aberrant function of fast-spiking parvalbumin-positive interneurons, which leads to altered excitation-inhibition balance.
“Pathologically, many diverse causes of schizophrenia and schizophrenia-like behaviours appear to converge on a similar deficit: the aberrant function of fast-spiking parvalbumin-positive interneurons (PVIs) 2 , which leads to altered excitation-inhibition balance 3 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [3]
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“Accompanied by low short-term recovery rates, difficult prognoses, and poor employment rates, SZ is deeply concerning [3].”
- Authors
- Insel, T. R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Insel, Thomas R.
- ORCID
- Insel, Thomas R.
- Venue
- Nature
- Published
- 2010-11-10
- Volume
- 468
- Issue
- 7321
- Pages
- 187-93
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4211063728
- Cited by
- 1,783
- References
- 13
- Citations by year
- 2026: 90 · 2025: 93 · 2024: 109 · 2023: 109 · 2022: 140 · 2021: 162 · 2020: 123 · 2019: 120 · 2018: 137 · 2017: 101 · 2016: 103 · 2015: 154 · 2014: 108 · 2013: 103 · 2012: 77
- FWCI
- 50.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, neurodevelopmental disorders, psychosis, schizophrenia risk factors, environmental risk factors, neuroimaging, antipsychotic treatment outcomes
- MeSH terms
- Cognition Disorders, Humans, Models, Neurological, Schizophrenia, Schizophrenic Psychology, History, 19th Century, History, 20th Century, History, 21st Century
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