Schizophrenia—An Overview
Abstract
Importance: Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations: The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance: Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D 2 receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.
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It has been suggested that subcortical dopamine dysfunction is the downstream consequence of dysregulation in glutamatergic function in frontal cortical regions linked to altered synaptic pruning and/or hippocampal regulation of midbrain dopamine neurons.
“It has been suggested that subcortical dopamine dysfunction is the downstream consequence of dysregulation in glutamatergic function in frontal cortical regions linked to altered synaptic pruning and/or hippocampal regulation of midbrain dopamine neurons (134, 136, 139).”
From Aberrant Salience, Information Processing, and Dopaminergic Signaling in People at Clinical High Risk for Psychosis (2020) · cites this paper as [134]
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- Authors
- McCutcheon, R. A., Reis Marques, T., & Howes, O. D.
- Affiliations
- King's College London (GB)
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, United Kingdom
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2020-02-01
- Volume
- 77
- Issue
- 2
- Pages
- 201
- ISSN
- 2168-622X (ISSN-L)
- OpenAlex
- W2982685163
- Cited by
- 1,481
- References
- 24
- Citations by year
- 2026: 246 · 2025: 313 · 2024: 298 · 2023: 257 · 2022: 216 · 2021: 106 · 2020: 42 · 2019: 2 · 2018: 1
- FWCI
- 15.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (200102/Z/15/Z, 094849/Z/10/Z)
- National Institute for Health and Care Research (CL-2019-17-004)
- Medical Research Council (MR/L022176/1, MR/N026063/1, MR/N027078/1)
- 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, prodromal symptoms, early life risk factors, brain development, excitatory-inhibitory imbalance, negative symptoms, cognitive symptoms, positive symptoms, psychosocial stress, dopaminergic dysfunction, frontal and temporal cortex, dopamine D2 receptor antagonists, antipsychotic adverse effects, treatment goals
- MeSH terms
- Brain, Humans, Schizophrenia, Antipsychotic Agents
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