Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence?
Abstract
Converging evidence indicates that a profound reorganization of human brain function takes place during adolescence: the amount of deep sleep and the rate of brain metabolism fall sharply; the latency of certain event-related potentials declines; the capacity to recover function after brain injury diminishes; and adult problem-solving "power" appears. A reduction in cortical synaptic density has recently been observed and might account for all of these changes. Such synaptic "pruning" may be analogous to the programmed elimination of neural elements in very early development. A defect in this maturational process may underlie those cases of schizophrenia that emerge during adolescence.
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Reduced synaptic connectivity in schizophrenia stems from disturbed adolescent brain development, including myelogenesis and synaptic pruning.
“this reduced synaptic connectivity stems from disturbances of key events of brain development during late adolescence and early adulthood, including myelogenesis (Bartzokis, 2002; Bartzokis et al., 2003; Benes, 1989) and synaptic pruning (Feinberg, 1982; Keshavan et al., 1994; McGlashan and Hoffman, 2000)”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Feinberg, 1982
A deficit in synaptic pruning has long been proposed to contribute to schizophrenia onset.
“In light of the fact that PNNs are known to play a role in regulating developmental synaptic pruning in the cerebral cortex and that synaptic pruning deficit has long been speculated to contribute to the onset of schizophrenia (McGlashan and Hoffman, 2000; Feinberg, 1982; Keshavan et al., 1994)”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Feinberg, 1982
Some recent studies have inferred changes in the activity of dopaminergic neurons from variations in the blood oxygen level-dependent signal in midbrain nuclei.
“some recent studies have inferred changes in the activity of dopaminergic neurons on the basis of variations in the blood oxygen level-dependent signal in midbrain nuclei, 82,83”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [83]
Exaggerated pruning of synapses and dysconnectivity of neural networks are longstanding neurobiological models of schizophrenia, and convergent evidence points to synaptic pathways being integral to conferring schizophrenia risk.
“Interestingly, exaggerated pruning of synapses 92 and dysconnectivity of neural networks, 93 are longstanding neurobiological models of schizophrenia, and convergent evidence points to synaptic pathways being integral to conferring schizophrenia risk.”
From Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations (2025) · cites this paper as [92]
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Spencer, R. M. C., & Riggins, T. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2123415119 · Cited by 41 · see citing works
Poland, R. E., Cloak, C., Lutchmansingh, P. J., McCracken, J. T., Chang, L., & Ernst, T. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(98)00043-0 · Cited by 37 · see citing works
Across-night dynamics in traveling sleep slow waves throughout childhood
Schoch, S. F., Riedner, B. A., Deoni, S. C., Huber, R., LeBourgeois, M. K., & Kurth, S. (2018) · Sleep · doi:10.1093/sleep/zsy165 · Cited by 31 · see citing works
- Authors
- Feinberg, I.
- Affiliations
- San Francisco VA Medical Center (US)
- Corresponding author
- Feinberg, I.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 1982-01
- Volume
- 17
- Issue
- 4
- Pages
- 319-334
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2025011978
- Cited by
- 1,395
- References
- 4
- Citations by year
- 2026: 29 · 2025: 33 · 2024: 60 · 2023: 49 · 2022: 52 · 2021: 55 · 2020: 44 · 2019: 72 · 2018: 30 · 2017: 38 · 2016: 36 · 2015: 42 · 2014: 38 · 2013: 46 · 2012: 31
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, synaptic pruning, adolescence, brain maturation, slow-wave sleep, brain metabolism, event-related potentials, brain injury recovery
- MeSH terms
- Adolescent, Cell Count, Cerebral Cortex, Cognition, Dopamine, Electroencephalography, Energy Metabolism, Evoked Potentials, Frontal Lobe, Humans, Models, Neurological, Nerve Degeneration, Neuronal Plasticity, Neurons, Reaction Time, Schizophrenia, Sleep Stages, Synapses
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