The genetics of sensory gating deficits in schizophrenia
Abstract
Sensory gating abnormalities are an early clinical symptom of schizophrenia, and are characterized by a decrease in the brain's normal ability to inhibit the response to unimportant stimuli. Patients appear hypervigilant and have difficulty focusing their attention. A neurobiologic mechanism involved in these difficulties is nicotinic cholinergic modulation of inhibitory neuronal activity in the hippocampus. One measure of sensory gating abnormalities, diminished inhibition of the P50 evoked response to repeated auditory stimuli, has been linked to the chromosome 15q14 locus of the alpha-7-nicotinic receptor gene. This site is one of several that have shown evidence for linkage to schizophrenia, as well as to bipolar disorder, across several studies. Polymorphisms in the core promoter of the gene are associated with schizophrenia and also with diminished inhibition of the P50 response. These genetic data may identify a new pathophysiologic target for drug discovery.
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α7 nAChRs are implicated in prepulse inhibition, a physiological marker associated with schizophrenia.
“Genetic and functional studies have implicated α7 nAChRs in prepulse inhibition, a physiological marker associated with schizophrenia (Leonard et al. 2000;Freedman et al. 2003).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Freedman et al. 2003
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Endophenotypes in the Genetic Analyses of Mental Disorders
Cannon, T. D., & Keller, M. C. (2006) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.2.022305.095232 · Cited by 399 · see citing works
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P50 gating deficit in Alzheimer dementia correlates to frontal neuropsychological function
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Cholinergic Circuits and Signaling in the Pathophysiology of Schizophrenia
Berman, J. A., Talmage, D. A., & Role, L. W. (2007) · International Review of Neurobiology · doi:10.1016/s0074-7742(06)78007-2 · Cited by 47 · see citing works
- Authors
- Freedman, R., Olincy, A., Ross, R. G., Waldo, M. C., Stevens, K. E., Adler, L. E., & Leonard, S.
- Affiliations
- University of Colorado Health (US)
- Venue
- Current Psychiatry Reports
- Published
- 2003-04
- Volume
- 5
- Issue
- 2
- Pages
- 155-161
- ISSN
- 1523-3812 (ISSN-L)
- 1535-1645
- OpenAlex
- W1964697111
- Cited by
- 153
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2022: 7 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 1 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 19
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Psychiatry Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, alpha7 nicotinic acetylcholine receptor, hippocampus, bipolar disorder, genetic linkage, attention deficits
- MeSH terms
- Brain, gamma-Aminobutyric Acid, Humans, Neural Inhibition, Perceptual Disorders, Polymorphism, Genetic, Promoter Regions, Genetic, Receptors, Nicotinic, Schizophrenia, alpha7 Nicotinic Acetylcholine Receptor
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