Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia
Open accessAbstract
Background The etiology of dementia that occurs in patients with schizophrenia is not well understood. Nicotinic acetylcholine receptors have been implicated in cognitive function, and deficits in these receptors have been reported in schizophrenia.Methods The present study investigates possible associations of nicotinic receptor subunit expression in the dorsal lateral prefrontal cortex, an area known to be affected in schizophrenia, and dementia rating.Results alpha7 immunoreactivity was reduced by 20% to 28% and [(3)H]epibatidine binding was increased twofold in groups of patients with schizophrenia compared to normal control subjects matched for age, postmortem delay, and low levels of brain nicotine and cotinine. In contrast, no significant differences in alpha4, alpha3, or beta2 immunoreactivity or alpha7 messenger RNA expression were observed in schizophrenia patients compared with control subject values. Clinical dementia ratings in patients with schizophrenia were correlated with neither [(3)H]epibatidine binding nor nicotinic receptor subunit expression.Conclusions These data indicate no relationship between the trend for reduced neocortical alpha7 subunit protein expression in schizophrenia and dementia. Further investigations are required to establish whether the reduction in alpha7 protein in the dorsal lateral prefrontal cortex is associated with clinical features other than dementia in schizophrenia.
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Anomalies in the availability or expression of specific nAChR subunits have been implicated in depression and schizophrenia patients.
“Notably, anomalies in the availability or expression of specific nAChR subunits have been implicated in depression [104] and schizophrenia patients [105, 106].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [105]
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Gotti, C., & Clementi, F. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.006 · Cited by 970 · see citing works
Brain nicotinic acetylcholine receptors: native subtypes and their relevance
Gotti, C., Zoli, M., & Clementi, F. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.07.004 · Cited by 882 · see citing works
Neurophysiological Endophenotypes of Schizophrenia: The Viability of Selected Candidate Measures
Turetsky, B. I., Calkins, M. E., Light, G. A., D, A. O. M., Radant, A. D., & Swerdlow, N. R. (2006) · Schizophrenia Bulletin · doi:10.1093/schbul/sbl060 · Cited by 563 · see citing works
Sofouglu, M., Herman, A. I., Robinson, C. D., & Waters, A. J. (2014) · Lincoln (University of Nebraska) · Cited by 417 · see citing works
The Influence of Working-Memory Demand and Subject Performance on Prefrontal Cortical Activity
Rypma, B., Berger, J. S., & D’Esposito, M. (2002) · Journal of Cognitive Neuroscience · doi:10.1162/08989290260138627 · Cited by 364 · see citing works
Cognitive Effects of Nicotine: Recent Progress
Valentine, G. W., & Sofuoglu, M. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666171103152136 · Cited by 280 · see citing works
Jones, C. K., Byun, N. E., & Bubser, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.199 · Cited by 228 · see citing works
Smoking, nicotine and neuropsychiatric disorders
Döme, P., Lazáry, J., Kalapos, M. P., & Rihmer, Z. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.07.013 · Cited by 215 · see citing works
Schizophrenia and the α7 Nicotinic Acetylcholine Receptor
Martin, L. F., & Freedman, R. (2007) · International Review of Neurobiology · doi:10.1016/s0074-7742(06)78008-4 · Cited by 213 · see citing works
Nicotinic modulation of neuronal networks: from receptors to cognition
Mansvelder, H. D., van Aerde, K. I., Couey, J. J., & Brussaard, A. B. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0070-z · Cited by 201 · see citing works
Neuromodulation by acetylcholine: examples from schizophrenia and depression
Higley, M. J., & Picciotto, M. R. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.06.004 · Cited by 184 · see citing works
Leiser, S. C., Bowlby, M. R., Comery, T. A., & Dunlop, J. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.03.009 · Cited by 166 · see citing works
Wischhof, L., Irrsack, E., Osorio, C., & Koch, M. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.10.004 · Cited by 158 · see citing works
Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions
Nguyen, T. T., Eyler, L. T., & Jeste, D. V. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx069 · Cited by 154 · see citing works
Young, J. W., & Geyer, M. A. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.06.031 · Cited by 123 · see citing works
Cholinergic connectivity: it's implications for psychiatric disorders
Scarr, E., Gibbons, A. S., Neo, J. H., Udawela, M., & Dean, B. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00055 · Cited by 117 · see citing works
Cholinergic Modulation of Neuroinflammation: Focus on α7 Nicotinic Receptor
Piovesana, R., Intriago, M. S. S., Dini, L., & Tata, A. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094912 · Cited by 115 · see citing works
Hashimoto, K., Ishima, T., Fujita, Y., Matsuo, M., Kobashi, T., Takahagi, M., Tsukada, H., & Iyo, M. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.034 · Cited by 102 · see citing works
Delayed procedural learning in α7-nicotinic acetylcholine receptor knockout mice
Young, J. W., Meves, J. M., Tarantino, I. S., Caldwell, S., & Geyer, M. A. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00711.x · Cited by 93 · see citing works
Very poor outcome schizophrenia: Clinical and neuroimaging aspects
Mitelman, S. A., & Buchsbaum, M. S. (2007) · International Review of Psychiatry · doi:10.1080/09540260701486563 · Cited by 81 · see citing works
Nicotinic acetylcholine receptors: an overview on drug discovery
D’hoedt, D., & Bertrand, D. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220902841045 · Cited by 79 · see citing works
Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia
Coyle, J. T., Balu, D. T., Benneyworth, M. A., Basu, A. C., & Roseman, A. S. (2010) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2010.12.3/jcoyle · Cited by 75 · see citing works
Greenbaum, L., & Lerer, B. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.59 · Cited by 73 · see citing works
Young, J. W., Meves, J. M., & Geyer, M. A. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.028 · Cited by 69 · see citing works
Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia
Maurus, I., Hasan, A., Röh, A., Takahashi, S., Rauchmann, B., Keeser, D., Malchow, B., Schmitt, A., & Falkai, P. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-019-01025-w · Cited by 62 · see citing works
Evidence for a role of nicotinic acetylcholine receptors in schizophrenia
Catherine, E. A. (2007) · Frontiers in bioscience · doi:10.2741/2424 · Cited by 63 · see citing works
Mathew, S., Law, A. J., Lipska, B. K., Dávila‐García, M. I., Zamora, E. D., Mitkus, S. N., Vakkalanka, R., Straub, R. E., Weinberger, D. R., Kleinman, J. E., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm253 · Cited by 63 · see citing works
Hashimoto, K., Nishiyama, S., Ohba, H., Matsuo, M., Kobashi, T., Takahagi, M., Iyo, M., Kitashoji, T., & Tsukada, H. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003231 · Cited by 59 · see citing works
Hashimoto, K. (2015) · Current Pharmaceutical Design · doi:10.2174/1381612821666150605111345 · Cited by 53 · see citing works
Novel α7 nicotinic receptor isoforms and deficient cholinergic transcription in schizophrenia
Severance, E. G., & Yolken, R. H. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00323.x · Cited by 51 · see citing works
REVIEW: Cognitive effects of nicotine: genetic moderators
Herman, A. I., & Sofuoglu, M. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00213.x · Cited by 50 · see citing works
Role of the cholinergic system in the pathology and treatment of schizophrenia
Scarr, E., & Dean, B. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.9.1.73 · Cited by 41 · see citing works
Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to Therapeutic Perspectives
Jaco, A. D., Bernardini, L., Rosati, J. D., & Tata, A. M. (2016) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524916666160729111446 · Cited by 40 · see citing works
Duffy, Á., Zhou, P., Milner, T. A., & Pickel, V. M. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.04.024 · Cited by 40 · see citing works
Rycroft, N., Hutton, S. B., & Rusted, J. M. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0455-7 · Cited by 39 · see citing works
Rowe, A. R., Mercer, L., Casetti, V., Sendt, K.-V., Giaroli, G., Shergill, S. S., & Tracy, D. K. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114564096 · Cited by 38 · see citing works
Horti, A. G. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.07.030 · Cited by 37 · see citing works
Increased antibodies for the α7 subunit of the nicotinic receptor in schizophrenia
Chandley, M., Miller, M. N., Kwasigroch, C. N., Wilson, T. D., & Miller, B. E. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.01.023 · Cited by 36 · see citing works
Lyukmanova, E. N., Shenkarev, Z. O., Schulga, A. A., Ermolyuk, Y. S., Mordvintsev, D. Y., Utkin, Y. N., Shoulepko, M. A., Hogg, R. C., Bertrand, D., Dolgikh, D. A., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611263200 · Cited by 35 · see citing works
Georgiou, R., Lamnisos, D., & Giannakou, K. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.779607 · Cited by 34 · see citing works
Coura, R. S., Cressant, A., Xia, J., de Chaumont, F., Olivo‐Marin, J. C., Pelloux, Y., Dalley, J. W., & Granon, S. (2013) · The FASEB Journal · doi:10.1096/fj.13-231084 · Cited by 33 · see citing works
Proxy measures of premortem cognitive aptitude in postmortem subjects with schizophrenia
Glausier, J. R., Kelly, M. A., Salem, S., Chen, K., & Lewis, D. A. (2019) · Psychological Medicine · doi:10.1017/s0033291719000382 · Cited by 31 · see citing works
Ogawa, M., Nishiyama, S., Tsukada, H., Hatano, K., Fuchigami, T., Yamaguchi, H., Matsushima, Y., Ito, K., & Magata, Y. (2010) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2009.11.007 · Cited by 31 · see citing works
Cholinergic system in schizophrenia: A systematic review and meta-analysis
Saint-Georges, Z., MacDonald, J., Al-Khalili, R., Hamati, R., Solmi, M., Keshavan, M. S., Tuominen, L. J., & Guimond, S. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03023-y · Cited by 30 · see citing works
Strube, W., Bunse, T., Nitsche, M. A., Wobrock, T., Aborowa, R., Misewitsch, K., Herrmann, M., Falkai, P., & Hasan, A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.275 · Cited by 27 · see citing works
Veselinović, T., & Neuner, I. (2022) · CNS Drugs · doi:10.1007/s40263-022-00935-z · Cited by 28 · see citing works
Acheson, D. T., Twamley, E. W., & Young, J. W. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00103 · Cited by 26 · see citing works
Reynolds, L. M., Faure, P., & Barik, J. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03110-0 · Cited by 26 · see citing works
“Notably, anomalies in the availability or expression of speci fi c nAChR subunits have been implicated in depression [104] and schizophrenia patients [105, 106].”
Boggs, D. L., Carlson, J., Cortes-Briones, J., Krystal, J. H., & D’Souza, D. C. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612819666131216121019 · Cited by 26 · see citing works
Saur, T., DeMarco, S., Ortiz, A., Sliwoski, G. R., Hao, L., Wang, X., Cohen, B. M., & Buttner, E. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003313 · Cited by 25 · see citing works
Neves, G. A., & Grace, A. A. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0066-0 · Cited by 25 · see citing works
Othman, A. A., Lenz, R. A., Zhang, J., Li, J., Awni, W. M., & Dutta, S. (2011) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010370460 · Cited by 24 · see citing works
Iwata, Y., Nakajima, M., Yamada, K., Nakamura, K., Sekine, Y., Tsuchiya, K. J., Sugihara, G., Matsuzaki, H., Suda, S., Suzuki, K., et al. (2006) · Neuroscience Research · doi:10.1016/j.neures.2006.10.002 · Cited by 22 · see citing works
Cameli, C., Bacchelli, E., Paola, M. D., Giucastro, G., Cifiello, S., Collo, G., Cainazzo, M. M., Pini, L. A., Maestrini, E., & Zoli, M. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0223-2 · Cited by 22 · see citing works
Ogawa, M., Tsukada, H., Hatano, K., Ouchi, Y., Saji, H., & Magata, Y. (2009) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.32.337 · Cited by 21 · see citing works
Horti, A. G., Ravert, H. T., Gao, Y., Holt, D. P., Bunnelle, W. H., Schrimpf, M. R., Li, T., Ji, J., Valentine, H., Scheffel, U., et al. (2013) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2012.11.013 · Cited by 20 · see citing works
Chronic Nicotine Exposure has Dissociable Behavioural Effects on Control and Beta2−/− Mice
Besson, M., Suárez, S., Cormier, A., Changeux, J., & Granon, S. (2008) · Behavior Genetics · doi:10.1007/s10519-008-9216-1 · Cited by 19 · see citing works
Ogawa, M., Tatsumi, R., Fujio, M., Katayama, J., & Magata, Y. (2006) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2005.12.016 · Cited by 20 · see citing works
Bois, F., Gallezot, J., Zheng, M., Lin, S.-F., Esterlis, I., Cosgrove, K., Carson, R. E., & Huang, Y. H. (2014) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2014.08.003 · Cited by 19 · see citing works
Azimi, M., Oemisch, M., & Womelsdorf, T. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05430-w · Cited by 19 · see citing works
Eickhoff, S., Franzen, L., Korda, A. I., Rogg, H. V., Trulley, V.-N., Borgwardt, S., & Avram, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.909961 · Cited by 17 · see citing works
Severance, E. G., Dickerson, F., Stallings, C. R., Origoni, A. E., Sullens, A., Monson, E. T., & Yolken, R. H. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0164-y · Cited by 16 · see citing works
Kobayashi, S., Toyooka, N., Zhou, D., Tsuneki, H., Wada, T., Sasaoka, T., 酒井, 秀., Nemoto, H., Garraffo, H. M., Spande, T. F., et al. (2007) · Beilstein Journal of Organic Chemistry · doi:10.1186/1860-5397-3-30 · Cited by 15 · see citing works
Beinat, C., Reekie, T. A., Banister, S. D., O’Brien-Brown, J., Xie, T., Olson, T. T., Xiao, Y., Harvey, A. J., O'Connor, S. M., Coles, C. J., et al. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.03.025 · Cited by 14 · see citing works
PET tracers for imaging brain α7 nicotinic receptors: an update
Chalon, S., Vercouillie, J., Guilloteau, D., Suzenet, F., & Routier, S. (2015) · Chemical Communications · doi:10.1039/c5cc04536c · Cited by 13 · see citing works
Impact of Nicotine on Cognition in Patients With Schizophrenia: A Narrative Review
Spasova, V., Mehmood, S., Minhas, A., Azhar, R., Anand, S., Abdelaal, S., Sham, S., Chauhan, T. M., & Dragas, D. (2022) · Cureus · doi:10.7759/cureus.24306 · Cited by 13 · see citing works
Hippocampal Availability of the α7 Nicotinic Acetylcholine Receptor in Recent-Onset Psychosis
Wong, N. R., Rubin, L. H., Harrington, C. K., Jenkins, K. R., Shinehouse, L. K., Yoon, M., Kilgore, J. J., Soule, A. R., Lesniak, W. G., Rowe, S. P., et al. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.27163 · Cited by 10 · see citing works
Assessing the acute effects of CDP-choline on sensory gating in schizophrenia: A pilot study
Aidelbaum, R., Labelle, A., Baddeley, A., & Knott, V. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881117746903 · Cited by 10 · see citing works
Beyond monoamines: II. Novel applications for PET imaging in psychiatric disorders
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Origine et renouveau du concept de démence dans la schizophrénie
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Onde P50 dans la schizophrénie
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T-cell receptors modify neuronal function in the central nervous system
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Alterations of Neurotransmitter Receptors in Schizophrenia: Evidence from Postmortem Studies
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Telomeres and the ageing process
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Schizophrenia: A Complex Mental Illness
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Chapter 1 Cholinergic components of frontal lobe function and dysfunction
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Nicotinic Receptors in Brain Diseases
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Cholinergic Mechanisms in Schizophrenia
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Central Cholinergic Nervous System and Its Correlates
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Compensatory hallucinogenesis across three neuropsychiatric disorders: a Bayesian account
Vin, R., Galbraith, J. A., Seabury, R. D., Yi, H. Y., Hernández-Busot, G., Oland, L., Epié, B., Trainer, A. E., Fredericks, C. A., & Powers, A. (2026) · Brain Communications · doi:10.1093/braincomms/fcag001
- Authors
- Martin-Ruiz, C. M., Haroutunian, V. H., Long, P., Young, A. H., Davis, K. L., Perry, E. K., & Court, J. A.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Newcastle University (GB)
- Corresponding author
- Court, Jennifer A
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 54
- Issue
- 11
- Pages
- 1222-1233
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2041781351
- Cited by
- 100
- References
- 99
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institutes of Health (5p01mh045212-05)
- National Institute of Mental Health (MH 45212)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, dementia, nicotinic acetylcholine receptors, dorsolateral prefrontal cortex, epibatidine binding, receptor subunit expression, Clinical Dementia Rating, cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Cotinine, Dementia, Female, Humans, Male, Middle Aged, Nicotine, Psychiatric Status Rating Scales, Pyridines, Radioligand Assay, Receptors, Nicotinic, RNA, Messenger, Schizophrenia, Severity of Illness Index, Smoking, Case-Control Studies, Prefrontal Cortex, Bridged Bicyclo Compounds, Heterocyclic
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