Diurnal rhythms in gene expression in the prefrontal cortex in schizophrenia
Open accessAbstract
Schizophrenia is associated with disrupted cognitive control and sleep-wake cycles. Here we identify diurnal rhythms in gene expression in the human dorsolateral prefrontal cortex (dlPFC), in schizophrenia and control subjects. We find significant diurnal (24 h) rhythms in control subjects, however, most of these transcripts are not rhythmic in subjects with schizophrenia. Instead, subjects with schizophrenia have a different set of rhythmic transcripts. The top pathways identified in transcripts rhythmic only in subjects with schizophrenia are associated with mitochondrial function. Importantly, these rhythms drive differential expression patterns of these and several other genes that have long been implicated in schizophrenia (including BDNF and GABAergic-related transcripts). Indeed, differential expression of these transcripts is only seen in subjects that died during the night, with no change in subjects that died during the day. These data provide insights into a potential mechanism that underlies changes in gene expression in the dlPFC with schizophrenia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genes previously implicated in schizophrenia (i.e., BDNF and GABAergic-related transcripts) were differentially expressed in schizophrenia subjects that died during the night.
“Additionally, genes that have previously been implicated in SZ (i.e. BDNF and GABAergic-related transcripts) were differentially expressed in SZ subjects that died during the night148.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [148]
Using postmortem brain tissues, Seney and colleagues demonstrated that subjects with schizophrenia lost rhythmicity in most genes within the prefrontal cortex that were rhythmic in healthy controls, but gained rhythmicity in a completely different set of genes not seen in healthy controls (e.g., mitochondrial related genes).
“Using postmortem brain tissues, Seney and colleagues148 demonstrated that subjects with SZ lost rhythmicity in most genes within the prefrontal cortex that were rhythmic in healthy controls. However, subjects with SZ gained rhythmicity in completely different set of genes not seen in healthy controls (e.g. mitochondrial related genes).”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [148]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692 · see citing works
Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E., & Storey, J. D. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts034 · Cited by 6,231 · see citing works
A circadian gene expression atlas in mammals: Implications for biology and medicine
Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408886111 · Cited by 2,304 · see citing works
Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
Gandal, M. J., Haney, J. R., Parikshak, N. N., Leppa, V., Ramaswami, G., Hartl, C., Schork, A. J., Appadurai, V., Buil, A., Werge, T. M., et al. (2018) · Science · doi:10.1126/science.aad6469 · Cited by 1,095 · see citing works
Gene expression elucidates functional impact of polygenic risk for schizophrenia
Fromer, M., Roussos, P., Sieberts, S. K., Johnson, J. S., Kavanagh, D. H., Perumal, T. M., Ruderfer, D. M., Oh, E. C., Topol, A., Shah, H. R., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4399 · Cited by 1,091 · see citing works
Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06315.2003 · Cited by 938 · see citing works
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
Li, J. Z., Bunney, B. G., Meng, F., Hagenauer, M. H., Walsh, D. M., Vawter, M. P., Evans, S. J., Choudary, P. V., Cartagena, P., Barchas, J. D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305814110 · Cited by 589 · see citing works
Callaghan, J. T., Bergstrom, R. F., Ptak, L. R., & Beasley, C. M. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199937030-00001 · Cited by 544 · see citing works
Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation
Miller, B. H., McDearmon, E. L., Panda, S., Hayes, K. R., Zhang, J., Andrews, J. L., Antoch, M. P., Walker, J. R., Esser, K. A., Hogenesch, J. B., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611724104 · Cited by 509 · see citing works
Iwamoto, K., Bundo, M., & Kato, T. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi022 · Cited by 496 · see citing works
Hashimoto, T., Arion, D., Unger, T., Maldonado-Avilés, J. G., Morris, H. M., Volk, D. W., Mirnics, K., & Lewis, D. A. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002011 · Cited by 490 · see citing works
Plaisier, S. B., Taschereau, R., Wong, J. A., & Graeber, T. G. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq636 · Cited by 468 · see citing works
Gene Expression Profiling Reveals Alterations of Specific Metabolic Pathways in Schizophrenia
Middleton, F. A., Mirnics, K., Pierri, J. N., Lewis, D. A., & Levitt, P. R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02718.2002 · Cited by 428 · see citing works
Sleep and circadian rhythm disruption in schizophrenia
Wulff, K., Dijk, D.-J., Middleton, B., Foster, R. G., & Joyce, E. M. (2012) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.096321 · Cited by 426 · see citing works
Clinical Pharmacokinetics of Quetiapine
DeVane, C. L., & Nemeroff, C. B. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140070-00003 · Cited by 390 · see citing works
Hashimoto, T., Bergen, S. E., Nguyen, Q. L., Xu, B., Monteggia, L. M., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4035-04.2005 · Cited by 384 · see citing works
Beasley, C. L., Zhang, Z. J., Patten, I., & Reynolds, G. P. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01360-4 · Cited by 374 · see citing works
Core circadian protein CLOCK is a positive regulator of NF-κB–mediated transcription
Spengler, M. L., Kuropatwinski, K. K., Comas, M., Gasparian, A. V., Fedtsova, N. G., Gleiberman, A. S., Gitlin, I. I., Artemicheva, N. M., Deluca, K. A., Gudkov, A. V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206274109 · Cited by 331 · see citing works
Cahill, K. M., Huo, Z., Tseng, G. C., Logan, R. W., & Seney, M. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-27903-2 · Cited by 294 · see citing works
Self-citationEffects of aging on circadian patterns of gene expression in the human prefrontal cortex
Chen, C.-Y., Logan, R. W., Ma, T., Lewis, D. A., Tseng, G. C., Sibille, E., & McClung, C. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508249112 · Cited by 277 · see citing works
Self-citationAlterations in cortical interneurons and cognitive function in schizophrenia
Dienel, S. J., & Lewis, D. A. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.06.020 · Cited by 267 · see citing works
Morris, H. M., Hashimoto, T., & Lewis, D. A. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhm186 · Cited by 213 · see citing works
Schizophrenia and sleep disorders: links, risks, and management challenges
Kaskie, R. E., Graziano, B., & Ferrarelli, F. (2017) · Nature and Science of Sleep · doi:10.2147/nss.s121076 · Cited by 201 · see citing works
Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons
Woo, T., Miller, J. L., & Lewis, D. A. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.7.1013 · Cited by 191 · see citing works
Delta Sleep Deficits in Schizophrenia: Evidence From Automated Analyses of Sleep Data
Keshavan, M. S., Reynolds, C. F., Miewald, J. M., Montrose, D. M., Sweeney, J. A., Vasko, R. C., & Kupfer, D. J. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.5.443 · Cited by 185 · see citing works
Cermakian, N., Waddington Lamont, E., Boudreau, P., & Boivin, D. B. (2011) · Journal of Biological Rhythms · doi:10.1177/0748730410395732 · Cited by 175 · see citing works
A hypothalamic circuit for the circadian control of aggression
Todd, W. D., Fenselau, H., Wang, J. L., Zhang, R., Machado, N. L., Venner, A., Broadhurst, R. Y., Kaur, S., Lynagh, T., Olson, D. P., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0126-0 · Cited by 154 · see citing works
Reinhart, V., Bove, S. E., Volfson, D., Lewis, D. A., Kleiman, R. J., & Lanz, T. A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.03.011 · Cited by 139 · see citing works
Molecular Mechanisms and Timing of Cortical Immune Activation in Schizophrenia
Volk, D. W., Chitrapu, A., Edelson, J. R., Roman, K. M., Moroco, A. E., & Lewis, D. A. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15010019 · Cited by 137 · see citing works
Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin
Green, C. B., & Besharse, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14884 · Cited by 134 · see citing works
Altered circadian clock gene expression in patients with schizophrenia
Johansson, A.-S., Owe-Larsson, B., Hetta, J., & Lundkvist, G. B. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.04.029 · Cited by 120 · see citing works
Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in micePreprint
Hong, H., Maury, E., Ramsey, K. M., Perelis, M., Marcheva, B., Omura, C., Kobayashi, Y., D, D. C. G., Barish, G. D., & Bass, J. T. (2018) · Genes & Development · doi:10.1101/gad.319228.118 · Cited by 114 · see citing works
Evidence of Mitochondrial Dysfunction within the Complex Genetic Etiology of Schizophrenia
Hjelm, B. E., Rollins, B. L., Mamdani, F., Lauterborn, J. C., Kirov, G., LYNCH, G. S., Gall, C. M., Sequeira, A., & Vawter, M. P. (2015) · Complex Psychiatry · doi:10.1159/000441252 · Cited by 94 · see citing works
Citrome, L. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000665 · Cited by 92 · see citing works
Volk, D. W., Moroco, A. E., Roman, K. M., Edelson, J. R., & Lewis, D. A. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.06.015 · Cited by 92 · see citing works
Lewis, D. A., Hashimoto, T., & Morris, H. M. (2008) · Neurotoxicity Research · doi:10.1007/bf03033813 · Cited by 79 · see citing works
Wang, X., Lin, Y., Song, C., Sibille, E. L., & Tseng, G. C. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-52 · Cited by 74 · see citing works
Self-citationCastelnovo, A., Graziano, B., Ferrarelli, F., & D’Agostino, A. (2017) · European Journal of Neuroscience · doi:10.1111/ejn.13815 · Cited by 64 · see citing works
Sundowning and circadian rhythm disorders in dementia.
Klaffke, S., & Staedt, J. (2006) · PubMed · Cited by 58 · see citing works
Mapping pathologic circuitry in schizophrenia
Glausier, J. R., & Lewis, D. A. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63639-3.00025-6 · Cited by 52 · see citing works
Tsubomoto, M., Kawabata, R., Zhu, X., Minabe, Y., Chen, K., Lewis, D. A., & Hashimoto, T. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy227 · Cited by 51 · see citing works
“Sundowning” as a biological phenomenon: current understandings and future directions: an update
Gnanasekaran, G. (2016) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0431-3 · Cited by 38 · see citing works
Circadian rhythms and cognition in schizophrenia
Wulff, K., & Joyce, E. M. (2011) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.110.085068 · Cited by 34 · see citing works
Hufford, M. R., Davis, V. G., Hilt, D. C., Dgetluck, N., Geffen, Y., Loebel, A. D., Haig, G. M., Santarelli, L., & Keefe, R. S. E. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.07.018 · Cited by 16 · see citing works
Olanzapine: a review of rapid and long-acting parenteral formulations
Owen, R. T. (2010) · Drugs of today · doi:10.1358/dot.2010.46.3.1476499 · Cited by 16 · see citing works
Preliminary Study on Quantitative Sleep EEG Characteristics in Patients with Schizophrenia
Oh, S. M., Lee, Y. J., Kim, J., Choi, J. W., & Jeong, D. U. (2017) · Psychiatry Investigation · doi:10.4306/pi.2017.14.2.219 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
McCarthy, M. J., Gottlieb, J. F., Gonzalez, R., McClung, C. A., Alloy, L. B., Cain, S., Dulcis, D., Etain, B., Frey, B. N., Garbazza, C., et al. (2022) · Bipolar Disorders · doi:10.1111/bdi.13165 · Cited by 136 · see citing works
Self-citationDisrupted sleep and circadian rhythms in schizophrenia and their interaction with dopamine signaling
Ashton, A., & Jagannath, A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00636 · Cited by 106 · see citing works
- Authors
- Seney, M. L., Cahill, K., Enwright, J. F., Logan, R. W., Huo, Z., Zong, W., Tseng, G., & McClung, C. A.
- Affiliations
- University of Pittsburgh (US)
- University of Florida (US)
- Corresponding author
- McClung, Colleen A.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-08-09
- Volume
- 10
- Issue
- 1
- Pages
- 3355-3355
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6689017
- OpenAlex
- W2969073480
- Cited by
- 108
- References
- 47
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 19 · 2023: 12 · 2022: 13 · 2021: 22 · 2020: 16 · 2019: 3
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH111601)
- Brain and Behavior Research Foundation
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, diurnal cycle, gene expression, dorsolateral prefrontal cortex, circadian rhythm, mitochondrial function, brain-derived neurotrophic factor, differential gene expression, sleep-wake cycle, cognitive control
- MeSH terms
- Adult, Circadian Rhythm, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Schizophrenia, Antipsychotic Agents, Cohort Studies, Case-Control Studies, Prefrontal Cortex, Sequence Analysis, RNA, Gene Expression Profiling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
