The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
Open accessAbstract
A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1) , and BHLHE41(DEC2) . The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.
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“Notably, neural systems associated with affect, such as the limbic brain regions, monoamine neurotransmitters, and the hypothalamic–pituitary–adrenal axis (HPA), are all under circadian regulation27–31.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [27]
In the citing paper
“Further, examination of circadian patterns of gene expression within postmortem brains of patients with MDD demonstrate reduced amplitude, shifted peaks, and altered phase relationship between genes, particularly in canonical clock genes27.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [27]
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,328
Summaries of Affymetrix GeneChip probe level data
Irizarry, R. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng015 · Cited by 4,837
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · cited 2×
“This artifact is analogous to the phenomenon of population stratification in genetic association studies; thus, we adopted a correction method similar to the genomic control method (17).”
BackgroundMethodMolecular Bases for Circadian Clocks
Dunlap, J. C. (1999) · Cell · doi:10.1016/s0092-8674(00)80566-8 · Cited by 2,900
KEGG for representation and analysis of molecular networks involving diseases and drugs
Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M., & Hirakawa, M. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp896 · Cited by 2,322
Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock
Panda, S., Antoch, M. P., Miller, B. H., Su, A. I., Schook, A. C., Straume, M., Schultz, P. G., Kay, S. A., Takahashi, J. S., & Hogenesch, J. B. (2002) · Cell · doi:10.1016/s0092-8674(02)00722-5 · Cited by 2,310
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Labonté, B., Engmann, O., Purushothaman, I., Menard, C., Wang, J., Tan, C., Scarpa, J. R., Moy, G., Loh, Y.-H. E., Cahill, M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4386 · Cited by 748
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Mure, L. S., Le, H. D., Benegiamo, G., Chang, M. W., Ríos, L., Jillani, N., Ngotho, M., Kariuki, T., Dkhissi‐Benyahya, O., Cooper, H. M., et al. (2018) · Science · doi:10.1126/science.aao0318 · Cited by 791
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“Thus, while the circadian expression signature of the control brain can pinpoint the time of death within an hour of its actual occurrence, the pattern in depressed brains is time shifted, making it impossible to match the circadian signature of the brain with the time of death (Li et al., 2013; Bunney et al., 2015).”
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Metadata
- Authors
- 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., Schatzberg, A. F., Jones, E. G., Myers, R. M., Watson, S. J., Akil, H., & Bunney, W. E.
- Affiliations
- University of Michigan (US)
- University of California, Irvine (US)
- University of California, Davis (US)
- Weill Cornell Medicine (US)
- Stanford University (US)
- HudsonAlpha Institute for Biotechnology (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-05-13
- Volume
- 110
- Issue
- 24
- Pages
- 9950-9955
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3683716
- OpenAlex
- W2027764072
- Cited by
- 589
- References
- 59
- Citations by year
- 2026: 26 · 2025: 37 · 2024: 44 · 2023: 39 · 2022: 52 · 2021: 54 · 2020: 60 · 2019: 49 · 2018: 49 · 2017: 48 · 2016: 35 · 2015: 52 · 2014: 35 · 2013: 9
- FWCI
- 23.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (NIMH R01MH085801)
- National Institute of Mental Health (P50MH60398, R01MH085801, P50MH060398)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- major depressive disorder, circadian rhythm, clock genes, gene expression rhythms, human brain transcriptome, postmortem brain, dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, cerebellum, Bmal1, per gene, DBP, BHLHE40, BHLHE41, mood disorders
- MeSH terms
- Adult, Aged, Autopsy, Brain, Circadian Rhythm, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Homeodomain Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Basic Helix-Loop-Helix Proteins, ARNTL Transcription Factors, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1, Circadian Clocks
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