ArticleProceedings of the National Academy of Sciences of the United States of America2013
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 306 papers, 2 of them syntheses that pooled it.
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Who cites it
306 citing papers in PubMed, 2 syntheses or guidelines pooled it, 596 citations in OpenAlex.
- Identification of suicide brain transcriptomic signatures using meta-analysis of multiple cohorts.Translational psychiatry · 2026Pooled it
- Depressive symptom screening in elderly by passive sensing data of smartphones or smartwatches: A systematic review.PloS one · 2024Pooled it
- Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study.Translational psychiatry · 2025Trial
- Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression.Translational psychiatry · 2024Trial
- Response to therapeutic sleep deprivation: a naturalistic study of clinical and genetic factors and post-treatment depressive symptom trajectory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies.Journal of biological rhythms · 2026Review
- Extracellular vesicles for liquid biopsy in major depressive disorder: Human evidence and clinical translation.iScience · 2026Review
- Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness.Molecular psychiatry · 2026Article
- Daily Rhythms in Clock Gene mRNA Expression in Serotonergic Brain Regions of Adult Male Rats.Journal of biological rhythms · 2026Article
- Chronic REM Sleep Deprivation Induces Metabolic and Neurotoxic Alterations Associated with Affective and Cognitive Deficit in Male Wistar Rats: Involvement of HPA Axis, Cholinergic, Inflammatory, and Oxidative Stress Pathways.Neurochemical research · 2026Article
- Biochemical Regulation of Brain Kynurenic Acid Synthesis and Inhibition in Rats Is Sensitive to the Time of Day.ACS chemical neuroscience · 2026Article
- Human Cerebral Blood Flow Activity with Diurnal Variation Differentially Correlated with the Suprachiasmatic Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Sleep Maintenance Insomnia in Older Adults: Cardiometabolic Comorbidities and Evidence of Antiviral Pathways Activation from Blood Transcriptome and dsRNA Expression Analyses.International journal of molecular sciences · 2026Article
- The mPFC molecular clock mediates the effects of sleep deprivation on depression-like behavior and regulates sleep consolidation and homeostasis.Molecular psychiatry · 2026Article
- Systems genomics reveals age- and sex-dependent metabolic dysregulation fromPhysiological genomics · 2026Article
- Protein Acylation Modifications in Sleep Disorders: Mechanisms and Therapeutic Potential.Journal of molecular neuroscience : MN · 2026Review
- Xylooligosaccharide in combination with Lactobacillus rhamnosus ameliorates disturbed circadian rhythm and associated neurological internal desynchronization by maintaining homeostasis of neuroactive molecules and gut microbiome.Archives of microbiology · 2026Article
- Spatial transcriptomics reveals brain-wide circadian disruption in an Alzheimer's disease model.bioRxiv : the preprint server for biology · 2026Article
- CCorGsDB: a database for clock correlated genes in the mouse and human central nervous systems.Npj biological timing and sleep · 2026Article
- Defining functional states and roles of microglia in neuropsychiatric disorders.Frontiers in cellular neuroscience · 2026Review
246 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.