2013
DOI: 10.1073/pnas.1305814110
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Circadian patterns of gene expression in the human brain and disruption in major depressive disorder

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 c… Show more

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Cited by 493 publications
(438 citation statements)
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“…2). Their patterns of expression were strikingly similar across the two brain regions and also to those published previously (24), demonstrating the consistency in the use of these analyses to detect significant rhythms in gene expression in human postmortem tissue. The top 50 genes with significant circadian rhythms in expression are listed in Fig.…”
Section: Resultssupporting
confidence: 80%
See 1 more Smart Citation
“…2). Their patterns of expression were strikingly similar across the two brain regions and also to those published previously (24), demonstrating the consistency in the use of these analyses to detect significant rhythms in gene expression in human postmortem tissue. The top 50 genes with significant circadian rhythms in expression are listed in Fig.…”
Section: Resultssupporting
confidence: 80%
“…In the human brain, the investigation of brain region-specific transcriptional rhythms across the life span has been challenging due to the lack of control of environmental factors, such as time of death, sleep-wake cycles, and exposure to other factors known to influence rhythms. A recent study overcame some of these obstacles by ordering postmortem samples around a 24-h clock based on their time of death, essentially reconstructing a pseudotime series by treating each individual sample as an independently sampled data point over one 24-h cycle (24). In 55 healthy controls and 34 patients with major depressive disorder (MDD), they found robust expression rhythms of hundreds of genes in several brain regions in control subjects, with many of these genes displaying significantly disrupted or altered expression rhythms in subjects with MDD.…”
Section: Significancementioning
confidence: 99%
“…If major depression is due to lack of reward, the analysis of molecular profiles in the nucleus accumbens from CUMS‐induced depression and resilience should help to figure out the role of the nucleus accumbens in major depression and resilience based on molecules analyzed. The alternations of certain genes have not been observed in previous analyses (Bai et al, 2014; Elizalde et al, 2010; Li et al, 2013; Liu et al, 2015; Moreau, Bruse, David‐Rus, Buyske, & Brzustowicz, 2011; Rajkowska et al, 2015; Smalheiser et al, 2012, 2011, 2014), including Cckar , Tshr , Kcnj5 , Alox12 , Slc17a6 , Per2 , Rtn4r , and Nrn1 . These genes in the nucleus accumbens may be newly working for major depression or resilience.…”
Section: Discussionmentioning
confidence: 80%
“…30. For further information regarding data collection procedures, please see Li et al (31). Final control and MDD sample sizes can be found in Table 1, and demographics are in Table S3.…”
Section: Methodsmentioning
confidence: 99%