Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

Habets, Philippe C; Kalafatakis, Konstantinos; Dzyubachyk, Oleh; Werff, Steven J.A. van der; Keo, Arlin; Thakrar, J.; Mahfouz, Ahmed; Pereira, Alberto M; Russell, Georgina; Lightman, Stafford; Meijer, Onno C.

doi:10.1016/j.ynstr.2023.100514

Cited by 2 publications

(3 citation statements)

References 54 publications

(104 reference statements)

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“…The dataset includes 20,737 genes with unique Entrez IDs detected by 58,692 probes extracted from 3702 tissue samples from different sites (Arnatkeviciute et al, 2019 ; Hawrylycz et al, 2012 ). To screen the most representative probes to annotate genes, the probes showing 50% higher than background signal of brain samples in all subjects based on expression intensity were selected (Habets et al, 2023 ). Removing duplicate annotations and probes with low correlation with RNA‐seq data (Spearman Rho <0.2), 10,027 genes with unique Entrez IDs annotated by 10,027 probes were finally used for further analyses.…”

Section: Methodsmentioning

confidence: 99%

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Chen,

Yang,

et al. 2024

Human Brain Mapping

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Although Postpartum depression (PPD) and PPD with anxiety (PPD‐A) have been well characterized as functional disruptions within or between multiple brain systems, however, how to quantitatively delineate brain functional system irregularity and the molecular basis of functional abnormalities in PPD and PPD‐A remains unclear. Here, brain sample entropy (SampEn), resting‐state functional connectivity (RSFC), transcriptomic and neurotransmitter density data were used to investigate brain functional system irregularity, functional connectivity abnormalities and associated molecular basis for PPD and PPD‐A. PPD‐A exhibited higher SampEn in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) than healthy postnatal women (HPW) and PPD while PPD showed lower SampEn in PPC compared to HPW and PPD‐A. The functional connectivity analysis with MPFC and PPC as seed areas revealed decreased functional couplings between PCC and paracentral lobule and between MPFC and angular gyrus in PPD compared to both PPD‐A and HPW. Moreover, abnormal SampEn and functional connectivity were associated with estrogenic level and clinical symptoms load. Importantly, spatial association analyses between functional changes and transcriptome and neurotransmitter density maps revealed that these functional changes were primarily associated with synaptic signaling, neuron projection, neurotransmitter level regulation, amino acid metabolism, cyclic adenosine monophosphate (cAMP) signaling pathways, and neurotransmitters of 5‐hydroxytryptamine (5‐HT), norepinephrine, glutamate, dopamine and so on. These results reveal abnormal brain entropy and functional connectivities primarily in default mode network (DMN) and link these changes to transcriptome and neurotransmitters to establish the molecular basis for PPD and PPD‐A for the first time. Our findings highlight the important role of DMN in neuropathology of PPD and PPD‐A.

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Section: Methodsmentioning

confidence: 99%

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Chen,

Yang,

et al. 2024

Human Brain Mapping

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“…A much greater challenge to the pharmaceutical industry is to provide a truly physiological replacement with both normal circadian and ultradian rhythms. At present, this has only been successfully achieved using subcutaneous pump technology [91,93,94,106]. Although this is a very useful technique for patients whose symptoms have proved hard to control on oral steroids, improvements in miniaturization and cost will be needed before this becomes more widely available.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…These GC rhythm‐dependent changes suggest differential effects of pulsatile and constant infusions of cortisol on functioning corticolimbic brain regions. These data also allowed us to combine our fMRI data with human cell type and transcriptomic atlas data, which suggested that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function [93].…”

Section: Human Studiesmentioning

confidence: 99%

Circadian and ultradian rhythms: Clinical implications

Lightman,

Conway‐Campbell

2024

J Intern Med

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The hypothalamic–pituitary–adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of ‘continuous dynamic equilibration’ provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC‐dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well‐known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24‐h cortisol profiles – including during sleep – and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.

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Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

Cited by 2 publications

References 54 publications

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Circadian and ultradian rhythms: Clinical implications

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