ArticleScientific reports2016
Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04181008 (Pharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The role of acid-sensitive ion channels in panic disorder: a systematic review of animal studies and meta-analysis of human studies.Translational psychiatry · 2018Pooled it
- Population Pharmacokinetics of Intranasal Amiloride in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2026Trial
- Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice.Neurobiology of stress · 2024Article
- Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.Current neuropharmacology · 2024Article
- Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride.Science advances · 2023Article
- Estrogens, age, and, neonatal stress: panic disorders and novel views on the contribution of non-medullary structures to respiratory control and COFrontiers in physiology · 2023Review
- Article
- Neuroimmune mechanisms in fear and panic pathophysiology.Frontiers in psychiatry · 2022Review
- Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety.Frontiers in psychiatry · 2021Review
- High Behavioral Sensitivity to Carbon Dioxide Associates with Enhanced Fear Memory and Altered Forebrain Neuronal Activation.Neuroscience · 2020Article
- The Potential Role of Epigenetic Drugs in the Treatment of Anxiety Disorders.Neuropsychiatric disease and treatment · 2020Review
- Article
- Genetic associations with suicide attempt severity and genetic overlap with major depression.Translational psychiatry · 2019Article
- Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings From Two Monozygotic Twin Studies.Psychosomatic medicine · 2018Observational
- Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for COScientific reports · 2018Article
- Methodological Challenges in Developmental Human Behavioral Epigenetics: Insights Into Study Design.Frontiers in behavioral neuroscience · 2018Article
- Differential behavioral sensitivity to carbon dioxide (CONeuroscience · 2017Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders.
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Registered trials
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.