ArticleMolecular psychiatry2016
Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 3 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Pooled it
- Identifying Risk Genes and Interpreting Pathogenesis for Parkinson's Disease by a Multiomics Analysis.Genes · 2020Pooled it
- Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.Molecular psychiatry · 2016Pooled it
- Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross-validation machine learning approach.International journal of methods in psychiatric research · 2020Trial
- The effect of human-specific genetic variants on neuronal spinogenesis.Frontiers in genetics · 2026Review
- Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis.Genes · 2023Article
- Article
- Neuroimmune connections between corticotropin-releasing hormone and mast cells: novel strategies for the treatment of neurodegenerative diseases.Neural regeneration research · 2021Review
- Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings.Translational psychiatry · 2020Article
- Sex differences in fear regulation and reward-seeking behaviors in a fear-safety-reward discrimination task.Behavioural brain research · 2019Article
- Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats.Behavioural brain research · 2019Article
- FAAH genotype, CRFR1 genotype, and cortisol interact to predict anxiety in an aging, rural Hispanic population: A Project FRONTIER study.Neurobiology of stress · 2019Article
- Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity.Biological psychiatry · 2018Review
- Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents.Metabolic brain disease · 2018Article
- The genetics of human personality.Genes, brain, and behavior · 2018Review
- A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N=223,773).EBioMedicine · 2018Article
- "DNA Methylation signatures in panic disorder".Translational psychiatry · 2017Article
- Modeling prior information of common genetic variants improves gene discovery for neuroticism.Human molecular genetics · 2017Article
- GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.Molecular psychiatry · 2017Article
- Anxiety disorders.Nature reviews. Disease primers · 2017Review
Corrections and comments
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Authors and funding
30 authors at 13 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.
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