ArticleTranslational psychiatry2016
Functional evaluation of a PTSD-associated genetic variant: estradiol regulation and ADCYAP1R1.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Hormonal mechanisms of women's risk in the face of traumatic stress.Proceedings of the National Academy of Sciences of the United States of America · 2025Trial
- Identification of an intrusive-hypervigilant phenotype of posttraumatic stress symptoms with unique stress peptide and amygdala functional connectivity profiles.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy.Molecular psychiatry · 2026Article
- The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.Journal of neuroendocrinology · 2026Review
- PACAP a mediator of inflammation following trauma exposure and mild traumatic brain injury: Differential effects in males and females.Brain, behavior, and immunity · 2025Article
- Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models.Molecular psychiatry · 2025Review
- PACAP associated with precise PTSD and fear extinction response in women.Psychoneuroendocrinology · 2025Article
- Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.Frontiers in neuroscience · 2025Review
- Article
- Testing Quantitative and Qualitative Sex Effects in a National Swedish Twin-Sibling Study of Posttraumatic Stress Disorder.The American journal of psychiatry · 2024Article
- Differential effects of the stress peptides PACAP and CRF on sleep architecture in mice.NPP - digital psychiatry and neuroscience · 2024Article
- Assessment of the Genetic Characteristics of a Generation Born during a Long-Term Socioeconomic Crisis.Genes · 2023Article
- PACAP Controls Endocrine and Behavioral Stress Responses via Separate Brain Circuits.Biological psychiatry global open science · 2023Article
- The functional heterogeneity of PACAP: Stress, learning, and pathology.Neurobiology of learning and memory · 2023Review
- Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.Journal of nanobiotechnology · 2023Article
- Does age matter in genetics? The role of ADCYAP1R1 in sex-specific risk for posttraumatic stress disorder in trauma-exposed preadolescent children.Journal of psychiatric research · 2023Article
- Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2023Article
- Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- The role of estrogen receptor manipulation during traumatic stress on changes in emotional memory induced by traumatic stress.Psychopharmacology · 2023Article
- Effect ofBiology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Posttraumatic stress disorder (PTSD) affects 5-10% percent of the US adult population with a higher prevalence among women compared with men. Although it remains unclear how biological sex associates with susceptibility to PTSD, one mechanism may involve a role for estrogen in a gene by environment interaction. We previously demonstrated a sex-dependent association between the pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) and PTSD, where carriers of a C allele at single-nucleotide polymorphism (SNP) rs2267735 within the PAC1 receptor gene (ADCYAP1R1) have increased symptoms of PTSD. This SNP is located within a predicted estrogen response element (ERE), which regulates gene transcription when bound to estradiol (E2) activated estrogen receptor alpha (ERα). In the current study, we examined E2 regulation of ADCYAP1R1 in vitro, in cell culture, and in vivo in mice and humans. We find in mice that fear conditioning and E2 additively increase ADCYAP1R1 expression. In vitro, we show that E2/ERα binds to the ADCYAP1R1 ERE, with less efficient binding to an ERE containing the C allele of rs2267735. In women with low serum E2, the CC genotype associates with lower ADCYAP1R1 expression, which further associates with higher PTSD symptoms. These findings lead to a model in which E2 induces the expression of ADCYAP1R1 through binding of ERα at the ERE as an adaptive response to stress. Inhibition of E2/ERα binding to the ERE containing the rs2267735 risk allele results in reduced expression of ADCYAP1R1, diminishing estrogen regulation as an adaptive stress response and increasing risk for PTSD.
Indexed as
Identifiers
What OpenQuestion holds
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.