ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- 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
- Lateral septal PACAP signaling regulates stress and anxiety reactions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Bed Nucleus of the Stria Terminalis PACAP Signaling in the Dorsal Medial Habenula Mediates Depression-Related Behavioral Responses After Chronic Stress.Biological psychiatry · 2026Article
- The ventral hippocampus to paraventricular thalamus circuit regulates context-dependent hyperlocomotion through PAC1 receptor signaling in the chronic stress-induced PTSD mouse model.Translational psychiatry · 2026Article
- Disruption of Pre-Bötzinger Complex neuropeptidergic tonality controls fear and metabolic response.bioRxiv : the preprint server for biology · 2026Article
- Use of Single Prolonged Stress to Model Post-traumatic Stress Disorder in Rodents: What We Found and Where to Next?Current neuropharmacology · 2026Review
- Pituitary adenylate cyclase-activating polypeptide modulates circadian feeding and emotional behavior in mice independent of stress-induced hyperphagia.Veterinary world · 2025Article
- PACAP Signalling Network in the Nucleus Accumbens Core Regulates Reinstatement Behaviour in Rat.Addiction biology · 2025Article
- Associations between PACAP levels and psychophysiological indicators of fear and arousal in adults with posttraumatic stress symptoms.Journal of mood and anxiety disorders · 2025Article
- Involvement of Matrix Metalloproteinases (MMP-2 and MMP-9), Inflammasome NLRP3, and Gamma-Aminobutyric Acid (GABA) Pathway in Cellular Mechanisms of Neuroinflammation in PTSD.International journal of molecular sciences · 2025Article
- Connectometry reveals differing associations of cortisol and PACAP with dorsal cingulum microstructure in posttraumatic stress.medRxiv : the preprint server for health sciences · 2025Article
- Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models.Molecular psychiatry · 2025Review
- Causal relationship between rosacea and psychiatric disorders: a bidirectional two-sample Mendelian randomization study.Archives of dermatological research · 2025Article
- PACAP associated with precise PTSD and fear extinction response in women.Psychoneuroendocrinology · 2025Article
- PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.Frontiers in neuroscience · 2025Review
- Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.European journal of psychotraumatology · 2024Article
- Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.Frontiers in psychiatry · 2024Review
- Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.
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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 Socratic graph.