Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor

Abstract

Half of the data points were inadvertently omitted from the published version of Fig. 4a; the statistical analyses in the text and figure legend, however, do refer to the complete data set. The corrected figure is shown here and has been corrected in the online versions of the paper.In addition, we present additional information to clarify two results reported in the Article regarding plasma pituitary adenylate cyclaseactivating polypeptide (PACAP) levels and post-traumatic stress disorder (PTSD) symptom associations. In the Article, we reported replication of the association between PACAP levels and hyperarousal subscale, because this was the most robust association in the initial cohort. We now present the analyses separately for initial, replication and combined cohorts in Table 1. All associations but one are significant in the replication cohort. The second issue concerns potential medical confounds that could underlie the reported association. Although we do not have medical chart data on most patients, we do have responses from a health questionnaire administered during collection of trauma history and other data. We have now reanalysed the associations for the PTSD symptom scale (PSS) hyperarousal and total symptoms using subjective reports of health condition from the questionnaires as covariates. These data are presented in Table 2 and do not show any effect of health-and illness-related questions on the relationship between PACAP and PTSD symptoms. None of these additions affect the results and conclusions of the original Article.

Asthma risk factors

“…65 In a study of more than 1200 (predominantly African American) adults exposed to traumatic events, the authors found implications of the pituitary adenylate cyclaseactivating peptide (PACAP)-PAC1 receptor pathway on the pathogenesis of PTSD. 66 In this study both PACAP38 (PACAP peptide containing 38 residues) blood levels and the C allele of a functional single-nucleotide polymorphism (SNP) (rs2267735) in an estrogen-receptor element of the gene for the PAC1 receptor (ADCYAP1R1) were significantly associated with PTSD or more PTSD symptoms in female but not in male subjects.…”

The Anxiety Spectrum and the Reflex Physiology of Defense: From Circumscribed Fear to Broad Distress

“…Longitudinal examination is necessary to determine whether these defensive and subjective response profiles are stable, time-invariant dispositions throughout the trajectories of anxious dysfunction, potentially reflecting genetic underpinnings. [147] Imagery-driven fearpotentiated startle might even be a useful endophenotype in investigations of genetic liability, preceding disorder onset. [148,149] Alternatively or additionally, we may be observing individuals at temporally different junctures in pathogenesis.…”

DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

“…This study detected a signature of DNA methylation that was associated with early life adversity (Borghol et al, 2011). Furthermore, the pituitary adenylate cyclase-activating polypeptide (PACAP) gene (ADCTAP1), a protein known to be involved in stress response in the pituitary, was found to be differentially methylated in peripheral blood cells in humans with posttraumatic stress syndrome (Ressler et al, 2011). Differences in DNA methylation of the GR promoter were also observed in peripheral blood cells among newborns exposed prenatally to maternal depression than a comparison group (Oberlander et al, 2008).…”