Acid-base dysregulation and chemosensory mechanisms in panic disorder: a translational update.
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ABSTRACT:
SUBMITTER: Vollmer LL
PROVIDER: S-EPMC4471296 | biostudies-other | 2015 May
REPOSITORIES: biostudies-other
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Project description:An Epigenome-Wide Association Study (EWAS) was conducted to compare medication-free panic disorder (PD) patients (n=89) with healthy controls (n=76) in peripheral blood samples.
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Project description:Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was conducted to compare medication-free PD patients (n?=?89) with healthy controls (n?=?76) stratified by gender. Replication was sought in an independent sample (131 cases, 169 controls) and functional analyses were conducted in a third sample (N?=?71). DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. One genome-wide association surviving FDR of 5% (cg07308824, P?=?1.094?×?10-7, P-adj?=?0.046) was identified in female PD patients (N?=?49) compared to controls (N?=?48). The same locus, located in an enhancer region of the HECA gene, was also hypermethylated in female PD patients in the replication sample (P?=?0.035) and the significance of the association improved in the meta-analysis (P-adj?=?0.004). Methylation at this CpG site was associated with HECA mRNA expression in another independent female sample (N?=?71) both at baseline (P?=?0.046) and after induction by dexamethasone (P?=?0.029). Of 15 candidates, 5 previously reported as associated with PD or anxiety traits also showed differences in DNA methylation after gene-wise correction and included SGK1, FHIT, ADCYAP1, HTR1A, HTR2A. Our study examines epigenome-wide differences in peripheral blood for PD patients. Our results point to possible sex-specific methylation changes in the HECA gene for PD but overall highlight that this disorder is not associated with extensive changes in DNA methylation in peripheral blood.
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Project description:Objectives:Previous research on alexithymia has led to controversy over its prevalence in panic disorder. The aim of this study was to assess the difference in the prevalence of alexithymia in panic disorder and other anxiety disorders. Design and Methods:We performed a cross-sectional study on a sample of 71 patients diagnosed with panic disorder and 113 patients diagnosed with other anxiety disorders; both groups were 18-50 years old. Primary outcome was the 20-item Toronto Alexithymia Scale (TAS) score. Secondary outcome was the prevalence of alexithymia defined as a TAS score ?61. Results:Patients diagnosed with panic disorder had a 25% higher score on the TAS subscale of difficulty identifying feelings than patients diagnosed with other anxiety disorders. The prevalence of alexithymia was 27% in patients with panic disorder and 13% in patients with other anxiety disorders. Patients diagnosed with panic disorder had significantly higher odds for alexithymia. Conclusions:The results of our study support the hypothesis of higher prevalence of alexithymia in individuals with panic disorder than in individuals with other anxiety disorders. In addition, difficulty identifying feelings as a salient feature of alexithymia is higher in panic disorder than in other anxiety disorders.
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Project description:ImportanceThe persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions.ObjectiveTo evaluate the impact of celebrity mental health disclosures on the incidence and prevalence of panic disorder diagnosis in South Korea.Design, setting, and participantsThis cohort study included the entire South Korean population from January 2004 to December 2021, as reflected in the National Health Insurance Service data. Analysis was conducted from May 2022 through January 2024.ExposureTime periods analyzed included the timeframe before (from January 2004 to December 2010) and after the public disclosures of panic disorder by 3 high-profile Korean celebrities between December 2010 and January 2012 (from January 2011 to December 2021).Main outcomes and measuresMonthly incidence and prevalence of panic disorder, defined by the presence of a clinical diagnosis of the condition. Trends were assessed using interrupted time series analysis with autoregressive integrated moving average models. To assess public interest in panic disorder, trends in search data were analyzed, examining the association between the timing of increased searches and changes in the incidence and prevalence of panic disorder. Data on obsessive-compulsive disorder (OCD) were included as a control.ResultsThe study covered the entire population of South Korea, including 48 559 946 individuals in January 2004 and 52 593 886 individuals in December 2021. Before 2011, the mean (SD) annual prevalence of panic disorder was stable at 560 (140) persons per 100 000 persons per year. The celebrity disclosure in December 2010 was associated with higher monthly incidence rates of panic disorder, as measured by insurance claims data, changes that were observed in both the level (5.8 persons; 95% CI, 2.2-9.5 persons) and slope (0.78 persons per month; 95% CI, 0.19-1.40 persons per month) per 100 000 persons. By 2021, the observed annual prevalence per 100 000 persons reached 7530 persons, an increase of 775.6% compared with the 860 persons (95% CI, 330-1400 persons) estimated if the disclosures had not occurred. Internet searches anticipated changes in monthly prevalence with a lag of 2 or 3 months (F = 4.26, P = .02 and F = 3.11, P = .03, respectively). The celebrity disclosures had no significant association with the incidence or prevalence of OCD.Conclusions and relevanceIn this observational cohort study, celebrity disclosure of mental health conditions was associated with a sustained reduction in stigma, as reflected in increased help-seeking behavior for the condition over more than a decade. This underscores the influential role celebrities can play in shaping public health perceptions and behaviors, offering valuable insights for the development of future mental health policies and public awareness campaigns.
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Project description:BACKGROUND:While disruption of acid-base homeostasis has been pathoetiologically implicated in panic disorder (PD), the mechanism by which pH imbalance is translated to panic pathophysiology is poorly understood. Recently, in a translational rodent model of PD, we reported a role of microglial acid sensing G-protein coupled receptor, T cell death associated gene-8 (TDAG8) in panic-associated behavior and physiology. However, the clinical validity of the TDAG8 receptor has not been investigated. OBJECTIVE:To assess TDAG8 in PD, we evaluated TDAG8 receptor expression in adolescents and young adults with PD and healthy comparison subjects. METHODS:Relative expression of TDAG8 mRNA was determined in peripheral blood mononuclear cells from patients with PD, and compared to expression in healthy subjects. Linear models were utilized to evaluate the relationship between TDAG8 expression and panic disorder symptom severity scale (PDSS) score as well as other potential explanatory variables (e.g., CRP, body mass index, sex, age). Models were refined based on the estimated parameter significance, evidence of omitted variable bias and Bayesian/Akaike information criteria. RESULTS:Relative to healthy comparison subjects (n=17), expression of TDAG8 mRNA was significantly increased in patients with PD (n=15) (1.60±0.65 vs. 1.01±0.50, p=0.008). TDAG8 mRNA expression predicted PD symptom severity in a fixed effect model incorporating age and sex (p=0.003). CONCLUSIONS:Collectively, our results suggest greater TDAG8 expression in patients with PD compared to healthy subjects, and directly link TDAG8 expression and the severity of the PD symptoms. Further investigation of the TDAG8 receptor in panic pathophysiology is warranted.
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Project description:A considerable body of evidence suggests the involvement of serotonin neurotransmission in the pathogenesis of panic disorder. Research on pathways and functions of tryptophan, an essential amino acid converted into serotonin, may advance our understanding of serotonergic actions in panic disorder and related phenomena. The investigative approaches in this field include manipulations of tryptophan availability as well as genetic association and functional brain imaging studies. In this review we examine the principle findings of these studies and propose further research directions.
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