No abstract

Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD.

Background: In Brazil, treatment of panic disorder is most frequently initiated with pharmacotherapy, but only half of the patients can be expected to be panic free after medication. Studies have suggested that individual or group cognitive-behavior therapy (CBT) is an effective treatment strategy for panic patients who have failed to respond to pharmacotherapy. Methods: Thirty-two patients diagnosed with panic disorder with agoraphobia having residual symptoms despite being on an adequate dose of medication were treated with 12 weeks of group CBT. The outcome was evaluated for panic frequency and severity, generalized anxiety, and global severity. Comorbid conditions, a childhood history of anxiety, and defense mechanism styles were assessed as potential predictors of treatment response. Results: Twenty-nine patients completed the 12-week protocol. Treatment was associated with significant reductions in symptom severity on all outcome measures (p < 0.001). Patients with depression had a poorer outcome of the treatment (p = 0.01) as did patients using more neurotic (p = 0.002) and immature defenses (p = 0.05). Conclusion: Consistent with previous reports, we found that CBT was effective for our sample of treatment-resistant patients. Among these patients, depression as well as neurotic defense style was associated with a poorer outcome. The use of CBT in Brazil for treatment-resistant and other panic patients is encouraged.

High power setting argon plasma coagulation combined with intensive acid suppression is an effective treatment for the total endoscopic ablation of Barrett's esophagus, at least in the short term. Long-term follow-up of treated patients in whom gastroesophageal reflux is surgically or medically alleviated seems mandatory before drawing definitive conclusions about this therapy.