Interoceptive hypersensitivity and interoceptive exposure in patients with panic disorder: specificity and effectiveness

BACKGROUND: Interoceptive exposure has been validated as an effective component of cognitive behavioral therapy (CBT) for the treatment of panic disorder but has hitherto received little research attention. We examined the effectiveness of various interoceptive exposure exercises using the Body Sensations Questionnaire (BSQ) (Chambless et al., 1984). METHODS: We first performed an exploratory principal factor analysis of all the items contained in the BSQ to obtain meaningful dimensions of interoceptive fears. Next, we examined the correlations between each interoceptive exposure task's degree of similarity to panic attacks and each BSQ factor and then examined whether the BSQ factor scores decreased in comparison with the baseline values when the corresponding exposure tasks were successfully completed by the subjects. RESULTS: The factor analyses revealed four factors, which we named "pseudoneurological fears", "gastrointestinal fears", "cardiorespiratory fears" and "fears of dissociative feelings." Among the nine interoceptive exposure tasks, 'hyperventilation', 'shaking head', 'holding breath' and 'chest breathing' were considered to reproduce pseudoneurological symptoms, 'breathing through a straw' was considered to reproduce gastrointestinal symptoms, and 'spinning' was considered to reproduce both pseudoneurological and dissociative symptoms; none of the interoceptive exercises were found to reproduce cardiorespiratory symptoms. Among each group of patients for whom 'hyperventilation', 'holding breath', 'spinning' or 'chest breathing' was effective, a significant improvement in the BSQ pseudoneurological fears factor scores was observed. On the other hand, no significant difference between the baseline and endpoint values of the BSQ gastrointestinal fears or the BSQ fears of dissociative feelings factor scores were observed among the patients for whom 'spinning' or 'breathing through a straw' was effective. CONCLUSION: Several interoceptive exposure tasks were particularly effective in reducing pseudoneurological fears. New interoceptive tasks, especially tasks related to cardiorespiratory and dissociative feelings, are needed

Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review

<p>Abstract</p> <p>Background:</p> <p>The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone.</p> <p>Methods:</p> <p>All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials.</p> <p>Results:</p> <p>Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6–12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment.</p> <p>One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials.</p> <p>Conclusion:</p> <p>Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.</p

On the buildup of massive early-type galaxies at z<~1. I- Reconciling their hierarchical assembly with mass-downsizing

Several studies have tried to ascertain whether or not the increase in abundance of the early-type galaxies (E-S0a's) with time is mainly due to major mergers, reaching opposite conclusions. We have tested it directly through semi-analytical modelling, by studying how the massive early-type galaxies with log(M_*/Msun)>11 at z~0 (mETGs) would have evolved backwards-in-time, under the hypothesis that each major merger gives place to an early-type galaxy. The study was carried out just considering the major mergers strictly reported by observations at each redshift, and assuming that gas-rich major mergers experience transitory phases of dust-reddened, star-forming galaxies (DSFs). The model is able to reproduce the observed evolution of the galaxy LFs at z<~1, simultaneously for different rest-frame bands (B, I, and K) and for different selection criteria on color and morphology. It also provides a framework in which apparently-contradictory results on the recent evolution of the luminosity function (LF) of massive, red galaxies can be reconciled, just considering that observational samples of red galaxies can be significantly contaminated by DSFs. The model proves that it is feasible to build up ~50-60% of the present-day mETG population at z<~1 and to reproduce the observational excess by a factor of ~4-5 of late-type galaxies at 0.8<z<1 through the coordinated action of wet, mixed, and dry major mergers, fulfilling global trends that are in general agreement with mass-downsizing. The bulk of this assembly takes place during ~1 Gyr elapsed at 0.8<z<1. The model suggests that major mergers have been the main driver for the observational migration of mass from the massive-end of the blue galaxy cloud to that of the red sequence in the last ~8 Gyr.(Abridged)Comment: Accepted for publication in Astronomy & Astrophysics; 21 pages, 8 figures. Minor corrections included, shortened title. Results and conclusions unchange

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)&gt;5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P&lt;5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development