Assessing Panic: Bridging the Gap Between Fundamental Mechanisms and Daily Life Experience

Panic disorder (PD) is one of the most common psychiatric disorders. Recurrent, unexpected panic attacks (PAs) are the primary symptom and strongly impact patients’ quality of life. Clinical manifestations are very heterogeneous between patients, emphasizing the need for a dimensional classification integrating various aspects of neurobiological and psychological circuits in line with the Research Domain Criteria (RDoC) proposed by the US National Institute of Mental Health. To go beyond data that can be collected in the daily clinical situation, experimental panic provocation is widely used, which has led to important insights into involved brain regions and systems. Genetic variants can determine the sensitivity to experimental models such as carbon dioxide (CO2) exposure and can increase the risk to develop PD. Recent developments now allow to better assess the dynamic course of PAs outside the laboratory in patients’ natural environment. This can provide novel insights into the underlying mechanisms and the influence of environmental factors that can alter gene regulation by changing DNA methylation. In this mini review, we discuss assessment of PAs in the clinic, in the laboratory using CO2 exposure, genetic associations, and the benefits of real-life assessment and epigenetic research

Priming associations between bodily sensations and catastrophic misinterpretations: Specific for panic disorder?

Cognitive models assume that panic disorder is characterised by a tendency to misinterpret benign bodily symptoms (e.g. breathlessness) in a catastrophic fashion (e.g. suffocation). This is a central part of the cognitive model which presents a core focus for treatment. Several studies have supported this hypothesis. These studies have, however, almost always relied on self-report. In addition to susceptibility to biases (e.g. distortions of memory), a limitation of research based on verbal report is its inability to capture the spontaneous/automatic nature that is attributed to these catastrophic interpretations. The present paper reports on two experiments in which a priming procedure was used to test the hypothesis that panic disorder is characterised by spontaneous catastrophic interpretations and whether this effect is ‘specific’ to panic disorder. In line with predictions from the cognitive model, it was observed in the first experiment that the panic group demonstrated facilitated responses to trials consisting of a ‘symptom’ prime and a ‘catastrophic outcome’ target (e.g. breathlessness - suffocate). Similar effects were not observed for an anxious control group and a nonclinical control group, supporting the specificity of this effect. Interestingly, however, significant priming effects were observed for a group of mental health professionals (part of the healthy control group) who had no history of panic disorder. Subsequently, this unexpected observation was explicitly addressed in a second experiment, which confirmed the findings of Experiment 1. Together, these results suggest that associations between mental representations of benign bodily symptoms and catastrophic outcomes might develop as part of professional knowledge and experience, and should not necessarily be viewed as pathogenic. Theoretical and clinical implications are discussed

Measuring Health-Related Quality of Life by Experiences: The Experience Sampling Method

AbstractObjectiveTo explore the potential value of obtaining momentary, instead of retrospective, accounts of the description and valuation of a person’s own health-related quality of life (HRQOL).MethodsMomentary HRQOL was examined with the experience sampling method (ESM) in 139 participants from four different samples. The ESM consists of a so-called beep questionnaire that was administered 10 times a day by an electronic device. Feasibility was determined by assessing willingness to participate in the study and by analyzing the percentage of dropouts and the number of completed beep questionnaires. Multilevel analysis was used to investigate the relation between momentary HRQOL and momentary feelings and symptoms. The relation between momentary outcomes and the EuroQol visual analogue scale was investigated with a multiple regression model.ResultsThe overall participation rate was low, but there were no dropouts and the number of completed beeps was comparable to that in other studies. Multilevel analysis showed that feelings and symptoms were significant predictors of momentary HRQOL. The strength of these relations differed among three patient groups and a population-based sample. The EuroQol visual analogue scale was not predicted by momentary feelings and symptoms.ConclusionsWe can conclude that the use of the ESM to measure accounts of the momentary experience of health in different populations is feasible. Retrospective measures may provide a biased account of the impact of health problems in the daily lives of people who are affected. Moreover, the bias may be different in different conditions

Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

Formal inverse integrating factors and the nilpotent center problem

We are interested in deepening knowledge of methods based on formal power series applied to the nilpotent center problem of planar local analytic monodromic vector fields X. As formal integrability is not enough to characterize such a centers we use a more general object, namely, formal inverse integrating factors V of X. Although by the existence of V is not possible to describe all nilpotent centers strata, we simplify, improve and also extend previous results on the relationship between these concepts. We use in the performed analysis the so-called Andreev number n N with n > 2 associated to X which is invariant under orbital conjugacy of X. Besides the leading terms in the (1,n)-quasihomogeneous expansions that V can have we also prove the following: (i) If n is even and there exists V then X has a center; (iii) If the existence of V characterizes all the centers; (iii) If there is a V with minimum ``vanishing multiplicity' at the singularity then, generically, X has a center.The author is partially supported by a MINECO grant number MTM2014-53703-P and by a CIRIT grant number 2014 SGR 1204

MARTÍN, ANA Mª [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking