Risk and protective factors for anxiety and obsessive-compulsive disorders: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases. METHODS: Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance. RESULTS: Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17-3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence. CONCLUSIONS: Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.

An Internet-based treatment for flying phobia (NO-FEAR Airlines): study protocol for a randomized controlled trial.

BACKGROUND: Flying phobia (FP) is a common and disabling mental disorder. Although in vivo exposure is the treatment of choice, it is linked to a number of limitations in its implementation. Particularly important, is the limited access to the feared stimulus (i.e., plane). Moreover, the economic cost of in vivo exposure should be specially considered as well as the difficulty of applying the exposure technique in an appropriate way; controlling important variables such as the duration of the exposure or the number of sessions. ICTs could help to reduce these limitations. Computer-assisted treatments have remarkable advantages in treating FP. Furthermore, they can be delivered through the Internet, increasing their advantages and reaching more people in need. The Internet has been established as an effective way to treat a wide range of mental disorders. However, as far as we know, no controlled studies exist on FP treatment via the Internet. This study aims to evaluate the efficacy of an Internet-based treatment for FP (NO-FEAR Airlines) versus a waiting list control group. Secondary objectives will be to explore two ways of delivering NO-FEAR Airlines, with or without therapist guidance, and study the patients' acceptance of the program. This paper presents the study protocol. METHODS/DESIGN: The study is a randomized controlled trial. A minimum of 57 participants will be randomly assigned to three conditions: a) NO-FEAR Airlines totally self-applied, b) NO-FEAR Airlines with therapist guidance, or c) a waiting list control group (6 weeks). Primary outcomes measures will be the Fear of Flying Questionnaire-II and the Fear of Flying Scale. Secondary outcomes will be included to assess other relevant clinical measures, such as the Fear and Avoidance Scales, Clinician Severity Scale, and Patient's Improvement scale. Analyses of post-treatment flights will be conducted. Treatment acceptance and preference measures will also be included. Intention-to-treat and per protocol analyses will be conducted. DISCUSSION: An Internet-based treatment for FP could have considerable advantages in managing in vivo exposure limitations, specifically in terms of access to treatment, acceptance, adherence, and the cost-effectiveness of the intervention. This is the first randomized controlled trial to study this issue. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02298478 . Trial registration date 3 November 2014.

Heart rate complexity and attentional orienting: a new look at the role of vagal tone.

This study is aimed at elucidating (a) whether heart rate (HR) complexity measures are associated with the attentional orienting function, and (b) which of these measures better predicts orienting efficiency indexes. Vagal tone, sample entropy, scaling exponents ?1 and ?2, and fractal dimension (FD) were calculated in HR time series (n=109). Vagal tone, entropy, and FD were positively associated with orienting, while this association was negative for ?2. These results show that HR scaling properties, which underlie the role of vagal tone and reflect allometric control mechanisms, are associated with orienting deficits. FD was the best predictor of attentional orienting.

Attentional control, attentional network functioning, and emotion regulation styles.

Attentional network functioning in emotionally neutral conditions and self-reported attentional control (AC) were analysed as predictors of the tendency to engage in dysfunctional emotion regulation strategies. Diminished attentional orienting predicted an increased tendency to engage in brooding rumination, and enhanced alertness predicted a greater chance of suppression, beyond trait anxiety and self-reported AC, which were not predictive of either rumination or suppression. This is the first study to show that some forms of dysfunctional emotion regulation are related to the attentional network functioning in emotionally neutral conditions. Results are discussed in relation to regulatory temperament and anxiety-related attentional biases literature.

Self-focused cognitive emotion regulation style as associated with widespread diminished EEG fractal dimension.

The cognitive regulation of emotions is important for human adaptation. Self-focused emotion regulation (ER) strategies have been linked to the development and persistence of anxiety and depression. A vast array of research has provided valuable knowledge about the neural correlates of the use of specific self-focused ER strategies; however, the resting neural correlates of cognitive ER styles, which reflect an individual's disposition to engage in different forms of ER in order to manage distress, are largely unknown. In this study, associations between theoretically negative ER style (self-focused or not) and the complexity (fractal dimension, FD) of the resting EEG at frontal, central, parietal, and occipital regions were investigated in 58 healthy volunteers. The Cognitive Emotion Regulation Questionnaire was used as the self-report measure of ER style. Results showed that a diminished FD over the scalp significantly correlated with self-focused ER style scores, even after controlling for negative affect, which has been also considered to influence the use of ER strategies. The lower the EEG FD, the higher were the self-focused ER style scores. Correlational analyses of specific self-focused ER strategies showed that self-blaming and rumination were negatively associated with diminished FD of the EEG, but catastrophizing and blaming others were not. No significant correlations were found for ER strategies more focused on situation or others. Results are discussed within the self-organized criticality theory of brain dynamics: The diminished FD of the EEG may reflect a disposition to engage in self-focused ER strategies as people prone to ruminate and self-blame show a less complex resting EEG activity, which may make it more difficult for them to exit their negative emotional state.

Distinguishing youths at risk for anxiety disorders from self-reported BIS sensitivity and its psychophysiological concomitants.

The aim of the study was to explore the psychophysiological concomitants of self-reported behavioral inhibition system (BIS) sensitivity in adolescents (12 to 17 years old) supposed to be at risk for anxiety disorders. Twenty participants with high scores in self-reported BIS sensitivity (at-risk group) were matched in age and sex to 20 participants scoring in the normal range in BIS sensitivity (control group). Negative affect, negative emotion regulation style, and anxiety symptomatology were assessed by means of self-reported measures. Cardiac and electrodermal response signals were recorded during baseline, paced breathing, exposure to an attentional task with response cost and fear-relevant slides conditions. The at-risk group exhibited higher scores on measures of negative affect, negative emotion regulation style, and anxiety symptomatology than their control counterparts. After controlling for negative styles of emotion regulation, groups did not differ in skin conductance reactivity during the attentional task with response cost, but participants at risk exhibited more nonspecific skin conductance responses than the control group during baseline recording. Regarding the cardiac concomitants, participants at risk presented lower vagal tone at resting conditions as compared to participants in the control group. Additionally, at-risk participants exhibited lower flexibility across experimental conditions in heart rate and cardiac sample entropy measures than participants in the control group. These findings add knowledge on psychophysiological concomitants of BIS sensitivity and are discussed in light of associations between temperament and development of anxiety disorders in youth. They show how psychophysiological patterns observed in resting conditions could be useful endophenotypes to reliably detect individuals at risk before the disorder onset.

Complexity of everyday life heart rate dynamics and attentional control in healthy students.

Effective regulation of emotions requires the ability to voluntarily manage attention, i.e. attentional control (AC), which has been related to heart rate variability and vagal tone in laboratory based research. In this study, we calculated the correlation dimension (CD), the fractal-like properties (scaling exponents ?1 and ?2, and fractal dimension) and the sample entropy of heart rate time series obtained from ECG recordings (4 hours long each) taken from a sample of healthy students (n=47) during everyday activities. AC was assessed through a self-reported questionnaire. As expected, a linear positive correlation was found between AC scores and CD and entropy, but no associations were found between AC and ?1 and fractal dimension. The association between AC and ?2 was negative and marginally significant. No associations were found between AC and linear heart rate variability measures. These results show that nonlinear measures of long, everyday life, heart rate time series may provide useful information about the AC ability of healthy students.

Development and Validation of a Smartphone-Based App for the Longitudinal Assessment of Anxiety in Daily Life.

Current methods to assess human anxiety often ignore that anxiety is a dynamic process and have limitations such as high recall bias and low generalizability to real life. Smartphone apps using ecological momentary assessment (EMA) may overcome such limitations. We developed a smartphone app for the longitudinal evaluation of anxiety symptoms using EMA. We assessed the feasibility (retention and compliance) and psychometric properties (reliability and validity) of the app over 6 months in a sample of 99 participants with different levels of anxiety. The EMA-based smartphone app was highly feasible. It showed excellent within-person and between-person reliability, high convergent and moderate discriminant validity, and significant incremental validity. Assessing anxiety longitudinally using a smartphone and following EMA principles is feasible and can be reliable and valid. Studies combining EMA-based anxiety longitudinal assessments with other assessment methods deserve further research and may offer novel insights into human anxiety.

Heart rate variability profiles and exposure therapy treatment outcome in flight phobia.

The goal of this study was to explore why certain patients in a previous study on exposure therapy for flight phobia did not experience an improvement in their conditions. Participants from a treatment study (N = 45) were selected according to post-treatment results and divided into two groups: the unsatisfactory treatment outcome group (UTO, N = 10) and the satisfactory treatment outcome group (STO, N = 10). The differences between these two groups prior to receiving exposure therapy were analyzed at the behavioral, physiological, and cognitive levels. The UTO participants had been avoiding flying longer than the STO phobics. Following Thayer and Lane's neurovisceral model of emotion regulation, heart rate variability was analyzed at two levels: tonic and phasic. Low frequency and high frequency (HF) power were calculated in the frequency domain and Sample Entropy was computed in the time domain. The tonic HF power of the UTO group was higher than the STO group's tonic HF power. In the phasic level, while the STO group's HF power decreased under exposure and subsequently returned to baseline level, the UTO group demonstrated a more rigid pattern. Finally, the STO group reported higher emotional involvement than the UTO group when they were shown a sample of the therapy. Based on these results, the challenge of matching exposure therapy to each patient's profile is discussed.

Effects of temperament and emotion regulation styles in determining negative emotional states.

INTRODUCTION: The interplay of reactive and regulatory temperamental processes appears to be essential for a better understanding of emotional states and disorders. In this study we explored the prospective relationship between reactive temperament (negative affect), regulatory temperament (effortful control), negative emotion regulation styles (rumination and suppression) and self-recorded anxiety, worry, and avoidance in naturalistic conditions. METHOD: Thirty-two young adults were first assessed through questionnaires on negative affectivity, effortful control, and two forms of negative emotion regulation (rumination and suppression). After this they recorded anxiety, worry, and avoidance three times a day over 50 consecutive days through an on-line access electronic diary. RESULTS: High levels of negative affect and low levels of effortful control were associated with higher levels of anxiety, worry, and avoidance (p<.01). The prospective association between negative affectivity and avoidance was moderated by effortful control (Total R(2)=.49). Moreover, the brooding facet of rumination totally mediated the association between negative affect and anxiety with a significant indirect effect (Effect=.30, Boot CI95%=.09 to .69). CONCLUSIONS: Avoidance patterns are significantly determined by negative affect--effortful control interaction and rumination, especially brooding, totally mediates the relationship between negative affect and anxiety.

Slope of change throughout exposure treatment for flight phobia: the role of autonomic flexibility.

This study tested the hypothesis that flight-phobic patients experience change at different rates even when they are receiving identical treatment. Faster within-session rates of change (WSRC) were expected for patients who required fewer exposure sessions. The study also tested the theoretical role of autonomic flexibility on WSRC. High flexibility should be associated with faster rates of change. Thirty-seven flight-phobic patients were successfully treated with a computer-assisted fear of flying treatment. A significant negative correlation was found between total number of sessions and WSRC: The fewer sessions patients attended, the faster their rate of change was. The role of autonomic flexibility was partially supported: A significant correlation between heart rate variability and WSRC revealed that flexible patients improved faster than less-flexible patients.

Diagnostic biomarkers for obsessive-compulsive disorder: A reasonable quest or ignis fatuus?

Obsessive-compulsive disorder (OCD) has been associated with a wide range of biological and neurocognitive findings, which could assist in the search for biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses to assess and grade the strength of the evidence of the association between OCD and several potential diagnostic biomarkers while controlling for several potential biases. Twenty-four systematic reviews and meta-analyses were included, comprising 352 individual studies, more than 10,000 individuals with OCD, and covering 73 potential biomarkers. OCD was significantly associated with several neurocognitive biomarkers, with varying degrees of evidence, ranging from weak to convincing. A number of biochemical, neurophysiological, and neuroimaging biomarkers also showed statistically significant, albeit weak, associations with OCD. Analyses in unmedicated samples (123 studies) weakened the strength of the evidence for most biomarkers or rendered them non-significant. None of the biomarkers seem to have sufficient sensitivity and specificity to become a diagnostic biomarker. A more promising avenue for future biomarker research in OCD might be the prediction of clinical outcomes rather than diagnosis.

Risk factors for posttraumatic stress disorder: An umbrella review of systematic reviews and meta-analyses.

Approximately one third of individuals who experience a severe traumatic event will develop posttraumatic stress disorder (PTSD). It is crucial to identify what factors may be associated with increased or decreased risk for PTSD. We conducted an umbrella review of systematic reviews and meta-analyses of risk/protective factors for PTSD and assessed and graded the evidence of the association between each factor and PTSD. Thirty-three systematic reviews and meta-analyses were included and 130 potential risk factors were identified. Of those, 57 showed a significant association with PTSD. Being female or being indigenous people of the Americas, among the sociodemographic factors; history of physical disease and family history of psychiatric disorder, among the pretrauma factors; and cumulative exposure to potentially traumatic experiences, trauma severity, and being trapped during an earthquake, among the peritrauma factors, showed convincing or highly suggestive evidence of an association with PTSD. Data from prospective studies were less conclusive. Our results have the potential of helping refine PTSD prediction models and contributing to the design of prevention strategies.

Deterioration rates in Virtual Reality Therapy: An individual patient data level meta-analysis.

Ample evidence supports the use of Virtual Reality (VR) for anxiety disorders. Nonetheless, currently there is no evidence about moderators or potential negative effects of VR treatment strategies. An Individual Patient Data (IPD) approach was employed with 15 retrieved datasets. The current study sample was composed of 810 patients. Randomized control trials (RCTs) for each primary outcome measure were performed, in addition to moderator analyses of the socio-demographic variables. Deterioration rates were 14 patients (4.0%) in VR, 8 (2.8%) in active control conditions, and 27 (15%) in the WL condition. With regard to receiving treatment, patients in a waiting list control condition had greater odds of deteriorating than in the two active conditions, odds ratios (ORs) 4.87, 95% confidence interval (CI) [0.05, 0.67]. In the case of the socio-demographic variables, none of them were associated with higher or lower odds of deterioration, with the exception of marital status in the WL condition; married people presented a significantly lower probability of deterioration, OR 0.19, 95% CI [0.05, 0.67]. Finally, when comparing pooled effects of VR versus all control conditions, the OR was 0.61 (95% CI 0.31-1.23) in favor of VR, although this result was not statistically significant. This study provides evidence about the deterioration rates of a therapeutic VR approach, showing that the number of deteriorated patients coincides with other therapeutic approaches, and that deterioration is less likely to occur, compared to patients in WL control groups.

Relationship between effortful control and facets of mindfulness in meditators, non-meditators and individuals with borderline personality disorder.

As dimensions of effortful control (EC), activation control, attentional control, and inhibitory control could mediate the relationship between mindfulness meditation practice and the facets of mindfulness (i.e., observing, describing, acting with awareness, non-judging and non-reacting to inner experience). In this study, we tested whether participant status: meditators (n = 330), healthy non-meditators (n = 254) and individuals with borderline personality disorder (BPD) diagnosis (n = 46) predicted the facets of mindfulness and if these potential effects were mediated through the three effortful control (EC) dimensions (activation, attentional and inhibitory control). Meditators scored higher than non-meditators on attentional and inhibitory control and on the facets of mindfulness with attentional and inhibitory control partially mediating this relationship between meditation status and mindfulness facets. Participants with BPD showed lower scores on EC along with lower scores on the facets of mindfulness compared with healthy non-meditators. All three aspects of EC partially mediated the relationship between BPD and mindfulness facets. Copyright © 2018 John Wiley & Sons, Ltd.

Vagally mediated heart rate variability and heart rate entropy as predictors of treatment outcome in flight phobia.

In the present study a computer-assisted exposure-based treatment was applied to 54 flight phobics and the predictive role of vagally mediated heart rate (HR) variability (high frequency, 0.15-0.4 Hz band power) and heart rate entropy (HR time series sample entropy) on treatment outcome was investigated. Both physiological measures were taken under controlled breathing at 0.2 Hz and during exposure to a fearful sequence of audiovisual stimuli. Hierarchical regression analyses were conducted to assess the predictive power of these variables in these conditions on treatment self-report measures at the end of treatment and at 6 months follow-up, as well as on the behavioral treatment outcome (i.e. flying at the end of treatment). Regression models predicting significant amounts of outcome variance could be built only when HR entropy was added to the HR variability measure in a second step of the regression analyses. HR variability alone was not found to be a good predictor of neither self-reported nor behavioral treatment outcomes.

Temporal stability of obsessive-compulsive symptom dimensions in an undergraduate sample: a prospective 2-year follow-up study.

The temporal stability of obsessive-compulsive symptom dimensions was studied in a nonclinical student sample. The Obsessive-Compulsive Inventory--Revised was administered twice to 132 undergraduate students during a 2-year period. There were no significant changes in symptom dimension scores between the baseline and follow-up, except for the Obsessing scale. The score of each dimension at follow-up was strongly and uniquely predicted from the score on the same dimension at baseline. The results indicate that obsessive-compulsive symptom dimensions tend to be temporally stable in nonclinical participants, replicating similar studies in clinical populations.

Attentional Control and Fear Extinction in Subclinical Fear: An Exploratory Study.

Attentional control (AC) and fear extinction learning are known to be involved in pathological anxiety. In this study we explored whether individual differences in non-emotional AC were associated with individual differences in the magnitude and gradient of fear extinction (learning and recall). In 50 individuals with fear of spiders, we collected measures of non-emotional AC by means of self-report and by assessing the functioning of the major attention networks (executive control, orienting, and alerting). The participants then underwent a paradigm assessing fear extinction learning and extinction recall. The two components of the orienting network functioning (costs and benefits) were significantly associated with fear extinction gradient over and above the effects of trait anxiety. Specifically, participants with enhanced orienting costs (i.e., difficulties in disengaging attention from cues not relevant for the task) showed faster extinction learning, while those with enhanced orienting benefits (i.e., attention facilitated by valid cues) exhibited faster extinction recall as measured by fear-potentiated startle and Unconditioned Stimulus expectancies, respectively. Our findings suggest that, in non-emotional conditions, the orienting component of attention may be predictive of fear extinction. They also show that the use of fear extinction gradients and the exploration of individual differences in non-emotional AC (using performance-based measures of attentional network functioning) can provide a better understanding of individual differences in fear learning. Our findings also may help to understand differences in exposure therapy outcomes.

Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study.

Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed.

Spanish version of the savings inventory-revised: adaptation, psychometric properties, and relationship to personality variables.

The factor structure, psychometric properties, and relationship with personality variables of a Spanish version of the Savings Inventory-Revised (SI-R) are investigated in a sample of 381 undergraduate students. A maximum likelihood factor analysis suggests a three-factor structure, which is similar but not identical to that of the original English version. The three factors mirror the three hypothesized domains of compulsive hoarding: acquisition, difficulty discarding, and clutter. The Spanish SI-R demonstrates acceptable high internal consistency and test-retest reliability, but its divergent validity is weaker than expected because of a significant overlap with depressive symptoms. Different SI-R factors are associated with different personality traits: Whereas the difficulty discarding dimension is predominantly associated with susceptibility to punishment, the acquisition dimension is predominantly associated with susceptibility to reward. The authors conclude that the Spanish SI-R is a promising instrument to measure hoarding symptoms.