Central and peripheral nervous system responses to chronic and paced hyperventilation in anxious and healthy subjects.

The aim of the present study was to examine self-report, peripheral nervous system, and central nervous system correlates of naturally-occurring, chronic hyperventilation (HV, assessed by hypocapnia or low resting state low end-tidal CO2), and to examine the additional effect of acute, experimentally-induced HV in anxious and healthy participants. By identifying the biomarkers of anxiety-related chronic HV and examining responses to acute HV, we hope to identify meaningful, mechanistic targets for further treatment development. Seventy anxious patients and 34 healthy control participants completed electroencephalogram (EEG) and peripheral nervous system recording at baseline and following a paced breathing task. Diagnosis x baseline hypnocapnia group analyses indicated that anxious/hypocapnic patients exhibited greater nonspecific skin conductance response amplitude than did anxious/normocapnic patients, and the anxious group reported greater HV-related symptoms and anxiety sensitivity than did the control group. However, no EEG abnormalities were noted as a function of anxiety group or baseline hypocapnia status. Following paced HV, anxious patients (but not controls) exhibited an increase in left-frontal alpha 1 power. Hypocapnic, but not normocapnic, participants exhibited an increase in skin conductance levels. Anxious patients reported an increase in negative cognitive appraisals of HV symptoms, and anxious/hypocapnic participants reported an increase in affective responses to HV. Thus, chronic HV is associated with greater arousal, and increased self-reported and physiological sensitivity to paced HV. Patients who chronically hyperventilate appear to be more sensitive to respiratory distress, responding with higher levels of anxiety and poorer tolerance of the physiological sensations accompanying acute HV.

A randomized controlled trial evaluating the efficacy of a brief computerized anxiety sensitivity reduction intervention for health anxiety.

It is estimated that individuals with severe health anxiety (HA) utilize 41 %-78 % more healthcare resources than individuals with identified medical diagnoses. Thus, identifying targets for intervention and prevention efforts for HA that are appropriate for primary care or specialty clinic settings is imperative. The aim of the present investigation was to evaluate the effect of a single-session, computerized anxiety sensitivity (AS) intervention on AS and HA. Participants were 68 university students (79.4 % female; Mage = 19.68) with elevated levels of AS and HA. Participants were randomized to either the AS intervention condition or an active control condition and completed self-report and behavioral follow-up assessments at post-intervention, 1-week follow-up, and 1-month follow-up. Results indicated a significant Time x Condition interaction for ASI-3 at each follow-up assessment (all ps < .001), such that individuals in the active condition exhibited greater reductions in AS compared to the control condition. There was no significant Time x Condition interaction for HA at any follow-up. Mediation analyses revealed a significant indirect effect of Condition on changes in HA through changes in AS. No significant effects were observed for behavioral outcomes. Findings suggest that this intervention successfully reduces AS among those who are high in HA and AS and may indirectly contribute to reductions in HA over time through reductions in AS.

The dose-response curve in cognitive-behavioral therapy for anxiety disorders.

Previous studies examining the dose-response curve in psychotherapy have suggested that 11-19 sessions may be necessary for at least 50% of individuals to show clinically significant improvement. However, this curve has not been examined specifically for cognitive-behavioral therapy (CBT) for anxiety disorders, for which a more rapid recovery curve may be expected. Survival analysis was used to assess the dose-response curve for 201 patients with anxiety disorders who received weekly CBT at an anxiety specialty clinic. The primary outcome measure was the Outcome Questionnaire-45.2, which patients completed prior to each treatment session. Sixty-four percent of the sample achieved reliable change, and this response occurred in approximately five sessions on average. Fifty percent of the sample achieved clinically significant improvement, which occurred in approximately eight sessions on average. The findings suggest that earlier response may be expected in CBT for anxiety disorders, and are discussed in terms of potential ways to further improve response rates for this treatment.

Biofeedback and Neurofeedback for Anxiety Disorders: A Quantitative and Qualitative Systematic Review.

Biofeedback refers to the operant training of physiological responding. Variants include electromyography (EMG), electrodermal activity (EDA), skin temperature, heart rate (HR) and heart rate variability (HRV), respiratory biofeedback of end-tidal CO2 (ETCO2), electroencephalography (EEG) signal, and blood oxygen-level dependent signal using functional magnetic resonance imaging (fMRI). This chapter presents a qualitative and quantitative systematic review of randomized controlled trials of biofeedback for anxiety disorders as defined by the 3rd through 5th editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Meta-analytic results indicated that biofeedback (broadly defined) is superior to wait list, but has not been shown to be superior to active treatment conditions or to conditions in which patients are trained to change their physiological responding in a countertherapeutic direction. Thus, although biofeedback appears generally efficacious for anxiety disorders, the specific effects of biofeedback cannot be distinguished from nonspecific effects of treatment. Further, significant limitations were identified in the existing literature, with the majority receiving a "weak" rating according to Effective Public Health Practice Project (EPHPP) rating system guidelines. Future directions for research are discussed.

Self-referential processing during observation of a speech performance task in social anxiety disorder from pre- to post-treatment: Evidence of disrupted neural activation.

Self-referential processing is critical to understanding social anxiety disorder (SAD). This study examined neural differences in self-referential processing in healthy controls (HC) and participants with SAD at pre- and post-treatment. Participants (n = 64) underwent fMRI scanning while viewing a video of themselves ("Self") or another person ("Other"). SAD participants were randomized to cognitive behavior therapy (CBT), acceptance and commitment therapy (ACT), or waitlist, and were re-scanned at post-treatment. In SAD vs. HC, the fusiform face area (FFA) showed significantly more activation during Self vs. Other, and greater SAD severity was associated with significantly more activation during Self vs. Other in the right FFA and the left extrastriate body area (EBA). Greater reduction in SAD severity was associated with stronger connectivity between the amygdala and FFA during Self vs. Other at post-treatment, whereas the strength of connectivity during Self and Other was comparable at post-treatment for those with less SAD reduction. Thus, there were significant differences in activation and functional connectivity of brain regions implicated in self-referential processing in SAD. Change in connectivity between the amygdala and FFA were observed as a function of change in SAD severity, suggesting that improvements in SAD severity may correct this altered functional connectivity.

Mediators of Change in Capnometry Guided Respiratory Intervention for Panic Disorder.

Capnometry guided respiratory interventions have shown promising results in the treatment of panic disorder, but mechanisms of change are not yet well-understood. The current study examined changes in end-tidal carbon dioxide (ETCO2), anxiety sensitivity, and perceived control as mediators of panic symptom change. Sixty-nine adults with panic disorder received 4 weeks of respiratory training, and panic symptom severity and potential mediators were assessed at Pre-treatment, Mid-treatment, Post-treatment, 2-month follow-up, and 12-month follow-up. Multilevel mediation analyses showed that changes in perceived control significantly mediated changes in panic disorder severity and that for individuals who were hypocapnic at pre-treatment, ETCO2 was a significant mediator of symptom outcome. Findings provide further evidence that changes in perceived control, and improvements in respiratory dysregulation for hypocapnic individuals specifically, underlie symptom improvement from capnometry guided respiratory intervention for panic disorder.

Linguistic processing and Script-Driven Imagery for trauma exposure: A proof of concept pilot trial.

While several empirically supported treatments for posttraumatic stress disorder (PTSD) have been developed, these treatments are neither widely available nor universally efficacious. This pilot, proof of concept study evaluated a computerized imaginal exposure Script-Driven Imagery Training (SDI-T) for individuals with elevated trauma reactivity. The training was supplemented with two forms of linguistic processing, affect labeling (SDI-T + AL) and distraction (SDI-T + D), to determine whether linguistic inhibitory regulation augmented the effects of SDI-T. METHODS: Participants (n = 64) with trauma-related distress were randomized to SDI-T, SDI-T + AL, or SDI-T + D. Physiology and self-reported trauma distress were measured at pre- and post-training. RESULTS: The training was acceptable to participants and effective at reducing self-reported distress (d = -0.41), and physiological activation from pre- to post-training (d = -0.49, ps < .01), with some evidence that linguistic processing (SDI-T + AL and SDIT-T + D) conferred a benefit over SDI-T. The linguistic processing groups had significantly steeper reduction in physiology relative to the non-linguistic processing group (p < .05, d = 0.59). There was no benefit of SDI-T + AL over SDI-T + D. CONCLUSIONS: This pilot study provides initial support for the acceptability and efficacy of computerized imaginal exposure training for PTSD. Clinical implications and future directions are discussed.

Altered time course of amygdala activation during speech anticipation in social anxiety disorder.

BACKGROUND: Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). METHOD: Participants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Repeated measures multi-level modeling analyses were used to examine group differences in time course activity during speech vs. control anticipation for regions of interest, including bilateral amygdala, insula, ventral striatum, and dorsal anterior cingulate cortex. RESULTS: The time course of amygdala activity was more prolonged and less variable throughout speech anticipation in SAD participants compared to HCs, whereas the overall magnitude of amygdala response did not differ between groups. Magnitude and time course of activity was largely similar between groups across other regions of interest. LIMITATIONS: Analyses were restricted to regions of interest and task order was the same across participants due to the nature of deception instructions. CONCLUSIONS: Sustained amygdala time course during anticipation may uniquely reflect heightened detection of threat or deficits in emotion regulation in socially anxious individuals. Findings highlight the importance of examining temporal dynamics of amygdala responding.

Psychophysiological responses to unpredictable threat: effects of cue and temporal unpredictability.

Although threat unpredictability plays an important role in determining emotional responses, little is known about what elements of unpredictability are responsible for these results. The current study examined the single and combined effects of two elements of unpredictable threat: (a) uncertainty about the timing of an aversive event (temporal unpredictability), and (b) uncertainty about whether an aversive event will occur at all (cue unpredictability). Seventy-two healthy young adult participants were randomly assigned to receive either temporally predictable or unpredictable shocks at varying levels of cue unpredictability. Dependent variables included skin conductance responses (SCRs) and eyeblink startle reflex. Combined cue and temporal unpredictability elicited weaker SCRs than either element of unpredictability alone, indicating that high unpredictability may induce anxiety-like physiological inhibition. Combined cue and temporal unpredictability and combined cue and temporal predictability produced the largest startle. Findings provide evidence that both cue and temporal unpredictability should be included in human models of anxiety.

Physiological and behavioral indices of emotion dysregulation as predictors of outcome from cognitive behavioral therapy and acceptance and commitment therapy for anxiety.

BACKGROUND AND OBJECTIVES: Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. METHODS: Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. RESULTS: Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. LIMITATIONS: Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. CONCLUSIONS: Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts.

Low baseline pCO2 predicts poorer outcome from behavioral treatment: evidence from a mixed anxiety disorders sample.

Low levels of end-tidal partial pressure of carbon dioxide (pCO2)-the amount of carbon dioxide measured from expired air-are commonly found in individuals with anxiety disorders but have not been examined as predictors of outcome from anxiety treatment. The current study examined pre-treatment baseline pCO2 as a predictor of outcome from cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. Sixty-one individuals with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defined principal anxiety disorder diagnosis completed 12 sessions of either CBT or ACT. Baseline pCO2 was measured prior to entering treatment. Self-reported anxiety symptoms and quality of life were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. Low baseline pCO2 was associated with higher anxiety symptoms and lower quality of life across follow-up timepoints, above and beyond baseline symptom severity. These results suggest that low baseline pCO2 predicts poorer outcome from CBT and ACT for anxiety and may warrant treatment that directly addresses respiratory dysregulation.

Homework compliance counts in cognitive-behavioral therapy.

BACKGROUND: Prior research has demonstrated that there is some association between treatment engagement and treatment outcome in behavioral therapy for anxiety disorders. However, many of these investigations have been limited by weak measurement of treatment engagement variables, failure to control for potentially important baseline variables, and failure to consider various treatment engagement variables simultaneously. The purpose of the present study is to examine the relationship between two treatment engagement variables (treatment expectancy and homework compliance) and the extent to which they predict improvement from cognitive-behavioral therapy (CBT) for anxiety disorders. METHODS: 84 adults with a DSM-IV-defined principal anxiety disorder took part in up to 12 sessions of CBT or acceptance and commitment therapy. Pre- and post-treatment disorder severity was assessed using clinical severity ratings from a semi-structured diagnostic interview. Participants made ratings of treatment expectancy after the first session. Homework compliance was assessed each session by the treating clinician. RESULTS: Contrary to hypotheses, treatment expectancy and homework compliance were poorly correlated. Regression analyses revealed that homework compliance, but not treatment expectancy, predicted a significant portion of the variance in treatment outcome (10%). CONCLUSIONS: The present research suggests that although treatment expectation and homework compliance likely represent unique constructs of treatment engagement, homework compliance may be the more important treatment engagement variable for outcomes. The present research suggests that improvement of homework compliance has the potential to be a highly practical and effective way to improve clinical outcomes in CBT targeting anxiety disorders.