An investigation of the role of estradiol in fear reduction during a single session of exposure therapy.

Research suggests that estradiol may moderate fear extinction. It is unclear whether these results generalize to exposure therapy. The aim of the current study was to determine whether estradiol moderates outcomes in exposure therapy among women with anxiety disorders. Participants were 35 women with a primary diagnosis of an anxiety disorder who participated in the study as part of routine care at an anxiety specialty clinic. Endogenous estradiol was assessed via saliva. They provided subjective distress ratings before (pre) and after (post) an exposure session, as well as after a brief delay (recall). Contrary to predictions, there were no significant differences in exposure outcomes between the high and low estradiol groups. However, among participants with primary obsessive-compulsive disorder (OCD), results were partially consistent with the hypotheses. Women with lower estradiol initially demonstrated more improvement in subjective distress from pre- to post-exposure, but after the delay, significantly greater distress (attenuated extinction recall). Results suggest that women with lower estradiol may respond less favorably to exposure therapy for OCD relative to women with higher estradiol. These findings await replication in larger samples with longer recall delays. Should replication occur, these results may inform the use of estradiol to augment exposure therapy.

Reductions in Anxiety are Associated with Decreased Expressive Suppression and Increased Cognitive Reappraisal After Cognitive-Behavioral Treatment: A Naturalistic Study in Youth.

Broad deficits in emotion regulation skills have been observed in children with anxiety-related disorders. These deficits typically improve during cognitive-behavioral therapy (CBT), but few studies have examined changes in expressive suppression and cognitive reappraisal in youth with anxiety disorders and/or obsessive-compulsive disorder (OCD) during CBT, especially in real-world settings. In a naturalistic treatment-seeking sample, 123 youth completed measures of anxiety, depression, and emotion regulation strategy use before and after 15 sessions of CBT. For anxious youth, anxiety and expressive suppression decreased over treatment, while cognitive reappraisal increased. Reductions in expressive suppression and increases in cognitive reappraisal were significantly associated with improvements in anxiety and remained significantly associated with post-treatment anxiety after accounting for baseline anxiety and depression. Changes in expressive suppression and cognitive reappraisal over the course of treatment were not found for youth with primary OCD. Thus, CBT improves emotion regulation abilities in anxious youth, and these improvements are associated with anxiety reduction; improvements in emotion regulation do not appear to drive changes in OCD symptoms. Further research is needed to determine whether changes in emotion regulation strategies mediate changes in anxiety among youth receiving CBT.

Moving beyond symptom reduction: A meta-analysis on the effect of exposure therapy for PTSD on quality of life.

OBJECTIVES: Quality of life (QOL) is a multidimensional construct including emotional well-being, life satisfaction, and physical health. Individuals with posttraumatic stress disorder (PTSD) consistently report low QOL, highlighting the importance of assessing the effectiveness of first-line PTSD treatments (e.g., exposure-based therapies) on QOL. This meta-analysis examined the efficacy of exposure therapy for PTSD on QOL compared to control conditions (e.g., waitlist, medication, treatment-as-usual) at posttreatment and follow-up (ranging from 1 month to 2 years). METHODS: Building on a previous meta-analysis of exposure-based therapy for PTSD, we searched PsycINFO and Medline in December 2021, July 2022, and March 2023 to include randomized controlled trials of exposure-based treatments for adult PTSD assessing QOL. We screened 295 abstracts for initial eligibility; 20 articles met inclusion criteria and were included (N = 2729 participants). Risk of bias was evaluated using the Cochrane Risk of Bias tool 2.0. RESULTS: At posttreatment, exposure-based therapies showed a medium effect on QOL relative to control conditions (k = 25, g = 0.67). This effect was not observed at follow-up for the small subset of studies with follow-up data (k = 8, g = 0.16). At posttreatment, effect size varied significantly as a function of the control condition (p < .0001). There were no differences in QOL effects across exposure therapies at posttreatment or follow-up (p = .09). CONCLUSION: Exposure therapy was associated with greater improvement in QOL compared to control conditions at posttreatment. Exposure was not superior to control conditions at follow-up, and the longer-term impact of exposure on QOL is unclear. The implications of these findings are discussed, along with the need for more PTSD treatment studies to examine QOL outcomes at posttreatment and follow-up.

Research Review: A meta-analysis of relapse rates in cognitive behavioral therapy for anxiety and related disorders in youth.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for youth with anxiety and related disorders, with a 59% remission rate at post-treatment. Results of reviews and meta-analyses indicate that treatment gains are maintained across long-term follow-up, at least in terms of symptom improvement. Less is known about relapse, defined as patients who initially achieve remission status but then experience a return of symptoms after a follow-up period. METHOD: The current study used meta-analysis to determine the overall rate of relapse in CBT for children and adolescents (age 18 years or younger) with anxiety and related disorders. Potential moderating factors of relapse rates, including demographic, methodological, and clinical/intervention characteristics, were also examined. Out of a pool of 78 abstracts, 13 full-text articles were retained for meta-analysis. An additional two articles were identified from other sources (total N = 535 patients). RESULTS: Results showed an overall relapse rate of 10.5% (including comorbid autism spectrum disorder) and 8% (excluding comorbid autism spectrum disorder) across studies. Moderator analyses demonstrated that relapse rates were higher among younger and more racially diverse samples, as well as among patients with comorbid externalizing disorders and those taking psychiatric medications. There were no differences in relapse rates as a function of primary diagnosis. CONCLUSIONS: Taken together, the findings indicate that relapse rates in CBT for anxious youth are relatively low, suggesting that treatment development and refinement efforts should focus on improving treatment response and remission rates for this population.

Mechanisms of Action in Exposure Therapy.

PURPOSE OF REVIEW: Exposure therapy is an effective treatment for anxiety-related disorders, but many individuals do not achieve full symptom relief, and return of fear is a common occurrence. Understanding how exposure therapy works enables further development of strategies to improve its effectiveness. RECENT FINDINGS: Recent studies have examined mechanisms of exposure-based interventions across multiple levels of analysis, from cognitive and behavioral changes that occur during treatment to the neurobiological mechanisms underlying fear extinction. Belief change and reductions in safety behaviors and avoidance mediate symptom improvements during exposure therapy, suggesting plausible cognitive and behavioral mechanisms. On the neural level, increased activation of prefrontal regions during extinction learning is a likely mechanism of exposure. Improved understanding of the biological mechanisms of exposure have led to exciting developments in clinical research, including pharmacological augmentation, though clinical translation of basic research has produced mixed results. Though still in development, such translational research is a promising future direction for exposure-based interventions.

Examining the generality and specificity of gender moderation in obsessive compulsive beliefs: Stacked prediction by correspondence analysis.

OBJECTIVES: In this study, we examined the degree of generality and specificity of OC beliefs are moderated by gender among individuals with OC disorders. METHODS: The diagnostic groups consisted of: (1) individuals with obsessive-compulsive disorder (OCD; N = 398); (2) individuals with other anxiety disorders (N = 104); and (3) undergraduate students (N = 285). To evaluate the gender moderating effect, we employed stacked prediction by correspondence analysis (CA). To conduct the analysis, we generated a two-way contingency table with rows of gender nested within the diagnostic groups and columns of OC beliefs stacked to OC symptom severity. To conduct prediction by CA of this stacked table, we considered OC beliefs as predictors and OC symptoms as outcomes. RESULTS: We confirmed with the CA results that OC belief generality, but not specificity because the OCD group members did show higher endorsement of OC beliefs compared to individuals with other anxiety disorders. Gender moderated the OC related beliefs of overestimation of threat, inflated responsibility, and intolerance of uncertainty, but not perfectionism in predicting OC symptoms. The correlational results obtained from the stacked prediction by CA further showed that as depression and anxiety increased, endorsement of OC beliefs was stronger for males than females. DISCUSSION: Clinical implications and future directions are discussed. PRACTITIONER POINTS: OC belief generality was evident in the study but not specificity. Gender moderation was demonstrated in overestimation of threat, inflated responsibility, and intolerance of uncertainty. As depression and anxiety increased, endorsement of OC beliefs was stronger for males than females.

Prevalence of Hoarding Behavior Among Formerly Homeless Persons Living in Supported Housing.

Hoarding disorder has become an official disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Hoarding disorder affects approximately 1.5% to 5% of the general population, and there is no known literature that has examined the prevalence of hoarding disorder among homeless populations or those living in supported housing, although hoarding problems can jeopardize their housing situation. This study used the Clutter Image Rating to estimate the prevalence of possible hoarding behavior among 660 adults living in supported housing. The results indicate that 18.5% of supported housing residents had hoarding behavior, which is more than three times the prevalence reported in the general population. These results suggest that hoarding behavior and possibly hoarding disorder may be more prevalent among those with histories of homelessness and housing instability, which may be of concern because it may affect both housing and health statuses.

Moving Beyond the Negative: Contributions of Positive and Negative Affect on Quality of Life in Patients With Generalized Anxiety Disorder.

Individuals with generalized anxiety disorder (GAD) report poorer quality of life (QOL) than do nonanxious controls. Further, although positive affect (PA) and negative affect (NA) have been shown to predict QOL, no previous literature has tested this relationship in the context of individuals with GAD. In the present study, we evaluated the unique and interactive contributions of PA and NA on QOL within a sample of individuals diagnosed with GAD (N = 50). Specifically, a hierarchical regression was conducted to evaluate the unique contributions of PA, NA, and their interaction on QOL, over and above symptoms of depression. PA and depression symptoms were both significant predictors of QOL, whereas neither the main effect for NA nor the PA × NA interaction was statistically significant. Results suggest that, for those with GAD, PA uniquely contributes to QOL. Strategies to upregulate PA may be a useful treatment target for increasing QOL in individuals with GAD.

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.

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.

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.

Utility of the Outcome Questionnaire-45.2 in outpatient anxiety clinics: A comparison between anxiety patients with and without co-occurring depression.

OBJECTIVE: The Outcome Questionnaire-45.2 (OQ-45) is a self-report measure of general psychological distress. Although intended to be transdiagnostic, the OQ-45 may be best conceptualized as a measure of depression; as such, its utility in assessing other symptoms such as anxiety is unclear. METHOD: We examined scores on the OQ-45 in a sample of 329 patients with anxiety and related disorders, half of whom had co-occurring depression. RESULTS: Eighty-two percent of patients scored above the OQ-45 cutoff, whereas 18% were incorrectly screened out. Patients with co-occurring depression were more likely to score above the OQ-45 cutoff than nondepressed patients. Depression severity predicted many of the OQ-45 scales, even after controlling for anxiety severity. By contrast, most of the anxiety-specific measures failed to predict the OQ-45 after controlling for depression severity. CONCLUSIONS: Findings suggest that the OQ-45 may not adequately capture anxiety symptoms and are discussed in terms of diagnostic screening and assessment.

Enhancing group cognitive-behavioral therapy for hoarding disorder with between-session Internet-based clinician support: A feasibility study.

OBJECTIVE: Hoarding disorder (HD) is difficult to treat. In an effort to increase efficacy and engagement in cognitive-behavioral therapy (CBT), we developed and evaluated a novel intervention comprising group CBT combined with between-session Internet-based clinician support for people with HD. METHOD: Twenty participants with HD received group CBT combined with an Internet-support system enabling therapist-participant communication between group sessions. RESULTS: The treatment was associated with a significant reduction on the Saving Inventory-Revised (SI-R) and a large effect size (Cohen's d = 1.57) was found at posttreatment. Treatment gains were maintained at the 3-month follow-up. Group attendance was high and no participants dropped out from treatment prematurely. Between-session motivational support from the therapist was most frequently mentioned as the main strength of the system. CONCLUSION: The results of this study support adding Internet-based clinician support to group CBT for HD to increase treatment adherence and, potentially, improve the overall efficacy of CBT.

A Multisite Benchmarking Trial of Capnometry Guided Respiratory Intervention for Panic Disorder in Naturalistic Treatment Settings.

Panic disorder (PD) is associated with hyperventilation. The efficacy of a brief respiratory feedback program for PD has been established. The aim of the present study was to expand these results by testing a similar program with more clinically representative patients and settings. Sixty-nine adults with PD received 4 weeks of Capnometry Guided Respiratory Intervention (CGRI) using Freespira, which provides feedback of end-tidal CO2 (PETCO2) and respiration rate (RR), in four non-academic clinical settings. This intervention is delivered via home use following initial training by a clinician and provides remote monitoring of client adherence and progress by the clinician. Outcomes were assessed post-treatment and at 2- and 12-month follow-up. CGRI was associated with an intent-to-treat response rate of 83% and a remission rate of 54%, and large decreases in panic severity. Similar decreases were found in functional impairment and in global illness severity. Gains were largely sustained at follow-up. PETCO2 moved from the slightly hypocapnic range to the normocapnic range. Benchmarking analyses against a previously-published controlled trial showed very similar outcomes, despite substantial differences in sample composition and treatment settings. The present study confirms prior clinical results and lends further support to the viability of CGRI in the treatment of PD.

Repetitive transcranial magnetic stimulation for generalised anxiety disorder: a pilot randomised, double-blind, sham-controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating generalised anxiety disorder (GAD) but has only been studied in uncontrolled research. AIMS: This is the first randomised controlled trial (clinicaltrials.gov: NCT01659736) to investigate the efficacy and neural correlates of rTMS in GAD. METHOD: Twenty five participants (active n = 13; sham, n = 12) enrolled. rTMS was targeted at the right dorsolateral prefrontal cortex (DLPFC, 1 Hz, 90% resting motor threshold). RESULTS: Response and remission rates were higher in the active v. sham groups and there were significant group × time interactions for anxiety, worry and depressive symptoms, favouring active v. sham. In addition, right DLPFC activation during a decision-making gambling task increased at post-treatment for active rTMS only, and changes in neuroactivation correlated significantly with changes in worry symptoms. CONCLUSIONS: Findings provide preliminary evidence that rTMS may improve GAD symptoms in association with modifying neural activity in the stimulation site.

RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER.

BACKGROUND: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. METHODS: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. RESULTS: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. CONCLUSIONS: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation.

Cognitive behavioral therapy for hoarding disorder: a meta-analysis.

BACKGROUND: Hoarding disorder (HD) is a new diagnosis in DSM-5 (American Psychiatric Association, 2013). Cognitive-behavioral therapy (CBT) appears promising for the treatment of HD, and has been tested in both individual and group settings. METHODS: The present study used meta-analytic techniques to examine the overall strength of effect of CBT on HD, as well as on its component symptoms (clutter, difficulty discarding, and acquiring) and associated functional impairment. Potential demographic and treatment-related moderators of CBT response, as well as the presence of clinically significant change were also examined. From 114 published articles, 10 articles comprising 12 distinct HD samples (N = 232) met inclusion criteria and were retained for analysis. RESULTS: HD symptom severity decreased significantly across studies with a large effect size. The strongest effects were seen for difficulty discarding, followed by clutter and acquiring. Functional impairment showed the smallest effect in the moderate range. Female gender, younger age, a greater number of CBT sessions, and a greater number of home visits were associated with better clinical outcomes. Reliable change was found in the majority of samples for each outcome domain. Rates of clinically significant change, however, were lower (percentage ranged from 24 to 43). Thus, in most cases, study patients' post-treatment scores remained closer to the HD range than to the normal range. CONCLUSIONS: CBT is a promising treatment for HD, although there is significant room for improvement. Results are discussed in terms of treatment refinement for HD, and additional moderator variables are suggested for further study.

FAMILIAL PATTERNS OF HOARDING SYMPTOMS.

BACKGROUND: Previous research suggests that hoarding aggregates in families and is associated with health and safety risks and family problems. The present study examined gender- and diagnosis-related differences in reports of hoarding symptoms among first-degree relatives of people who hoard, and of clinical and community samples. METHODS: The present study included 443 participants in a study of hoarding behavior: 217 with hoarding disorder (HD), 96 with obsessive-compulsive disorder (OCD), and 130 nonclinical community controls (CC). Assessment included a detailed interview of familial patterns of hoarding behaviors among parents and siblings and measures of hoarding severity. RESULTS: In the combined sample, participants reported more hoarding among female (mothers, sisters) than male (fathers, brothers) relatives. Significantly more female than male participants indicated they had a parent or any first-degree relative with hoarding behaviors. However, within the HD sample no significant gender effects were found for household, safety, and functioning variables, or for hoarding symptom severity. In an age- and gender-matched subsample (total n = 150), HD participants reported more hallmark hoarding symptoms (difficulty discarding and saving/clutter), and acquiring among their relatives compared to OCD and CC samples, and parents had higher rates than siblings. CONCLUSIONS: Hoarding symptoms appear to be common among first-degree relatives of people who hoard and are also found among relatives of control samples. The predominance of hoarding symptoms among female relatives may indicate genetic or modeling transmission but this requires further study using large twin samples. Clinicians should consider that family members may also have significant hoarding symptoms.

Cognitive behavior therapy for hoarding disorder: follow-up findings and predictors of outcome.

BACKGROUND: A cognitive-behavioral model of hoarding posits deficits in information processing, maladaptive beliefs about and attachments to possessions that provoke distress and avoidance, and positive emotional responses to saving and acquiring that reinforce these behaviors. A 26-session individual cognitive-behavioral therapy (CBT) based on this model showed significant reductions in hoarding symptoms and large effect sizes (Steketee et al.([1])). METHODS: The present study presents findings at follow-up (up to 12 months), as well as predictors of outcome at posttreatment (n = 37) and follow-up (n = 31). RESULTS: Significant improvements at post-treatment were sustained at follow-up with large effects, and Clinical Global Impression-Improvement (CGI-I) ratings by clinicians and patients at follow-up indicated that 62 and 79% of patients were rated "much improved" or "very much improved," respectively. The most prevalent patterns of outcome were improvement followed by stable gains or little improvement across all time points. Pretreatment severity of hoarding, overall clinical status, gender, perfectionism, and social anxiety were all associated with worse outcome. Only perfectionism and gender emerged as significant predictors after controlling for initial hoarding severity. CONCLUSIONS: The present findings suggest general stability of individual CBT outcomes for hoarding and indicated that gender, perfectionism, and social anxiety may affect outcomes. More research on larger samples is needed to direct efforts to improve treatment for hoarding.

Assessing squalor in hoarding: the Home Environment Index.

The current study examined a new measure of squalor associated with hoarding, the Home Environment Index (HEI). Participants (N = 793) were recruited from a large database of individuals who sought information about hoarding following national media appearances and consented to an internet study. Participants completed measures of hoarding and related psychopathology, including the HEI. The HEI showed good internal consistency and construct validity and reflected a single factor of home squalor (15 items). The HEI correlated positively with measures of hoarding and mood psychopathology. Recommendations for future modifications and further study are provided.