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.

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.

An Investigation of the Moderating Role of Estradiol in Interoceptive Exposure Therapy for Women with Panic Disorder.

Emerging research in animal models and healthy women indicates that the sex hormone estradiol may moderate fear of extinction. There is limited research on estradiol in exposure-based therapy among clinically anxious women. The current pilot study aimed to address this gap by comparing exposure outcomes in women with panic disorder (PD) who had high (HE) vs. low estradiol (LE). Twenty-eight women (14 per group) with PD completed two interoceptive exposure sessions on consecutive days as well as self-report measures of panic severity. Electrodermal activity was assessed continuously throughout the exposure sessions. Results showed that although anxiety sensitivity and subjective distress improved from pre- to postexposure, suggesting that the intervention was effective in reducing panic-related anxiety, there were no differences in outcomes between the HE and LE groups. The findings suggest that estradiol may not moderate outcomes in exposure therapy in clinically anxious samples, although replication in larger samples will be needed.

Changes in neural activity following a randomized trial of cognitive behavioral therapy for hoarding disorder.

OBJECTIVE: Cognitive behavioral therapy (CBT) is efficacious for hoarding disorder (HD), though results are modest. HD patients show an increase in activity in the dorsal anterior cingulate cortex (dACC) when making decisions. The aim of this study is to determine whether CBT's benefits follow improvements in dACC dysfunction or abnormalities previously identified in other brain regions. METHOD: In this randomized clinical trial of 64 treatment-seeking HD patients, patients received group CBT, delivered weekly for 16 weeks, versus wait list. Functional magnetic resonance imaging was used to examine neural activity during simulated decisions about whether to acquire and discard objects. RESULTS: During acquiring decisions, activity decreased in several regions, including right dorsolateral prefrontal, right anterior intraparietal area, both right and left medial intraparietal areas, left and right amygdala, and left accumbens. During discarding decisions, activity decreased in right and left dorsolateral prefrontal, right and left rostral cingulate, left anterior ventral insular cortex, and right medial intraparietal areas. None of the a priori brain parcels of interest significantly mediated symptom reduction. Moderation effects were found for left rostral cingulate, right and left caudal cingulate, and left medial intraparietal parcels. CONCLUSIONS: Therapeutic benefits of CBT for HD do not appear to be mediated by changes in dACC activation. However, pretreatment dACC activation predicts outcome. Findings suggest the need to re-evaluate emerging neurobiological models of HD and our understanding of how CBT affects the brain in HD, and perhaps shift focuses to new neural target discovery and target engagement trials. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exposure therapy for PTSD in military populations: A systematic review and meta-analysis of randomized clinical trials.

Military populations are disproportionally affected by posttraumatic stress disorder (PTSD) and may experience less benefit from first line psychotherapies for PTSD relative to civilians. We examined the efficacy of exposure therapy among Veterans and active duty military personnel across various control conditions and tested potential treatment-related, demographic, and clinical moderators. Randomized controlled trials of exposure-based therapies for PTSD in military populations were identified from a recent meta-analysis and through PsycINFO and Medline. Nineteen studies met inclusion criteria and were included in the meta-analysis (total N = 2905). Exposure therapy had medium to large effects compared to waitlist and treatment as usual, a small effect compared to non-trauma-focused therapy, and no effect relative to other trauma-focused therapy. The overall effect was similar at post-treatment and follow up. The effect size for exposure was larger in studies with younger participants, more women, fewer participants with comorbid major depression, and fewer participants taking psychiatric medication. Effect sizes were not impacted by treatment length or type, participant race or ethnicity, comorbid substance use, Veteran versus active duty status, or study risk of bias. Findings document the variable efficacy of exposure therapy in military populations across comparator types and point to several potentially important moderators of outcome that should be examined in future research.

Exposure therapy for PTSD: A meta-analysis.

Posttraumatic stress disorder (PTSD) is associated with high morbidity and functional impairment in the absence of effective treatment. Exposure therapy for PTSD is a trauma-focused treatment that typically includes in vivo and/or imaginal exposure. The goal of this meta-analysis was to examine the overall efficacy of exposure therapy for PTSD compared to various control conditions. We also assessed the efficacy of individual exposure-based treatments and the potentially moderating impact of various demographic, clinical, and treatment-related factors. PsycINFO and Medline were searched for randomized controlled trials of exposure-based therapies for adult PTSD. A total of 934 abstracts were screened for initial eligibility; of these, 65 articles met inclusion criteria and were included in the meta-analysis (total N = 4929 patients). Exposure therapy showed large effects relative to waitlist and treatment-as-usual, a small effect relative to non-trauma-focused comparators and a negligible effect relative to other trauma-focused treatments or medication. At follow-up most effects sizes were stable, except for a medium effect favoring exposure over medication. The individual exposure-based therapies examined were similarly effective. Moderator analyses revealed larger effect sizes in studies with fewer sessions, younger samples, fewer participants diagnosed with substance use disorder, and fewer participants on psychiatric medication. Effect sizes were also larger in studies of refugees and civilians compared to military samples, studies of PTSD related to natural disasters and transportation accidents vs. other traumatic events, and studies of individual vs. group therapy. Findings support the overall efficacy of exposure therapy and highlight that there are a number of efficacious exposure-based therapies available.

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.

Low Estradiol May Not Impede Cognitive Restructuring in Women With Anxiety Disorders.

Prior research suggests that estradiol may moderate fear extinction in animal models and humans. Based on these findings, estradiol may also moderate cognitive reappraisal, which is theorized to be an important mechanism of change in extinction-based therapy (exposure therapy). We compared cognitive restructuring (CR) skills acquisition and outcome between women with primary anxiety disorders who had high versus low estradiol using a standardized CR task that closely resembles clinical practice. As a proxy of CR outcome, we assessed subjective distress ratings before and after the task and psychophysiological arousal (heart rate and electrodermal activity) throughout the task. Contrary to predictions, results showed that CR skills acquisition and outcome did not differ between the high and low estradiol groups. Although both groups demonstrated reductions in negative affect and skin conductance responses during the CR task, suggesting that participants were able to acquire CR skills and use them effectively to regulate distress, the groups did not differ with respect to CR ability or outcome. The findings suggest that estradiol may not moderate cognitive reappraisal, and may have more of an effect on basic habituation and extinction processes instead.

Psychophysiological assessment of stress reactivity and recovery in anxiety disorders.

The present study aimed to examine changes in psychophysiological arousal from baseline to a stressor phase (reactivity) and from the stressor phase to a second resting phase (recovery) in patients with anxiety disorders. Fifty adult patients with DSM-5 anxiety disorders (panic disorder, generalized anxiety disorder, or social anxiety disorder) and 28 healthy control (HC) participants underwent psychophysiological monitoring including electrocardiogram, respiration rate, electrodermal activity, gastrocnemius electromyograph, and end-tidal CO2 for a 3-min resting phase, a 6-min mild stressor phase, and a 3-min recovery phase. Anxious patients then went on to receive naturalistic cognitive-behavioral therapy (CBT) in a specialty outpatient clinic. Results for the reactivity phase indicated that compared to HCs, patients with social anxiety disorder exhibited heightened psychophysiological reactivity while patients with panic disorder and generalized anxiety disorder exhibited attenuated reactivity. Results for physiological recovery (return to baseline after the stressor was withdrawn) were mixed, but provided some support for slower autonomic recovery in patients with generalized anxiety disorder and panic disorder compared to HCs. Participants with all anxiety disorders exhibited diminished change in high frequency heart rate variability compared to HCs. Generally, psychophysiological reactivity and recovery were not associated with CBT outcome, though exploratory analyses indicated that greater respiration rate reactivity and stronger respiration rate recovery were associated with better CBT outcomes in patients with panic disorder.

A meta-analysis of relapse rates in cognitive-behavioral therapy for anxiety disorders.

Cognitive-behavioral therapy (CBT) is a first-line treatment for anxiety and related disorders, with large pre- to post-treatment effect sizes. Rates of relapse, or the likelihood that a state of remission will be maintained once treatment is withdrawn, have been relatively neglected in CBT outcome studies. The present meta-analysis aimed to determine the overall rate of relapse in CBT for anxiety and related disorders. A secondary aim was to assess whether demographic, clinical, and methodological factors were associated with rates of relapse in CBT. Articles were identified from prior CBT meta-analyses and review papers and from literature searches using the PsycINFO and Medline electronic databases, with 17 full-length articles retained for meta-analysis (total N = 337 patients). Results showed an overall relapse rate of 14 %, which did not significantly differ between diagnoses. The way in which relapse was defined was significantly associated with relapse rates; when relapse was defined as meeting diagnostic criteria, estimates were lower than when alternative definitions were used. The findings indicate that relapse following symptom remission occurs in a minority of patients, suggesting that future treatment development and refinement efforts should focus on improving relapse prevention skills and interventions to minimize risk of relapse.

An Examination of the Association Between Subjective Distress and Functional Connectivity During Discarding Decisions in Hoarding Disorder.

BACKGROUND: Individuals with hoarding disorder (HD) demonstrate exaggerated subjective distress and hyperactivation of cingulate and insular cortex regions when discarding personal possessions. No prior study has sought to determine whether this subjective distress is associated with specific profiles of abnormal brain function in individuals with HD. METHODS: We used multimodal canonical correlation analysis plus joint independent component analysis to test whether five hoarding-relevant domains of subjective distress when deciding to discard possessions (anxiety, sadness, monetary value, importance, and sentimental attachment) are associated with functional magnetic resonance imaging-measured whole-brain functional connectivity in 72 participants with HD and 44 healthy controls. RESULTS: Three extracted components differed between HD participants and healthy control subjects. Each of these components depicted an abnormal profile of functional connectivity in HD participants relative to control subjects during discarding decisions, and a specific distress response profile. One component pair showed a relationship between anxiety ratings during discarding decisions and connectivity among the pallidum, perirhinal ectorhinal cortex, and dorsolateral prefrontal cortex. Another component comprised sadness ratings during discarding decisions and connectivity in the pallidum, nucleus accumbens, amygdala, and dorsolateral prefrontal cortex. The third component linked HD brain connectivity in several dorsolateral prefrontal cortex regions with perceived importance ratings during discarding decisions. CONCLUSIONS: The findings indicate that in patients with HD, the subjective intensity of anxiety, sadness, and perceived possession importance is related to abnormal functional connectivity in key frontal and emotional processing brain regions. The findings are discussed in terms of emerging neurobiological models of HD.

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.

Functional Neuroimaging Test of an Emerging Neurobiological Model of Hoarding Disorder.

BACKGROUND: Over the past decade, functional neuroimaging studies have found abnormal brain function in several cortical systems when patients with compulsive hoarding behaviors make decisions about personal possessions. The purpose of this study was to use functional magnetic resonance imaging to test a neurobiological model of hoarding disorder (HD) that has begun to emerge from these small studies by confirming HD-related brain dysfunction in previously implicated brain regions in the largest sample of HD patients examined to date. METHODS: We compared 79 adults diagnosed with DSM-5 HD with 44 non-HD control participants using a functional magnetic resonance imaging task of decision making to acquire or discard material possessions and on a control task involving semantic processing. RESULTS: HD brain activation profiles prominently featured insular and anterior cingulate cortex overengagement during possession-related choices that were not seen in non-HD brain activation profiles and also correlated with hoarders' clutter and difficulty discarding. Although HD patients overengaged the insula when deciding to discard, relative to when performing the non-decision making task contrast, the HD insula also was generally blunted. CONCLUSIONS: This study links the defining behavioral symptoms of HD to localized brain dysfunction within cingulo-opercular brain systems and firmly establishes the context-dependent importance of this network dysfunction in HD. The relevance of dysfunction in these brain regions is highlighted by a failure to replicate HD-related abnormalities in other brain regions implicated in prior HD functional magnetic resonance imaging studies. This study also raises the novel possibility that HD may involve abnormality in the inferior frontal cortex engaged for executive control over semantic processing.

A Comparison of Cognitive Restructuring and Thought Listing for Excessive Acquiring in Hoarding Disorder.

Excessive acquiring is a common symptom of hoarding disorder (HD). Little is known about subjective distress associated with acquiring in HD. The present study examined acquiring- related distress and reactions to cognitive restructuring (CR) in 92 individuals with HD and 66 community control (CC) participants. All participants identified an item of interest at a high-risk acquiring location and then decided whether or not to acquire the item. HD participants completed the acquiring task while receiving a CR-based intervention or a thought-listing (TL) control condition. Results showed that HD participants reported more severe distress and greater urges to acquire the item of interest than did CC participants. Nevertheless, subjective distress decreased in both groups following the acquiring task. There were no differences in acquiring- related distress between the CR and TL conditions. The findings indicate that subjective distress may decrease after relatively short periods of time in individuals with HD, but that a single session of CR may not alleviate acquiring-related distress in HD participants.

Quality of Life in Patients with Hoarding Disorder.

The aim of this study was to investigate health-related quality of life (QoL) in patients with hoarding disorder (HD). Fifty-four patients with a primary diagnosis of HD, and 24 age- and sex-matched healthy control (HC) participants, completed a battery of questionnaires including the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), Saving Inventory-Revised, and Depression, Anxiety, Stress Scales. Compared to HC participants, those with HD reported poorer health-related QoL across all domains of the SF-36. When controlling for comorbid affective symptoms, HD participants scored lower than did HC participants in the QoL domains of social functioning, emotional well-being, role limitations due to emotional problems, vitality, and general health. HD symptom severity predicted, beyond the effects of affective symptoms, lower QoL in social functioning, emotional well-being, role limitations due to emotional problems, vitality, and general health.

Validation of a Behavioral Measure of Acquiring and Discarding in Hoarding Disorder.

Behavioral assessment is an important component of evidence-based assessment and treatment in anxiety and related disorders. The purpose of the current study was to validate a behavioral measure of difficulty discarding and acquiring, the core features of hoarding disorder (HD). Seventy-eight patients with a primary diagnosis of HD completed a computerized acquiring and discarding task; the task consisted of making simulated decisions about acquiring and discarding items of varying monetary value. A subset of patients (n = 42) went on to receive cognitive behavioral therapy (CBT) for HD and completed the computer tasks again after treatment. An additional 30 age- and sex-matched healthy control participants (HCs) also completed the acquiring and discarding tasks. Results showed that HD patients saved and acquired more items than the HC group, and had longer response times during the tasks. In support of the convergent validity of the tasks, item decisions and reaction times were positively correlated with established measures of HD symptoms. Among treatment completers, items saved and acquired and response times decreased from pre- to post-CBT, suggesting that the tasks were sensitive to detect treatment-related changes in difficulty discarding and acquiring behaviors. The findings support the validity of the discarding and acquiring tasks in measuring HD symptoms, and are discussed in terms of the potential advantages of behavioral measures in HD treatment and research.

Distinct resting state functional connectivity abnormalities in hoarding disorder and major depressive disorder.

Emerging research suggests that hoarding disorder (HD) is associated with abnormal hemodynamic activity in frontal brain regions. Prior studies have not examined intrinsic network connectivity in HD during unstructured "resting state" fMRI. Furthermore, it remains unclear whether previously observed HD abnormalities might be better explained by the presence of other disorders frequently comorbid with HD, such as major depressive disorder (MDD). The current study compared resting state functional connectivity in HD-only patients (n = 17), MDD-only patients (n = 8), patients with co-occurring HD and MDD (n = 10), and healthy control participants (n = 18). Using independent component analysis, we found that HD-only patients exhibited lower functional connectivity in a "task positive" cognitive control network, compared to the other three groups. The HD group also had greater connectivity in regions of the "task negative" default mode network than did the other groups. Findings suggest that HD is associated with a unique neurobiological profile, and are discussed in terms of recent neurological and neuropsychological findings and models in HD and related disorders.

Efficacy and mediators of a group cognitive-behavioral therapy for hoarding disorder: A randomized trial.

OBJECTIVE: Hoarding disorder (HD) is a common and potentially debilitating psychiatric disorder. Thus far, psychological treatments have yielded modest effects and/or were time-consuming and costly to deliver. The aim of the present study was to test the efficacy of a brief group cognitive-behavioral therapy (CBT) for adults with HD and to test hypothesized mediators of treatment outcome. METHOD: Eighty-seven adults with a primary diagnosis of HD were randomized to either immediate CBT or wait list. CBT consisted of 16 weekly, 90-min group sessions that emphasized in-session practice of discarding and refraining from acquiring, decision-making and problem-solving training, emotional distress tolerance, motivational interviewing strategies, and contingency management. Participants were assessed at pretreatment, midtreatment, and posttreatment by an independent evaluator unaware of treatment condition. RESULTS: CBT was efficacious for the symptoms of HD compared with wait list. Saving-related cognitions, but not subjective cognitive impairment, partially mediated treatment outcomes. CONCLUSION: Brief Group CBT is an efficacious and feasible treatment for adults with HD, and is partially mediated by reductions in maladaptive beliefs about possessions. Superiority trials comparing CBT to active treatments, and additional research into mechanisms of treatment outcome, are warranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Discarding personal possessions increases psychophysiological activation in patients with hoarding disorder.

Difficulty discarding is the core behavioral symptom of hoarding disorder (HD). Patients with HD report greater subjective distress when discarding their own possessions as compared to others' possessions. To date, no prior studies have examined psychophysiological activation, an objective measure of anxious arousal, during discarding among individuals with HD. The current study assessed psychophysiological responses during a baseline resting period and two discarding tasks, one involving personal possessions and the other involving matched control ("experimenter-owned") items in 52 patients with a primary diagnosis of HD. Results showed that, compared to discarding control items, discarding personal possessions increased skin conductance and heart rate and decreased end tidal carbon dioxide. There were no differences in heart rate variability, respiratory sinus arrhythmia, and respiration rate between the two discarding tasks. Despite the fact that discarding increased psychophysiological arousal, self-reported HD symptoms (including difficulty discarding) failed to predict psychophysiological responses during the discarding tasks. The findings suggest that there may be discordance between objective and subjective measures of hoarding-related distress, and are discussed in terms of incorporating psychophysiological measures into the assessment and treatment of HD.

An investigation of delay and probability discounting in hoarding disorder.

Behavioral impulsivity may be a mechanism of hoarding disorder (HD). A commonly used and well-validated measure of impulsivity is the delay and probability discounting task, which consists of making decisions about receiving monetary rewards after varying delay intervals and delivery probabilities. We compared delay and probability discounting and self-reported behavioral impulsivity in 81 patients with a primary diagnosis of HD and 45 nonclinical controls. HD participants completed the impulsivity measures before and after 16 weekly sessions of cognitive-behavioral therapy (CBT), whereas control group participants completed the measures before and after a 16-week waiting period. Despite the fact that self-reported impulsivity was greater in the HD group than the control group, delay and probability discounting did not differ between groups. Additionally, while self-reported behavioral impulsivity improved over the course of CBT in HD participants, delay and probability discounting did not change during treatment. Furthermore, higher delay discounting scores (i.e., greater preference for immediate rewards, indicating greater impulsivity) were associated with lower hoarding symptom severity. The findings suggest that self-reported impulsivity, but not objective performance on a behavioral impulsivity task, may be impaired in HD, and are discussed in terms of cognitive and affective factors in decision-making.