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 exploration of neural predictors of treatment compliance in cognitive-behavioral group therapy for hoarding disorder.

A persistent and influential barrier to effective cognitive-behavioral therapy (CBT) for patients with hoarding disorder (HD) is treatment retention and compliance. Recent research has suggested that HD patients have abnormal brain activity identified by functional magnetic resonance (fMRI) in regions often engaged for executive functioning (e.g., right superior frontal gyrus, anterior insula, and anterior cingulate), which raises questions about whether these abnormalities could relate to patients' ability to attend, understand, and engage in HD treatment. We examined data from 74 HD-diagnosed adults who completed fMRI-measured brain activity during a discarding task designed to elicit symptom-related brain dysfunction, exploring which regions' activity might predict treatment compliance variables, including treatment engagement (within-session compliance), homework completion (between-session compliance), and treatment attendance. Brain activity that was significantly related to within- and between-session compliance was found largely in insula, parietal, and premotor areas. No brain regions were associated with treatment attendance. The results add to findings from prior research that have found prefrontal, cingulate, and insula activity abnormalities in HD by suggesting that some aspects of HD brain dysfunction might play a role in preventing the engagement needed for therapeutic benefit.

Cognitive-Behavioral Therapy Enhancement Strategies.

We review the literature on various strategies to augment cognitive-behavioral therapy (CBT). Although traditional pharmacotherapy has only a small additive effect, research demonstrates that it is possible to select interventions that potentiate known mechanisms of CBT. D-cycloserine appears to potentiate activity at the N-methyl D-ethyl aspartate receptor and thereby facilitates fear extinction. Exercise may increase neural plasticity and thereby increase the efficacy of CBT for depression and anxiety. Noninvasive brain stimulation is thought to target the specific cortical regions needed for CBT response, but results have been mixed. Several other compounds appear promising but await controlled research before their efficacy as an augmentation strategy can be determined.

Borderline Personality Traits Do Not Moderate the Relationship Between Depression, Beliefs, and Suicidal Thoughts and Behaviors.

Adults with clinically significant borderline personality disorder traits (BPTs) are at high risk of experiencing suicidal thoughts and behaviors (STBs). STBs among those with BPTs have been associated with suicidal beliefs (e.g., that one is unlovable or that distress is intolerable). However, the extent to which suicidal beliefs uniquely mediate the relationship between emotional distress and STBs among individuals with BPTs is not known. Individuals admitted to an inpatient unit (N = 198) with recent STBs completed assessments of BPTs, depression, suicidal beliefs, suicidal ideation, and suicide attempt history. Moderated mediation models were used to explore whether suicidal beliefs mediated the relationship between depression and STBs conditional on BPTs. Suicidal patients with versus without BPTs reported stronger suicidal beliefs and more severe STBs (i.e., suicidal ideation, lifetime attempts). Exploratory moderated mediation analysis demonstrated that suicidal beliefs mediated the relationship between depression and suicidal ideation as well as suicide attempts. The mediation effect of suicidal beliefs on the depression-ideation and depression-attempt relationship was not significantly moderated by BPTs. This study was cross-sectional and therefore the estimated mediation models must be considered exploratory. Longitudinal research will be needed to assess the potential causal mediation of suicidal beliefs on the relationship between depression and STBs. The results of this study suggest that suicidal beliefs may play a significant role in the relationship between depression and STBs for inpatients with a history of suicidality regardless of BPTs. This suggests suicidal beliefs may be an important treatment target for adults with a history of STBs.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

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.

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.

Symptom distress and psychosocial functioning improve bidirectionally during cognitive-behavioral therapy for anxiety disorders.

The efficacy of cognitive-behavioral therapy (CBT) for reducing anxiety disorder symptoms is well documented. However, limited research has investigated how symptom amelioration is temporally associated with changes in psychosocial functioning, such as interpersonal and social role functioning, during CBT. Participants were 288 (M age = 37.00 [SD = 14.41]; 59.0% female; 69.0% White; 6.6% Hispanic/Latino) outpatients diagnosed with an anxiety disorder who received CBT at a specialized hospital-based clinic. Participants completed the Outcome Questionnaire-45, a measure of symptom distress, social role performance, and interpersonal problems, at initial assessment and prior to each treatment session. Symptom distress and indicators of psychosocial functioning were robustly related during 25 sessions of CBT. Cross-lagged analyses revealed that reductions in symptom distress predicted subsequent improvements in psychosocial functioning during treatment, and vice versa. Associations from symptom distress to subsequent psychosocial functioning evidenced larger effect sizes than the reverse. Lower levels of severity at intake and presence of comorbid depression attenuated the association between symptom reduction and subsequent social role performance improvement. In sum, anxiety symptoms and psychosocial functioning bidirectionally improve during CBT for anxiety disorders. Maximally effective treatments may be those that simultaneously ameliorate symptoms and focus on improving functioning in key domains.

Uncovering the role of substance use in suicide attempts using a mixed-methods approach.

INTRODUCTION: Substance use is an established risk factor for suicide attempt. Clarifying the role of substance use in suicide attempts may identify modifiable treatment targets. This study used mixed methods to associate substance use with suicide attempt history and identify pathways through which substance use contributes to attempts. METHODS: Study 1 included 213 adult inpatients (n = 127 with substance use disorder [SUD]), who completed assessments of suicide attempt history as well as demographic and clinical suicide risk factors. Study 2 was a narrative analysis of suicide attempt stories described by 20 inpatients diagnosed with SUD. RESULTS: In Study 1, patients with co-occurring alcohol and drug use disorders reported more actual lifetime suicide attempts than did those without SUD. In addition, alcohol and drug use disorders were independently associated with lifetime suicide attempts after controlling for demographic and clinical confounders. In Study 2, substance use played a role in all suicide attempts through at least one pathway before, during, or after a triggering stressor, or as suicide attempt method. CONCLUSIONS: Substances play a role in suicide attempt baseline risk, acute risk and as means. It is important to target chronic and acute substance use in suicide prevention treatment plans.

On the importance of identifying mechanisms and active ingredients of psychological treatments.

This commentary addresses the thought-provoking article by Lorenzo-Luaces (in press). We review areas of both agreement and disagreement with the author's points, noting that readers should not infer that research into active ingredients and mechanisms is pointless. We conclude with a call for more research into the mechanisms of therapeutic change and the active ingredients of therapeutic interventions, with the aim of disseminating treatments that are both effective and efficient.

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).

The DIAMOND-KID: Psychometric Properties of a Structured Diagnostic Interview for DSM-5 Anxiety, Mood, and Obsessive-Compulsive and Related Disorders in Children and Adolescents.

The objective of the present study was to examine the reliability and validity of a new semi-structured interview for pediatric psychiatric disorders, which is needed as existing interviews do not cover the full range of anxiety, mood, and obsessive-compulsive disorder (OCD)-related disorders. Three hundred eleven child patients (aged 10-17) were administered the Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders-Child and Adolescent Version (DIAMOND-KID). Of these, 65 provided interrater reliability data and 59 provided test-retest reliability data. Participants also completed self-report measures that assessed symptoms of anxiety, mood, and OCD and related disorders. Although parents/guardians could participate in the interview at the clinician's discretion, most of the initial interviews and all of the reliability interviews were based on the child's self-report. Test-retest reliability ranged from very good to excellent. Interrater reliability was more variable, with estimates for generalized anxiety disorder and major depressive disorder in the questionable range; the other interrater reliability estimates ranged from good to very good. Convergent validity was established by significant between-group comparisons on applicable self-report measures for all diagnoses. The results of the present study indicate that the DIAMOND-KID is a promising semi-structured diagnostic interview for 5th edition of the Diagnostic and Statistical Manual of Mental Disorders in pediatric populations.

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.

Brief adjunctive mindfulness-based cognitive therapy via Telehealth for anxiety during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: While cognitive-behavioral therapy is a highly efficacious treatment for anxiety, additional research is needed to identify adjunctive interventions that may augment treatment outcome. DESIGN: In response to the COVID-19 pandemic, we conducted an open feasibility trial of brief (i.e., four 75- to 90-minute sessions) mindfulness-based cognitive therapy (MBCT) for anxiety via telehealth for patients (N = 23) receiving individual CBT at an outpatient specialty clinic. METHODS: Self-report measures of home practice compliance (weekly), intervention acceptability (post-intervention), mindfulness and self-compassion, anxiety and depressive symptoms, and transdiagnostic processes (pre- and post-intervention) were administered as part of routine clinical practice. RESULTS: Results indicated good retention and attendance rates, few technical difficulties, good home practice compliance, and high levels of perceived importance. Participants indicated that they would highly recommend the group to others and also recommended extending the group beyond four sessions. There were significant improvements in mindfulness and self-compassion and reductions in intolerance of uncertainty, anxiety sensitivity, distress intolerance, emotion dysregulation, and anxiety symptoms from pre- to post-intervention. CONCLUSIONS: Brief MBCT as an adjunctive treatment for anxiety via telehealth is feasible and acceptable, and shows promise in terms of engaging treatment targets and transdiagnostic processes and reducing anxiety symptoms.

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.

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.

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.

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.