Cognitive behavioral therapy (CBT) plus attention bias modification (ABM) reduces anxiety sensitivity and depressive symptoms in panic disorder: A pilot randomized trial.

BACKGROUND: Cognitive bias theories propose that reducing threat hypervigilance in mental disorders can augment cognitive behavioral therapy (CBT) outcomes. However, no studies have tested whether adding attention bias modification (ABM) can effectively enhance CBT's effects on anxiety sensitivity (AS), electromyography (EMG), and skin conductance (SC) for panic disorder (PD). This pilot randomized controlled trial (RCT) thus aimed to evaluate the efficacy of CBT + ABM (vs. CBT plus attention training placebo; PBO) on those outcomes. METHOD: This study is a secondary analysis (Baker et al., 2020). Adults with PD were randomized to receive CBT + ABM (n = 11) or CBT + PBO (n = 12). Before each of the first five CBT sessions, CBT + ABM and CBT + PBO participants completed a 15-min ABM task or attention training PBO, respectively. AS and depression severity as well as SC and EMG during habituation to a loud-tone startle paradigm were assessed. Hierarchical Bayesian analyses were conducted. RESULTS: During pre-post-treatment and pre-follow-up, CBM + ABM (vs. CBT + PBO) led to a notably greater reduction in ASI-Physical (between-group d = -1.26 to -1.25), ASI-Cognitive (d = -1.16 to -1.10), and depression severity (d = -1.23 to -0.99). However, no between-group difference was observed for ASI-Social, EMG, or SC indices. DISCUSSION: Adding a brief computerized ABM intervention to CBT for PD protocols may enhance therapeutic change.

Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial.

Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, Setting, and Participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main Outcomes and Measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and Relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial Registration: ClinicalTrials.gov Identifier: NCT03522844.

The influence of posttraumatic stress disorder treatment on anxiety sensitivity: Impact of prolonged exposure, sertraline, and their combination.

Trauma-informed beliefs often decrease during posttraumatic stress disorder (PTSD) treatment. This may also extend to anxiety sensitivity (AS), defined as a fear of anxiety-related sensations and beliefs that anxiety is dangerous and/or intolerable. However, little is known about how AS changes during exposure-based and psychopharmacological PTSD treatments. Further, high AS may be a risk factor for diminished PTSD symptom improvement and increased treatment dropout. To better understand how AS impacts and is impacted by PTSD treatment, we conducted a secondary analysis of a randomized clinical trial with a sample of 223 veterans (87.0% male, 57.5% White) with PTSD from four U.S. sites. Veterans were randomized to receive prolonged exposure (PE) plus placebo (n = 74), sertraline plus enhanced medication management (n = 74), or PE plus sertraline (n = 75). Veterans answered questions about PTSD symptoms and AS at baseline and 6-, 12-, 24-, 36-, and 52-week follow-ups. High baseline AS was related to high levels of PTSD severity at 24 weeks across all conditions, ß = .244, p = .013, but did not predict dropout from exposure-based, ß = .077, p = .374, or psychopharmacological therapy, ß = .009, p = .893. AS also significantly decreased across all three treatment arms, with no between-group differences; these reductions were maintained at the 52-week follow-up. These findings suggest that high AS is a risk factor for attenuated PTSD treatment response but also provide evidence that AS can be improved by both PE and an enhanced psychopharmacological intervention for PTSD.

Cognitive-Behavioral Treatments for Anxiety and Stress-Related Disorders.

Cognitive-behavioral therapy (CBT) is a first-line, empirically supported intervention for anxiety disorders. CBT refers to a family of techniques that are designed to target maladaptive thoughts and behaviors that maintain anxiety over time. Several individual CBT protocols have been developed for individual presentations of anxiety. The article describes common and unique components of CBT interventions for the treatment of patients with anxiety and related disorders (i.e., panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, prolonged grief). Recent strategies for enhancing the efficacy of CBT protocols are highlighted as well.

Predictors of Response to Prolonged Exposure, Sertraline, and Their Combination for the Treatment of Military PTSD.

Objective: The current study is an analysis of predictors of posttraumatic stress disorder (PTSD) treatment response in a clinical trial comparing (1) prolonged exposure plus placebo (PE + PLB), (2) PE + sertraline (PE + SERT), and (3) sertraline + enhanced medication management (SERT + EMM) with predictors including time since trauma (TST), self-report of pain, alcohol use, baseline symptoms, and demographics.Methods: Participants (N = 196) were veterans with combat-related PTSD (DSM-IV-TR) of at least 3 months' duration recruited between 2012 and 2016 from 4 sites in the 24-week PROlonGed ExpoSure and Sertraline (PROGrESS) clinical trial (assessments at weeks 0 [intake], 6, 12, 24, 36, and 52).Results: Across treatment conditions, (1) longer TST was predictive of greater week 24 PTSD symptom improvement (ß = 1.72, P = .01) after adjusting for baseline, (2) higher baseline pain severity was predictive of smaller symptom improvement (ß = -2.96, P = .003), and (3) Hispanic patients showed greater improvement than non-Hispanic patients (ß = 12.33, P = .03). No other baseline characteristics, including alcohol consumption, were significantly predictive of week 24 improvement. Comparison of TST by treatment condition revealed a significant relationship only in those randomized to the PE + SERT condition (ß = 2.53, P = .03). Longitudinal analyses showed similar results.Conclusions: The finding that longer TST shows larger symptom reductions is promising for PTSD patients who might not seek help for years following trauma. Higher baseline pain severity robustly predicted attenuated and slower response to all treatment conditions, suggesting a common neuropathologic substrate. Finally, in the current study, alcohol use did not impede the effectiveness of pharmacotherapy for PTSD.Trial Registration: ClinicalTrials.gov identifier: NCT01524133.

Anhedonia is central for the association between quality of life, metacognition, sleep, and affective symptoms in generalized anxiety disorder: A complex network analysis.

BACKGROUND: Poor quality of life, sleep problems, anhedonia, and negative metacognitions are common in anxiety and depression. To examine the nature of the relationship between these features and the role of metacognitions, anhedonia, and quality of life in anxiety and depression, we conducted a complex network analysis with items of self-report measures assessing quality of life, sleep, negative thinking styles, anxiety, and depression. METHODS: Participants were 226 treatment seeking individuals with a primary DSM-5 diagnosis of generalized anxiety disorder. Node centrality, strength, expected influence, community, and bridge estimation were calculated using partial correlation coefficients and glasso regularization. RESULTS: Results revealed that anhedonia was the most central node followed by quality of life nodes. Moreover, anhedonia exhibited the highest strength and expected influence, which were both stable, reliable metrics within the network. Metacognitions were not central nodes in the network, but were strong bridge symptoms between communities. LIMITATIONS: The results are limited by the cross-sectional nature of the data and the administration of self-report scales at one time-point, despite different rating anchors. CONCLUSION: These findings suggest that anhedonia is a crucial element for the association between quality of life, sleep problems, and negative cognitions.

Towards a precision psychiatry approach to anxiety disorders with ecological momentary assessment: the example of panic disorder.

BACKGROUND: Treatments for anxiety disorders are among the most effective in psychiatry. Yet, there is considerable room for improvement. AIM: In this paper, we discuss the value of ecological momentary assessment as a research method and clinical tool. METHODS: We begin by describing ecological momentary assessment and its advantages, including the ability to collect ecologically valid information about mental disorders, in real time, in individual patients. We then illustrate the value of this approach for anxiety disorder treatment using two patients with panic disorder who completed ecological momentary assessments for 2 weeks before and after a cognitive-behavioural therapy intervention. We focus especially on two key pieces of information provided by ecological momentary assessment data: information about symptom dynamics and information about the relationships among symptoms as they unfold over time within individual patients. PERSPECTIVE: Although considerable work is needed to further develop this methodology in the context of anxiety disorder treatment, we believe that these pieces of information may ultimately inform our understanding of how anxiety disorder treatments have their effect and how those treatments can be tailored to individual patients.

Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post-9/11 service members and veterans.

BACKGROUND: Complicated grief (CG) is a bereavement-specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes. METHODS: To evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat-related PTSD (n = 194). Assessment of PTSD, trauma-related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24-week trial. RESULTS: CG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma-related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011). CONCLUSIONS: Comorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat-related PTSD, suggesting that screening and additional intervention for CG may be needed.

Barriers to mental health treatment among individuals with social anxiety disorder and generalized anxiety disorder.

Individuals with social anxiety disorder (SAD) or generalized anxiety disorder (GAD) are at risk for not utilizing mental health treatment. The purpose of this research was to examine barriers to treatment in a sample of adults with clinically significant SAD or GAD. Participants were 226 nontreatment-seeking adults with SAD or GAD who underwent semistructured diagnostic interview and received a clinician assessment of symptom severity as part of a clinical research study. Participants completed a self-report measure of barriers to treatment. Individual and combined associations of demographic and symptom severity variables with number of perceived barriers to treatment were examined. Individuals with GAD or SAD endorsed a similar number of overall barriers to treatment. Shame and stigma were the highest cited barriers followed by logistical and financial barriers. Both groups also endorsed not knowing where to seek treatment at high rates. Individuals with greater symptom severity reported more barriers to treatment. Racial and ethnic minorities reported more barriers to treatment even after controlling for symptom severity. Among individuals with GAD or SAD, increased education and culturally sensitive outreach initiatives are needed to reduce barriers to mental health treatment. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Facets of Mindfulness in Adults with Generalized Anxiety Disorder and Impact of Co-occurring Depression.

Anxiety and depressive symptoms are associated with lower levels of mindfulness, yet few studies to date have examined facets of mindfulness in adults with Generalized Anxiety Disorder (GAD). In this study, we examined differences in mindfulness between individuals with GAD with and without concurrent Major Depressive Disorder (MDD) and/or Dysthymic Disorder (DD). We also examined the associations of anxiety and depressive symptoms with facets (subscales) of mindfulness. We hypothesized that individuals with primary GAD and co-occurring MDD/DD would exhibit lower mindfulness than those without a concurrent depressive disorder. We also hypothesized that mindfulness would be negatively correlated with worry and depressive symptom severity. Subjects were 140 adults (M (SD) age = 33.4 (12.9); 73% female) with a primary diagnosis of GAD; 30.8% (n = 43) also met criteria for current MDD/DD as determined by a structured clinical interview for DSM-IV. Current worry and depressive symptoms were assessed using self-report measures at baseline of a 12-week treatment study. Individuals with GAD and co-occurring MDD/DD exhibited significantly lower mindfulness than those without a depressive disorder diagnosis and specifically lower scores on the Awareness sub-scale compared to individuals with primary GAD and no comorbid depression. In terms of the dimensional impact of worry and depression ratings, depression symptoms independently predicted lower Awareness scores and worry independently predicted lower levels of Nonreacting and Nonjudging sub-scales. This may have direct treatment implications.

Five-factor model in bereaved adults with and without complicated grief.

Knowledge about what psychological characteristics underlie complicated grief (CG) is limited. The current study examined the five-factor personality traits in 81 bereaved adults with (n = 51) and without (n = 30) CG. A trained doctoral-level clinician evaluated participants using a structured, diagnostic psychiatric interview, and they completed self-report measures of grief and personality. A multiple regression model indicated that higher levels of neuroticism were associated with greater CG symptom severity, implicating neuroticism in the development of CG. Future prospective studies confirming it as a risk factor for the development of CG are warranted.

Effects of post-exposure naps on exposure therapy for social anxiety.

Exposure therapy for social anxiety disorder (SAD) utilizes fear extinction, a memory process enhanced by sleep. We investigated whether naps following exposure sessions might improve symptoms and biomarkers in response to social stress in adults undergoing 5-week exposure-based group SAD therapy. Thirty-two participants aged 18-39 (18 females) with SAD were randomized. Before and after treatment, participants completed the Liebowitz Social Anxiety Scale (LSAS) and underwent a Trier Social Stress Test with psychophysiological monitoring (mpTSST) that included skin conductance (SCL), electromyographic (EMG) and electrocardiographic recording, and an auditory startle procedure while anticipating the social stressor. At sessions 3 and 4, exposure was followed by either a 120-min polysomnographically monitored sleep opportunity (Nap, N = 17) or wakefulness (Wake, N = 15). Primary hypotheses about SAD symptom change (LSAS) and EMG blink-startle response failed to differ with naps, despite significant symptom improvement (LSAS) with therapy. Some secondary biomarkers, however, provided preliminary support for enhanced extinction learning with naps, with trend-level Time (pre-, post-treatment) × Arm interactions and significant reduction from pre- to post treatment in the Nap arm alone for mpTSST SCL and salivary cortisol rise. Because of the small sample size and limited sleep duration, additional well-powered studies with more robust sleep interventions are indicated.

The loss of a fellow service member: Complicated grief in post-9/11 service members and veterans with combat-related posttraumatic stress disorder.

Bereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 post-9/11, when service members and veterans with combat-related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; n = 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, n = 39) compared to those bereaved who did not (16.92%, n = 11; OR = 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, trauma-related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combat-related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.

Examining the Role of Anxiety Sensitivity in Sleep Dysfunction Across Anxiety Disorders.

Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.

Inflammatory cytokines in major depressive disorder: A case-control study.

INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). RESULTS: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). CONCLUSION: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

The Influence of Anxiety Sensitivity on a Wish to Die in Complicated Grief.

Individuals with complicated grief are at elevated risk of suicidal thoughts. Anxiety sensitivity has recently emerged as a risk factor of suicide. This study aimed to investigate a possible association between anxiety sensitivity and a wish to die in individuals with complicated grief. Participants were evaluated for participation in a treatment study and completed an ancillary questionnaire-based study. Participants were 51 bereaved adults evaluated (age: mean, 54 [SD, 13.6] years; 78% [n = 40] women). Logistic regression was used to examine the relationship between anxiety sensitivity and a wish to die. Overall, anxiety sensitivity was associated with a wish to die at the level of a medium effect size, although it did not reach statistical significance. The anxiety sensitivity social concerns subscale was significantly associated with a wish to die. These findings add to a growing literature implicating anxiety sensitivity in reporting a wish to die.