Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

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.

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.

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.

Geriatric anxiety inventory: factor structure and associations with cognitive status.

OBJECTIVES: The factor structure and clinical correlates of the Geriatric Anxiety Inventory were determined within a sample of patients with cognitive impairment. METHODS: Using a cross-sectional design, data were collected within an outpatient Memory Disorders Center. Clinical participants were diagnosed with either mild dementia (N = 45) or cognitive impairment, no dementia (N = 55). A comparison group of participants without subjective memory complaints (N = 50) was also included. The Geriatric Anxiety Inventory was administered and scored as both the 20-item version and 5-item short form. Measures of cognitive status, depressive symptoms, and functioning were also completed. RESULTS: Clinical participants reported more severe anxiety than did participants in the comparison group; however, the two patient groups did not differ. Principal components analysis revealed a four-factor structure of the Geriatric Anxiety Inventory. Item endorsement on factors characterized by excessive worry and difficulty making decisions were associated with a nearly twofold (odds ratio [OR]: 1.86) and nearly sixfold (OR: 5.70) odds of having cognitive impairment, respectively. The short-form version was composed of a single factor, and item endorsement was associated with a twofold increased odds of having cognitive impairment (OR: 2.02). CONCLUSION: Psychometric properties of the Geriatric Anxiety Inventory are acceptable among patients with cognitive impairment. Anxiety symptoms were common, and symptoms characterized by excessive worry and difficulty making decisions demonstrated the strongest associations with cognitive status.

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.

Subscales of alexithymia show unique pathways through reappraisal and suppression to anxiety, depression and stress.

The goal of this work was to explore associations of constituent factors of alexithymia on mental health and potential mediating effects of emotion regulation strategies, specifically suppression and reappraisal. Data were collected through the crowd-sourcing platform Amazon Mechanical Turk (MTURK). Three hundred seventy-seven individuals completed questionnaires related to distress (Depression Anxiety Stress Scales [DASS]), emotion regulation (Emotion Regulation Questionnaire [ERQ]) and Alexithymia (Bermond-Vorst Alexithymia Questionnaire [BVAQ]). Three mediation models were constructed for depression, anxiety and stress, with BVAQ subscales (verbalizing, identifying, emotionalizing, fantasizing, and analyzing) as predictors and ERQ subscales (suppression and reappraisal) as mediators. Results indicated 37.3 % variance in depression, 25.2 % variance in anxiety, and 35.3 % variance in stress was explained by each model. Direct associations revealed emotionalizing and fantasizing were negatively associated with depression, anxiety, and stress, while verbalizing was additionally associated with depression, identifying was additionally associated with anxiety, and all four BVAQ subscales were associated with stress. BVAQ subscales demonstrated negative associations with reappraisal and positive associations with suppression that mediated anxiety and depression. However, suppression did not mediate relationships between BVAQ subscales with stress. Findings support the importance of examining multiple factors of alexithymia and associations with emotion regulation strategies and distress.

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.

Characteristics of hoarding in older adults.

OBJECTIVE: This study determined the clinical characteristics of late-life hoarding disorder (HD). METHODS: Older adults (age 60 and older) with HD (n = 55) and without psychiatric diagnoses (n = 39) were compared on psychiatric, functional, cognitive, and health-related measures. Associations between age and clinical characteristics in a large sample of mixed age (n = 210; age range: 20-78) participants with HD were also determined. RESULTS: Individuals with late-life HD were characterized by substantial impairments in psychiatric, functional, cognitive, and medical status. Health risks (e.g., risks of falls and fire) were also common. However, older age was generally not associated with increased severity of hoarding or other clinical correlates (with the exception of one global clinician-rated measure of severity). CONCLUSIONS: Late-life HD is characterized by considerable morbidity and health risks, and these characteristics may be consistent across the lifespan in cross-sectional mixed-age samples of individuals with HD.

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.

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).

Impairments in life quality among clients in geriatric home care: associations with depressive and anxiety symptoms.

OBJECTIVE: The aim of this study was to determine the independent contributions of depressive and anxiety symptoms to quality of life among older adults who were receiving services through a home care program. METHODS: The study sample consisted of 66 community-dwelling older adults (ages 65 years and older), who were experiencing chronic medical illness and concomitant functional disability necessitating home care. Participants completed self-report measures of depression, anxiety, and health-related quality of life. Additional data on cognitive, health, and functional status were collected to be used as covariates. RESULTS: The associations of depressive symptoms with quality of life impairments in home care were substantial and pervasive. Depressive symptoms were significantly associated with quality of life impairments in nearly all domains. After controlling for depressive symptoms, anxiety symptoms accounted for additional and statistically significant variance in impaired life quality in the domains of mental health, role emotional functioning, and bodily pain. CONCLUSIONS: These results indicate that depressive and anxiety symptoms demonstrate negative associations with life quality among older adults in home care and highlight the importance of developing community-based programs to assess and treat depressive and anxiety symptoms among home care clients.

Autistic Traits Moderate Reappraisal Success for Depression and Anxiety Symptoms.

Cognitive reappraisal is associated with reduced emotional distress; however, little is known about the nature of this relationship in autism. This study tested whether autistic traits moderate reappraisal success (i.e., the negative correlation between reappraisal use and emotional symptom severity). Emotional symptoms were assessed using measures of depression, anxiety, and stress. It was hypothesized that more severe autistic traits would be associated with weaker reappraisal success across all scales. Data were collected from 377 adults using an on-line survey. Structural equation models found moderation effects for depression and anxiety, but not stress. Contrary to hypotheses, more severe autistic traits were associated with stronger reappraisal success. These preliminary results support including reappraisal in emotion regulation treatments for individuals with autistic traits.

Stepped care versus standard cognitive-behavioral therapy for obsessive-compulsive disorder: a preliminary study of efficacy and costs.

BACKGROUND: Exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) is underutilized, in part because of costs and time requirements. This study extends pilot work investigating the use of a stepped care ERP administration, in which patients are first given a low-intensity, low-cost treatment and the more costly intervention is reserved for those who do not respond to the first intervention. METHODS: Thirty adults with OCD were randomized to receive stepped care ERP or standard ERP. Those receiving stepped care started with three sessions over 6 weeks of low-intensity counseling with ERP bibliotherapy; patients failing to meet strict responder criteria after 6 weeks were given the more traditional treatment of therapist-administered ERP (17 sessions twice weekly). Those receiving standard ERP received the therapist-administered ERP with no lower-intensity lead-in. RESULTS: The two treatments were equally efficacious, with 67% of stepped care completers and 50% of standard treatment completers meeting criteria for clinically significant change at posttreatment. Similarly, no differences in client satisfaction ratings were obtained between the two groups. Examination of treatment costs, however, revealed that stepped care resulted in significantly lower costs to patients and third-party payers than did standard ERP, with large effect sizes. CONCLUSIONS: These results suggest that stepped care ERP can significantly reduce treatment costs, without evidence of diminished treatment efficacy or patient satisfaction. Additional research is needed to determine the long-term efficacy and costs of stepped care for OCD, and to examine the financial and therapeutic impact of implementing stepped care in community settings.

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.

Measuring Within-Session and Between-Session Compliance in Hoarding Disorder: A Preliminary Investigation of the Psychometric Properties of the CBT Compliance Measure (CCM) and Patient Exposure/Response Prevention Adherence Scale for Hoarding (PEAS-H).

Hoarding disorder (HD) is a new psychiatric diagnosis in Diagnostic and Statistical Manual of Mental Disorders-Fifth edition and preliminary evidence suggests that cognitive-behavioral treatments are effective in treating this condition. However, it has been demonstrated that individuals with HD generally display poor compliance during treatment, which may lead to poor outcomes. Treatment compliance can be conceptualized as either within-session or between-session compliance, but currently there are no validated measures of within-session or between-session compliance specifically for HD. The aim of this study was to provide an initial validation of the CBT Compliance Measure and the Patient Exposure/Response Prevention Adherence Scale for Hoarding in a sample of participants with HD who were undergoing group cognitive behavioral therapy (CBT) for HD (N = 70). Both measures, which were administered at each relevant treatment session, demonstrated a unidimensional structure, good reliability, as well as predictive validity, and are thus promising in the measurement of within-session and between-session compliance with CBT for HD.

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

A Cross-National Analysis of the Psychometric Properties of the Geriatric Anxiety Inventory.

OBJECTIVES: Assessing late-life anxiety using an instrument with sound psychometric properties including cross-cultural invariance is essential for cross-national aging research and clinical assessment. To date, no cross-national research studies have examined the psychometric properties of the frequently used Geriatric Anxiety Inventory (GAI) in depth. METHOD: Using data from 3,731 older adults from 10 national samples (Australia, Brazil, Canada, The Netherlands, Norway, Portugal, Spain, Singapore, Thailand, and United States), this study used bifactor modeling to analyze the dimensionality of the GAI. We evaluated the "fitness" of individual items based on the explained common variance for each item across all nations. In addition, a multigroup confirmatory factor analysis was applied, testing for measurement invariance across the samples. RESULTS: Across samples, the presence of a strong G factor provides support that a general factor is of primary importance, rather than subfactors. That is, the data support a primarily unidimensional representation of the GAI, still acknowledging the presence of multidimensional factors. A GAI score in one of the countries would be directly comparable to a GAI score in any of the other countries tested, perhaps with the exception of Singapore. DISCUSSION: Although several items demonstrated relatively weak common variance with the general factor, the unidimensional structure remained strong even with these items retained. Thus, it is recommended that the GAI be administered using all items.

The association between self-reported anxiety symptoms and suicidality.

This cross-sectional study assessed the association between self-reported anxiety symptoms and self-reported suicidality among a mixed diagnostic sample of psychiatric outpatients. Data were obtained from chart review of 2,778 outpatients who completed a routine diagnostic clinical interview and a standardized self-report of psychiatric symptoms on admission. Bivariate analyses indicated that those with >or= moderate anxiety symptoms were over three times as likely to report >or= moderate difficulty with suicidality. Self-reported anxiety symptoms were associated with a 2-fold increased likelihood of reporting suicidality after controlling for confounding (demographics, depressive symptoms, and diagnoses). These data are consistent with a growing literature demonstrating an association between anxiety symptoms and suicidality, and suggest that this association is not accounted for by coexisting mood symptoms or diagnoses. A single item, self-report may be a useful screening tool for symptoms that are pertinent to assessment of suicide risk.

Anxious depression among Puerto Rican and African-American older adults.

OBJECTIVES: To determine racial/ethnic differences in the prevalence and impact of anxious depression (i.e. major depressive disorder, MDD, occurring concomitant with generalized anxiety symptoms) among older adults. METHOD: Interviews were conducted with 218 Puerto Rican and 206 African American older (age > or =60) urban senior housing residents. Data were collected on diagnostic status, depression severity and psychosocial functioning. RESULTS: Results indicated a higher prevalence of MDD and anxious depression among Puerto Rican participants. Anxious depression was associated with more severe ratings of distress and suicidality compared with MDD alone, and the impact of depression and anxiety was most pronounced for the Puerto Rican participants. Puerto Rican participants also reported poorer subjective health and more substantial disability; however, these effects were independent of depression or anxiety status. CONCLUSIONS: Anxious depression is common among older ethnic minority adults and the impact of these symptoms differs by race/ethnicity. These results highlight the importance of conducting culturally sensitive assessments of depression and anxiety among older adults.