Examining the latent structure of worry and generalized anxiety in a clinical sample

Generalized anxiety disorder (GAD) is characterized by “pathological” worry, suggesting that GAD worriers differ qualitatively from non-GAD worriers. However, results from taxometric studies of worry in undergraduate and community samples have been mixed and to date, no studies have utilized clinical samples. The current study examined the latent structure of worry and GAD symptoms in a diagnostically heterogeneous clinical sample. Indicators were selected from the Penn State Worry Questionnaire-Abbreviated (n = 1175) and the GAD-7 (n = 638) and submitted to three taxometric procedures: MAXCOV, MAMBAC, and L-Mode. Results from all three procedures suggested that both worry and generalized anxiety are best conceptualized as dimensional constructs. Findings also indicated that ongoing conceptualization, assessment, and treatment of worry and GAD may be hampered by the application of a categorical framework.     

Intolerance of uncertainty as a mediator of reductions in worry in a cognitive behavioral treatment program for generalized anxiety disorder

Growing evidence suggests that intolerance of uncertainty (IU) is a cognitive vulnerability that is a central feature across diverse anxiety disorders, including generalized anxiety disorder (GAD). Although cognitive behavioral therapy (CBT) has been shown to reduce IU, it remains to be established whether or not reductions in IU mediate reductions in worry. This study examined the process of change in IU and worry in a sample of 28 individuals with GAD who completed CBT. Changes in IU and worry, assessed bi-weekly during treatment, were analyzed using multilevel mediation models. Results revealed that change in IU mediated change in worry (ab = −0.20; 95% CI [−.35, −.09]), but change in worry did not mediate change in IU (ab = −0.16; 95% CI [−.06, .12]). Findings indicated that reductions in IU accounted for 59% of the reductions in worry observed over the course of treatment, suggesting that changes in IU are not simply concomitants of changes in worry. Findings support the idea that IU is a critical construct underlying GAD.     

Intolerance of uncertainty and negative metacognitive beliefs as transdiagnostic mediators of repetitive negative thinking in a clinical sample with anxiety disorders

This study aimed to replicate and extend a hierarchical model of vulnerability to worry, with neuroticism and extraversion as higher-order factors and negative metacognitions and intolerance of uncertainty as second-order factors. The model also included a transdiagnostic measure of repetitive negative thinking (RNT) and depression symptoms as outcome variables to determine whether relationships would extend beyond worry, which has traditionally been studied within the context of generalized anxiety disorder (GAD). Participants (N = 99) were referrals to a specialist anxiety disorders clinic with a principal anxiety disorder who completed a battery of self-report questionnaires assessing neuroticism, extraversion, metacognitions, intolerance of uncertainty, worry, RNT, and depression symptoms. Mediational analyses using bootstrapping provided support for transdiagnostic and diagnosis-specific mediation effects. Negative metacognitions fully mediated the relationship between neuroticism and RNT for the whole sample and for subsamples with and without GAD. Intolerance of uncertainty mediated the relationship between neuroticism and worry (for the whole sample and for those with GAD) and between neuroticism and RNT (for those with GAD). Implications for theory, treatment, and nosology are discussed.     

A randomized controlled trial of guided internet-delivered cognitive behaviour therapy for older adults with generalized anxiety

This study aimed to establish the efficacy of guided Internet-delivered cognitive-behaviour therapy (ICBT) for older adults with generalized anxiety disorder (GAD) or subclinical GAD. Participants were randomized to receive seven modules of ICBT (n = 24) or to a waiting list condition (WLC; n = 22). Faster improvements in symptoms of anxiety and depression were observed for participants in the ICBT condition relative to the WLC, with large between-group effect sizes on the Generalized anxiety disorder-7 (d = .85) and the Patient health questionnaire (d = 1.17) obtained at post-treatment. Further reduction in generalized anxiety symptoms was reported over the one-month follow-up. Treatment effects were replicated when control participants subsequently underwent treatment. Higher ratings of treatment credibility, but not expectancy, prior to ICBT predicted improvements over time. The results support the efficacy of ICBT as treatment for older adults with GAD.     

A hierarchical model for the relationships between general and specific vulnerability factors and symptom levels of generalized anxiety disorder

The present study examined a hierarchical model for the relationships between general and specific vulnerability factors and symptom manifestations of generalized anxiety disorder (GAD). A clinical sample of patients with GAD (N = 137) completed a set of self-report questionnaires for measuring neuroticism, extraversion, intolerance of uncertainty, metacognitive beliefs, and symptoms of generalized anxiety (i.e., worry) and depression. A bootstrapping analysis yielded support for a model in which the relation between the general vulnerability factor of neuroticism and symptoms of GAD were mediated by the specific vulnerability factors of intolerance of uncertainty and negative metacognitions. Implications for the classification and treatment of GAD are discussed.     

Association between generalized anxiety levels and pain in a community sample: Evidence for diagnostic specificity

BackgroundIt is unclear whether generalized anxiety disorder (GAD) has a specific relationship to pain syndromes, going beyond the established association of pain with anxiety syndromes in general.MethodsMental disorders were assessed in a community sample (N = 4181; 18–65 years) using the DSM-IV/M-CIDI. Several threshold definitions were used to define GAD and medically unexplained pain.ResultsThe association between pain and GAD (odds ratio, OR = 5.8 pain symptoms; OR = 16.0 pain disorder) is stronger than the association between pain and other anxiety disorders (OR = 2.4 pain symptoms; OR = 4.0 pain disorder). This association extends to subthreshold level definitions of GAD with some indication for a non-linear dose–response relationship. The GAD-pain link cannot sufficiently be explained by demographic factors, comorbid mental or physical disorders.ConclusionsThe association of pain and generalized anxiety is not artifactual. Compared to other anxiety syndromes, it appears to be stronger and more specific suggesting the need to explore clinical and public health implications.     

The anxious heart in whose mind? A systematic review and meta-regression of factors associated with anxiety disorder diagnosis,treatment and morbidity risk in coronary heart disease

ObjectiveTo (1) report the prognostic association between anxiety disorder subtypes and major adverse cardiac events (MACE), (2) report anxiety disorder prevalence in coronary heart disease (CHD), and (3) report the efficacy of anxiety disorder treatments in CHD.MethodsA comprehensive electronic database search was performed in November 2013 for studies reporting anxiety disorder prevalence according to structured interview in CHD samples or MACE, and randomized controlled trials (RCTs) comparing anxiety disorder treatment with placebo or usual care. From 4041 articles 42 samples were selected for extraction (8 for MACE prognosis, 39 for prevalence, no RCTs were eligible).ResultsFive generalized anxiety disorder (GAD) studies reported 883 MACE events (combined n = 2851). There was a non-significant association between GAD and MACE (risk ratio = 1.20, 95% CI .86–1.68, P = .28) however the effect size was highly significant in outpatient samples (adjusted hazard ratio = 1.94, 95% CI 1.45–2.60, P < .001). No other anxiety disorder subtype was associated with MACE. Prevalence data showed high comorbidity with depression (49.06%; 95% CI 34.28–64.01) and substantial heterogeneity between studies. Panic disorder prevalence was higher in psychiatrist/psychologist raters (9.92% vs. 4.74%) as was GAD (18.45% vs. 13.01%). Panic and GAD estimates were also heterogeneous according to DSM-III-R versus DSM-IV taxonomies.ConclusionsThe paucity of extant anxiety disorder RCTs, alongside MACE risk for GAD outpatients, should stimulate further anxiety disorder intervention in CHD populations. Research should focus on depression and anxiety, thereby unraveling disorder specific and more generic pathways.     

Inattention symptoms and the diagnosis of comorbid attention-deficit/hyperactivity disorder among youth with generalized anxiety disorder

Generalized anxiety disorder (GAD) and attention-deficit/hyperactivity disorder (ADHD) commonly co-occur in childhood. Inattention symptoms can be hallmarks of both conditions, however assessment tools of inattention may not effectively distinguish between the two conditions. The present study used receiver operating characteristic (ROC) analyses to examine the high-end specificity of the Attention Problems Scale of the Child Behavior Checklist (CBCL) for detecting comorbid ADHD among youth with GAD (N = 46). Results support the utility of the Attention Problems Scale for accurately distinguishing between the two groups (AUC = .84, SE = .06). Specifically, a cut score of 63 achieved the most favorable values across diagnostic utility indices; 74% of GAD youth with ADHD scored above this cutoff and 91% of GAD youth without ADHD scored below this cutoff. Findings provide support for the use of the CBCL Attention Problems Scale to supplement diagnostic interviews and identify inattention associated with ADHD among GAD youth.     

Unique relations among anxiety sensitivity factors and anxiety,depression, and suicidal ideation

Anxiety sensitivity (AS) is composed of three lower-order dimensions, cognitive concerns, physical concerns, and social concerns. We examined the relations between AS dimensions using a more adequate assessment of subscales (ASI-3) than has previously been used, and measures of anxiety and mood disorders as well as suicidal ideation in a sample of 256 (M age = 37.10 years, SD = 16.40) treatment-seeking individuals using structural equation modeling. AS cognitive concerns was uniquely associated with generalized anxiety disorder (GAD), obsessive–compulsive disorder (OCD), major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and suicidal ideation. AS physical concerns was uniquely associated with OCD, social anxiety disorder (SAD), panic disorder (PD), and specific phobia. AS social concerns was uniquely associated with SAD, GAD, OCD, and MDD. These results highlight the importance of considering the lower-order AS dimensions when examining the relations between AS and psychopathology.     

Improvements in emotion regulation following repetitive transcranial magnetic stimulation for generalized anxiety disorder

Generalized anxiety disorder (GAD) is characterized by emotion regulation difficulties, which are associated with abnormalities in neural circuits encompassing fronto-limbic regions including the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to determine whether DLPFC neuromodulation improves emotion regulation in patients with GAD. This is a secondary analysis from a randomized-controlled trial comparing 30 sessions of low-frequency right-sided active (n = 13) versus sham (n = 12, sham coil) repetitive transcranial magnetic stimulation (rTMS) at the right DLPFC in patients with GAD. Results indicated statistically significant improvements in self-reported emotion regulation difficulties at posttreatment and 3-month follow-up in the active group only. Improvements were found primarily in the domains of goal-directed behaviors and impulse control and were significantly associated with a global clinician rating of improvement. These preliminary results support rTMS as a treatment for GAD and suggest improved emotion regulation as a possible mechanism of change.     

Relative effects of cognitive and behavioral therapies on generalized anxiety disorder,social anxiety disorder and panic disorder: A meta-analysis

Although cognitive and behavioral therapies are effective in the treatment of anxiety disorders, it is not clear what the relative effects of these treatments are. We conducted a meta-analysis of trials comparing cognitive and behavioral therapies with a control condition, in patients with social anxiety disorder (SAD), generalized anxiety disorder (GAD) and panic disorder. We included 42 studies in which generic measures of anxiety were used (BAI, HAMA, STAI-State and Trait). Only the effects of treatment for panic disorder as measured on the BAI (13.33 points; 95% CI: 10.58–16.07) were significantly (p = 0.001) larger than the effect sizes on GAD (6.06 points; 95% CI: 3.96–8.16) and SAD (5.92 points; 95% CI: 4.64–7.20). The effects remained significant after adjusting for baseline severity and other major characteristics of the trials. The results should be considered with caution because of the small number of studies in many subgroups and the high risk of bias in most studies.     

Using the GAD-Q-IV to identify generalized anxiety disorder in psychiatric treatment seeking and primary care medical samples

The fourth edition of the Generalized Anxiety Disorder Questionnaire (GAD-Q-IV) is a self-report measure that is commonly used to screen for the presence of generalized anxiety disorder (GAD). The current investigation attempted to identify an optimal cut score using samples obtained from an outpatient psychiatric (n = 163) and primary care clinic (n = 99). Results indicated that a cut score of 7.67 provided an optimal balance of sensitivity (.85) and specificity (.74) comparable to a previously identified cut score (5.7) across both samples (sensitivity = .90, specificity = .66). However, both cut scores were consistently outperformed by a score representing the criteria for GAD described in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (sensitivity = .89, specificity = .82).     

Cortical surface anatomy in pediatric patients with generalized anxiety disorder

BackgroundIt is established that pediatric patients with generalized anxiety disorder (GAD) exhibit functional abnormalities and altered gray matter volumes in neural structures that subserve emotional processing, yet there are no data regarding the surface anatomy of the cerebral cortex in youth with GAD.MethodsUsing an automated surface-based approach (FreeSurfer), cortical thickness was assessed node-by-node over the entire cerebral cortex in adolescents with GAD and no co-occurring major depressive disorder (n = 13) and healthy subjects (n = 19).ResultsCompared with healthy adolescents, youth with GAD exhibited increased cortical thickness in the right inferolateral and ventromedial prefrontal cortex (i.e., inferior frontal gyrus), the left inferior and middle temporal cortex as well as the right lateral occipital cortex. No relationships were observed between cortical thickness and the severity of anxiety symptoms in the significant regions that were identified in the vertex-wise analysis.ConclusionsThese findings suggest that, in adolescents with GAD, abnormalities in cortical thickness are present in an ensemble of regions responsible for fear learning, fear extinction, reflective functioning (e.g., mentalization), and regulation of the amygdala.     

Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder

Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n = 111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A < 7) and non-remitters in risperidone treatment (n = 54) and placebo (n = 57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.     

The independent relationships between insomnia,depression, subtypes of anxiety,and chronotype during adolescence

ObjectivesTo investigate the independent effects of depression and subtypes of anxiety on insomnia, and vice versa, and the independent effect of chronotype on insomnia, depression, and subtypes of anxiety.MethodsIn all, 318 South Australian high school students from grades 7–11 (age range, 12–18 years; mean, 14.97 ± 1.34) participated in this cross-sectional study. Validated self-report questionnaires were used to assess insomnia, depression, subtypes of anxiety, and chronotype.ResultsAfter confounder variables were controlled, insomnia predicted depression and panic disorder (PD), whereas insomnia was predicted by depression and generalized anxiety disorder (GAD). Obsessive–compulsive disorder (OCD), separation anxiety (SAD), and social phobia (SP) were not significantly related to insomnia. Eveningness predicted the models in which depression and PD predicted insomnia and vice versa. Eveningness also predicted the models in which insomnia was predicted by OCD, SAD, and SP.ConclusionsInsomnia independently predicts depression and is predicted by depression and GAD, but not by other forms of anxiety. The independent prediction of insomnia on PD is unlikely to be clinically significant. Chronotype independently predicts and hence is a risk factor for insomnia and depression, but not subtypes of anxiety. Theoretical and clinical implications are discussed.     

Subthreshold and threshold DSM-IV generalized anxiety disorder in Singapore: Results from a nationally representative sample

Previous nationally representative studies have reported prevalence of DSM-IV generalized anxiety disorder (GAD). However, subthreshold and threshold GAD expressions remain poorly understood. The current study examined the prevalence, correlates and co-morbidity of a broader diagnosis of GAD in Singapore. The Singapore Mental Health Study (SMHS) was an epidemiological survey conducted in the population (N = 6616) aged 18 years and older. The Composite International Diagnostic Interview version 3.0 (CIDI 3.0) was used to establish mental disorder diagnoses. The lifetime prevalence for subthreshold GAD (2.1%) and threshold GAD (1.5%) in the current sample was found to be lower than in Western populations. Younger age group, Indian ethnicity, previously married, chronic physical conditions, and being unemployed were associated with higher odds of having more severe expression of generalized anxiety. The relatively lower prevalence rate of subthreshold GAD expression suggests possible cultural interferences in the reporting and manifestation of anxiety symptomatology. Despite the low prevalence, significant impacts on functioning and comorbidity among subthreshold generalized anxiety cases indicate the importance of early treatment to ensure a better prognosis.     

Evaluating quality of life in epilepsy: The role of screening for adverse drug effects,depression, and anxiety

ObjectiveThe objective of this study was to evaluate the contribution of validated screening tools for antiepileptic drug (AED) adverse effects, depression, and anxiety to measure the quality of life (QoL) in people with epilepsy (PWE).MethodsPatients in a tertiary epilepsy service were screened for quality of life (using QOLIE-31), major depressive disorder (MDD) (NDDI-E), generalized anxiety disorder (GAD) (GAD-7), and AED effects (AEP). Mini International Neuropsychiatric Interview (MINI) generalized anxiety disorder module was also performed. For AEP validation in French, the internal structural validity was analyzed. Dimensional (NDDI-E and GAD-7 scores) and categorical (MDD and GAD) analyses were performed to investigate interactions between QoL and AEP.ResultsA total of 132 (87 females) subjects were included. The French version of the AEP demonstrated satisfactory psychometric properties (Cronbach's α 0.87). Correlations between NDDI-E, GAD-7, AEP, and QOLIE-31 scores were high, and significant for all subscales of QOLIE-31; no effect of seizure-related variables was seen. Some sex differences in QOLIE-31 subscales were found, and mean AEP score was higher in females. Age, sex, NDDI-E, GAD-7, and AEP scores accounted for 61% of variance of QOLIE-31 scores. Differential effects were seen on QOLIE-31 subscales: AEP strongly correlated with all subscales; GAD-7 scores more strongly correlated with “Seizure Worry”; NDDI-E with “Energy-Fatigue”; and both NDDI-E and GAD-7 scores strongly correlated with “Emotional Well-Being”. Categorical analysis of groups with MDD alone, GAD alone, MDD + GAD, and neither MDD nor GAD showed significant differences in AEP and QOLIE-31 scores, with MDD + GAD showing the most AED effects and the poorest QoL.SignificanceThe combination of screening tools for depression (NDDI-E), anxiety (GAD-7), and AED effects (AEP) has a strong power for evaluating QoL in PWE. Coexisting MMD and GAD were associated with the poorest quality of life and the highest AEP scores.     

Does cognitive-behavioral therapy response among adults with obsessive–compulsive disorder differ as a function of certain comorbidities?

This study examines the impact of several of the most common comorbid psychiatric disorders (i.e., generalized anxiety disorder (GAD); major depressive disorder (MDD); social phobia, and panic disorder) on cognitive-behavioral therapy (CBT) response in adults with obsessive–compulsive disorder (OCD). One hundred and forty-three adults with OCD (range = 18–79 years) received 14 sessions of weekly or intensive CBT. Assessments were conducted before and after treatment. Primary outcomes included scores on the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), response rates, and remission status. Sixty-nine percent of participants met criteria for at least one comorbid diagnosis. Although baseline OCD severity was slightly higher among individuals with OCD + MDD and OCD + GAD (in comparison to those with OCD-only), neither the presence nor the number of pre-treatment comorbid disorders predicated symptom severity, treatment response, remission, or clinically significant change rates at post-treatment. These data suggest that CBT for OCD is robust to the presence of certain common Axis-I comorbidities.     

Toxoplasma gondii and anxiety disorders in a community-based sample

A growing body of literature suggests that exposure to the neurotropic parasite Toxoplasma gondii (T. gondii) is associated with increased risk of mental disorders, particularly schizophrenia. However, a potential association between T. gondii exposure and anxiety disorders has not been rigorously explored. Here, we examine the association of T. gondii infection with both anxiety and mood disorders. Participants (n = 484) were drawn from the Detroit Neighborhood Health Study, a population-representative sample of Detroit residents. Logistic regression was used to examine the associations between T. gondii exposure (defined by seropositivity and IgG antibody levels) and three mental disorders: generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD) and depression. We found that T. gondii seropositivity was associated with a 2 times greater odds of GAD (odds ratio (OR), 2.25; 95% confidence interval (CI), 1.11–4.53) after adjusting for age, gender, race, income, marital status, and medication. Individuals in the highest antibody level category had more than 3 times higher odds of GAD (OR, 3.35; 95% CI, 1.41–7.97). Neither T. gondii seropositivity nor IgG antibody levels was significantly associated with PTSD or depression. Our findings indicate that T. gondii infection is strongly and significantly associated with GAD. While prospective confirmation is needed, T. gondii infection may play a role in the development of GAD.