Andrew T. Gloster

Psychometric properties of the Depression Anxiety and Stress Scale-21 in older primary care patients

The Depression Anxiety Stress Scale (DASS) was designed to efficiently measure the core symptoms of anxiety and depression and has demonstrated positive psychometric properties in adult samples of anxiety and depression patients and student samples. Despite these findings, the psychometric properties of the DASS remain untested in older adults, for whom the identification of efficient measures of these constructs is especially important. To determine the psychometric properties of the DASS 21-item version in older adults, we analyzed data from 222 medical patients seeking treatment to manage worry. Consistent with younger samples, a three-factor structure best fit the data. Results also indicated good internal consistency, excellent convergent validity, and good discriminative validity, especially for the Depression scale. Receiver operating curve analyses indicated that the DASS-21 predicted the diagnostic presence of generalized anxiety disorder and depression as well as other commonly used measures. These data suggest that the DASS may be used with older adults in lieu of multiple scales designed to measure similar constructs, thereby reducing participant burden and facilitating assessment in settings with limited assessment resources.

Neuropeptide S receptor gene—converging evidence for a role in panic disorder

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn107Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

Worry Exposure versus Applied Relaxation in the Treatment of Generalized Anxiety Disorder

Background: Worry exposure (WE) is a core element of cognitive-behavioral treatment for generalized anxiety disorder (GAD). Its efficacy as a stand-alone treatment method (without further cognitive-behavioral therapy interventions) has never been tested.We aimed to examine whether WE alone is as efficacious as the empirically supported stand-alone treatment for GAD, applied relaxation (AR). Methods: In a randomized controlled study, 73 outpatients meeting DSM-IV criteria for GAD as primary diagnosis were allocated to either WE or AR or a waiting list control group; in a 2nd randomization procedure the waiting list subjects were reallocated to WE or AR. The treatment was manualized (15 sessions with WE or AR), included 6-month and 1-year follow-ups, as well as last observation carried forward and completer analyses, and was controlled for allegiance effects.The Hamilton Anxiety Rating Scale and the State-Trait Anxiety Scale were used as primary outcome measures. Self-report scales of anxiety, worrying and depression including negative metacognition about worrying and thought suppression served as secondary outcome measures. Results: The dropout rate was moderate. The pre-/posttreatment effects were high for the Hamilton Anxiety Rating Scale (standardized mean difference >1) and for the State-Trait Anxiety Inventory (standardized mean difference >0.87). The proportion of patients reaching high end state functioning was 48% (WE) and 56% (AR). WE and AR did not differ with regard to dropout rate or treatment effects. The treatment effects were stable at 6 month and 1 year follow-up. Conclusion: This is the first study to show that a stand-alone exposure in sensu technique – WE – is efficacious in the treatment of GAD. Both AR and WE seem to represent effective principles of change in GAD.

Agoraphobia and Panic

Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.

Assessing Psychological Flexibility: What Does It Add above and beyond Existing Constructs?.

The construct of psychological flexibility (PF) is a central concept in acceptance and commitment therapy. It is defined as the process of contacting the present moment fully as a conscious human being and persisting in or changing behavior in the service of chosen values. PF is hypothesized to be an important aspect of healthy psychological functioning. Despite its potential importance, the distinctness of PF from other constructs has not been adequately demonstrated, and psychometric evaluations of measures designed to assess it are limited. This study aimed at extending current knowledge about PF by examining the construct in 2 help-seeking samples, including panic disorder with agoraphobia (n = 368), clinically relevant social phobia (n = 209), and 2 nonclinical samples including students (n = 495) and individuals visiting an employment office (n = 95). Results across all samples indicate that PF, as measured by the Acceptance and Action Questionnaire (2nd version; AAQ-II), is a unitary construct with a 1 factor model. PF correlated with other variables largely consistent with predictions, differentiated patients from healthy controls, and showed preliminary indications of treatment sensitivity. Incremental validity was partially demonstrated, especially for indices of functioning. Surprisingly, PF also explained unique variance above more established measures for some indices of symptomatology. Results suggest that PF adds some incremental clinical validity, yet further and more stringent tests are required to fully elucidate its strengths and limitations.

The role of parental psychopathology and family environment for social phobia in the first three decades of life.

Background: To examine the role of parental psychopathology and family environment for the risk of social phobia (SP) in offspring from childhood to early adulthood, encompassing the high risk period for SP. Methods: A community sample of 1,395 adolescents was prospectively followed‐up over 10 years. Offspring and parental psychopathology were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) using the Munich Composite International Diagnostic Interview (M‐CIDI), and direct diagnostic interviews in parents were supplemented by family history reports. Parental rearing was assessed by the Questionnaire of Recalled Rearing Behavior administered to offspring. Family functioning was assessed by the McMaster Family Assessment Device administered to parents. Results: Parental SP was associated with offsprings risk to develop SP (OR=3.3, 95%CI:1.4–8.0). Other parental anxiety disorders (OR=2.9, 95%CI:1.4–6.1), depression (OR=2.6, 95%CI:1.2–5.4), and alcohol use disorders (OR=2.8, 95%CI:1.3–6.1) were also associated with offspring SP. Parental rearing styles of overprotection, rejection, and lack of emotional warmth were associated with offspring SP. Family functioning measures were not associated with offspring SP. Analyses of interaction of parental psychopathology and parental rearing indicated combined effects on the risk for offspring SP. Conclusions: Parental psychopathology and rearing were associated with offspring SP, independently as well as in their interaction. Further delineation of these associations is warranted as malleable components of these risk factors may provide potential targets for prevention programs. In addition, parent‐to‐offspring transmission of other internalizing disorders should be considered to examine the degree of diagnostic specificity. Depression and Anxiety, 2009.

MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy

Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.

Mechanism of action in CBT (MAC): methods of a multi-center randomized controlled trial in 369 patients with panic disorder and agoraphobia

Cognitive behavioral therapy (CBT) is efficacious for panic disorder with agoraphobia (PD/A). Nevertheless, the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown. The mechanisms of action in CBT (MAC) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center, randomized controlled design, with two active treatment conditions in which the administration of exposure was varied, and a wait-list control group. The special feature of MAC is the way in which imbedded experimental, psychophysiological, and neurobiological paradigms were included to elucidate therapeutic and psychopathological processes. This paper describes the aims and goals of the MAC study and the methods utilized to achieve them. All aspects of the research design (e.g., assessments, treatment, experimental procedures) were implemented so as to facilitate the detection of active therapeutic components, and the mediators and moderators of therapeutic change. To this end, clinical, behavioral, physiological, experimental, and genetic data were collected and will be integrated.

The structure of common mental disorders: A replication study in a community sample of adolescents and young adults

Previous research suggests that patterns of comorbidity of common mental disorders among adults are best reflected by a hierarchical three‐factor structure with two correlated factors (‘anxious‐misery’ and ‘fear’) summarized in a second‐order ‘internalizing’ factor and one ‘externalizing’ factor. This three‐factor structure has not been examined yet in a sample of adolescents and young adults.

The structure of mental disorders re-examined: Is it developmentally stable and robust against additions?†

Previous research suggests that patterns of comorbidity of a limited number of anxiety, depressive, substance use and antisocial personality (ASP) disorders among adults are best reflected by a hierarchical three‐factor structure with two correlated factors (‘anxious‐misery’ and ‘fear’) that are summarized in a second‐order ‘internalizing’ factor and one ‘externalizing’ factor. It has not been examined whether this structure is developmentally stable and robust against additions of more diagnoses. Using data from a prospective‐longitudinal community study of adolescents and young adults we re‐evaluate the three‐factor model originally proposed by Krueger (Archives of General Psychiatry, 1999; 56, 921–926). Using confirmatory factor analysis with identical conventions as in Kruegers original work we found that the three factor model did not fit robustly across age or a wider range of diagnoses. Using explanatory factor analysis we examined alternative structures. We found various clinically meaningful patterns with good fit that go substantially beyond the original three‐factor structure. However, again, there is little consistency in findings when different age groups or different diagnoses are considered. Our findings suggest that psychopathology cannot be reduced to any simple structure. Copyright