Love yourself as a therapist, doubt yourself as an institution? Therapist and institution effects on outcome, treatment length, and dropout.

OBJECTIVE: Research suggests that some therapists achieve better outcomes than others. However, an overlooked area of study is how institution differences impact patient outcomes independent of therapist variance. This study aimed to examine the role of institution and therapist differences in adult outpatient psychotherapy. METHOD: The study included 1428 patients who were treated by 196 therapists at 10 clinics. Two- and three-level hierarchical linear regression models were employed to investigate the effects of therapists and institutions on three dependent patient variables: (1) symptom change, (2) treatment duration, and (3) dropout. Level three explanatory variables were tested. RESULTS: The results showed that therapist effects (TE) were significant for all three types of treatment outcome (7.8%-18.2%). When a third level (institution) was added to the model, the differences between therapists decreased, and significant institution effects (IE) were found: 6.3% for symptom change, 10.6% for treatment duration, and 6.5% for dropout. The exploratory analyses found no predictors able to explain the systematic variation at the institution level. DISCUSSION: TE on psychotherapy outcomes remain a relevant factor but may have been overestimated in previous studies due to not properly distinguishing them from differences at the institution level.

Transfer of exposure therapy effects to a threat context not considered during treatment in patients with panic disorder and agoraphobia: Implications for potential mechanisms of change.

Further developments of exposure-based therapy (EBT) require more knowledge about transfer of treatment to non-trained everyday contexts. However, little is known about transfer effects of EBT. Using a standardized EBT protocol in 275 patients with panic disorder and agoraphobia we investigated the transfer of EBT to a highly standardized context during a Behavioral Avoidance Test (BAT; being entrapped in a small and dark test chamber) and not part of the exposure sessions. Patients of a treatment group underwent the BATs before treatment (t1), after a preparatory treatment phase (t2), and after an agoraphobic exposure phase (t3) and were compared with wait-list control patients, who repeated BAT assessments across the same time period. We found stronger reductions in avoidance behavior, reported fear, and autonomic arousal during the BAT from t1 to t3 in the treatment group patients who were anxious during t1 relative to the anxious but untreated patients. Fear reduction was related to treatment outcome indicating the contribution of transfer effects to successful EBT. Interestingly, reduction varied for different fear response systems suggesting different processes to may be involved in transfer effects. Importantly, final BAT assessment still evoked residual fear in the treatment group as compared to BAT non-anxious control patients, suggesting limited transfer effects - one possible reason for the return of symptoms in new situations.

Vagal control of the heart decreases during increasing imminence of interoceptive threat in patients with panic disorder and agoraphobia.

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense.Trial Registration Number: ISRCTN80046034.

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

Association of rs7688285 allelic variation coding for GLRB with fear reactivity and exposure-based therapy in patients with panic disorder and agoraphobia.

The gene coding for glycine receptor ß subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk¼) in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes.

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

Anxious and alert? Hypervigilance in social anxiety disorder.

The vast majority of research on attentional biases to threat focusses on selective attention, even though several cognitive-behavioral models furthermore assume hypervigilance to be important in this regard. Thus, the current study examined hypervigilance in trait and state social anxiety. We analyzed visual scanpath lengths and fixation counts of participants with Social Anxiety Disorder (SAD) (n = 61) and healthy controls (n = 60) in a combined visual search and eye tracking paradigm, including photographs of facial expressions. Half of all participants were randomly assigned to a state anxiety induction. Interaction effects revealed opposed attentional patterns of participants with SAD as compared to healthy controls considering overall visual scanpath lengths (F(1,117) = 5.32, p = 0.023, η2partial = 0.043) and fixation counts (F(1,117) = 5.10, p = 0.026, η2partial = 0.042). Accordingly, participants with SAD showed signs of hypervigilance in the anxiety induction condition. In contrast, there was no main effect of diagnostic group, indicating that individuals with SAD shift their attentional focus to broad scanning behavior only under conditions of threat. Our results add to the small number of existing studies on hypervigilance in SAD and suggest the topic to be promising for future research.

Attentional biases to threat in social anxiety disorder: time to focus our attention elsewhere?

BACKGROUND: Cognitive models propose that attentional biases to threat contribute to the maintenance of social anxiety disorder (SAD). However, the specific characteristics of such biases are still object to debate. OBJECTIVES: The current study aimed to disentangle effects of trait and state social anxiety on attention allocation towards social stimuli. METHODS: Participants with SAD (n = 67) and healthy controls (n = 62) completed three visual search tasks while their eye movements were recorded. Half of the participants in each group were randomly assigned to a state anxiety induction. RESULTS: Contrary to our predictions, neither trait nor state social anxiety was associated with a facilitated attention to or a delayed disengagement from threat. However, participants with SAD did show reduced fixation durations for threatening stimuli, indicating an avoidance of threat. Induction of state anxiety led to an increased distractibility by threat. CONCLUSIONS: We suggest that attention allocation in SAD is characterized by an avoidant rather than a vigilant attentional bias. Accordingly, our results contradict previous results that associate SAD with facilitated attention to threat and existing approaches to modify attentional biases, that aim to decrease attention towards threatening stimuli.

Using Functional Analysis as a Framework to Guide Individualized Treatment for Negative Symptoms.

Although numerous interventions are available for negative symptoms, outcomes have been unsatisfactory with pharmacological and psychological interventions producing changes of only limited clinical significance. Here, we argue that because negative symptoms occur as a complex syndrome caused and maintained by numerous factors that vary between individuals they are unlikely to be treated effectively by the present "one size fits all" approaches. Instead, a well-founded selection of those interventions relevant to each individual is needed to optimize both the efficiency and the efficacy of existing approaches. The concept of functional analysis (FA) can be used to structure existing knowledge so that it can guide individualized treatment planning. FA is based on stimulus-response learning mechanisms taking into account the characteristics of the organism that contribute to the responses, their consequences and the contingency with which consequences are tied to the response. FA can thus be flexibly applied to the level of individual patients to understand the factors causing and maintaining negative symptoms and derive suitable interventions. In this article we will briefly introduce the concept of FA and demonstrate-exemplarily-how known psychological and biological correlates of negative symptoms can be incorporated into its framework. We then outline the framework's implications for individual assessment and treatment. Following the logic of FA, we argue that a detailed assessment is needed to identify the key factors causing or maintaining negative symptoms for each individual patient. Interventions can then be selected according to their likelihood of changing these key factors and need to take interactions between different factors into account. Supplementary case vignettes exemplify the usefulness of functional analysis for individual treatment planning. Finally, we discuss and point to avenues for future research guided by this model.

Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohn's Disease.

BACKGROUND: The presentation of Crohn's disease (CD) is heterogeneous and often leads to serious complications and need for surgery. We tested serum anti-zymogen granule glycoprotein 2 (GP2) antibodies, including its novel isoform alpha, for association with genetic variants, diagnosis, disease stratification, and prediction of CD courses in a combined cross-sectional and cohort study. METHODS: Serum samples of 303 CD, 108 ulcerative colitis, 72 other inflammatory gastrointestinal diseases, and 206 controls without predominant gastrointestinal diseases controls (HC) were tested for the presence of Anti-GP2 and Anti-Saccharomyces cervisiae (ASCA) by enzyme-linked immunosorbent assay. Genetic analysis was performed using the Illumina Immunochip. RESULTS: GP2 IgA and IgG had the highest discriminatory capability for CD versus ulcerative colitis and CD versus inflammatory gastrointestinal diseases. We identified an association of GP2 IgA and IgG each with 5 distinct single-nucleotide polymorphisms. Levels of anti-GP2 IgG were moderately associated with ileal disease location. Interestingly, both, anti-GP2 IgA and IgG were exclusively associated with the occurrence of stenosis and need for surgery, independently of disease location, but not with fistulizing CD, early disease onset or disease activity. ASCA IgG and IgA were qualitatively and quantitatively linked to CD, CD complications, and need for surgery. Increased levels of ASCA IgG and IgA and positivity for ASCA IgG, but neither levels nor positivity for GP2 IgG or IgA were predictive of the earlier occurrence of complications or surgery. CONCLUSIONS: Anti-GP2 antibodies may aid as a tool for diagnosis and differentiation of CD and could indicate a more complicated CD course.

Post-event processing in social anxiety disorder after real-life social situations - An ambulatory assessment study.

Excessive post-mortem processing after social situations, a core symptom of social anxiety disorder (SAD), is thought to contribute to the perpetuation of social anxiety by consolidating negative self-schemata. Empirical findings on actual mechanisms underlying this so-called Post-Event Processing (PEP) are still scarce. The present study sought to identify variables associated with the experience of PEP after real-life social situations in a sample of 49 individuals diagnosed with SAD. Using an ambulatory assessment approach, individuals were asked to report on each distressing social event experienced during one week. A total of 192 events were captured. Hierarchical linear modeling indicated that next to trait social anxiety, the type of social situation (performance vs. interaction situations), self-focused attention, safety behavior use, and negative affect predicted levels of PEP after social situations. These findings add to the growing literature that emphasizes the importance of situational factors for the experience of PEP, and highlight potential venues to prevent it.

Performance perceptions and self-focused attention predict post-event processing after a real-life social performance situation.

BACKGROUND AND OBJECTIVES: Cognitive approaches to social anxiety suggest that an excessive brooding about one's performance in a social situation (post-event processing; PEP) is involved in the maintenance of anxiety. To date, most studies investigating PEP were conducted in laboratory settings. The present study sought to replicate previous findings on predictors of PEP after a naturalistic social performance situation. METHODS: Sixty-five students, who had to give an evaluated presentation for credits, completed measures of trait social anxiety. Immediately after their presentation, participants rated state anxiety and attentional focus during the presentation, and provided an overall evaluation of their performance. One week after the presentation, they rated PEP during the preceding week, and reappraised their performance. RESULTS: Regression analyses demonstrated that the performance ratings after and self-focused attention during the presentation were unique predictors of PEP over and above the effects of trait and state anxiety. There was no evidence that PEP was associated with a biased recall of individual performance evaluations. CONCLUSIONS: The results support cognitive theories that emphasize the importance of negative self-perceptions in the development of social anxiety and related processes, and underline self-focused attention and self-evaluative processes as important targets during treatment.

The strategy does not matter: Effects of acceptance, reappraisal, and distraction on the course of anticipatory anxiety in social anxiety disorder.

OBJECTIVES: Anticipatory anxiety is a core feature of social anxiety disorder (SAD); however, there is a paucity of data on effective strategies for dealing with this affective state. The present study examined the effects of reappraisal, acceptance, and distraction on the course of anticipatory anxiety. DESIGN: The study used an experimental design, randomly assigning participants to one of three strategy groups. Participants were instructed to employ these strategies during the anticipation of an impromptu speech. METHODS: Participants with SAD (n = 67) and healthy controls (n = 72) were compared with regard to their ability to adopt the prescribed strategies and with regard to the effects of strategy use on self-reported and psychophysiological markers of arousal. RESULTS: SAD participants reported more problems in adopting the assigned strategies than controls, although the time spent with each strategy did not differ by group. In both groups, acceptance was rated as more difficult to adopt than reappraisal and distraction. Subjective ratings of anxiety decreased during the first 10 min of anticipation regardless of diagnostic group or strategy, but anxiety increased again immediately prior to the speech. Psychophysiological parameters were largely unaffected by group or strategy. CONCLUSION: The results question whether there are differential benefits of different emotion regulation (ER) strategies in dealing with anticipatory anxiety. The observed rebound of anxiety prior to the social event calls into doubt the long-term effectiveness of these strategies, at least during the regulation of anticipatory anxiety. PRACTITIONER POINTS: Coping with anticipatory anxiety is an important issue in treating SAD. Compared to healthy controls, individuals diagnosed with SAD experienced more problems in adopting prescribed ER strategies for dealing with anticipatory anxiety. We found no differences between acceptance, reappraisal, and distraction, calling into question that one strategy should be generally recommended by clinicians.

Emotion regulation difficulties in social anxiety disorder and their specific contributions to anxious responding.

OBJECTIVE: Recent theories emphasize the contribution of emotion regulation (ER) difficulties to psychopathology. The present study sought to identify patterns of ER difficulties in social anxiety disorder (SAD) and to test the predictive value of these difficulties for actual anxious responding during the anticipation of a social evaluative task. METHOD: Participants diagnosed with SAD (n = 67) and healthy controls (n = 59) completed self-ratings of ER difficulties (DERS) and depressive symptoms. This was followed by the announcement of an impromptu speech. During the anticipation period, subjective ratings of anxiety and arousal were assessed. RESULTS: Compared to healthy controls, SAD participants reported significantly higher levels of ER difficulties. With the exception of "lack of emotional awareness," these differences remained significant when controlling for depression. ER difficulties also contributed to anxious responding during the stress test; but this held true only for nonclinical participants. CONCLUSION: SAD is characterized by a wide range of ER deficits. However, the associations between ER difficulties and symptoms of anxiety remain poorly understood.

The role of safety behaviors in exposure-based treatment for panic disorder and agoraphobia: associations to symptom severity, treatment course, and outcome.

The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N=268 patients that aimed at evaluating efficacy and mechanisms of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α=0.89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine.

Symptoms and treatment of mental illness among prisoners: a study of Michigan state prisons.

This study reports on a representative sample of prisoners in Michigan correctional facilities to determine the prevalence of psychiatric illness and the delivery of mental health (MH) services. Mental health assessments were conducted with 618 incarcerated subjects using the interRAI Correctional Facilities (interRAI CF). Subjects were randomly sampled based on four strata: males in the general population, males in administrative segregation, males in special units, and females. The interRAI CF assessments were merged with secondary data provided by the Michigan Department of Corrections (MDOC) containing information on MH diagnoses or services that the subjects were receiving within the facilities, demographics, and sentencing. Study results show that 20.1% of men and 24.8% of women in Michigan prisons have a substantial level of MH symptoms and that 16.5% and 28.9%, respectively, are receiving MH services. However, when compared with Michigan Department of Corrections MH care records, 65.0% of prisoners who are experiencing symptoms of mental illness are not currently receiving any psychiatric services. The mis-match between symptoms and service delivery suggests the need for improved procedures for identifying and measuring psychiatric symptoms within Michigan correctional facilities to ensure that appropriate individuals receive needed care. It is recommended that a standardized assessment process be implemented and conducted at regular intervals for targeting and improving psychiatric care in the prison system.

Specificity of homework compliance effects on treatment outcome in CBT: evidence from a controlled trial on panic disorder and agoraphobia.

OBJECTIVES: Although homework assignments are an integral component of cognitive-behavioral therapy (CBT) and relate to positive therapy outcomes, it is unclear whether specific homework types and their completion have specific effects on outcome. METHOD: Data from N = 292 patients (75% female, mean age 36 years) with panic disorder and agoraphobia and treated with standardized CBT were analyzed with homework compliance quality and quantity for different types of homework serving as predictors for different outcome variables. RESULTS: Quality ratings of homework completion were stronger outcome predictors than quantitative compliance ratings. Exposure homework was a better outcome predictor than homework relating to psychoeducation and self-monitoring. CONCLUSION: Different aspects of homework compliance and specific homework types might differentially relate to CBT outcome.

Internet-delivered attention modification training as a treatment for social phobia: a randomized controlled trial.

Attentional biases toward social threat are a well-known phenomenon in social phobia. Recently, computer-delivered trainings have been developed to modify these patterns of attention and thereby reduce anxiety symptoms. Distribution of such attention trainings (ATs) via internet might be a promising approach in overcoming obstacles in health care utilization. However, there is no evidence supporting the effectiveness of internet-based ATs in clinical populations. The current trial examined effects of an internet-based AT on self-report measures, behavioral data and diagnostic status in individuals with social phobia (N = 56). Participants were randomly assigned to either AT using a modified dot probe paradigm or a control condition without attention modification. After training and at a 4-month follow-up, both groups showed small, albeit significant reductions in social anxiety and depression, but there was no evidence for superiority of the AT condition. The present findings question the effectiveness of internet-based ATs in social phobia. Future studies need to investigate effective variants of internet-based ATs before they can be widely applied.

Dynamics of defensive reactivity in patients with panic disorder and agoraphobia: implications for the etiology of panic disorder.

BACKGROUND: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). METHODS: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. RESULTS: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. CONCLUSIONS: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.