Michael Rufer

Symptom dimensions in obsessive–compulsive disorder: prediction of cognitive-behavior therapy outcome

Objective:  A significant number of patients with obsessive–compulsive disorder (OCD) fail to benefit sufficiently from treatments. This study aimed to evaluate whether certain OCD symptom dimensions were associated with cognitive‐behavioral therapy (CBT) outcome.

Successful Opacification of the Left Heart Chambers on Echocardiographic Examination after Intravenous Injection of a New Saccharide Based Contrast Agent

A new monosaccharide microparticle based echocardiographic contrast agent (SH U 508) was injected intravenously into five healthy male volunteers following which the heart was imaged in an apical four‐chamber view. Volumes of 2, 4, 8, and 16 mL of SH U 508 were incrementally injected into each volunteer. Concentrations of 50, 100, 200, 300, and 400 mg microparticles per mL of suspension were used in five successive examinations. Left heart opacification of diagnostic value was obtained during the whole cardiac cycle with concentrations of 300 and 400 mg/mL. There was no interference in imaging of the left ventricular walls due to increased attenuation. SH U 508 showed a good tolerance. No side effect was observed and no clinical relevant changes were observed in the heart rate, blood pressure, ECC, blood chemistry, hematology or urinalysis findings. This new agent may greatly extend the role of cardiac ultrasound and may also permit the examination of the arterial circulation in other organs.

Dissociation as a Predictor of Cognitive Behavior Therapy Outcome in Patients with Obsessive-Compulsive Disorder

Background: Previous studies have found a strong association between dissociation and obsessive-compulsive disorder (OCD). The purpose of the present study was to evaluate whether dissociation is a predictor of cognitive behavior therapy (CBT) outcome in patients with OCD. Methods: Fifty-two patients with OCD were assessed using the Dissociative Experience Scale (DES), the Yale-Brown Obsessive-Compulsive Scale and the Beck Depression Inventory. CBT lasted on average 9.5 weeks and included exposure therapy. Results: Patients who dropped out due to noncompliance had higher baseline DES scores and depression scores compared to the 43 patients (83%) who completed the study. Significant OCD symptom reduction at posttreatment was observed in study completers with a large effect size (d = 1.7). More severe OCD symptoms at posttreatment were associated with higher DES scores at baseline, and treatment nonresponders had significantly higher baseline DES scores compared to responders. These associations with outcome were mainly due to the DES subfactor absorption-imaginative involvement. In regression analyses, higher absorption-imaginative involvement scores at baseline predicted poorer CBT outcome, even after controlling for depressive symptoms, comorbid axis I disorders and concomitant psychotropic drugs. Conclusions: Results from this preliminary study suggest that higher levels of dissociation (particularly absorption-imaginative involvement) in patients with OCD might predict poorer CBT outcome. If our results can be replicated, treatment outcome might be improved by additional interventions for those patients with OCD who indicate high levels of dissociation, for example by using interventions aimed at improving coping with emotionally stressful situations.

Mindfulness and Emotion Regulation – an fMRI Study

Mindfulness--an attentive non-judgmental focus on present experiences--is increasingly incorporated in psychotherapeutic treatments as a skill fostering emotion regulation. Neurobiological mechanisms of actively induced emotion regulation are associated with prefrontally mediated down-regulation of, for instance, the amygdala. We were interested in neurobiological correlates of a short mindfulness instruction during emotional arousal. Using functional magnetic resonance imaging, we investigated effects of a short mindfulness intervention during the cued expectation and perception of negative and potentially negative pictures (50% probability) in 24 healthy individuals compared to 22 controls. The mindfulness intervention was associated with increased activations in prefrontal regions during the expectation of negative and potentially negative pictures compared to controls. During the perception of negative stimuli, reduced activation was identified in regions involved in emotion processing (amygdala, parahippocampal gyrus). Prefrontal and right insular activations when expecting negative pictures correlated negatively with trait mindfulness, suggesting that more mindful individuals required less regulatory resources to attenuate emotional arousal. Our findings suggest emotion regulatory effects of a short mindfulness intervention on a neurobiological level.

Long–term course and outcome of obsessive–compulsive patientsafter cognitive–behavioral therapy in combination with eitherfluvoxamine or placebo

AbstractLongitudinal studies with very long follow–up periods of patients with obsessive–compulsive disorder (OCD) who have received adequate treatment are rare. In the current study, 30 of 37 inpatients (81%) with severe OCD were followed up 6–8 years after treatment with cognitive–behavioral therapy (CBT) in combination with either fluvoxamine or placebo in a randomized design. The significant improvements (with large effectsizes) in obsessive–compulsive symptoms from pre- to post–treatment (41% reduction on the Y–BOCS) remained stable at follow–up (45 %). Responder rates, defined as ≥35% reduction on the Y–BOCS, were 67% and 60%, respectively. Depressive symptoms decreased significantly not only from pre- to post–treatment but also during follow–up. Re–hospitalization, which occurred in 11 patients (37 %), was associated with more severe depressive symptoms at pre–treatment and living without a partner. Full symptom remission at follow–up, defined as both Y–BOCS total score ≤ 7 and no longer meeting diagnostic criteria for OCD, was achieved by 8 patients (27 %). Patients without full remission at follow–up had a significantly longer history of OCD, assessed at pretreatment, compared to remitted patients. The shortterm treatment outcome had no predictive value for the long–term course. Throughout the naturalistic follow–up, nearly all patients (29 patients) received additional psychotherapy and/or medication. This might indicate that such chronic OCD patients usually need additional therapeutic support after effective inpatient treatment to maintain their improvements over long periods.

Neural correlates of altered general emotion processing in social anxiety disorder

Specific anxiety disorders are characterized by altered emotion processing of phobia-specific stimuli at the neurobiological level. Recent work has concentrated on specific anxiety-provoking stimuli; focusing on arousal- or fear-related brain areas such as the amygdala. We analyzed brain activation during the cued anticipation of unpleasant or uncertain emotional stimuli as a means of modeling an unspecific anxiety-laden situation. Sixteen patients with social anxiety disorder (SAD) and eighteen healthy control subjects completed a task during functional magnetic resonance imaging involving the anticipation of cued visual stimuli with prior known emotional valence (positive, negative, and neutral) or prior unknown/ambiguous emotional content. The anticipated stimuli had no social phobia specific content. During the anticipation of emotional stimuli of prior known negative and prior ambiguous emotional valence, brain activity in patients with SAD was increased in the upper midbrain/dorsal thalamus, the amygdala, and in temporo-occipital and parietal regions as compared to control subjects. Activity was decreased in SAD in left orbitofrontal cortex. Activations in the amygdala and in occipital regions correlated with trait anxiety and social anxiety measures. In conclusion, SAD was associated with enhanced activation in brain regions involved in emotional arousal as well as in attention and perception processing during the anticipation of non-specific, general emotional stimuli. Hence, our results suggest that patients with SAD not only have an altered processing of specific feared stimuli, but also a more generally disturbed emotion processing in basic neural pathways. These findings have implications for diagnostic models and the treatment of SAD.

Positive schizotypal symptoms predict treatment outcome in obsessive–compulsive disorder

Previous research has suggested that the presence of schizotypal personality disorder may represent a risk factor for treatment failure in obsessive-compulsive disorder (OCD). Relying on a dimensional approach, the present study investigated whether the predictive importance of schizotypal personality is shared by all of its features to the same extent or whether it is confined to a subset of symptoms. Fifty-three patients underwent multi-modal cognitive-behavioral therapy with or without adjunctive antidepressive medication. Therapy response was defined as a 35% decline of the Y-BOCS total score. At baseline assessment, patients were asked to fill out the schizotypal personality questionnaire, the perceptual aberration scale and the Beck depression inventory. Stepwise regression analysis and group comparisons conducted with the schizotypal and depression scales revealed that elevated scores in the positive schizotypal scales, especially perceptual aberrations, were highly predictive for treatment failure. Responders to treatment and non-responders did not significantly differ on other variables or on scores in two scales which measured response biases. The study provides evidence that positive schizotypal symptoms are antecendents for treatment failure in OCD. It needs to be evaluated whether these at-risk individuals benefit from additional intervention, such as the adminstration of low-dose atypical neuroleptics and specifically tailored behavorial intervention.

A Prospective Study of Alexithymia in Obsessive-Compulsive Patients Treated with Multimodal Cognitive-Behavioral Therapy

Background: Alexithymia as a predictor of treatment outcome in psychotherapy has often been discussed but rarely evaluated in prospective studies. The present study evaluated the absolute and relative stability of alexithymia in patients with obsessive-compulsive disorder (OCD), and the predictive value of alexithymia for the outcome of treatment. Methods: We conducted a prospective study with 42 inpatients receiving intensive, multimodal cognitive-behavioral therapy (CBT). Patients were assessed for alexithymia at pre- and post-treatment with the 20-item Toronto Alexithymia Scale (TAS-20), for obsessive-compulsive symptoms and depression with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the 21-item Hamilton Depression Rating Scale (HDRS). Results: OCD and comorbid depression showed a highly significant symptom-reduction from pre- to post-treatment while no absolute changes in the TAS-20 total scores and its factors 1 and 3 occurred. Only factor 2 scores decreased significantly, but with a smaller effect size than the effect sizes for the changes in Y-BOCS and HDRS. Alexithymia scores at pre-treatment correlated significantly with alexithymia scores at the end of treatment, indicating its relative stability. In the linear regression analyses, no variables were identified that predicted significantly the outcome of treatment. Conclusions: Our findings support the view that alexithymia is a stable personality trait rather than a state-dependent phenomenon in obsessive-compulsive patients. Alexithymia scores do not predict response to multimodal CBT in OCD. It might be an effect of CBT that patients could at least partly regain or newly learn the capability to describe their feelings.

Evidence of Frontotemporal Structural Hypoconnectivity in Social Anxiety Disorder: A Quantitative Fiber Tractography Study

Investigation of the brains white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito‐) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large‐scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto‐occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher‐level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies. Hum Brain Mapp, 2013.

Examination of emotional Stroop interference in obsessive-compulsive disorder

Previous research has produced conflicting findings on whether or not patients with subclinical or manifest obsessive-compulsive disorder (OCD) share an attentional bias for anxiety-related material. In the present study, 35 OCD patients were compared with 20 healthy controls on their performance in an emotional Stroop paradigm. Nine different stimulus conditions were compiled, including sets for depression-related and anxiety-related words as well as stimuli from two constructs with a potential relevance for the pathogenesis and maintenance of OCD symptomatology: responsibility and conscientiousness. Patients did not show enhanced interference for any of the conditions. Syndrome subtype and severity, avoidance and speed of information processing did not moderate results. The present study concurs with most prior research that OCD patients display no interference effect for general threat words. It deserves further consideration, that emotional interference effects in OCD as seen in other anxiety disorders occur when using idiosyncratic word material with a direct relation to the individuals primary concerns.