Bartosz Zurowski

Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study.

Objective: Although many patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of them do not respond. The objective of the present study was to evaluate the efficacy of quetiapine added to baseline treatment with SRIs for the treatment of OCD in severely ill adult subjects. Method: Forty patients (21 men, 19 women) with primary OCD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria participated in a 12-week, double-blind, placebo-controlled trial. They were randomly assigned to dosages of quetiapine titrated up to 400 mg/d (n = 20) or to placebo (n = 20) in addition to their SRI treatment. During the continuation phase (weeks 6-12), subjects received different dosages between 400 and 600 mg/d depending on clinical response. At entry, all patients were unresponsive to at least 1 course of at least 12 weeks of treatment with SRIs at defined doses. The total Yale-Brown Obsessive-Compulsive Scale score was the primary efficacy parameter. Results: Intention-to-treat, last-observation-carried-forward analysis demonstrated a mean ± SD decrease in Yale-Brown Obsessive-Compulsive Scale score of 5.2 ± 5.4 in the quetiapine group and 3.9 ± 4.9 in the placebo group. The analysis of treatment effects between the 2 groups showed no significant difference. There were no significant group differences in any of the other self-rating scales or clinician-administered rating scales. Conclusions: In this study, augmentation of SRI treatment with quetiapine in severe OCD had no additional effect.

Decreased limbic and increased fronto-parietal connectivity in unmedicated patients with obsessive-compulsive disorder

Obsessive‐compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto‐striato‐thalamo‐cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting‐state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto‐parietal regions relevant for (re)‐appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty. Hum Brain Mapp 35:5617–5632, 2014.

Differences and similarities between obsessive and ruminative thoughts in obsessive-compulsive and depressed patients : a comparative study

Repetitive, intrusive cognitive phenomena are central both to obsessive-compulsive patients - typically as obsessive thoughts - and to depressed patients - typically as ruminative thoughts. The objective of the present study is to compare obsessive and ruminative thoughts in non-depressed obsessive-compulsive and depressed patients. Thirty-four patients diagnosed with obsessive-compulsive disorder and 34xa0patients diagnosed with major depression disorder were asked to identify both a personally relevant obsessive and a personally relevant ruminative thought and to subsequently evaluate these thoughts on a modified version of the Cognitive Intrusions Questionnaire (CIQ) developed by Freeston, Ladouceur, Thibodeau, and Gagnon (1991). The CIQ assesses general descriptors, emotional reactions, appraisal and coping strategies on a nine-point Likert scale. A mixed-model ANOVA demonstrated that obsessive and ruminative thoughts are distinct cognitive processes, clearly distinguishable in form, appraisal and temporal orientation across disorders. In obsessive-compulsive patients, ruminative thoughts were more common and more emotionally distressing than predicted. In depressed patients, obsessive thoughts occurred infrequently and were not associated with high negative emotions. Clarifying similarities and differences between ruminative and obsessive thoughts and understanding their interaction might ultimately help to expand on the role of cognitive vulnerability factors in obsessive-compulsive and major depression disorder.

Relations between a ruminative thinking style and obsessive-compulsive symptoms in non-clinical samples

Abstract There is tremendous interest in understanding the cognitive processes behind obsessive–compulsive disorder (OCD). Whereas previous research on cognitive OCD models has focused on the dysfunctional content of obsessional thinking, processes and styles of thinking have not yet been investigated. The present study investigated the relationship between a ruminative response style and obsessive–compulsive (OC) symptomatology in two non-clinical samples. In Sample 1, 261 students completed the Ruminative Response Scale, the Padua-Inventory, Revised, and the Beck Depression Inventory. Tendency to ruminate was positively correlated with the severity of OC symptoms and particularly with obsessive rumination, even after controlling for depression. Results were replicated in Sample 2 (211 students). Data indicate that a ruminative response style and obsessive rumination share common processual features. Understanding the interaction between rumination and obsessional thinking might help to further elucidate the role of cognitive vulnerability factors in OCD and to expand cognitive and metacognitive models of OCD.

Resting-state connectivity of the amygdala predicts response to cognitive behavioral therapy in obsessive compulsive disorder

BACKGROUNDnObsessive-compulsive disorder (OCD) is a psychiatric disorder which is characterized by recurrent intrusive thoughts (obsessions) and ritualized, repetitive behaviors or mental acts (compulsions). The gold standard for the treatment of OCD is cognitive behavioral therapy (CBT) with exposure and response prevention. This is the first study exploring the predictive value of resting-state functional connectivity for the outcome of CBT.nnnMETHODSnWe assessed whole-brain resting-state functional connectivity in a group of 17 un-medicated OCD inpatients prior to CBT compared to 19 healthy controls using functional magnetic resonance imaging. The graph theoretical metric degree centrality served as indicator for altered voxel-wise whole-brain functional connectivity. The relative change in the Yale-Brown Obsessive Compulsive Scale (YBOCS) score was used to evaluate treatment outcome.nnnRESULTSnThe degree centrality of the right basolateral nuclei group of the amygdala was positively correlated with the response to subsequent CBT. OCD patients showed a lower degree centrality of the superficial amygdala (bilateral).nnnCONCLUSIONSnOur results suggest that two different sub-regions of the amygdala and their respective neural networks are affected in OCD: the superficial amygdala and networks related to evaluation of reinforcers and risk anticipation and the basolateral amygdala which is implicated in fear processing. The diminished CBT response in patients showing a lower degree centrality of the basolateral amygdala reflects a deficient fear circuit in these patients which may impact fear extinction as a core mechanism of exposure-based CBT.

Brain Potentials of Conflict and Error-Likelihood Following Errorful and Errorless Learning in Obsessive-Compulsive Disorder

Background The anterior cingulate cortex (ACC) is thought to be overacting in patients with Obsessive Compulsive Disorder (OCD) reflecting an enhanced action monitoring system. However, influences of conflict and error-likelihood have not been explored. Here, the error-related negativity (ERN) originating in ACC served as a measure of conflict and error-likelihood during memory recognition following different learning modes. Errorless learning prevents the generation of false memory candidates and has been shown to be superior to trial-and-error-learning. The latter, errorful learning, introduces false memory candidates which interfere with correct information in later recognition leading to enhanced conflict processing. Methodology/Principal Findings Sixteen OCD patients according to DSM-IV criteria and 16 closely matched healthy controls participated voluntarily in the event-related potential study. Both, OCD- and control group showed enhanced memory performance following errorless compared to errorful learning. Nevertheless, response-locked data showed clear modulations of the ERN amplitude. OCD patients compared to controls showed an increased error-likelihood effect after errorless learning. However, with increased conflict after errorful learning, OCD patients showed a reduced error-likelihood effect in contrast to controls who showed an increase. Conclusion/Significance The increase of the errorlikelihood effect for OCD patients within low conflict situations (recognition after errorless learning) might be conceptualized as a hyperactive monitoring system. However, within high conflict situations (recognition after EF-learning) the opposite effect was observed: whereas the control group showed an increased error-likelihood effect, the OCD group showed a reduction of the error-likelihood effect based on altered ACC learning rates in response to errors. These findings support theoretical frameworks explaining differences in ACC activity on the basis of conflict and perceived error-likelihood as influenced by individual error learning rate.

Relevance of orbitofrontal neurochemistry for the outcome of cognitive-behavioural therapy in patients with obsessive-compulsive disorder

Since the advent of non-invasive methods such as proton magnetic resonance spectroscopy (1H-MRS), obsessive–compulsive disorder (OCD) has been increasingly associated with an altered composition of neurometabolites and neurotransmitters in several brain areas. Particularly, Inositol has not only been implicated in OCD pathophysiology, but also shown effective in pilot studies in therapy-refractory OCD patients. However, the relevance of regional brain neurochemistry for therapy outcome has not yet been investigated. Whereas numerous neuroimaging findings support a dysfunction of the orbitofrontal cortex (OFC) in OCD, MR-spectroscopic investigations of this region are missing. 1H-MRS and psychometric measurements were obtained from twenty unmedicated patients with OCD, subsequently enrolled in a 3-month structured inpatient cognitive-behavioural therapy programme, and from eleven matched control subjects. Multiple regression of symptom score changes (Y-BOCS) on (myo-)inositol concentrations in three areas (right orbitofrontal cortex (OFC), right striatum and anterior cingulate cortex) was performed. The concentration of (myo-)inositol in the OFC only predicted the outcome of subsequent CBT regarding Y-BOCS score reduction (Spearman’s rsxa0=xa0.81, Pxa0<xa00.003, corrected). The (myo-)inositol concentration did not differ between OCD patients and healthy controls and did not change during therapy. We provide preliminary evidence for a neurochemical marker that may prove informative about a patient’s future benefit from behaviour therapy. Inositol, a metabolite involved in cellular signal transduction and a spectroscopic marker of glial activity, predicted the response to CBT selectively in the OFC, adding to the evidence for OFC involvement in OCD and highlighting neurobiological underpinnings of psychotherapy.

Managing Obsessive Thoughts During Brief Exposure: An Experimental Study Comparing Mindfulness-Based Strategies and Distraction in Obsessive–Compulsive Disorder

In mindful meditation, negative thoughts such as obsessive thoughts are observed simply as mental events that come and go, rather than as accurate reflections of reality. This experimental study tested the efficacy of a mindfulness-based instruction compared to distraction during brief exposure to obsessive thoughts in obsessive–compulsive patients. Thirty patients diagnosed with obsessive–compulsive disorder were asked to listen to their own obsessive thoughts through headphones during three time phases: at baseline, during an experimental condition and during a return to baseline. During the experimental condition, they were instructed to deal with their obsessive thoughts using either a mindfulness-based strategy or a distraction strategy (random allocation). Results showed that a mindfulness-based strategy reduced anxiety and urge to neutralize from first to second baseline, whereas a distraction strategy did not. Data offer initial evidence that using mindfulness-based metaphors during brief exposure with obsessive thoughts may be a useful alternative to distraction.

Lesion of the dorsorostral midbrain sparing the nigrostriatal tract mimics axial rigidity seen in progressive supranuclear palsy

We report on a patient with a residual dorsorostral midbrain lesion after resection of a pineal gland tumor. In addition to severe vertical gaze palsy, this patient exhibited other neurological features closely resembling progressive supranuclear palsy. Normal dopamine transporter single‐photon emission computed tomography imaging excluded significant dopamine deficiency. We suggest that dorsorostral midbrain pathology rather than dopamine deficiency due to degeneration of nigrostriatal dopaminergic neurons or basal ganglia nuclei might be responsible for axial rigidity in extension.

Diagnostik und evidenzbasierte Psychotherapie der Zwangsstörung

Das klinische Bild der Zwangsstörung wird von Zwangsgedanken und Zwangshandlungen bestimmt. Zwangsgedanken sind unangenehme Gedanken, Vorstellungen und Handlungsimpulse (= Intrusionen), die sich dem Bewusstsein aufdrängen (englisch: obsessions). Bei Zwangshandlungen handelt es sich meist um ritualisierte Gedankenoder Handlungsketten (englisch: compulsions), die mit dem Ziel ausgeführt werden, die aversiven Intrusionen abzuwehren oder zu neutralisieren. Zwangsgedanken ähneln alltäglichen Gedanken und Befürchtungen, entwickeln aber aufgrund der ihnen zugeschriebenen Bedeutsamkeit eine intensivere Qualität. Mitunter handelt es sich um bizarr anmutende Gedanken, die (auch für den Patienten) rational schwer bis gar nicht nachvollziehbar sind. Typische Themen von Zwangsgedanken betreffen: Ansteckung, Vergiftung, Verschmutzung, Krankheit, Streben nach Symmetrie, Ordnung, Aggression, Sexualität und Religion. Patienten erleben ihre Zwangsgedanken als lästig und aufdringlich und betrachten sie als abstoßend, unannehmbar, beschämend und sinnlos. Die Gedanken können durch eine Vielzahl auslösender Reize provoziert werden, aber auch spontan auftreten. Die Zwangshandlungen sollen der Erleichterung von Anspannung und Befürchtungen dienen. Die Erleichterung ist jedoch meist nur von kurzer Dauer, langfristig erhöht sich die Auftretenswahrscheinlichkeit der Zwangsgedanken und der damit verbundenen Befürchtungen. Die Ausführungen der Zwangshandlungen bedeuten oft einen erheblichen Aufwand und gehen mit Einschränkungen der Leistungsfähigkeit und des sozialen Lebens einher. In der Regel werden sie gegen einen innerenWiderstand ausgeführt und als unsinnig erlebt. Trotz der Einsicht in die Unsinnigkeit können sie vom Patienten nicht oder nur schwer unterlassen werden. Den Themen der vorausgehenden Zwangsgedanken entsprechend handelt es sich bei den Zwangshandlungen um dazu passende Wasch-, Reinigungsund Putzzwänge sowie Kontrollund Ordnungszwänge oder andere Rituale, die der Neutralisierung dienen. Zwangshandlungen können auch rein in Gedanken durchgeführt werden und werden als Grübelzwang oder mentale bzw. kognitive Zwangshandlungen bezeichnet. Obwohl sie wie die Zwangsgedanken auf gedanklicher Ebene stattfinden, werden sie zu den Zwangshandlungen gerechnet, weil sie dem Zweck dienen, Anspannung und Angst zu neutralisieren. Typische Beispiele sind Zählzwänge, gedankliches Rekonstruieren oder Betrituale.