Sabine Wilhelm

The emotional counting stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division

BACKGROUND The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). METHODS Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. RESULTS We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. CONCLUSIONS In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.

Behavior therapy for children with Tourette disorder: a randomized controlled trial.

CONTEXT Tourette disorder is a chronic and typically impairing childhood-onset neurologic condition. Antipsychotic medications, the first-line treatments for moderate to severe tics, are often associated with adverse effects. Behavioral interventions, although promising, have not been evaluated in large-scale controlled trials. OBJECTIVE To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS Randomized, observer-blind, controlled trial of 126 children recruited from December 2004 through May 2007 and aged 9 through 17 years, with impairing Tourette or chronic tic disorder as a primary diagnosis, randomly assigned to 8 sessions during 10 weeks of behavior therapy (n = 61) or a control treatment consisting of supportive therapy and education (n = 65). Responders received 3 monthly booster treatment sessions and were reassessed at 3 and 6 months following treatment. INTERVENTION Comprehensive behavioral intervention. MAIN OUTCOME MEASURES Yale Global Tic Severity Scale (range 0-50, score >15 indicating clinically significant tics) and Clinical Global Impressions-Improvement Scale (range 1 [very much improved] to 8 [very much worse]). RESULTS Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7 [95% confidence interval {CI}, 23.1-26.3] to 17.1 [95% CI, 15.1-19.1]) from baseline to end point compared with the control treatment (24.6 [95% CI, 23.2-26.0] to 21.1 [95% CI, 19.2-23.0]) (P < .001; difference between groups, 4.1; 95% CI, 2.0-6.2) (effect size = 0.68). Significantly more children receiving behavioral intervention compared with those in the control group were rated as being very much improved or much improved on the Clinical Global Impressions-Improvement scale (52.5% vs 18.5%, respectively; P < .001; number needed to treat = 3). Attrition was low (12/126, or 9.5%); tic worsening was reported by 4% of children (5/126). Treatment gains were durable, with 87% of available responders to behavior therapy exhibiting continued benefit 6 months following treatment. CONCLUSION A comprehensive behavioral intervention, compared with supportive therapy and education, resulted in greater improvement in symptom severity among children with Tourette and chronic tic disorder. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00218777.

Psychometric validation of the Obsessive Beliefs Questionnaire and the Interpretation of Intrusions Inventory: Part I

This article reports on the validation of the Obsessive Beliefs Questionnaire (OBQ) and Interpretations of Intrusions Inventory (III) developed by the Obsessive Compulsive Cognitions Working Group (OCCWG) to assess the primary beliefs and appraisals considered critical to the pathogenesis of obsessions. A battery of questionnaires that assessed symptoms of anxiety, depression, obsessive-compulsive symptoms and worry was administered to 248 outpatients with a DSM-IV diagnosis of Obsessive-Compulsive Disorder (OCD), 105 non-obsessional anxious patients, 87 non-clinical adults from the community, and 291 undergraduate students. Tests of internal consistency and test-retest reliability indicated that the OBQ and III assessed stable aspects of OC-related thinking. Between-group differences and correlations with existing measures of OC symptoms indicated that the OBQ and III assess core cognitive features of obsessionality. However, the various subscales of the OBQ and III are highly correlated, and both measures evidenced low discriminant validity. The findings are discussed in terms of the relevance and specificity of cognitive constructs like responsibility, control and importance of thoughts, overestimated threat, tolerance of uncertainty and perfectionism for OCD.

Extensive Immunoglobulin Production Sensitizes Myeloma Cells for Proteasome Inhibition

Multiple myeloma is an incurable plasma cell neoplasia characterized by the production of large amounts of monoclonal immunoglobulins. The proteasome inhibitor bortezomib (PS-341, Velcade) induces apoptosis in various malignant cells and has been approved for treatment of refractory multiple myeloma. Inhibition of the antiapoptotic transcription factor nuclear factor-kappaB (NF-kappaB) apparently contributes to the antitumor effects of bortezomib; however, this mechanism cannot fully explain the exceptional sensitivity of myeloma cells. Extensive protein synthesis as in myeloma cells is inherently accompanied by unfolded proteins, including defective ribosomal products (DRiPs), which need to be degraded by the ubiquitin-proteasome system. Therefore, we hypothesized that the proapoptotic effect of bortezomib in multiple myeloma is mainly due to the accumulation of unfolded proteins in cells with high protein biosynthesis. Using the IgG-secreting human myeloma cell line JK-6L and murine muH-chain-transfected Ag8.H myeloma cells, apoptosis induction upon proteasome inhibition was clearly correlated with the amount of immunoglobulin production. Preferentially in immunoglobulin-high myeloma cells, bortezomib triggered activation of caspases and induction of proapoptotic CHOP, a component of the terminal unfolded protein response induced by endoplasmic reticulum (ER) stress. In immunoglobulin-high cells, bortezomib increased the levels of proapoptotic Bax while reducing antiapoptotic Bcl-2. Finally, IgG-DRiPs were detected in proteasome inhibitor-treated cells. Hence, proteasome inhibitors induce apoptosis preferentially in cells with high synthesis rate of immunoglobulin associated with accumulation of unfolded proteins/DRiPs inducing ER stress. These findings further elucidate the antitumor activities of proteasome inhibitors and have important implications for optimizing clinical applications.

Augmentation of Behavior Therapy With d -Cycloserine for Obsessive-Compulsive Disorder

OBJECTIVE This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). METHOD A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. RESULTS Relative to the placebo group, the D-cycloserine groups OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine groups depressive symptoms were significantly more improved at posttreatment. CONCLUSIONS These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist.

Hoarding disorder: a new diagnosis for DSM-V?

This article provides a focused review of the literature on compulsive hoarding and presents a number of options and preliminary recommendations to be considered for DSM‐V. In DSM‐IV‐TR, hoarding is listed as one of the diagnostic criteria for obsessive–compulsive personality disorder (OCPD). According to DSM‐IV‐TR, when hoarding is extreme, clinicians should consider a diagnosis of obsessive–compulsive disorder (OCD) and may diagnose both OCPD and OCD if the criteria for both are met. However, compulsive hoarding seems to frequently be independent from other neurological and psychiatric disorders, including OCD and OCPD. In this review, we first address whether hoarding should be considered a symptom of OCD and/or a criterion of OCPD. Second, we address whether compulsive hoarding should be classified as a separate disorder in DSM‐V, weighing the advantages and disadvantages of doing so. Finally, we discuss where compulsive hoarding should be classified in DSM‐V if included as a separate disorder. We conclude that there is sufficient evidence to recommend the creation of a new disorder, provisionally called hoarding disorder. Given the historical link between hoarding and OCD/OCPD, and the conservative approach adopted by DSM‐V, it may make sense to provisionally list it as an obsessive–compulsive spectrum disorder. An alternative to our recommendation would be to include it in an Appendix of Criteria Sets Provided for Further Study. The creation of a new diagnosis in DSM‐V would likely increase public awareness, improve identification of cases, and stimulate both research and the development of specific treatments for hoarding disorder. Depression and Anxiety, 2010.© 2010 Wiley‐Liss, Inc.

The prevalence of body dysmorphic disorder: a population-based survey

BACKGROUND Body dysmorphic disorder (BDD) is a highly distressing and impairing disorder characterized by a preoccupation with imagined or slight physical defects in appearance. Well designed studies on its prevalence and on base rates for diagnostic criteria are rare. Therefore this study aimed to reveal prevalence rates of BDD in the general population and to examine clinical features associated with BDD. METHOD Of 4152 selected participants 2552, aged 14-99 years, participated in this German nationwide survey. Participants were carefully selected to ensure that the sample was representative; they were visited by a study assistant who provided instructions and help if needed. Participation rate was 62.3%. DSM-IV criteria for BDD, as well as subthreshold features (e.g. individuals who consider some part(s) of their body as ugly or disfigured, but do not fulfill all BDD criteria) were examined. We also assessed suicidal ideation associated with the belief of having an ugly body part, as well as the desire for cosmetic surgery. Furthermore, somatization symptoms were assessed. RESULTS The prevalence of current BDD was 1.7% (CI 1.2-2.1%). Individuals with BDD reported higher rates of suicidal ideation (19% v. 3%) and suicide attempts due to appearance concerns (7% v. 1%) than individuals who did not meet criteria for BDD. Somatization scores were also increased in individuals with BDD, relative to those without. BDD was associated with lower financial income, lower rates of living with a partner, and higher rates of unemployment. CONCLUSIONS Our study shows that self-reported BDD is relatively common and associated with significant morbidity.

Strategic processing and episodic memory impairment in obsessive compulsive disorder.

There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.

Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V?

The obsessive–compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive–compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or “chapter”) in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM‐V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM‐V Research Planning Conference on Obsessive–Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC‐spectrum grouping of disorders be included in DSM‐V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of “Anxiety and Obsessive–Compulsive Spectrum Disorders.” These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM‐V. Depression and Anxiety, 2010.

A Preliminary Study of D-Cycloserine Augmentation of Cognitive-Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder

BACKGROUND Research on the neural circuitry underlying fear extinction has led to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, as a method to enhance exposure therapy outcome. Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood anxiety disorder. Thus, we sought to preliminarily examine whether weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). METHOD Participants were 30 youth (aged 8-17) with a primary diagnosis of OCD. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining CBT + DCS versus CBT + Placebo (15 youth per group). All patients received seven exposure and response prevention sessions paired with DCS or placebo taken 1 hour before sessions. RESULTS Although not significantly different, compared with the CBT + Placebo group, youth in the CBT + DCS arm showed small-to-moderate treatment effects (d = .31-.47 on primary outcomes). No adverse events were recorded. CONCLUSIONS These results complement findings in adult OCD and non-OCD anxiety disorders and provide initial support for a more extensive study of DCS augmentation of CBT among youth with OCD.