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Biomedical subjects

Sabine Wilhelm

Publications and source records attributed to Sabine Wilhelm.

At least 19 recordsLinked to original sources

Motor inhibition in trichotillomania and obsessive-compulsive disorder.

We investigated motor inhibition abilities in trichotillomania (TTM) and obsessive-compulsive disorder (OCD), two disorders characterized by repetitive, intentionally performed behaviors. Performance in a GoNogo experiment of 25 TTM and 21 OCD participants was compared to the performance of 26 HC participants. In contrast to OCD and HC participants, TTM participants tended to perform either 'fast and inaccurate' (indicating poor motor inhibition) or 'slow and accurate'. TTM participants with poor motor inhibition reported a significantly earlier age of TTM onset than those TTM participants who performed well. There was no evidence for motor inhibition deficits in OCD. Based on our data, a subgroup of TTM sufferers seems to be characterized by motor inhibition deficits.

Adult↗

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder.

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.

Adolescent↗

Factors masking HMGB1 in human serum and plasma.

High mobility group box 1 protein (HMGB1) is a ubiquitously expressed architectural chromosomal protein. Recently, it has become obvious that HMGB1 can also act as a proinflammatory mediator when actively secreted during cell activation or passively released from necrotic cells. HMGB1 appears to play an important role in the pathogenesis of diseases, including sepsis and rheumatoid arthritis. However, easy, sensitive, and reliable detection systems are required to investigate the clinical significance of HMGB1 in clinical samples for diagnosis and prognosis of diseases. Here, we describe sensitive ELISAs for the detection of HMGB1 in cell culture medium and cell lysates. However, these assays failed to reliably quantitate HMGB1 in serum and plasma when compared with immunoblot analysis. We found that serum/plasma components bind to HMGB1 and interfere with its detection by ELISA systems. In most serum/plasma samples investigated, including those from healthy individuals, we detected IgG antibodies binding to HMGB1. The titers of these antibodies correlated with the capacity of sera to interfere with the detection of recombinant HMGB1 by ELISA. Furthermore, HMGB1 coimmunoprecipitated with several proteins including IgG1, as identified by mass spectrometry. These HMGB1 interacting proteins are currently characterized and may contribute to complex formation, masking, and possibly, modulation of cytokine activity of HMGB1.

Biomarkers↗

Cognitive retraining for organizational impairment in obsessive-compulsive disorder.

Individuals with obsessive-compulsive disorder (OCD) have difficulties in organizing information during encoding associated with subsequent memory impairments. This study was designed to investigate whether impairments in organization in individuals with OCD can be alleviated with cognitive training. Thirty-five OCD subjects and 36 controls copied and recalled the Rey-Osterrieth Complex Figure Test (RCFT) [Osterrieth, P.A., 1944. Le test de copie d'une figure complexe: Contribution a l'étude de la perception et de la memoire (The test of copying a complex figure: A contribution to the study of perception and memory). Archive de Psychologie 30, 286-350.] before being randomly assigned to a training or non-training condition. The training condition was designed to improve the ability to organize complex visuospatial information in a meaningful way. The intervention phase was followed by another copy and recall trial of the RCFT. Both OCD and control subjects who underwent training improved more in organization and memory than subjects who did not receive organizational training, providing evidence that the training procedure was effective. OCD subjects improved more in organizational during encoding than control subjects, irrespective of whether or not they had received training. This suggests that organization impairment in OCD affects primarily the ability to spontaneously utilize strategies when faced with complex, ambiguous information but that the ability to implement such strategies when provided with additional trials is preserved. These findings support a distinction in OCD between failure to utilize a strategy and incapacity to implement a strategy.

Adult↗

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.

Adolescent↗

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

Adult↗

Emotion recognition bias for contempt and anger in body dysmorphic disorder.

Body dysmorphic disorder (BDD) patients are preoccupied with imagined defects or flaws in appearance (e.g., size or shape of nose). They are afraid of negative evaluations by others and often suffer significant morbidity including hospitalization and suicide attempts. Many patients experience ideas of reference, e.g., they often believe others take special notice of their "flaw". Facial expressions play an important role in conveying negative or positive feelings, and sympathy or rejection. In this study, we investigated emotion recognition deficits in 18 BDD patients and 18 healthy controls. Participants were presented with two questionnaires accompanying facial photographs. One questionnaire included self-referent scenarios ("Imagine that the bank teller is looking at you. What is his facial expression like?"), whereas the other one included other-referent scenarios ("Imagine that the bank teller is looking at a friend of yours," etc.), and participants were asked to identify the corresponding emotion (e.g., anger, contempt, neutral, or surprise). Overall, BDD patients, relative to controls, had difficulty identifying emotional expressions in self-referent scenarios. They misinterpreted more expressions as contemptuous and angry in self-referent scenarios than did controls. However, they did not have significantly more difficulties identifying emotional expressions in other-referent scenarios than controls. Thus, poor insight and ideas of reference, common in BDD, might be related to a bias for misinterpreting other people's emotional expressions as negative. Perceiving others as rejecting might reinforce concerns about one's personal perceived ugliness and social desirability.

Adult↗

Alkaline-shifted pHo sensitivity of AE2c1-mediated anion exchange reveals novel regulatory determinants in the AE2 N-terminal cytoplasmic domain.

The mouse anion exchanger AE2/SLC4A2 Cl(-)/HCO(-)(3) exchanger is essential to post-weaning life. AE2 polypeptides regulate pH(i), chloride concentration, cell volume, and transepithelial ion transport in many tissues. Although the AE2a isoform has been extensively studied, the function and regulation of the other AE2 N-terminal variant mRNAs of mouse (AE2b1, AE2b2, AE2c1, and AE2c2) have not been examined. We now present an extended analysis of AE2 variant mRNA tissue distribution and function. We show in Xenopus oocytes that all AE2 variant polypeptides except AE2c2 mediated Cl(-) transport are subject to inhibition by acidic pH(i) and to activation by hypertonicity and NH(+)(4). However, AE2c1 differs from AE2a, AE2b1, and AE2b2 in its alkaline-shifted pH(o)((50)) (7.70 +/- 0.11 versus 6.80 +/- 0.05), suggesting the presence of a novel AE2a pH-sensitive regulatory site between amino acids 99 and 198. Initial N-terminal deletion mutagenesis restricted this site to the region between amino acids 120 and 150. Further analysis identified AE2a residues 127-129, 130-134, and 145-149 as jointly responsible for the difference in pH(o)((50)) between AE2c1 and the longer AE2a, AE2b1, and AE2b2 polypeptides. Thus, AE2c1 exhibits a unique pH(o) sensitivity among the murine AE2 variant polypeptides, in addition to a unique tissue distribution. Physiological coexpression of AE2c1 with other AE2 variant polypeptides in the same cell should extend the range over which changing pH(o) can regulate AE2 transport activity.

Animals↗

Habit reversal versus supportive psychotherapy in Tourette's disorder: a randomized controlled trial and predictors of treatment response.

Tourette syndrome (TS) is characterized by chronic motor and vocal tics. Habit reversal therapy (HR) is a behavioral treatment for tics which has received recent empirical support. The present study compared the efficacy of HRT in reducing tics, improving life-satisfaction and psychosocial functioning in comparison with supportive psychotherapy (SP) in outpatients with TS. In addition, we investigated whether impairments in response inhibition in patients with TS predict response to HR treatment which specifically aims to inhibit tics. Thirty adult outpatients with DSM-IV TS were randomized to 14 individual sessions of HR (n = 15); or SP (n = 15). HR but not SP reduced tic severity over the course of the treatment. Both groups improved in life-satisfaction and psychosocial functioning during active treatment. Reductions in tic severity (HR) and improvements in life-satisfaction and psychosocial functioning (HR and SP) remained stable at the 6-month follow-up. The extent of pre-treatment response inhibition impairment in the HR group predicted reductions in tic-severity from pre- to post-treatment. Our results suggest that HR has specific tic-reducing effects although SP is effective in improving life-satisfaction and psychosocial functioning. Assessments of response inhibition may be of value for predicting treatment response to HR.

Adult↗

Do dysfunctional beliefs play a role in all types of obsessive-compulsive disorder?

Some but not all models of obsessive-compulsive disorder (OCD) emphasize the role of dysfunctional beliefs in the etiology and maintenance of this disorder. Clinical observations suggest that some OCD patients have prominent dysfunctional beliefs associated with their obsessions and compulsions, while other patients do not show this pattern. It is possible that dysfunctional beliefs play a role in only a subgroup of cases of OCD and, by extension, that different models might apply to different subtypes of the disorder. To examine this issue, patients with OCD (N = 244) completed measures of dysfunctional OC-related beliefs, along with measures of OC symptoms and demographics. These measures were also completed by three comparison groups; anxious (N = 103), student (N = 284), and community (N = 86) controls. Cluster analysis revealed two OCD clusters: low versus high scores on beliefs (OC-low, OC-high). Belief scores for OC-low were in the range of scores for the comparison groups, which were all significantly lower than those of OC-high. Thus, a cluster of OCD patients was identified who did not have elevated scores on measures of dysfunctional beliefs. OC-low and OC-high did not differ on some OC measures (contamination, checking, grooming), but OC-high had higher scores on measures of harming obsessions. These results are consistent with the view that dysfunctional beliefs may play a role in only some types of OCD.

Adult↗

Cognitive inhibition in trichotillomania and obsessive-compulsive disorder.

Cognitive inhibition was investigated in 21 trichotillomania (TTM), 21 obsessive-compulsive disorder (OCD) and 26 healthy control (HC) participants using a block cued directed forgetting task. After encoding a word list, participants were instructed to intentionally FORGET these words and to REMEMBER another word list. Both lists included TTM-related and neutral (kitchen-related) words in equal proportions, with the TTM-related words generally of negative valence and the kitchen-related words generally of neutral valence for all participants. A superior free recall of REMEMBER versus FORGET words suggests intact cognitive inhibition. The performance of OCD participants indicated a specific deficit in inhibiting the retrieval of information with negative valence, which was not found in TTM. HC participants, in contrast to TTM and OCD participants, were rather inattentive to negative information. In conclusion, although attention was disproportionately directed towards negative information in both disorders, cognitive inhibition deficits appeared specific to OCD.

Adult↗

Visuospatial abilities, memory, and executive functioning in trichotillomania and obsessive-compulsive disorder.

Few studies have compared neuropsychological functioning in trichotillomania (TTM) and obsessive-compulsive disorder (OCD). In OCD, most studies suggest abnormal visuospatial abilities, memory, and executive functioning. We compared 23 TTM, 21 OCD and 26 healthy control individuals on neuropsychological tasks assessing these abilities. Neither the TTM nor the OCD groups suffered from generalized neuropsychological deficits compared to the healthy control group. TTM participants showed increased perseveration on the Object Alternation Task suggesting difficulties with response flexibility. OCD participants showed impaired ability to learn from feedback on the Wisconsin Card Sorting Test. Other executive functions, as well as memory and visuospatial abilities were unimpaired in TTM and OCD. Our data suggest that TTM and OCD are characterized by different patterns of neuropsychological dysfunction.

Adult↗

Amygdala responses to human faces in obsessive-compulsive disorder.

BACKGROUND: To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI). METHODS: Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross. RESULTS: Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed. CONCLUSIONS: Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders.

Adult↗

Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions.

beta-Catenin controls both cadherin-mediated cell adhesion and activation of Wnt target genes. We demonstrate here that the beta-catenin-binding protein BCL9-2, a homolog of the human proto-oncogene product BCL9, induces epithelial-mesenchymal transitions of nontransformed cells and increases beta-catenin-dependent transcription. RNA interference of BCL9-2 in carcinoma cells induces an epithelial phenotype and translocates beta-catenin from the nucleus to the cell membrane. The switch between beta-catenin's adhesive and transcriptional functions is modulated by phosphorylation of Tyr 142 of beta-catenin, which favors BCL9-2 binding and precludes interaction with alpha-catenin. During zebrafish embryogenesis, BCL9-2 acts in the Wnt8-signaling pathway and regulates mesoderm patterning.

Animals↗

Challenges in treating obsessive-compulsive disorder: introduction.

This issue of In Session is devoted to challenges in the treatment of obsessive-compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises. Articles focus on the treatment of OCD with comorbid depression, compulsive hoarding, incompleteness, and repugnant obsessions, and on treatment of children who have OCD. The final article describes pharmacotherapy for OCD. All articles feature case vignettes and provide practitioners with clinical recommendations.

Adult↗

A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus mechanisms.

Recently, experts have suggested that obsessive-compulsive disorder (OCD), a highly heterogeneous condition, is actually composed of distinct subtypes. Research to identify specific subtypes of OCD has focused primarily on symptom presentation. Subtype models have been proposed using factor analyses that yield dimensional systems of symptom categories, but not necessarily distinct subtypes. Other empirical work has considered the role of neuropsychological functioning and comorbidity as part of a comprehensive scheme for subtyping OCD. The identified dimensions from all of these studies have implications for the treatment of OCD. In this article, we review the research on subtypes of OCD, focusing on subtype schemes based upon overt symptom presentation and neuropsychological profiles. We also review research pertinent to alternative subtyping schemes, both conceptually and methodologically. The research is critically examined and implications for treatment are discussed. Recommendations for future investigations are offered.

Diagnosis, Differential↗

No disgust recognition deficit in obsessive-compulsive disorder.

BACKGROUND: Patients with basal ganglia abnormalities misclassify facial expressions of disgust as expressions of anger when asked to identify the emotion depicted in photographs of individuals displaying different emotions. Sprengelmeyer, Young, Pundt et al. (1997) reported a similar disgust recognition deficit in patients with obsessive-compulsive disorder (OCD)--an anxiety disorder associated with basal ganglia abnormality. METHODS: In the present experiment, we attempted to replicate Sprengelmeyer, Young, Pundt et al.'s (1997) findings. RESULTS: We failed to replicate Sprengelmeyer, Young, Pundt et al.'s finding of disgust recognition deficits in OCD patients relative to healthy control subjects. One patient with especially severe OCD did, however, exhibit impairment by misclassifying disgust expressions as anger expressions. DISCUSSION: These data do not confirm the presence of disgust recognition deficits in individuals with OCD. In light of the deficits exhibited by one subject with severe OCD, disgust recognition deficits may be confined to an unidentified subset of people with OCD.

Adult↗

Habit reversal versus supportive psychotherapy for Tourette's disorder: a randomized controlled trial.

OBJECTIVE: The authors investigated the efficacy of habit reversal for Tourette's disorder, which is characterized by multiple motor and vocal tics. METHOD: Thirty-two patients with Tourette's disorder were randomly assigned to 14 sessions of either habit reversal or supportive psychotherapy. Habit reversal consisted of awareness training, self-monitoring, relaxation training, competing response training, and contingency management. Changes in severity of Tourette's disorder and psychosocial impairment were investigated over the course of the 14-session treatment for the 29 patients who completed at least eight treatment sessions. RESULTS: In contrast to the 13 patients in the supportive psychotherapy group, the 16 patients in the habit reversal group improved significantly. The habit reversal patients remained significantly improved over pretreatment at 10-month follow-up. CONCLUSIONS: Habit reversal may be an effective behavioral treatment for Tourette's disorder.

Adult↗