Metacognitive therapy versus exposure and response prevention for obsessive-compulsive disorder - A non-inferiority randomized controlled trial.

OBJECTIVE: Exposure with response prevention (ERP) is the first-line treatment for obsessive-compulsive disorder (OCD). However, refusals, dropouts and the required high time and logistic effort constitute barriers to the use of ERP. In a non-inferiority randomized controlled trial, we compared metacognitive therapy (MCT) to exposure with response prevention (ERP) as treatments for OCD. METHOD: 74 outpatients received 12 weekly sessions of either manualized MCT or ERP, with primary outcomes assessed by blinded assessors using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at pre-treatment, mid-treatment, post-treatment, and 6-month follow-up. Secondary outcomes included measures of depression and anxiety. Non-inferiority margin was specified at no less than d = 0.38 below the improvement reached by ERP, corresponding to a difference of about 3 points on the Y-BOCS. RESULTS: Drop-out rates were low (<14%) and similar in both groups. Linear models indicated non-inferiority of MCT to ERP at post-treatment, but not at 6-month follow-up. While both groups showed comparable Y-BOCS improvements, the MCT group demonstrated a significantly greater reduction in state anxiety scores at post-treatment and follow-up. CONCLUSIONS: Overall, MCT was not inferior to ERP, especially at post-treatment, suggesting it could be a treatment alternative. However, further research is needed to explore differential treatment indications.

Empathy, compassion, and theory of mind in obsessive-compulsive disorder.

OBJECTIVES: Individuals with obsessive-compulsive disorder (OCD) often suffer from impairments in social functioning. This study investigates differences in empathy, compassion, and Theory of Mind (ToM) in individuals with OCD as a possible cause for social functioning deficits. DESIGN: Sixty-four individuals diagnosed with OCD and 62 healthy individuals completed a naturalistic behavioural task (EmpaToM) and a self-report measure (Interpersonal Reactivity Index, IRI). METHODS: Three preregistered repeated measures analyses of variance (ANOVAs). RESULTS: People with OCD exhibited higher empathy levels - namely increased sharing of others' suffering - in the EmpaToM task and reported more distress (IRI) compared with healthy individuals. Furthermore, no differences in compassion (EmpaToM) between both groups emerged, although people with OCD reported more concern for others (IRI) compared with healthy individuals. Concerning the ToM, no group differences were detected, neither in the behavioural task, nor self-report. CONCLUSION: By investigating OCD with diverse scientific practices we shed light on the higher levels of empathy exhibited by individuals with OCD, which are relevant for clinical practice and our understanding of OCD symptomatology. PRACTITIONER POINTS: ●People with obsessive-compulsive disorder show higher levels of empathy, that is the increased sharing of others' suffering, compared with healthy individuals in both a traditional self-report and a naturalistic task. ●Regarding compassion, that is caring for others, their self-reported compassion was higher in people with OCD. ●In Theory of Mind, that is cognitively understanding the situation of another person, no differences have been found neither at self-report nor in a naturalistic task compared with healthy individuals. ●Independent of traditional interventions, it could prove useful to improve emotion regulation skills so people with OCD learn to cope with empathic distress. Furthermore, it might strengthen the treatment gains and lower dropout rates if the social mind and consequently social relationships become a topic in the treatment and prevention of OCD.

Further evidence for genetic variation at the serotonin transporter gene SLC6A4 contributing toward anxiety.

OBJECTIVES: Social anxiety disorder (SAD) is a common and heritable psychiatric disorder. However, genetic studies in SAD are rare and only a few candidate genes have been implicated so far. In the present study, we investigated whether single-nucleotide polymorphisms (SNPs) associated with other psychiatric disorders also contribute toward the development of SAD and followed up variants associated with SAD on the phenotypic level. PATIENTS AND METHODS: We genotyped a total of 24 SNPs in a German sample of 321 SAD patients and 804 controls. We carried out single-marker analyses as well as quantitative association analyses of SAD severity and harm avoidance. RESULTS: None of the variants investigated showed an association with SAD in our case-control sample after Bonferroni correction. Two SNPs reached nominal significance (rs818702, P=0.032; rs140701, P=0.048). Of these, only rs140701 showed an association in the same allelic direction as reported previously. This SNP is located within the serotonin transporter gene SLC6A4, which is the primary target of selective-serotonin reuptake inhibitors used for the treatment of depressive and anxiety disorders. The quantitative association analysis of all cases with available data on symptom severity showed four SNPs with a nominal significant association. Among these SNPs, rs10994359 showed the strongest association (P=0.001) and was located near the ANK3 gene. In addition, rs10994359 was nominally associated with harm avoidance scores (P=0.001). CONCLUSION: Our results provide further evidence for an involvement of the serotonin transporter gene SLC6A4 in the etiology of anxiety-related traits. Furthermore, our study implicates that genetic variation at the genome-wide associated bipolar disorder locus ANK3 might influence anxiety-related personality traits.

Psychosocial assessment of living kidney donors: What implications have temperament and character for decision-making?

OBJECTIVE: We compared the personality of kidney donor candidates to non-donor controls and analyzed the personality profile of candidates psychosocially at risk. METHODS: 49 consecutive living kidney donor candidates underwent an extensive psychosocial evaluation. Psychosocial risk factors concerning knowledge of donation risks (1), donor-recipient-relationship (2), and/or mental health (3) were rated on a 3-point rating scale (0=high risk, 2=no risk). Furthermore, candidates as well as 49 age-and gender-matched non-donor controls filled in questionnaires concerning psychological distress (Symptom Checklist 90-R) and personality (Temperament and Character Inventory). RESULTS: There were no significant differences between candidates and controls concerning psychological distress or personality. Psychosocial assessment identified 13 candidates (26.5%) with increased psychosocial risk. This group displayed compared to candidates without psychosocial risk no difference concerning age, gender, formal education, donor-recipient relationship and psychological distress. However, this group scored significantly higher on reward dependence compared to suitable donors and controls (p<0.05). Reward dependence was associated with a lack of adequate knowledge on donation (r=-0.35, p<0.05). CONCLUSION: Reward dependence has important implications for decision-making, because it is associated with an increased tendency to deny potential risks of donation. Careful identification and assessment of reward dependent donor candidates is needed to ensure a free-willed decision.

Psychophysiological decoupling in alexithymic pain disorder patients.

Considering that impaired coping with stress is closely linked with emergence of stress-sensitive disorders most notably in alexithymic individuals, we conducted the first study examining stress-related autonomic reactivity in alexithymic pain disorder patients. Twenty-one pain disorder patients with high and an equivalent patient group with low alexithymia scores were exposed to three types of affect-inductive stimuli with variable affective involvement: arithmetic task, watching arousing video material and giving an oral presentation. Subjective appraisal of the induced emotional experience and physiological reactivity (heart rate, muscle tension and skin conductance) was documented. During oral presentation high alexithymia patients showed significantly lower skin conductance in combination with increased subjective negative affect compared to low alexithymia patients. Our results thus demonstrate a decoupling between physiological and affect processing in pain disorder patients with high alexithymia during a stressful situation that was subjectively associated with negative affect.

Changes of explicitly and implicitly measured self-esteem in the treatment of major depression: evidence for implicit self-esteem compensation.

BACKGROUND AND OBJECTIVES: Self-esteem has been claimed to be an important factor in the development and maintenance of depression. Whereas explicit self-esteem is usually reduced in depressed individuals, studies on implicitly measured self-esteem in depression exhibit a more heterogeneous pattern of results, and the role of implicit self-esteem in depression is still ambiguous. Previous research on implicit self-esteem compensation (ISEC) revealed that implicit self-esteem can mirror processes of self-esteem compensation under conditions that threaten self-esteem. We assume that depressed individuals experience a permanent threat to their selves resulting in enduring processes of ISEC. We hypothesize that ISEC as measured by implicit self-esteem will decrease when individuals recover from depression. METHODS: 45 patients with major depression received an integrative in-patient treatment in the Psychosomatic University Hospital Bonn, Germany. Depression was measured by the depression score of the Hospital Anxiety and Depression Scale (HADS-D). Self-esteem was assessed explicitly using the Rosenberg Self-Esteem Scale (RSES) and implicitly by the Implicit Association Test (IAT) and the Name Letter Test (NLT). RESULTS: As expected for a successful treatment of depression, depression scores declined during the eight weeks of treatment and explicit self-esteem rose. In line with our hypothesis, both measures of implicit self-esteem decreased, indicating reduced processes of ISEC. LIMITATIONS: It still remains unclear, under which conditions there is an overlap of measures of implicit and explicit self-esteem. CONCLUSIONS: The results lend support to the concept of ISEC and demonstrate the relevance of implicit self-esteem and self-esteem compensation for the understanding of depression.

Factorial structure of the 20-item Toronto Alexithymia Scale in a large sample of somatoform patients.

Although a strong association between alexithymia and somatization has been postulated in numerous studies, no systematic study has investigated the psychometric properties of the 20-item Toronto Alexithymia Scale (TAS-20) in a sample of patients with somatoform disorder yet. The purpose of this study was to ensure a valid assessment by the German version of the TAS-20 in somatoform samples. We investigated whether the original three-factor model proposed by Bagby et al. (1994a), which is widely used in clinical research and practice, is replicable in a large sample of somatoform patients (n=806). Using confirmatory factor analysis (CFA) the goodness-of-fit of the originally proposed factor structure was compared to three factor models generated with exploratory factor analysis (EFA) and other factorial solutions derived from the literature. Our results demonstrate that the original three-factor model is not replicable in somatoform patients. Instead, the four-factor model by Franz et al. (2001b) described the data best. However, none of the models met all criteria of confirmatory factor analysis. Our results indicate that the three-factor model is not robust in the German version of the TAS-20. At this state of research we recommend to use the TAS-20 sum-score as a measure of alexithymia in somatoform patients in clinical practice.

Temperament and character personality profile and illness-related stress in central serous chorioretinopathy.

Psychological stress is a risk factor as well as a consequence of central serous chorioretinopathy (CSC). Impulsiveness, overachievement, emotional instability, and hard-driving competitiveness have been discussed as personality features in CSC patients. We investigated 57 consecutive CSC patients and 57 age- and gender-matched controls by means of the Symptom Checklist 90-R and the Temperament and Character Inventory. Somatic risk factors, illness characteristics, subjective assessment of severity of illness, and illness-related stress in different areas of life (work, private life) were evaluated. CSC patients showed significantly higher emotional distress as measured by the Global Severity Index. The CSC personality was characterized by lower scoring on the character dimension cooperativeness and the temperament dimension reward dependence. Cooperativeness as well as subjective assessment of severity of CSC has been recognized as significant predictors of illness-related work stress accounting for 30% of variance. Implicating competitiveness, hostility and emotional detachment, lower level of cooperativeness, and reward dependence support the existence of specific aspects of type A behaviour in CSC patients. Low perceived social support and loss of control may explain the significant contribution of this personality dimension to illness-related work stress. Treatment of CSC should thus incorporate psychoeducation about factors contributing to illness-related stress.

Neural correlates of impaired emotion processing in manifest Huntington's disease.

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

Diminished activation of motor working-memory networks in Parkinson's disease.

Parkinson's disease (PD) is characterized by typical extrapyramidal motor features and increasingly recognized non-motor symptoms such as working memory (WM) deficits. Using functional magnetic resonance imaging (fMRI), we investigated differences in neuronal activation during a motor WM task in 23 non-demented PD patients and 23 age- and gender-matched healthy controls. Participants had to memorize and retype variably long visuo-spatial stimulus sequences after short or long delays (immediate or delayed serial recall). PD patients showed deficient WM performance compared to controls, which was accompanied by reduced encoding-related activation in WM-related regions. Mirroring slower motor initiation and execution, reduced activation in motor structures such as the basal ganglia and superior parietal cortex was detected for both immediate and delayed recall. Increased activation in limbic, parietal and cerebellar regions was found during delayed recall only. Increased load-related activation for delayed recall was found in the posterior midline and the cerebellum. Overall, our results demonstrate that impairment of WM in PD is primarily associated with a widespread reduction of task-relevant activation, whereas additional parietal, limbic and cerebellar regions become more activated relative to matched controls. While the reduced WM-related activity mirrors the deficient WM performance, the additional recruitment may point to either dysfunctional compensatory strategies or detrimental crosstalk from "default-mode" regions, contributing to the observed impairment.

Temperament, character, and personality disorders in chronic pain.

In the past decades investigators have used personality inventories to help explain the relationship between personality and pain experience. This article reviews empirical research, which has examined temperament and character features in chronic pain patients. Robert Cloninger's temperament and character model of personality based on a bio-psychosocial approach to personality and psychopathology has been used in multiple studies investigating the temperament and character profile of chronic pain patients. According to Cloninger's model, research portrayed a common personality profile of chronic pain patients characterized by prevailing harm avoidance and lower self-directedness, which has been shown to predict the presence of a personality disorder. Pain-prone patients could benefit from the measurement of personality by the temperament and character inventory with improved treatment response.

Elevated IGF2 prevents leptin induction and terminal adipocyte differentiation in hemangioma stem cells.

Infantile hemangioma is a benign vascular tumor that exhibits a unique yet predictable lifecycle of rapid proliferation followed by spontaneous regression. Recent studies have identified that insulin-like growth factor-2 (IGF2), a fetal mitogen, is highly expressed during the proliferative phase of hemangioma growth. Since hemangiomas arise from CD133+ stem cells, high levels of IGF2 may regulate the activity of the stem cells and therefore, hemangioma growth. The aim of this study was to understand the functional significance of elevated IGF2 in hemangiomas. We show that IGF2 localizes to the CD133+ cells in hemangioma specimens. We, therefore, hypothesized that IGF2 may be regulating the plasticity of hemangioma stem cells. To test our hypothesis, we used CD133-selected cells from hemangiomas to knockdown the expression of IGF2. We found that IGF2 is a mitogen for hemangioma stem cells and prevents leptin induction and full terminal differentiation of hemangioma stem cells into adipocytes. We also show that IGF2 does not alter the initial commitment phase. These findings implicate an important role of IGF2 in expanding hemangioma stem cells and preventing terminal adipocyte differentiation.

Evolution of hemangioma endothelium.

Infantile hemangioma is a benign vascular tumor, characterized by a unique life cycle consisting of rapid growth and spontaneous regression. Three distinct phases (proliferating, involuting, and involuted) take place over the course of approximately 5-8 years, with specific cell types defining each separate phase. The origin of the cells comprising hemangiomas has been deliberated over since the late 1800s. We have recently provided experimental evidence that hemangiomas arise from multipotent stem cells. These hemangioma stem cells that give rise to the endothelial cells are also the essential source of adipocytes during hemangioma involution. The molecular mechanisms that regulate the differentiation of the hemangioma stem cells remain unclear. Although recent studies have elucidated a number of signaling pathways underlying hemangioma pathogenesis, many unanswered questions remain. Herein, we review the unique cellular composition of infantile hemangioma, as well as some of the signaling pathways active within hemangioma-genesis. Understanding the mechanisms behind changes in cellular fate throughout the hemangioma growth pattern will not only provide insight into the stem cell population that resides within the tumor, but will help to establish more effective eradicating therapies.

Increased gray matter density in patients with schizophrenia and cannabis use: a voxel-based morphometric study using DARTEL.

Alterations in gray matter density as well as cognitive impairments are commonly described in patients with schizophrenia (SCH patients). Both gray matter deficits and cognitive impairments have recently been discussed to represent vulnerability markers of schizophrenia. The counterintuitive finding of better cognitive performance in patients with schizophrenia and cannabis use (SCH+CAN patients) compared to cannabis naïve patients is discussed as a reflection of lower vulnerability for schizophrenia in at least one subgroup of SCH+CAN patients. We hypothesized that SCH+CAN patients would display fewer gray matter deficits compared to SCH patients reflecting their presumed lower vulnerability. We therefore compared gray matter density in 30 first episode SCH+CAN and 24 first episode SCH patients using a fast diffeomorphic registration algorithm (DARTEL) and voxel-based morphometry (VBM). We found less severe cognitive impairments and middle frontal gray matter deficits in the SCH+CAN patients. In the pooled sample gray matter density was positively associated with cognitive functioning. Results may support the hypothesis of a lower biological vulnerability in at least one subgroup of SCH+CAN patients.

Neuroanatomic changes and their association with cognitive decline in mild cognitive impairment: a meta-analysis.

Mild cognitive impairment (MCI) is an acquired syndrome characterised by cognitive decline not affecting activities of daily living. Using a quantitative meta-analytic approach, we aimed to identify consistent neuroanatomic correlates of MCI and how they are related to cognitive dysfunction. The meta-analysis enrols 22 studies, involving 917 MCI (848 amnestic MCI) patients and 809 healthy controls. Only studies investigating local changes in grey matter and reporting whole-brain results in stereotactic coordinates were included and analysed using the activation likelihood estimation approach. Probabilistic cytoarchitectonic maps were used to compare the localization of the obtained significant effects to histological areas. A correlation between the probability of grey matter changes and cognitive performance of MCI patients was performed. In MCI patients, the meta-analysis revealed three significant clusters of convergent grey matter atrophy, which were mainly situated in the bilateral amygdala and hippocampus, extending to the left medial temporal pole and thalamus, as well as in the bilateral precuneus. A sub-analysis in only amnestic MCI revealed a similar pattern. A voxel-wise analysis revealed a correlation between grey matter reduction and cognitive decline in the right hippocampus and amygdala as well as in the left thalamus. This study provides convergent evidence of a distinct neuroanatomical pattern in MCI. The correlation analysis with cognitive-mnestic decline further highlights the impact of limbic structures and the linkage with data from a functional neuroimaging database provides additional insight into underlying functions. Although different pathologies are underlying MCI, the observed neuroanatomical pattern of structural changes may reflect the common clinical denominator of cognitive impairment.

CAG repeats determine brain atrophy in spinocerebellar ataxia 17: a VBM study.

BACKGROUND: Abnormal repeat length has been associated with an earlier age of onset and more severe disease progression in the rare neurodegenerative disorder spinocerebellar ataxia 17 (SCA17). METHODOLOGY/PRINCIPAL FINDINGS: To determine whether specific structural brain degeneration and rate of disease progression in SCA17 might be associated with the CAG repeat size, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 16 patients with SCA17 and 16 age-matched healthy controls. The main finding contrasting SCA17 patients with healthy controls demonstrated atrophy in the cerebellum bilaterally. Multiple regression analyses with available genetic data and also post-hoc correlations revealed an inverse relationship again with cerebellar atrophy. Moreover, we found an inverse relationship between the CAG repeat length and rate of disease progression. CONCLUSIONS: Our results highlight the fundamental role of the cerebellum in this neurodegenerative disease and support the genotype-phenotype relationship in SCA17 patients. Genetic factors may determine individual susceptibility to neurodegeneration and rate of disease progression.