Neural correlates of emotional reactivity predict response to cognitive-behavioral therapy in obsessive-compulsive disorder.

BACKGROUND: Examining predictive biomarkers to identify individuals who will likely benefit from a specific treatment is important for the development of targeted interventions. The late positive potential (LPP) is a neural marker of attention and elaborated stimulus processing, and increased LPP responses to negative stimuli are characteristic of pathological anxiety. The present study investigated whether LPP reactivity would prospectively predict response to cognitive-behavioral therapy (CBT), the first-line treatment for obsessive-compulsive disorder (OCD). METHODS: To this end, the LPP in response to negative as compared to neutral pictures was examined in 45 patients with OCD, who underwent CBT in a naturalistic outpatient setting. LPP amplitudes were used as predictors of symptom reduction after CBT. RESULTS: We found that higher LPP amplitudes to negative relative to neutral stimuli were predictive of lower self-reported OCD symptoms after completion of CBT, controlling for pre-treatment symptoms. Further, LPP reactivity was negatively correlated with self-reported habitual use of suppression in everyday life. LIMITATIONS: Some participants had already begun treatment at the time of study participation. Overall, results need further replication in larger samples and standardized therapy settings. CONCLUSIONS: The current findings suggest that patients with increased emotional reactivity benefit more from CBT, possibly through less avoidance of anxiety-provoking stimuli during exposure with response prevention, a crucial component in CBT for OCD. Although its clinical utility still needs to be evaluated further, the LPP constitutes a promising candidate as a prognostic marker for CBT response in OCD.

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Evidence of interactions between white sharks and large squids in Guadalupe Island, Mexico.

Shark-cephalopod interactions have been documented in trophic ecology studies around the world. However, there is little information about the encounters between white sharks Carcharodon carcharias and squids in the eastern North Pacific Ocean. Here we provide evidence of interactions between white sharks and large squids in the waters of Guadalupe Island, Mexico. Through the use of non-invasive techniques, we found the presence of evident scars made by large squids on the body of the white sharks, mainly on the head and trunk, of at least 14 sharks recorded during August-December in the years 2008, 2012, 2013, 2017 and 2019. The mean length of the white sharks was 3.7 m (SD ± 0.6; total length), although the majority of the sharks with scars were adult and subadult males (n = 9; 64%). One of these males was photographically recaptured during the same season in which the individual showed new scars, confirming that the squid-white shark interaction likely occurs near Guadalupe Island. Our results highlight the importance of the twilight zone for white sharks and the use of shared habitat and trophic interactions between squid and white sharks, in which future ecosystem studies should consider both species for management and conservation purposes.

Heightened degree connectivity of the striatum in obsessive-compulsive disorder induced by symptom provocation.

BACKGROUND: Neurosurgical intervention studies have provided direct evidence that the ventral striatum/nucleus accumbens (NAc) mediates symptoms of obsessive-compulsive disorder (OCD), yet meta-analysis of functional neuroimaging studies using symptom provocation revealed no striatal activation differences, and the existing studies reporting hyperactivity found abnormalities in dorsal but not ventral striatal subdivisions. Resting-state neuroimaging evidence holds that corticostriatal areas are more connected both locally and to distant regions, but the functional inferences to be drawn from these altered network characteristics regarding the present experience of OCD symptoms remain limited. METHODS: The present study tested whether symptom provocation induces abnormally high striatal network connectivity using two independent datasets of unmedicated patients with OCD. One study (14 patients, 14 matched controls) required passive viewing of OC-related, emotionally aversive and neutral pictures, the other (21 patients, 21 controls) involved self-referential evaluation of the same picture types, as well as distraction from these stimuli (engagement in a simple task). RESULTS: Heightened local connectivity of the dorsal striatum occurred during passive viewing of briefly presented OC-related pictures in patients, however group differences were also observed in a neutral control condition. In contrast, distracted symptom provocation selectively yielded local connectivity differences of the ventral striatum, as heightened NAc connectivity to its immediate neighborhood was exclusively observed when OC-related pictures were accompanied by concurrent task demands. LIMITATIONS: Small samples sizes. CONCLUSIONS: In moderately affected patients with OCD, symptom provocation induces a discrete, condition-specific network abnormality anchored in NAc, the location targeted by deep brain stimulation for refractory patients with OCD.

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

BACKGROUND: Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. METHODS: Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. RESULTS: During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. CONCLUSIONS: Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Adapting another person's affective state modulates brain potentials to unpleasant pictures.

Emotional processing is influenced by top-down processes such as reappraisal of emotion-inducing events. Besides one's own stimulus appraisal, information from the social environment can be used to modify the stimulus' meaning. This study investigated whether perspective taking changes participants' brain potentials to unpleasant pictures. Event-related potentials (ERPs) were measured while twenty-nine participants evaluated arousal of neutral or negative pictures. Subsequently, they received bogus feedback about another person's picture evaluation. Then, the same picture was presented again and participants were instructed to view the picture from the other person's perspective. Higher bogus- versus self-ratings of picture arousal increased P300 and late positive potential (LPP) amplitudes to unpleasant stimuli, whereas lower bogus- versus self-ratings did not influence ERPs. Thus, perspective taking only modulated ERPs when bogus ratings signaled potential underestimation of arousal. Resulting increases in responsiveness might constitute an adaptive mechanism preparing the organism against harm.

Amygdala hyperactivation during symptom provocation in obsessive-compulsive disorder and its modulation by distraction.

Anxiety disorders have been linked to a hyperactivated cortico-amygdalar circuitry. Recent findings highlight the amygdala's role in mediating elevated anxiety in obsessive-compulsive disorder (OCD). However, modulation of amygdala hyperactivation by attentional distraction - an effective emotion regulation strategy in healthy individuals - has not yet been examined. While undergoing functional magnetic resonance imaging twenty-one unmedicated OCD patients and 21 controls performed an evaluation and a distraction task during symptom provocation with individually tailored OCD-relevant pictures. To test the specificity of responses, additional aversive and neutral stimuli were included. Significant group-by-picture type interactions were observed within fronto-striato-limbic circuits including the amygdala. In these regions patients showed increased BOLD responses during processing of OCD triggers relative to healthy controls. Amygdala hyperactivation was present across OCD symptom dimensions indicating that it represents a common neural correlate. During distraction, we observed dampening of patients' amygdala hyperactivity to OCD-relevant stimuli. Augmented amygdala involvement in patients during symptom provocation, present across OCD symptom dimensions, might constitute a correlate of fear expression in OCD linking it to other anxiety disorders. Attentional distraction seemed to dampen emotional processing of disorder-relevant stimuli via amygdala downregulation. The clinical impact of this strategy to manage anxiety in OCD should be further elucidated.

Altered frontal EEG asymmetry in obsessive-compulsive disorder.

Hemispheric topography of alpha band power in the electroencephalogram has been linked to approach/avoidance motivation and may index the risk for anxiety disorders and depression. We quantified lower alpha band power (8-10 Hz) in 20 patients with obsessive-compulsive disorder (OCD) and 20 matched healthy controls during blocks of rest and presentation of neutral, aversive, and OCD-related pictures. Compared to the control group, OCD patients showed altered asymmetry, with frontal alpha power in the 8-10 Hz band being more dominant in the left hemisphere across all conditions. This alteration was not observed over parietal areas, and also did not show in the upper alpha, and the theta and beta bands. This change in hemispheric topography of lower alpha band power supports the hypothesis of relatively increased avoidance motivation in OCD. Altered asymmetry appears to be traitlike in OCD, suggesting a link to depressive disorders.

Autonomic responses and neural-cardiac coupling during individually tailored symptom provocation in obsessive-compulsive disorder.

Elevated anxiety in obsessive-compulsive disorder (OCD) has been linked to cortico-limbic hyperactivation, whereas hyperarousal of the autonomous nerve system (ANS) has inconsistently been found. We investigate ANS functioning during symptom provocation with individually tailored OCD-relevant pictures in 14 unmedicated patients and 14 controls and link it to activation in brain areas involved in ANS regulation. In addition to OCD-triggers, aversive and neutral control stimuli were included. Both groups showed increased skin conductance and heart rate changes to aversive control stimuli, whereas only patients demonstrated augmented skin conductance responses to OCD-triggers. Overall ANS hyperarousal in patients relative to controls was found at trend level. Activity in limbic and paralimbic areas in OCD patients was increased to both generally aversive and OCD-relevant stimuli, whereas dorsolateral prefrontal cortex (DLPFC) hyperactivation, covarying with cardiac responses in patients but not in controls, was present for disorder-relevant triggers only. Despite the small study group, these preliminary findings suggest ANS hyperactivity during OCD symptom provocation that could reflect arousal to the perceived threatening value of OCD-triggers and might mediate elevated anxiety.

Timing effects of antecedent- and response-focused emotion regulation strategies.

Distraction and cognitive reappraisal influence the emotion-generative process at early stages and have been shown to effectively attenuate emotional responding. Inhibiting emotion-expressive behavior is thought to be less beneficial due to later implementation, but empirical results are mixed. Thus, the current study examined the temporal dynamics of these emotion regulation strategies at attenuating the late positive potential (LPP) while participants were shown unpleasant pictures. Results revealed that all strategies successfully reduced the LPP and self-reported negative affect. We confirmed that distraction attenuated the LPP earlier than cognitive reappraisal. Surprisingly, expressive suppression affected emotional responding as early as distraction. This suggests that suppression was used preventively and disrupted the emotion-generative process from the very beginning instead of targeting the emotional response itself. Thus, the obtained results point to the importance of considering the point in time when response-focused emotion regulation strategies are being implemented.

Reduced thickness of anterior cingulate cortex in obsessive-compulsive disorder.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is characterized by a pattern of repetitive, intrusive thoughts and behaviours that patients do not want to but feel they have to perform. Functional brain imaging revealed dysfunctional pathways in OCD involving the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia. Structural alterations in OCD have been discussed but analysis tools focussing on specific morphometric aspects such as cortical thickness have rarely been employed. METHODS: We acquired MRI scans from 101 OCD patients and 95 healthy control subjects. FreeSurfer analysis software was employed to model the individual grey-white and pial surfaces to compute cortical thickness as our target measure. RESULTS: Relative to controls, OCD patients demonstrate cortical thinning in dorsal and subgenual ACC (false discovery rate corrected at p < .001), as well as in several other regions within the fronto-parietal network (false discovery rate corrected at p < .05). Cortical thickness could not be predicted in whole brain analyses from symptom state, but there was a modest correlation of left dorsal ACC thickness with the obsession subscore of the Yale-Brown Obsessive-Compulsive Scale as well as with the Beck Depression Inventory score. CONCLUSIONS: The findings confirm and extend previous reports showing that OCD is associated with morphometric alterations. The location of the most robust cortical thinning in ACC regions matches the previously reported topography of functional alterations at resting state and during cognitive task execution.

Flow cytometric evaluation of peripheral blood and bone marrow and fine-needle aspirate samples from multiple sites in dogs with multicentric lymphoma.

OBJECTIVE: To determine whether the extent of disease in dogs with lymphoma can be assessed via flow cytometry and to evaluate the suitability of fine-needle aspirates from the liver and spleen of dogs for flow cytometric examination. ANIMALS: 44 dogs with multicentric B-cell (n = 35) or T-cell lymphoma (9) and 5 healthy control dogs. Procedures-Peripheral blood and bone marrow samples and fine-needle aspirates of lymph node, liver, and spleen were examined via flow cytometry. Logarithmically transformed T-cell-to-B-cell percentage ratio (log[T:B]) values were calculated. Thresholds defined by use of log(T:B) values of samples from control dogs were used to determine extranodal lymphoma involvement in lymphoma-affected dogs; results were compared with cytologic findings. RESULTS: 12 of 245 (5%) samples (9 liver, 1 spleen, and 2 bone marrow) had insufficient cellularity for flow cytometric evaluation. Mean log(T:B) values of samples from dogs with B-cell lymphoma were significantly lower than those of samples from the same site in dogs with T-cell lymphoma and in control dogs. In dogs with T-cell lymphoma, the log(T:B) of lymph node, bone marrow, and spleen samples was significantly higher than in control dogs. Of 165 samples assessed for extranodal lymphoma involvement, 116 (70%) tested positive via flow cytometric analysis; results agreed with cytologic findings in 133 of 161 (83%) samples evaluated via both methods. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that flow cytometry may aid in detection of extranodal lymphoma involvement in dogs, but further research is needed. Most fine-needle aspirates of liver and spleen were suitable for flow cytometric evaluation.

A pilot study on the validity of using pictures and videos for individualized symptom provocation in obsessive-compulsive disorder.

Distressing symptom-related anxiety is difficult to study in obsessive-compulsive disorder (OCD) due to the disorder's heterogeneity. Our aim was to develop and validate a set of pictures and films comprising a variety of prominent OCD triggers that can be used for individually tailored symptom provocation in experimental studies. In a two-staged production procedure a large pool of OCD triggers and neutral contents was produced and preselected by three psychotherapists specialized in OCD. A sample of 13 OCD patients and 13 controls rated their anxiety, aversiveness and arousal during exposure to OCD-relevant, aversive and neutral control stimuli. Our findings demonstrate differences between the responses of patients and controls to OCD triggers only. Symptom-related anxiety was stronger in response to dynamic compared with static OCD-relevant stimuli. Due to the small number of 13 patients included in the study, only tentative conclusions can be drawn and this study merely provides a first step of validation. These standardized sets constitute valuable tools that can be used in experimental studies on the brain correlates of OCD symptoms and for the study of therapeutic interventions in order to contribute to future developments in the field.

Effectiveness of a web-based, individually tailored decision aid for depression or acute low back pain: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a web-based, individually tailored decision aid (Patient Dialogue) on depression or acute low back pain for insurees of a German sickness fund. METHODS: Patient Dialogue (PD) was compared to the non-tailored Static Patient Information (SPI) in an online randomized controlled trial (RCT). The primary outcome was decisional conflict; secondary outcomes included knowledge, preparation for decision-making, preference for participation, involvement in decision-making, decision regret, and adherence. RESULTS: Out of 2480 randomized participants, 657 (26.5%) provided analyzable data immediately after using the system. Three months later, data from 131 (5.3%) participants could be included in the analysis. The PD group reported a significantly lower overall decisional conflict than the SPI group (38.7 vs. 45.1; p=0.028 via multiple imputation estimator). The largest standardized effect (Cohen's d 0.56) resulted from the preparation for decision-making (PD 59.4 vs. SPI 46.8; p<0.001). CONCLUSION: PD may be an effective tool to reduce decisional conflict and prepare participants for treatment decision-making. However, the large dropout rate needs to be taken into account. PRACTICE IMPLICATIONS: This study shows how a health insurance fund can support shared decision-making and how a decision aid can be evaluated in a RCT under routine care conditions.

Auditory novelty processing is enhanced in obsessive-compulsive disorder.

BACKGROUND: Cognitive models propose that anxiety disorders are associated with an attentional bias toward potentially threatening stimuli. In this study, it was analyzed whether patients with obsessive-compulsive disorder (OCD) show enhanced responses of their event-related brain potentials to novel stimuli, either in a context of potential threat or in a neutral context. METHODS: In this study, 20 OCD patients and 20 matched healthy control subjects performed a visual recognition task during which irrelevant repeated standard sounds and unitary novel sounds were interspersed. RESULTS: As expected, OCD patients showed an increase in the novelty-P3 amplitude elicited by unitary novel sounds. However, no effect of emotional context conditions was observed. CONCLUSION: It is suggested that the novelty P3 amplitude increase in OCD patients represents a physiological indicator of an enhanced cortical orienting response implicating stronger involuntary shifts of attention. This characteristic is driven by novelty per se and not moderated by potential threat of upcoming events.

Methicillin-resistant Staphylococcus pseudintermedius among dogs admitted to a small animal hospital.

The aim of this study was to determine the frequency of carriage of methicillin-resistant Staphylococcus pseudintermedius (MRSP) among dogs admitted to a small animal hospital during a 17-month period, to characterize these isolates and to initially screen for possible factors associated with MRSP carriage. Swabs were taken from the nose/pharynx and the perineum as well as from wounds and skin infections (if present) of 814 dogs before entering the small animal hospital. A questionnaire for background information was completed. The staphylococcal species and methicillin resistance were confirmed pheno- and genotypically. The identified MRSP isolates were characterized by SCCmec typing, testing for susceptibility to 25 antimicrobial agents and SmaI-directed pulsed-field gel electrophoresis. A first screening for possible risk factors for MRSP carriage was performed by means of unifactorial contingency tables and CART analysis. Sixty (7.4%) dogs were positive for MRSP. All MRSP isolates harboured a type II-III SCCmec cassette and showed extended resistance to antimicrobial agents. Fifteen different SmaI patterns were observed. The major factors that clustered with MRSP carriage were former hospitalization and antibiotic treatment within the last six months before sampling. This study showed that only a minor part of the sampled dogs carried multi-resistant MRSP isolates. The facts that prior hospitalization and/or antibiotic therapy are potential associated factors for MRSP carriage underline the necessity of a judicious use of antibiotics in small animal medicine.

How does a German audience appraise an American decision aid on early stage breast cancer?

OBJECTIVE: To investigate how a German audience appraises an American video-based decision aid on early stage breast cancer for potential use in Germany. METHODS: A German synchronized voice-over version was produced and subject to different focus groups with patients (n=9), health care providers (n=7) and German health care experts (n=15) using an individual questionnaire-based evaluation and a moderated group discussion. Research questions included a general appraisal of the decision aid and the exploration of adaptation needs for use in Germany. Descriptive statistics were calculated and the qualitative data were analyzed applying an inductive approach to categorize the statements. RESULTS: The general appraisal of the decision aid revealed positive results in all groups, especially with regard to comprehensible presentation of information and integration of patients' testimonials. However, cultural differences between the American decision aid and Germany were debated in all groups. CONCLUSION: Despite a high general interest and positive appraisal of the decision aid, the results of this study suggest that it cannot just be translated and used in another country. PRACTICE IMPLICATIONS: The decision aid needs further cultural adaptation and testing in an implementation study before it can be transferred to Germany.

High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in canine lymphoma.

BACKGROUND: Canine lymphoma is a commonly occurring, spontaneously developing neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a valuable model for human malignancy. HMGB1 and RAGE are strongly associated with tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1 may play an important role in the mechanisms involved in lymphoma progression. MATERIALS AND METHODS: Expression patterns of HMGB1 and RAGE were analysed in 22 canine lymphoma and three canine non-neoplastic control samples via real time PCR and canine beta-glucuronidase gene (GUSB) as endogenous control. RESULTS: HMGB1 was up-regulated in the neoplastic samples, while RAGE expression remained inconspicuous. CONCLUSION: This study demonstrated similar mechanisms in lymphoma progression in humans and dogs due to overexpression of HMGB1, which was described in human lymphomas. RAGE remained stable in terms of expression indicating that the extracellular HMGB1-induced effects are regulated by HMGB1 itself.

Evaluation of the association between plasma concentration of N-terminal proatrial natriuretic peptide and outcome in cats with cardiomyopathy.

OBJECTIVE: To determine whether plasma N-terminal proatrial natriuretic peptide (NT-proANP) concentration could predict the outcome (survival duration) of cats with cardiomyopathy (CM). DESIGN: Case-control study. ANIMALS: 51 cats with CM (25 with and 26 without congestive heart failure [CHF]) and 17 healthy cats. PROCEDURES: Cats were thoroughly examined and assigned to 1 of 3 groups (control, CM with CHF, and CM alone). Plasma NT-proANP concentrations were measured by use of a human proANP(1-98) ELISA. Survival durations were compared between CM groups. RESULTS: Plasma NT-proANP concentrations differed significantly among the 3 groups, and survival durations differed significantly between the 2 CM groups. Median (range) NT-proANP concentration was 413 fmol/mL (52 to 940 fmol/mL) in the control group, 1,254 fmol/mL (167 to 2,818 fmol/mL) in the CM alone group, and 3,208 fmol/mL (1,189 to 15,462 fmol/mL) in the CM with CHF group. At a cutoff of 517 fmol/mL, NT-proANP concentration had a sensitivity of 90% and specificity of 82% for detecting CM. Multivariate analysis revealed that only the variable left atrium-to-aortic diameter ratio was a significant predictor of survival duration. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma NT-proANP concentration may have potential as a testing marker for distinguishing healthy cats from cats with CM. It may also be useful for distinguishing CM cats with CHF from those without CHF The value of NT-proANP concentration as a predictor of survival duration was not supported in this study and requires further evaluation.