Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial.

BACKGROUND: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions. METHODS: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression. RESULTS: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin = 1.50, PeEx-S: dwithin = 1.78) and follow-up (PeEx-I: dwithin = 2.34; PeEx-S: dwithin = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse. CONCLUSIONS: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.

[Medical education in psychosocial disciplines in times of the COVID-19 pandemic - first experiences]. / Lehre in den psychosozialen medizinischen Fächern in Zeiten der COVID-19-Pandemie ­ erste Erfahrungen.

AIM: In specialties that heavily rely on communication skills such as psychiatry, psychotherapy and psychosomatic medicine, teaching in times of the COVID-19 pandemic is especially challenging. In this overview, educators and course directors report their experiences in eteaching and share their innovative solutions. METHODS: We present a collection of methods that relate to teaching and assessment as well as student activation. RESULTS: A range of helpful tools for teaching were compiled. This includes instructional videos with simulated patients, structured homework to document a mental status examination, structured hand-offs, and practical examinations in video format. Motivational techniques include podcasts with interviews with clinicians and patients and teaching with the use of cinematic material. DISCUSSION: Switching to online formats creates opportunities and advantages for the advancement of time- and location-independent learning. A fast conversion in this direction might also pose some disadvantages. A direct patient-student interaction is critical for engaging with transference, countertransference and situational aspects for teaching in psychosocial disciplines. Empirical studies of the effectiveness of these newly developed formats and faculty development for digital teaching are necessary.

[Implementation and evaluation of a revised curriculum for psychiatry and psychotherapy]. / Einführung und Evaluation eines neuen Kurrikulums Psychiatrie und Psychotherapie.

BACKGROUND: Medical education in the discipline of psychiatry and psychotherapy at the University of Münster was traditionally focused on the transfer of knowledge via lectures. According to the current guidelines, the medical curriculum was modified as from the winter semester 2016/2017 to be more competency-based and the changes were evaluated. OBJECTIVE: Lectures and seminars were reduced to achieve a better linkage between theoretical and practical knowledge. Moreover, learning goals were formulated based on the German National Competence-based Catalogue of Learning Objectives in Medicine (NKLM) and entrustable professional activities (EPAs). MATERIAL AND METHODS: Almost all previous lectures are now replaced by an inverted classroom concept with e­learning. Theoretical knowledge is deepened by immediate multiple choice (MC) examinations and a seminar, which now focusses on specific practical EPAs. At the end of the semester, the students now undergo a practical, formative examination with simulated patients (actors) in addition to the former MC test. For evaluation, a representative sample of a semester cohort which took part in the previous curriculum and a similar cohort which attended the revised curriculum were investigated. Moreover, variables which might have an impact on the results were assessed, e. g. pre-existing psychiatric knowledge and motivation. RESULTS: Students taught by the modified curriculum showed a significantly better practical performance and no reduction of theoretical knowledge. Relevant influencing factors were not identified. CONCLUSION: The results show that a competency-based modification of the curriculum in the discipline of psychiatry and psychotherapy leads to more practical abilities and thus helps future physicians to be more self-determined.

Social cognition in schizophrenia: The role of mentalizing in moral dilemma decision-making.

BACKGROUND: Patients with schizophrenia have difficulties in several aspects of social cognition, e.g. emotion recognition and mentalizing. It is yet unclear if patients also show deficits in moral decision-making and whether the two aspects interact. Deficits in moral decision-making abilities might put patients in disadvantageous positions in every-day interactions. METHOD: Twenty-five patients with schizophrenia and twenty-five matched healthy controls participated in six moral dilemma tasks, a standard moral competency test and two mentalizing tasks. In addition, we assessed psychopathology and empathy abilities. In a brief intervention patients were asked to empathize with characters in the moral dilemmas. We expected that the decisions made by patients with schizophrenia would be more out-come-oriented, i.e. utilitarian, as compared to those made by healthy controls. RESULTS: Patients and healthy controls did not decide significantly differently on the moral dilemmas and patients showed normal moral competencies. Deficits in mentalizing in patients were replicated. Only in a regression analysis, however, we were able to show that PANSS positive scores and the Comic Strip task scores contributed to the moral decisions. Empathy training did not have an altering influence on decision-making. DISCUSSION: Although an overlap between social cognition and moral decision-making networks has been proposed, deficits in moral decision-making and explicit associations with mentalizing were not present in patients. Psychopathology together with mentalizing abilities, however, contributed to decision-making in patients. Our findings suggest that in schizophrenia some aspects, e.g. mentalizing, are more strongly impaired while other aspects, e.g. moral decision-making, are preserved. Further research is needed to elucidate the different aspects forming social cognition and their mutual contributions, specifically in schizophrenia.

The PsyLOG mobile application: development of a tool for the assessment and monitoring of side effects of psychotropic medication.

Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.

The contribution of cortical thickness and surface area to gray matter asymmetries in the healthy human brain.

Human cortical gray matter (GM) is structurally asymmetrical and this asymmetry has been discussed to be partly responsible for functional lateralization of human cognition and behavior. Past studies on brain asymmetry have shown mixed results so far, with some studies focusing on the global shapes of the brain's surface, such as gyrification patterns, while others focused on regional brain volumes. In this study, we investigated cortical GM asymmetries in a large sample of right-handed healthy volunteers (n = 101), using a surface-based method which allows to analyze brain cortical thickness and surface area separately. As a result, substantially different patterns of symmetry emerged between cortical thickness and surface area measures. In general, asymmetry is more prominent in the measure of surface compared to that of thickness. Such a detailed investigation of structural asymmetries in the normal brain contributes largely to our knowledge of normal brain development and also offers insights into the neurodevelopmental basis of psychiatric disorders, such as schizophrenia.

Systematic analysis of combined oral contraceptive prescription patterns in psychotropic drug users across twelve European countries.

OBJECTIVE: To investigate prescription patterns of combined oral contraceptives (COC) among psychotropic drug users compared to non-psychotropic drug users in routine clinical practice in Europe. STUDY DESIGN: A pooled analysis of three large, prospective, multinational cohort studies including women with a new prescription of COC from 12 European countries. We calculated standardized mean differences (SMD) to investigate whether the status of psychotropic drug use (use/no use) or the psychotropic drug class (psycholeptics/psychoanaleptics) is associated with the healthcare professional's choice of a specific type of COC progestin. RESULTS: Our analysis comprised 143,069 non-psychotropic drug users and 2174 psychotropic drug users. Progestins with the highest frequency in the cohorts were levonorgestrel (non-psychotropic drug users: 33.8%; psychotropic drug users: 32.4%), nomegestrol/nomegestrol acetate (non-psychotropic drug users: 19.1%; psychotropic drug users: 26.4%), and drospirenone (non-psychotropic drug users: 15.9%; psychotropic drug users: 14.8%). SMD analysis indicated no substantial differences in COC prescription patterns between the two cohorts. However, we observed association signals for users of the herbal antidepressant St. John's wort in that those individuals more often received a prescription for drospirenone and less frequently for nomegestrol/nomegestrol acetate compared to non-psychotropic drug users. CONCLUSIONS: Psychotropic drug user status does not seem to affect healthcare professionals' decisions when prescribing COC. However, limited evidence suggests that the risk for drug interactions might differ by progestin type, and some COC might be more suitable for psychotropic drug users than others. Specific guidelines should be conveyed to healthcare professionals to assist them in contraceptive counseling. IMPLICATIONS: With exception of St. John's wort, our analysis showed no differential prescription behavior of combined oral contraceptives in psychotropic drug users and non-users. However, healthcare professionals should carefully consider psychotropic drug use in contraceptive counseling as it is still unclear whether drug interactions exist when co-administered with certain oral contraceptives.

Autistic and non-autistic individuals show the same amygdala activity during emotional face processing.

BACKGROUND: Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples. METHODS: In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns. RESULTS: We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment. LIMITATIONS: Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations. CONCLUSIONS: Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing.

What do the teachers want? A targeted needs assessment survey for prospective didactic training of psychiatry medical educators.

Objectives: Physicians and psychologists at psychiatric university hospitals are assigned teaching tasks from the first day of work without necessarily having the prerequisite training in teaching methods. This exploratory survey provides a needs-based analysis for the prospective didactic training of physicians and psychologists at psychiatric hospitals in Germany, Austria and Switzerland. Methods: An online questionnaire was distributed at medical schools via email in German-speaking countries in Europe. All physicians involved in teaching medical students at psychiatry faculties were eligible to participate in the survey. Participants were further requested to recruit eligible participants (snowball sampling). Responses were analyzed descriptively, and differences between groups were calculated using nonparametric Mann-Whitney U tests (p<.05). Results: Overall, 97 respondents (male=55, female=42; mean age= 40.6) from 19 medical schools completed the survey. The respondents consisted of 43 residents, 39 specialists, 6 chief physicians and 9 psychologists. Of the respondents, 97.6% rated didactic competence as either highly relevant or rather relevant for teaching medical students. The highest overall interest was shown for bedside teaching (mode=4; IQR: 2-4) and error culture (mode=3; IQR: 2-4). Respondents expressed the highest training needs for topics regarding presentation and communication (mode=3; IQR: 2-3). Resident physicians were significantly more interested in bedside teaching (U=362.0, p=0.004) and roleplay (U=425.0; p=0.036) than specialist physicians, who were more interested in examination didactics (U=415.0; p=0.022). Chief physicians displayed significantly deeper interest in group dynamics (U=51; p=0.023) than specialist physicians. In-person training was preferred by a majority of respondents, and 27.4% preferred online/web-based training. Conclusions: The majority of physicians and psychologists at psychiatric university hospitals considered professional development for faculty to be helpful for teaching medical students. Bedside teaching and error culture management were the most desired teaching topics for training medical teachers. Tailored educational interventions are recommended, with target-oriented priorities for different hierarchical levels.

Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.

OBJECTIVE: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults). METHODS: Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis. RESULTS: Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents. CONCLUSIONS: Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.

Mentalising and depression: a mini-review on behavior, neural substrates, and treatment options.

Major depression is one of the most common mental disorders, affecting millions of people around the globe. In recent years, researchers increasingly investigated social cognition in depression and discovered pronounced alterations. A special focus has been put on mentalising or Theory of Mind, the ability to recognize and understand another person's thoughts and feelings. While there is behavioral evidence for deficits in this ability in patients with depression as well as specialized therapeutic interventions, the neuroscientific substrates are only beginning to be understood. In this mini-review, we take a social neuroscience perspective to analyse the importance of altered mentalising in depression and whether it can help to understand the origins and perpetuation of the disorder. We will put a special focus on treatment options and corresponding neural changes to identify relevant paths for future (neuroscientific) research.

Interpersonal problems and recognition of facial emotions in healthy individuals.

Background: Recognition of emotions in faces is important for successful social interaction. Results from previous research based on clinical samples suggest that difficulties in identifying threat-related or negative emotions can go along with interpersonal problems. The present study examined whether associations between interpersonal difficulties and emotion decoding ability can be found in healthy individuals. Our analysis was focused on two main dimensions of interpersonal problems: agency (social dominance) and communion (social closeness). Materials and methods: We constructed an emotion recognition task with facial expressions depicting six basic emotions (happiness, surprise, anger, disgust, sadness, and fear) in frontal and profile view, which was administered to 190 healthy adults (95 women) with a mean age of 23.9 years (SD = 3.8) along with the Inventory of Interpersonal Problems, measures of negative affect and verbal intelligence. The majority of participants were university students (80%). Emotion recognition accuracy was assessed using unbiased hit rates. Results: Negative correlations were observed between interpersonal agency and recognition of facial anger and disgust that were independent of participants' gender and negative affect. Interpersonal communion was not related to recognition of facial emotions. Discussion: Poor identification of other people's facial signals of anger and disgust might be a factor contributing to interpersonal problems with social dominance and intrusiveness. Anger expressions signal goal obstruction and proneness to engage in conflict whereas facial disgust indicates a request to increase social distance. The interpersonal problem dimension of communion appears not to be linked to the ability to recognize emotions from facial expressions.

Study protocol: effects of treatment expectation toward repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder-a randomized controlled clinical trial.

BACKGROUND: Patients' expectations toward any given treatment are highly important for the effectiveness of such treatment, as has been demonstrated for several disorders. In particular, in major depressive disorder (MDD), one of the most frequent and most serious mental disorders with severe consequences for the affected, the augmentation of available treatment options could mean a ground-breaking success. Repetitive transcranial magnetic stimulation (rTMS), a new, non-invasive, and well-tolerated intervention with proven effects in the treatment of MDD, appears particularly suitable in this context as it is assumed to exert its effect via structures implicated in networks relevant for both expectation and depression. METHODS: All patients will receive rTMS according to its approval. Half of the patients will be randomized to a psychological intervention, which is a comprehensive medical consultation aiming to improve positive treatment expectations; the control group will receive a conventional informed consent discussion (in the sense of a treatment-as-usual condition). As outcome parameters, instruments for both self-assessment and external assessment of depression symptoms will be applied. Furthermore, psycho-immunological parameters such as inflammation markers and the cortisol awakening response in saliva will be investigated. Resting-state functional magnetic resonance imaging (rs fMRI) will be performed to analyze functional connectivity, including the cerebellum, and to identify neuronal predictors of expectation effects. In addition, possible cerebellar involvement will be assessed based on a cerebellar-dependent motor learning paradigm (i.e., eyeblink conditioning). DISCUSSION: In this study, the effects of treatment expectations towards rTMS are investigated in patients with MDD. The aim of this study is to identify the mechanisms underlying the expectation effects and, beyond that, to expand the potential of non-invasive and well-tolerated treatments of MDD. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS DRKS00028017. Registered on 2022/03/07. URL: https://www.drks.de/drks_web/ .

Speech disturbances in schizophrenia: Assessing cross-linguistic generalizability of NLP automated measures of coherence.

INTRODUCTION: Language disorders - disorganized and incoherent speech in particular - are distinctive features of schizophrenia. Natural language processing (NLP) offers automated measures of incoherent speech as promising markers for schizophrenia. However, the scientific and clinical impact of NLP markers depends on their generalizability across contexts, samples, and languages, which we systematically assessed in the present study relying on a large, novel, cross-linguistic corpus. METHODS: We collected a Danish (DK), German (GE), and Chinese (CH) cross-linguistic dataset involving transcripts from 187 participants with schizophrenia (111DK, 25GE, 51CH) and 200 matched controls (129DK, 29GE, 42CH) performing the Animated Triangles Task. Fourteen previously published NLP coherence measures were calculated, and between-groups differences and association with symptoms were tested for cross-linguistic generalizability. RESULTS: One coherence measure, i.e. second-order coherence, robustly generalized across samples and languages. We found several language-specific effects, some of which partially replicated previous findings (lower coherence in German and Chinese patients), while others did not (higher coherence in Danish patients). We found several associations between symptoms and measures of coherence, but the effects were generally inconsistent across languages and rating scales. CONCLUSIONS: Using a cumulative approach, we have shown that NLP findings of reduced semantic coherence in schizophrenia have limited generalizability across different languages, samples, and measures. We argue that several factors such as sociodemographic and clinical heterogeneity, cross-linguistic variation, and the different NLP measures reflecting different clinical aspects may be responsible for this variability. Future studies should take this variability into account in order to develop effective clinical applications targeting different patient populations.

Voice Patterns as Markers of Schizophrenia: Building a Cumulative Generalizable Approach Via a Cross-Linguistic and Meta-analysis Based Investigation.

BACKGROUND AND HYPOTHESIS: Voice atypicalities are potential markers of clinical features of schizophrenia (eg, negative symptoms). A recent meta-analysis identified an acoustic profile associated with schizophrenia (reduced pitch variability and increased pauses), but also highlighted shortcomings in the field: small sample sizes, little attention to the heterogeneity of the disorder, and to generalizing findings to diverse samples and languages. STUDY DESIGN: We provide a critical cumulative approach to vocal atypicalities in schizophrenia, where we conceptually and statistically build on previous studies. We aim at identifying a cross-linguistically reliable acoustic profile of schizophrenia and assessing sources of heterogeneity (symptomatology, pharmacotherapy, clinical and social characteristics). We relied on previous meta-analysis to build and analyze a large cross-linguistic dataset of audio recordings of 231 patients with schizophrenia and 238 matched controls (>4000 recordings in Danish, German, Mandarin and Japanese). We used multilevel Bayesian modeling, contrasting meta-analytically informed and skeptical inferences. STUDY RESULTS: We found only a minimal generalizable acoustic profile of schizophrenia (reduced pitch variability), while duration atypicalities replicated only in some languages. We identified reliable associations between acoustic profile and individual differences in clinical ratings of negative symptoms, medication, age and gender. However, these associations vary across languages. CONCLUSIONS: The findings indicate that a strong cross-linguistically reliable acoustic profile of schizophrenia is unlikely. Rather, if we are to devise effective clinical applications able to target different ranges of patients, we need first to establish larger and more diverse cross-linguistic datasets, focus on individual differences, and build self-critical cumulative approaches.

Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging.

A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward-shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex.

Anterior cingulate cortex activation is related to learning potential on the WCST in schizophrenia patients.

The remediation of executive function in patients with schizophrenia is important in rehabilitation because these skills affect the patient's capacity to function in the community. There is evidence that instructional techniques can improve deficits in the Wisconsin Card Sorting Test (WCST) in some schizophrenia patients. We used a standard test/training phase/standard test format of the WCST to classify 36 schizophrenia patients as high-achievers, learners or non-retainers. All healthy controls performed as high-achievers. An event-related fMRI design assessed neural activation patterns during post-training WCST performance. Patients showed a linear trend between set-shifting related activation in the anterior cingulate cortex and learning potential, i.e. increased activation in high-achievers, a trend for increased activation in learners, and no activation in non-retainers compared to controls. In addition, activation in the temporoparietal cortex was highest in patients classified as learners, whereas in non-retainers activation was increased in the inferior frontal gyrus compared to controls and high-achieving patients. These results emphasize the relevance of the ACC's neural integrity in learning set-shifting strategies for patients with schizophrenia. Also, our results support the hypothesis that compensatory neural activation in patients with schizophrenia helps them to catch up with healthy controls on cognitive tasks.

Cortical changes in patients with schizophrenia across two ethnic backgrounds.

While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.

Sometimes I feel the fear of uncertainty: How intolerance of uncertainty and trait anxiety impact fear acquisition, extinction and the return of fear.

It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition, we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments.