Adaptive coding of reward in schizophrenia, its change over time and relationship to apathy.

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia.

Striatal Functional Hypoconnectivity in Patients With Schizophrenia Suffering From Negative Symptoms, Longitudinal Findings.

BACKGROUND: Negative symptoms in schizophrenia (SZ), such as apathy and diminished expression, have limited treatments and significantly impact daily life. Our study focuses on the functional division of the striatum: limbic-motivation and reward, associative-cognition, and sensorimotor-sensory and motor processing, aiming to identify potential biomarkers for negative symptoms. STUDY DESIGN: This longitudinal, 2-center resting-state-fMRI (rsfMRI) study examines striatal seeds-to-whole-brain functional connectivity. We examined connectivity aberrations in patients with schizophrenia (PwSZ), focusing on stable group differences across 2-time points using intra-class-correlation and associated these with negative symptoms and measures of cognition. Additionally, in PwSZ, we used negative symptoms to predict striatal connectivity aberrations at the baseline and used the striatal aberration to predict symptoms 9 months later. STUDY RESULTS: A total of 143 participants (77 PwSZ, 66 controls) from 2 centers (Berlin/Geneva) participated. We found sensorimotor-striatum and associative-striatum hypoconnectivity. We identified 4 stable hypoconnectivity findings over 3 months, revealing striatal-fronto-parietal-cerebellar hypoconnectivity in PwSZ. From those findings, we found hypoconnectivity in the bilateral associative striatum with the bilateral paracingulate-gyrus and the anterior cingulate cortex in PwSZ. Additionally, hypoconnectivity between the associative striatum and the superior frontal gyrus was associated with lower cognition scores in PwSZ, and weaker sensorimotor striatum connectivity with the superior parietal lobule correlated negatively with diminished expression and could predict symptom severity 9 months later. CONCLUSIONS: Importantly, patterns of weaker sensorimotor striatum and superior parietal lobule connectivity fulfilled the biomarker criteria: clinical significance, reflecting underlying pathophysiology, and stability across time and centers.

The combination of oxytocin and mindfulness-based group therapy for empathy and negative symptoms in schizophrenia spectrum disorders - A double-blinded, randomized, placebo-controlled pilot study.

Treatment options for social cognition and negative symptoms in schizophrenia spectrum disorders (SSD) remain limited. Oxytocin could be a promising augmentation approach, but the social context influences the effect in humans. This pilot study hypothesized that oxytocin in a positive social setting through mindfulness-based group therapy (MBGT) would positively affect empathy and negative symptoms as well as affect and stress in an exploratory approach in SSD. An experimental, randomized, double-blinded (participants, psychotherapists), placebo-controlled pilot study with 41 individuals with SSD was conducted at the Charité - Universitätsmedizin Berlin. Oxytocin or placebo (24 I.U.) was administered intranasally 45 min before two sessions of MBGT each. A 2 × 2 mixed model ANCOVA design was calculated to assess empathy by the Interpersonal Reactivity Index and the Multifaceted Empathy Test and negative symptoms by the Self-Evaluation of Negative Symptoms. No benefit of oxytocin compared to placebo on empathy was observed, but significant between-group differences favoring oxytocin were found regarding the negative symptoms Diminished emotional range and Avolition. Negative affect and stress were significantly reduced compared to baseline. Mindfulness increased in both groups. Results indicated protocol adherence and retention rate of 91.1%, a drop-out rate of 8.9 % and a completion of 96 % of all sessions by the participants. No severe adverse events or side effects were reported. Our findings indicate proof-of-concept and suggest a potential role of oxytocin on negative symptoms and related variables in SSD in combination with MBGT. Future research should examine the stability of these effects with larger sample sizes.

Changes in attitudes toward persons with mental disorders after attendance of a psychiatric curriculum among medical students in Vietnam: A cross-sectional study.

This study aimed to determine the influence of psychiatric training and hands-on learning with individuals with mental illness on increasing medical students' benevolent attitudes towards psychiatry and psychiatric patients. The cross-sectional study compares medical students' attitudes before and after a compulsory psychiatry curriculum and psychiatric bedside training at Hanoi Medical University with those of non-medical students who have yet to undergo similar training. Two validated scales regarding the attitudes toward psychiatry and psychiatric patients were evaluated. Analysis of the Medical Conditions Regard Scale[1] revealed a significant difference, indicating that medical students displayed more accepting and benevolent attitudes towards psychiatry and psychiatric patients after completing the curriculum and bedside training than medical students before participation. Most stigmatising and rejecting attitudes were found among non-medical students. This study is the first to examine medical students' attitudes toward psychiatry and psychiatric patients compared to non-medical students in Vietnam. It can guide the development of the medical curriculum to increase benevolence towards psychiatric patients and interest in the psychiatric field of work in Vietnam and Southeast Asia, aiming to improve the mental health care sector.

Mechanisms of action and processes of yoga-based group intervention for inpatients with schizophrenia spectrum disorders-A longitudinal qualitative study.

Background: Research exploring the effects of yoga therapy (YT) on individuals with schizophrenia spectrum disorders (SSD) is scarce. Therefore, the current study aimed to explore possible mechanisms of actions and processes, as well as adverse effects of a novel yoga-based group intervention (YoGI) for in-patients with SSD in a German university hospital setting. Material and methods: A longitudinal qualitative study was integrated into a rater-blinded randomized controlled trial, exploring the impact of a 4-week YoGI as add-on treatment. In-depth interviews were conducted with participants receiving YoGI (n = 19) in addition to treatment as usual (TAU) and a control group (n = 14) which only received TAU. Interviews were conducted at baseline (n = 33) and 4 weeks post-intervention (N = 28) to assess the participant's experiences and how they changed over time. The interviews (N = 61) were audio-taped, translated, coded, and analyzed by means of inductive thematic analysis. Separate case summaries were prepared for each participant to analyze longitudinal changes within subjects. The research team members collaboratively discussed the final list of themes and subcodes. Rater-based questionnaires, such as the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), and Personal and Social Performance Scale (PSP) were administered at baseline to assess clinical outcomes. Results: At baseline, participants reported a desire to improve their stress- and symptom management. A minority of participants expressed reservations toward yoga, and several psychosocial barriers were named, including worries about symptom exacerbation. At post-intervention, four mechanisms of change became evident from the interviews: (1) acquiring competence in relaxation, (2) increased interoceptive awareness, (3) feeling connected, and (4) a sense of spiritual wellbeing. A small number of participants reported difficulties with YoGI. Conclusion: Generally, YoGI positively influenced participants' experiences of their inpatient stay, regarding distress, self- and body awareness, social connectedness, and spiritual wellbeing. However, participants also illuminated necessary adjustments to improve the intervention. YoGI will therefore be adapted and further developed in an iterative process based on a participant involvement approach. The efficacy regarding outcomes and processes needs to be investigated in a future larger-scaled randomized controlled trial.

Mindfulness, cognitive fusion, and self-compassion in patients with schizophrenia spectrum disorders-A cross-sectional study.

In the last decades, third wave approaches in cognitive-behavioral therapies (CBT) have shown effectiveness in treating several mental disorders, including schizophrenia spectrum disorders (SSD). Three crucial processes associated with clinical changes in patients include mindfulness, psychological flexibility (PF) and self-compassion (SC). PF is generally assessed by cognitive fusion (CF), a negative formulated key process of PF. The current study encompasses a cross-sectional design to examine the interplay of mindfulness, CF, SC and symptom severity in SSD. It was hypothesized that mindfulness is negatively correlated with symptom severity, CF mediates the negative relation between mindfulness and symptom severity, and SC moderates the link between mindfulness and CF. In total, 79 persons with SSD were recruited at the Department of Psychiatry and Neurosciences at the Charité - Universitätsmedizin Berlin. Correlations, as well as moderated mediation analyses, were performed using the analysis modeling tool PROCESS with total symptom severity and negative symptom severity as outcome variables, measured by the Positive and Negative Syndrome Scale (PANSS) and the Self-Evaluation of Negative Symptoms Scale (SNS). Results show that the moderated mediation hypothesis was confirmed for negative symptom severity assessed by SNS, however, not for total symptom severity assessed by PANSS. In general, the association between mindfulness and CF was stronger for participants with higher SC scores in our data. Future studies should investigate the relationship between mindfulness, SC, and PF regarding symptom severity in SSD in longitudinal designs while considering the impact on different outcomes and differences regarding assessment tools.

The Relationship Between the Recognition of Basic Emotions and Negative Symptoms in Individuals With Schizophrenia Spectrum Disorders - An Exploratory Study.

Current research suggests that emotion recognition is impaired in individuals affected by schizophrenia spectrum disorders (SSD). However, the specific impact of negative symptoms on the ability to recognize single basic emotions has not yet been explored sufficiently and is the aim of the present study. A sample of N = 66 individuals diagnosed with SSD was recruited at the Charité - Universitätsmedizin Berlin. In a first step, correlation analyses were conducted between seven different negative symptom subdomains of the Positive and Negative Syndrome Scale (PANSS) and the accuracy and latency in recognizing the six basic emotions (anger, disgust, fear, happiness, sadness, surprise) using the Emotion Recognition Task (ERT) of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The significant correlations were subjected to linear regression models that controlled for the significant covariates diagnoses, age, sex, and education. Results revealed that in individuals with SSD the negative symptom domain of blunted affect significantly predicted the accuracy of emotion recognition performance (p < 0.05), particularly, when recognizing happiness (p < 0.05). Additionally, we found that stereotyped thinking also predicted the performance of emotion recognition, especially the response latency (p < 0.05) and difficulty in abstract thinking predicted the recognition of fear (p < 0.05). However, the nominal significances did not withstand correction for multiple tests and therefore need to be followed up in further studies with a larger sample.

Yoga-Based Group Intervention for In-patients With Schizophrenia Spectrum Disorders-A Qualitative Approach.

Background: Yoga may pose a promising complementary therapy in the multimodal treatment of in-patients with schizophrenia spectrum disorders (SSD). However, to date, no studies have qualitatively examined in-patients' with SSD experiences of Yoga as well as their perceptions of its limitations and benefits as a treatment component. This qualitative study aimed to explore for the first time the mechanisms and processes of Yoga-based Group Intervention (YoGI) for in-patients with SSD in Germany by asking for their subjective experiences. Findings could serve as a preliminary basis for developing an effective and evidence-based YoGI manual tailored to this patient group. Materials and Methods: In total, 25 semi-structured interviews were conducted directly after YoGI, for which responses were either noted down by hand or audio-recorded. The interview guide was pilot-tested and consisted of 14 questions to explore the personal articulated experiences of participation in YoGI from in-patients with SSD. Positive, negative, depressive, and anxiety symptoms were assessed during a diagnostic interview and through questionnaires. The interview data was transcribed, coded by two independent researchers, and analysed using an inductive thematic approach. The research team collaboratively discussed emerging categories to reduce redundancy and form meaningful themes and subthemes. Results: The analysis revealed seven main themes. YoGI was perceived as feasible and focusing on individual adaptation, captured by the theme inclusivity. Nevertheless, participants encountered challenges; thus, physical limitations need to be considered. While practising together, participants experienced interconnectedness and developed a mindful stance as they accepted their limitations and adapted exercises with self-compassion. Patients described that following the flow of the asanas required physical persistence, which ultimately led many participants to experience confidence and relaxation. YoGI affected symptom representation as heightened awareness led participants to notice impeding as well as improved symptoms. Conclusion: YoGI showed various promising effects on in-patients with SSD. Future research should examine to what extent these effects can be sustained and how the mindful approach during YoGI can be transferred to areas outside the Yoga class. Furthermore, a randomised controlled trial could investigate the effectiveness of a manualised YoGI.

The Relationship Between Mindfulness, Depression, Anxiety, and Quality of Life in Individuals With Schizophrenia Spectrum Disorders.

Background: Schizophrenia spectrum disorders (SSD) are frequently accompanied by comorbid depressive and anxiety symptoms, as well as impaired quality of life (QoL). A growing body of evidence has demonstrated the relevance of mindfulness for SSD in recent years. The study examined the association between mindfulness, depression, anxiety, and QoL. Materials and Methods: A total of 83 participants with SSD were recruited at the in- and outpatient psychiatric hospital care. Participants completed the Southampton Mindfulness Questionnaire, Comprehensive Inventory for Mindful Experiences, and Freiburger Mindfulness Inventory, the Depression, Anxiety, Stress Scale to assess depression and anxiety, and the WHO-QoL Questionnaire. Multiple regression analyses examined the relationship between mindfulness and QoL and the mediating role of depression and anxiety. Results: Mindfulness had a significant statistical positive effect on QoL domains physical health, psychological, and environmental QoL in patients with SSD. Depression was identified as a significant mediator of this relationship. Conclusion: This study provides novel insight into mindfulness' mechanisms and paves the way for a process-oriented approach to treat SSD. The results provide first evidence for the process-based value of mindfulness for SSD; future studies can focus on the role of mindfulness for central therapeutic processes of change by employing longitudinal designs.

Mindfulness-based group therapy for in-patients with schizophrenia spectrum disorders - Feasibility, acceptability, and preliminary outcomes of a rater-blinded randomized controlled trial.

BACKGROUND: A Growing body of literature indicates therapeutic effectiveness of mindfulness for mental disorders. Only few trials have been conducted with schizophrenia spectrum disorders (SSD), mostly in outpatient settings. Primary objective was to assess feasibility, acceptability, and preliminary outcomes of mindfulness-based group therapy (MBGT) for in-patients with SSD. METHODS: A pre-registered randomized controlled trial was conducted to assess feasibility and acceptability of the MBGT. The primary outcome was mindfulness measured with the Southampton Mindfulness Questionnaire (SMQ). Secondary outcomes were rater-blinded positive- and negative symptoms, depression, social functioning, and self-reported mindfulness, depression, anxiety, psychological flexibility, quality of life, and medication regime at baseline, post-intervention, and follow-up (Clinical Trails NCT03671005). RESULTS: 40 participants received either treatment-as-usual (TAU; n=19) or (MBGT+TAU; n = 21) for four weeks. At post-intervention, protocol adherence was 95.2%, and retention rate was 95%. ANCOVA revealed significant improvements in the MBGT+TAU for the primary outcome SMQ as well as negative symptoms at post-intervention between groups. In exploratory analyses, secondary outcomes showed medium-to-large pre-to-post-intervention effects on mindfulness, positive-, negative-, and depressive symptoms, psychological flexibility, quality of life, and social functioning for MBGT+TAU and small-to-moderate changes on positive symptoms and social functioning for TAU. No serious adverse effects were reported. CONCLUSIONS: MBGT appears feasible and acceptable for in-patient settings, with high protocol adherence and retention rates. Preliminary findings highlight a proof of concept of MBGT and various improvements in clinical- and process dimensions. A fully powered trial is warranted to determine efficacy, cost-efficiency, and longitudinal changes based on these promising outcomes.

Role of purinergic signaling in experimental pneumococcal meningitis.

Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1ß pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR. ATP levels were determined in murine CSF and cell culture experiments. Treatment with the P2R antagonists suramin or brilliant blue G did not have any impact on disease course. This lack of effect might be attributed to meningitis-associated down-regulation of brain P2R expression and/or a drop of cerebrospinal fluid (CSF) ATP, as demonstrated by RT-PCR and ATP analyses. Supplemental cell culture experiments suggest that the reduction in CSF ATP is, at least partly, due to ATP hydrolysis by ectonucleotidases of neutrophils and macrophages. In conclusion, this study suggests that ATP-P2R signaling is only of minor or even no significance in PM. This may be explained by down-regulation of P2R expression and decreased CSF ATP levels.