Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders.

INTRODUCTION: Psychiatric disorders are common and significantly impact the quality of life. Inflammatory processes are proposed to contribute to the emergence of psychiatric disorders. In addition to inflammation, disturbances in metabolic pathways have been observed in individuals with different psychiatric disorders. A suggested key player in the interaction between inflammation and metabolism is the Nod-like receptor 3 (NLRP3) inflammasome, and NLRP3 is known to react to a number of specific metabolites. However, little is known about the interplay between these immunometabolites and the NLRP3 inflammasome in mental health disorders. AIM: To assess the interplay between immunometabolites and inflammasome function in a transdiagnostic cohort of individuals with severe mental disorders. METHODS: Mass spectrometry-based analysis of selected immunometabolites, previously known to affect inflammasome function, were performed in plasma from low-functioning individuals with severe mental disorders (n = 39) and sex and aged-matched healthy controls (n = 39) using a transdiagnostic approach. Mann Whitney U test was used to test differences in immunometabolites between psychiatric patients and controls. To assess the relationship between inflammasome parameters, disease severity, and the immunometabolites, Spearman's rank-order correlation test was used. Conditional logistic regression was used to control for potential confounding variables. Principal component analysis was performed to explore immunometabolic patterns. RESULTS: Among the selected immunometabolites (n = 9), serine, glutamine, and lactic acid were significantly higher in the patient group compared to the controls. After adjusting for confounders, the differences remained significant for all three immunometabolites. No significant correlations were found between immunometabolites and disease severity. CONCLUSION: Previous research on metabolic changes in mental disorders has not been conclusive. This study shows that severely ill patients have common metabolic perturbations. The changes in serine, glutamine, and lactic acid could constitute a direct contribution to the low-grade inflammation observed in severe psychiatric disorders.

Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients.

In this explorative study, we investigated if an adjunctive treatment with one single dose of the monoclonal antibody rituximab would improve symptoms and function in treatment-resistant patients with schizophrenia spectrum disorder (SSD, n = 9) or obsessive-compulsive disorder (OCD, n = 10), based on the inflammatory hypothesis for mental disorders. Patients were followed for one year. Disability was measured with the Personal and Social Performance score (PSP). At baseline, the mean PANSS score in the SSD group was 99 ± 32 and the mean Y-BOCS score in the OCD group was 27.5 ± 7. Mean PSP scores were 32 ± 10.2 and 42.5 ± 9.9 in the SSD and OCD groups, respectively. Seven had Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) in retrospect, and 3 SSD patients had schizo-obsessive subtype. 4/8 SSD patients showed a ≥40% reduction in PANSS at endpoint I week 20, however, 7/9 were similarly improved already at week 12. Among the OCD patients, 2/10 showed a ≥35% reduction in Y-BOCS at week 20. Disability was significantly improved only in the SSD group. The percentual decrease of PANSS scores in SSD patients was associated with the increase in immunoglobulin levels week 20 (n = 8: IgG r = 0.85, p = .007; IgA r = 0.79, p = .019; IgM r = 0.73, p = .038). Rituximab was generally well tolerated in these patients. Self-rated improvements since baseline were reported for psychic (p = .021), neurological (p = .059), and autonomic (p < .001) side effects (UKU-SERS-Pat side-effect scale). Anxiety was commonly reported by OCD patients, while an initial increase in psychotic symptoms was seen in a few SSD patients. An RCT is underway to evaluate rituximab in SSD.

Potential Transdiagnostic Lipid Mediators of Inflammatory Activity in Individuals With Serious Mental Illness.

Mental disorders are heterogeneous and psychiatric comorbidities are common. Previous studies have suggested a link between inflammation and mental disorders. This link can manifest as increased levels of proinflammatory mediators in circulation and as signs of neuroinflammation. Furthermore, there is strong evidence that individuals suffering from psychiatric disorders have increased risk of developing metabolic comorbidities. Our group has previously shown that, in a cohort of low-functioning individuals with serious mental disorders, there is increased expression of genes associated with the NLRP3 inflammasome, a known sensor of metabolic perturbations, as well as increased levels of IL-1-family cytokines. In the current study, we set out to explore the interplay between disease-specific changes in lipid metabolism and known markers of inflammation. To this end, we performed mass spectrometry-based lipidomic analysis of plasma samples from low-functioning individuals with serious mental disorders (n = 39) and matched healthy controls (n = 39). By identifying non-spurious immune-lipid associations, we derived a partial correlation network of inflammatory markers and molecular lipids. We identified levels of lipids as being altered between individuals with serious mental disorders and controls, showing associations between lipids and inflammatory mediators, e.g., osteopontin and IL-1 receptor antagonist. These results indicate that, in low-functioning individuals with serious mental disorders, changes in specific lipids associate with immune mediators that are known to affect neuroinflammatory diseases.

Joint Hypermobility in Paediatric Acute-Onset Neuropsychiatric Syndrome-A Preliminary Case-Control Study.

Background: Individuals with generalised joint hypermobility (GJH, present in 10-20% of the general population) are at increased risk of being diagnosed with a range of psychiatric and rheumatological conditions. It is unknown whether Paediatric acute-onset neuropsychiatric syndrome (PANS), characterised by childhood onset obsessive-compulsive disorder or restricted eating and typically associated with several comorbid neuropsychiatric symptoms, is associated with GJH. It is also unknown whether extensive psychiatric comorbidity is associated with GJH. Method: This is a case-control study including 105 participants. We compared three groups: Individuals with PANS, individuals with other mental disorders and healthy controls. Joint mobility was assessed with the Beighton scoring system, psychiatric comorbidity with the M.I.N.I. or MINI-KID interview and symptoms of PANS with the PsychoNeuroInflammatory related Signs and Symptoms Inventory (PNISSI). Results: Hypermobility was similar across groups, and high rates of psychiatric comorbidity was not associated with higher Beighton scores. Conclusion: Although GJH is associated with several psychiatric conditions, such as ADHD and anxiety, this does not seem to be the case for PANS according to this preliminary study.

An Internet Based Intervention for Adults With Autism Spectrum Disorder-A Qualitative Study of Participants Experiences.

Background: Adults with autism spectrum disorder face several barriers to accessing evidence-based care, including difficulties in communicating needs, social anxiety or in traveling to a health care unit. In recent years, several forms of internet-based treatments have shown to be effective for a variety of psychiatric conditions. Internet-based treatment alternatives allow convenient and flexible formats, and therefore have the potential to increase access to health care for individuals with autism spectrum disorder. However, knowledge about how internet-based treatment features may suit the needs of individuals with autism is limited. The aim of this study was to explore the participant experiences of an internet-based intervention for adults with autism spectrum disorder. The primary focus of the investigation was on autism-specific needs in relation to the features unique to the online format. Methods: In this qualitative study, semi-structured telephone interviews were conducted with 14 participants who had completed a text-based internet-based intervention for adults with autism spectrum disorder. We used an inductive approach and analyzed the data using qualitative content analysis. Results: Five main categories were identified: (1) implications of the online format, (2) the fixed non-individualized model, (3) therapist interaction, (4) interacting with other participants, and (5) making use of the treatment content. Overall, participants appreciated the availability and that they could work on their treatment independent of time or location. Among those participating in group-based chat-sessions with the other participants, it was considered a generally positive experience. Furthermore, most participants felt safe and relaxed in relation to the therapist and appreciated the text-based format. However, several participants felt that the format and content of the treatment was not sufficiently adapted to their individual life situation. Conclusion: In conclusion, this internet-based treatment constitutes an accessible and energy-saving treatment alternative for adults with autism. Further, integrating group-based components seems feasible in an otherwise individual internet-based treatment for individuals with autism. However, group-based components do require a clear purpose and rationale. Future studies should develop and evaluate treatment adaptations tailored to individual needs.

Increased inflammasome activity in markedly ill psychiatric patients: An explorative study.

The aim of this study was to investigate inflammatory perturbations in 40 patients with severe and complex psychiatric disorders by studying the activity of the NLRP3 inflammasome, with a trans-diagnostic approach. Gene expression of CASP1, NLRP3, PYCARD, IL1B, IL1RN, TNF showed a significant increase in the patient group compared to a matched control group. Plasma levels of IL1Ra, IL-18, TNF, IL-6 and CRP were increased in the patient group. Within the patient group, increased gene expression of inflammatory markers correlated with increased disease severity. The findings support the inflammation hypothesis for markedly ill psychiatric patients across diagnostic groups.

Different forms of informal coercion in psychiatry: a qualitative study.

OBJECTIVES: The objective of the study was to investigate how mental health professionals describe and reflect upon different forms of informal coercion. RESULTS: In a deductive qualitative content analysis of focus group interviews, several examples of persuasion, interpersonal leverage, inducements, and threats were found. Persuasion was sometimes described as being more like a negotiation. Some participants worried about that the use of interpersonal leverage and inducements risked to pass into blackmail in some situations. In a following inductive analysis, three more categories of informal coercion was found: cheating, using a disciplinary style and referring to rules and routines. Participants also described situations of coercion from other stakeholders: relatives and other authorities than psychiatry. The results indicate that informal coercion includes forms that are not obviously arranged in a hierarchy, and that its use is complex with a variety of pathways between different forms before treatment is accepted by the patient or compulsion is imposed.

Feeling safe or unsafe in psychiatric inpatient care, a hospital-based qualitative interview study with inpatients in Sweden.

BACKGROUND: A major challenge in psychiatric inpatient care is to create an environment that promotes patient recovery, patient safety and good working environment for staff. Since guidelines and programs addressing this issue stress the importance of primary prevention in creating safe environments, more insight is needed regarding patient perceptions of feeling safe. The aim of this study is to enhance our understanding of feelings of being safe or unsafe in psychiatric inpatient care. METHODS: In this qualitative study, interviews with open-ended questions were conducted with 17 adult patients, five women and 12 men, from four settings: one general psychiatric, one psychiatric addiction and two forensic psychiatric clinics. The main question in the interview guide concerned patients' feelings of being safe or unsafe. Thematic content analysis with an inductive approach was used to generate codes and, thereafter, themes and subthemes. RESULTS: The main results can be summarized in three themes: (1) Predictable and supportive services are necessary for feeling safe. This concerns the ability of psychiatric and social services to meet the needs of patients. Descriptions of delayed care and unpredictable processes were common. The structured environment was mostly perceived as positive. (2) Communication and taking responsibility enhance safety. This is about daily life in the ward, which was often perceived as being socially poor and boring with non-communicative staff. Participants emphasized that patients have to take responsibility for their actions and for co-patients. (3) Powerlessness and unpleasant encounters undermine safety. This addresses the participants' way of doing risk analyses and handling unpleasant or aggressive patients or staff members. The usual way to act in risk situations was to keep away. CONCLUSIONS: Our results indicate that creating reliable treatment and care processes, a stimulating social climate in wards, and better staff-patient communication could enhance patient perceptions of feeling safe. It seems to be important that staff provide patients with general information about the safety situation at the ward, without violating individual patients right to confidentiality, and to have an ongoing process that aims to create organizational values promoting safe environments for patients and staff.

Providing Good Care in the Shadow of Violence - An Interview Study with Nursing Staff and Ward Managers in Psychiatric Inpatient Care in Sweden.

The aim was to describe the nursing staff and ward managers' experiences of safety and violence in everyday meetings with the patients. The qualitative content analyses resulted in four themes: the relationship with the patient is the basis of care; the organizational culture affects the care given; knowledge and competence are important for safe care; and the importance of balancing influence and coercion in care. The staff had a varied ability to meet patients in a respectful way. One way of creating a common approach could be to discuss and reflect upon different options in the meeting with the patient.