To Örebro University

Schizophrenia and obsessive-compulsive disorder (OCD) are complex neuropsychiatric disorders with emerging evidence implicating immune and neuroinflammatory mechanisms. This exploratory pilot study investigated aquaporin-4 positive (AQP4+) extracellular vesicles (EVs) in the cerebrospinal fluid (CSF) of 11 treatment-resistant patients with schizophrenia (n = 5) or obsessive-compulsive disorder (OCD, n = 6) receiving an add-on, single-infusion rituximab (1000 mg) treatment, a B-cell depleting therapy. CSF samples were collected pre-treatment and, for a subset, again five months post-treatment. AQP4+ EV levels in CSF were quantified using flow cytometry with antibodies targeting different regions of the AQP4 molecule. We also measured selected cytokines in CSF and plasma and cytokine gene expression in peripheral blood cells. Patients with schizophrenia exhibited higher AQP4+ EV levels compared to those with OCD. In schizophrenia, AQP4+ EVs correlated positively with the inflammatory marker CXCL8/IL-8 but negatively with CSF-TNF-α. Plasma markers CXCL8/IL-8 and TGF-β1 were positively associated with CSF-AQP4+ EVs in schizophrenia. Between 24- and 40-times higher concentrations of CXCL8/IL-8 in CSF than in plasma suggest intrathecal production of this chemokine in both disorders. Post-treatment, AQP4+ EV levels decreased in the patients who improved following rituximab but remained stable in non-responders. These findings suggest that astrocyte-derived extracellular vesicles may play a role in neuroinflammatory processes linked to schizophrenia and possibly also to severe OCD. The observed relationships between AQP4+ EVs and cytokines support the hypothesis that astrocyte-derived EVs could modulate intrathecal immune responses and potentially also interact with peripheral immune mechanisms. Larger studies are warranted to validate these preliminary findings.

Introduction: Individuals with ADHD are at higher risk of being bullied than individuals without ADHD 1,2,3 Over the past decades, there has been a shift from a categorical to a dimensional conceptualization of ADHD 4. It remains unknown if the association between ADHD and bullying also extends to non-clinical popula-tions.

Objectives: To assess if subclinical ADHD symptoms associates with bully victimization in childhood and adolescence.

Methods: 1557 non-clinical adults completed the 6-item Adult Self-Report Scale Screener (ASRS) and answered questions concerning bully victimization. ADHD and ASD diagnoses served as exclusion criteria. Prevalence rates of bully victimization (defined as bullied ≥twice monthly) were compared at different time periods between those with- and without a positive ASRS-screener (cut-off score ≥4/6) by chi-square tests. Moreover, logistic regression evaluated the association while adjusting for candidate covariates age and sex.

Results: Out of the total sample 1332 individuals (mean age=42, 60% female) scored negative and 217 individuals (mean age=36, 70% female) scored positive on the ASRS-screener while 8 had missing data on age or sex. Prevalence rates of bully victimization comparing those with- and without a positive score were as following; 20% vs 11%, p<.001 at 7-9 years, 26% vs 15%, p<.001 at 10-12 years, 20% vs 13%, p=.005 at 13-15 years and 6% vs 2%, p=.002 at 16-18 years. The statistically significant associations seen in the prevalence comparisons up until working life remained in thelogistic regression models.

Conclusions: More pronounced subclinical ADHD symptoms were associated with approximately twice as high prevalence of bully victimization in childhood and adolescence. Thus, ADHD characteristics appear to have serious consequences across the full clinical and non-clinical parts of the spectrum.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more.

METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed.

RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067).

CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM). A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Introduction: Tattoos and piercings are associated with impulsive and risk-taking personality traits, which are also common along the ADHD continuum. However, studies on ADHD and body modification are lacking. Thus, this study aimed to assess the association between body modification and subclinical ADHD symptom severity and to investigate if body modification can serve as an indication for ADHD examination.

Methods: A total of 762 adults (529 women and 233 men) without a diagnosis of ADHD completed the adult ADHD Self-Report Scale (ASRS) and answered questions concerning body modification. Two different ASRS versions were utilized: the 18-item ASRS Symptom Checklist and the 6-item ASRS Screener. Three categorizations of body modifications were analyzed: (i) having at least one tattoo, (ii) having at least one piercing other than ear piercing, and (iii) the combination of simultaneously having at least one tattoo and one piercing. Mean 18-item ASRS total and subscale scores and the proportion of positive results on the 6-item ASRS Screener were compared between those with and those without body modifications while adjusting for covariates age and sex. Additional analyses were performed for >= 2 and >= 3 body modifications.

Results: In our cohort, 26% had a tattoo, 14% had a piercing other than ear piercing, and 8% had a combination of tattoo and piercing. Having any kind of body modification was associated with more pronounced symptoms of ADHD and with a cutoff score on the ASRS screener indicating ADHD. Whereas, the effect sizes were small for tattoos, medium to large effect sizes were seen for >= 2 piercings in the ASRS. Moreover, moderately strong associations emerged for >= 1 piercing and a positive ASRS screening result.

Conclusion: Our results suggest that acquiring a body modification, especially a tattoo, is entering the mainstream in Sweden. Correspondingly, differences in subclinical ADHD symptomatology between non-clinical adults with and without body modifications are subtle. Having >= 2 piercings other than ear piercings, on the other hand, is associated with clinically relevant differences in ADHD symptoms. Moreover, piercing status may serve as an indicator, among others, for further ADHD assessments. However, more research is needed to ascertain the possible signaling functions of body modifications in clinical settings.

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.

BACKGROUND: The increased prevalence of Autism Spectrum Disorder (ASD) diagnoses in combination with psychiatric comorbidity, has led to an increased need for effective interventions. The evidence for internet-based interventions for several mental health problems is established but has not been evaluated for adults with ASD.

OBJECTIVE: The aim of this randomized controlled trial is to evaluate the feasibility and effects of an internet-based intervention targeting quality of life and psychiatric symptoms (depression and anxiety) in adults with ASD. METHODS: 84 participants were randomly allocated to intervention (n = 42) or control (n = 42). The 18-week internet-based intervention covered a range of themes related to difficulties common in ASD, and exercises based on cognitive behavioral strategies. Participants were provided with individual feedback following each module and were invited to regular chat sessions with peer participants. The primary outcomes were subjective quality of life and sense of coherence, and secondary outcomes were symptoms of depression and anxiety. All outcomes were measured at five occasions and analysed with linear mixed effect models. Participant satisfaction and adherence was also analysed.

RESULTS: Participant satisfaction and adherence was satisfactory but no significant interaction between group and time was found for any outcome measure. Autistic traits were negatively related to quality of life and sense of coherence and positively related to anxiety and depressive symptoms.

CONCLUSIONS: This internet-based intervention showed feasibility regarding adherence and participant satisfaction. However, no significant effects on quality of life, sense of coherence or psychiatric symptoms were found, likely due to limitations in the design and methodology of this specific trial in combination to the heterogeneity of the group. Individuals with ASD may require interventions that are flexible and individually tailored in regard to both format, content and therapeutic support. The current trial provides useful information and suggestions for the future research on internet-based interventions for ASD.

BACKGROUND: Apathy is one of the most prevalent neurobehavioral manifestations in mild cognitive impairment (MCI) and is included among the behavioral and psychological symptoms of dementia (BPSD). Studies suggest that the presence of apathy could be associated with increased dementia risk. The role of apathy in conversion from MCI to dementia, and whether apathy could be a relevant predictor for dementia progression, are still matters of investigation.

AIM: To study the relationship between apathy and progression to dementia in individuals with MCI.

METHODS: A systematic literature search in Medline, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included longitudinal studies reporting on the association between apathy and dementia.

RESULTS: The main outcome was pooled unadjusted hazard ratios (HR) of apathy in dementia conversion and included 11 studies with 9504 individuals. There was a significant association between apathy and dementia conversion, HR = 1.54; 95% CI, 1.29, 1.84. Subgroup analysis showed a significant association between apathy and progression to AD.

CONCLUSION: Apathy was associated with an increased risk of conversion to AD and all-cause dementia in patients with MCI. The role of apathy as a marker for incident dementia needs to be investigated in large, high-quality studies.