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Bejerot, S., Hietala, A. M., Söderbergh, A. & Humble, M. B. (2025). Circular reasoning concerning Red flags for predicting rituximab response in OCD [Letter to the editor]. Molecular Psychiatry
Open this publication in new window or tab >>Circular reasoning concerning Red flags for predicting rituximab response in OCD
2025 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal, Letter (Other academic) Epub ahead of print
Place, publisher, year, edition, pages
Springer Nature, 2025
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-118180 (URN)10.1038/s41380-024-02885-y (DOI)001389693700001 ()39753888 (PubMedID)2-s2.0-85213893455 (Scopus ID)
Available from: 2025-01-10 Created: 2025-01-10 Last updated: 2025-01-20Bibliographically approved
Glans, M. & Bejerot, S. (2024). ADHD symptoms are associated with bully victimization in non-clinical populations too. Paper presented at 32nd European Congress of Psychiatry (EPA 2024), Budapest, Hungary, April 6-9, 2024. European psychiatry, 67(Suppl. 1), S453-S453, Article ID EPV0165.
Open this publication in new window or tab >>ADHD symptoms are associated with bully victimization in non-clinical populations too
2024 (English)In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 67, no Suppl. 1, p. S453-S453, article id EPV0165Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Cambridge University Press, 2024
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-116738 (URN)10.1192/j.eurpsy.2024.940 (DOI)001310523502151 ()
Conference
32nd European Congress of Psychiatry (EPA 2024), Budapest, Hungary, April 6-9, 2024
Available from: 2024-10-16 Created: 2024-10-16 Last updated: 2024-10-16Bibliographically approved
Popiolek, K., Arnison, T., Bejerot, S., Fall, K., Landén, M. & Nordenskjöld, A. (2024). Association between electroconvulsive therapy and time to readmission after a manic episode. Acta Psychiatrica Scandinavica, 150(1), 22-34
Open this publication in new window or tab >>Association between electroconvulsive therapy and time to readmission after a manic episode
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2024 (English)In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 150, no 1, p. 22-34Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
Bipolar disorder, electroconvulsive therapy, mania, readmission, rehospitalization
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-113093 (URN)10.1111/acps.13689 (DOI)001199821200001 ()38604233 (PubMedID)2-s2.0-85190443565 (Scopus ID)
Funder
Region Örebro County, OLL-972634NyckelfondenSwedish Research Council, 2022-01643The Swedish Brain Foundation, FO2022-0217
Available from: 2024-04-12 Created: 2024-04-12 Last updated: 2024-06-05Bibliographically approved
Thunberg, P., Fresnais, D., Hamilton, P., Bejerot, S. & Humble, M. B. (2024). Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders. Brain, Behavior, and Immunity - Health, 41, Article ID 100864.
Open this publication in new window or tab >>Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders
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2024 (English)In: Brain, Behavior, and Immunity - Health, E-ISSN 2666-3546, Vol. 41, article id 100864Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Functional magnetic resonance imaging, Immunopsychiatry, Neuroinflammation, Obsessive-compulsive disorder, Resting state functional connectivity, Rituximab, Schizophrenia, Voxel-based morphometry
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-116449 (URN)10.1016/j.bbih.2024.100864 (DOI)001319797800001 ()39350952 (PubMedID)2-s2.0-85204368404 (Scopus ID)
Funder
Nyckelfonden, OLL-878311Nyckelfonden, OLL-779081Torsten Söderbergs stiftelse, M84/19The Swedish Brain Foundation, FO2019-0094
Available from: 2024-10-02 Created: 2024-10-02 Last updated: 2024-10-02Bibliographically approved
Glans, M. R., Nilsson, J. & Bejerot, S. (2024). Tattoos, piercings, and symptoms of ADHD in non-clinical adults: a cross-sectional study. Frontiers in Psychiatry, 14, Article ID 1224811.
Open this publication in new window or tab >>Tattoos, piercings, and symptoms of ADHD in non-clinical adults: a cross-sectional study
2024 (English)In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 14, article id 1224811Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2024
Keywords
impulsivity, hyperactivity, inattention, tattoo, piercing
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-110942 (URN)10.3389/fpsyt.2023.1224811 (DOI)001142692400001 ()38234366 (PubMedID)2-s2.0-85182494270 (Scopus ID)
Funder
Swedish Research Council, K2012- 62X-22130-04-6
Note

Funding agency:

Bror Gadelius Minnesfond

Available from: 2024-01-23 Created: 2024-01-23 Last updated: 2024-01-23Bibliographically approved
Hylén, U., Särndahl, E., Bejerot, S., Humble, M. B., Hyötyläinen, T., Salihovic, S. & Eklund, D. (2023). Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders. BMC Psychiatry, 23(1), Article ID 268.
Open this publication in new window or tab >>Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders
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2023 (English)In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 23, no 1, article id 268Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Comorbidity, Inflammasomes, Inflammation, Mental Disorders, Metabolic pathways, Psychoneuroimmunology
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-105613 (URN)10.1186/s12888-023-04784-y (DOI)000975250300004 ()37076825 (PubMedID)2-s2.0-85152978734 (Scopus ID)
Funder
Knowledge Foundation, 20200017
Available from: 2023-04-21 Created: 2023-04-21 Last updated: 2024-04-08Bibliographically approved
Westerberg, B., Holländare, F. & Bejerot, S. (2023). An internet-based behavioral intervention for adults with autism spectrum disorder - A randomized controlled trial and feasibility study. Internet Interventions, 34, Article ID 100672.
Open this publication in new window or tab >>An internet-based behavioral intervention for adults with autism spectrum disorder - A randomized controlled trial and feasibility study
2023 (English)In: Internet Interventions, ISSN 2214-7829, Vol. 34, article id 100672Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Autism spectrum disorder, Cognitive-behavioral therapy, Internet-based intervention, Psychiatry, Quality of life
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-108661 (URN)10.1016/j.invent.2023.100672 (DOI)001079510200001 ()37772160 (PubMedID)2-s2.0-85171486066 (Scopus ID)
Funder
Region Örebro County, OLL-935396 OLL-879651 OLL-887401 OLL-833131 OLL-785501 OLL-736321 OLL-878311
Available from: 2023-10-02 Created: 2023-10-02 Last updated: 2025-01-28Bibliographically approved
Fresnais, D., Humble, M. B., Bejerot, S., Meehan, A. D. & Fure, B. (2023). Apathy as a Predictor for Conversion From Mild Cognitive Impairment to Dementia: A Systematic Review and Meta-Analysis of Longitudinal Studies. Journal of Geriatric Psychiatry and Neurology, 36(1), 3-17
Open this publication in new window or tab >>Apathy as a Predictor for Conversion From Mild Cognitive Impairment to Dementia: A Systematic Review and Meta-Analysis of Longitudinal Studies
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2023 (English)In: Journal of Geriatric Psychiatry and Neurology, ISSN 0891-9887, E-ISSN 1552-5708, Vol. 36, no 1, p. 3-17Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Sage Publications, 2023
Keywords
Apathy, behavioral disturbance, cognitive impairment, dementia, elderly
National Category
Neurosciences
Identifiers
urn:nbn:se:oru:diva-98668 (URN)10.1177/08919887221093361 (DOI)000786601700001 ()35446723 (PubMedID)2-s2.0-85129677798 (Scopus ID)
Note

Funding agencies:

Örebro University, School of Medical Sciences, Örebro, Sweden

Karlstad Central Hospital, Karlstad, Sweden

Available from: 2022-04-22 Created: 2022-04-22 Last updated: 2023-12-08Bibliographically approved
Bejerot, S., Sigra, S., Welin, E., Eklund, D., Hylén, U. & Humble, M. B. (2023). Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients. Journal of Psychiatric Research, 158, 319-329
Open this publication in new window or tab >>Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients
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2023 (English)In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 158, p. 319-329Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
B-Cells, Clinical trial, Monoclonal antibody, Neuroinflammation, Obsessive-compulsive disorder, Schizophrenia, Treatment-resistant
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-103171 (URN)10.1016/j.jpsychires.2022.12.003 (DOI)000976718200001 ()36638622 (PubMedID)2-s2.0-85146076210 (Scopus ID)
Funder
Nyckelfonden, OLL-878311 OLL-779081Torsten Söderbergs stiftelse, M84/19The Swedish Brain Foundation, FO2019-0094
Available from: 2023-01-17 Created: 2023-01-17 Last updated: 2024-04-08Bibliographically approved
Humble, M. B., Eklund, D., Fresnais, D., Hylén, U., Sigra, S., Thunberg, P. & Bejerot, S. (2023). Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD): functional connectivity and cytokines associated with symptomatic improvements. Paper presented at 31st European Congress of Psychiatry (EPA 2023), Paris, France, March 25-28, 2023. European psychiatry, 66(Suppl. 1), S629-S629, Article ID EPP1035.
Open this publication in new window or tab >>Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD): functional connectivity and cytokines associated with symptomatic improvements
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2023 (English)In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 66, no Suppl. 1, p. S629-S629, article id EPP1035Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction: Immunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.

Objectives: We aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).

Methods: In an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.

Results: Nineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.

Conclusions: Aberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.

Place, publisher, year, edition, pages
Cambridge University Press, 2023
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-109391 (URN)10.1192/j.eurpsy.2023.1309 (DOI)001060676601588 ()
Conference
31st European Congress of Psychiatry (EPA 2023), Paris, France, March 25-28, 2023
Available from: 2023-10-25 Created: 2023-10-25 Last updated: 2024-03-18Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3587-6075

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