To Örebro University

BACKGROUND: To meet the needs of individuals diagnosed with autism, internet-based interventions have been developed with a variety of objectives. A deeper understanding of the mechanisms of change may help tailor interventions to individual needs. The communicative behaviors of individuals with autism participating in text-based internet-based interventions remain largely unexplored, as do their potential relations to clinical outcomes. An improved understanding of participants' behaviors may help therapists better tailor support, promote engagement, and enhance treatment outcomes.

OBJECTIVE: This study aimed to explore the communicative behaviors of individuals with autism participating in an internet-based intervention and to examine whether different behavioral patterns were associated with treatment outcomes or treatment adherence.

METHODS: Messages from 34 participants enrolled in an 18-week internet-based cognitive behavioral therapy program were analyzed using abductive qualitative content analysis. Correlational analyses were used to examine the relationships between qualitative categories and change scores on outcome measures and rates of module completion.

RESULTS: Fourteen behavioral categories were identified and grouped into three overarching domains: (1) "This is me," which encompasses the participants' narratives on identity, personality, autistic functioning, current and past circumstances, and worldview; (2) "Working with the treatment," which included statements related to engagement with the treatment process; and (3) "I struggle," which comprised of past and present negative experiences and challenges. Correlational analyses revealed associations between several behavioral categories and improvements in quality of life and treatment adherence.

CONCLUSIONS: The findings highlight the importance of self-narrative formulation among individuals with autism and suggest that certain communicative behaviors-particularly those involving identity reflection and recognition of treatment-related gains-were positively associated with therapeutic outcomes. The findings enhance our understanding of how individuals with autism engage in internet-based cognitive behavioral therapy and may serve as a valuable source of information for therapists when guiding expectations regarding client outcomes and identifying participants who may benefit from additional support.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03570372; https://clinicaltrials.gov/study/NCT03570372.

Sense of coherence reflects the ability to comprehend and interpret one's environment as coherent and to experience life as manageable and meaningful. Sense of coherence is predictive of quality of life in several populations, but this relation has not been investigated among autistic individuals. Even though autistic individuals often describe difficulties perceiving the world in a coherent way, the sense of coherence concept is relatively unexplored in autism. The aim of this study was to explore the relationship between autistic traits, sense of coherence and quality of life in autistic individuals in Sweden. A total of 81 adults with autism completed questionnaires covering their sense of coherence, quality of life and autistic traits. The results showed that sense of coherence predicted quality of life and that autistic traits predicted sense of coherence levels in our sample. Based on the results, we suggest that sense of coherence may be important for the understanding of autistic functioning and that sense of coherence is essential for quality of life in this group. The study contributes to the understanding of autistic functioning and adds useful knowledge for the development of appropriate interventions for autistic individuals. Interventions that address aspects aimed at increasing the individual's sense of coherence may therefore be warranted.

Sense of coherence reflects a person's sense that their environment is understandable, that they can manage life's challenges and that they judge it to be meaningful. In many populations, a strong sense of coherence is linked to a higher quality of life, but this relation has not been studied among autistic individuals. Even though autistic individuals often describe difficulties perceiving the world in a coherent way, the concept of sense of coherence is relatively unexplored among individuals with autism. This study explored the links between autistic traits, sense of coherence and quality of life in 81 autistic adults in Sweden who completed a series of questionnaires. We found that sense of coherence was a strong predictor of quality of life. We also discovered that having more autistic traits was linked to a weak sense of coherence. Based on our results, we suggest that sense of coherence may be important to understand autistic functioning. We also conclude that sense of coherence is important for quality of life in this group. This suggests that interventions designed to help individuals see their world as more coherent and manageable could be a valuable way to improve their quality of life.

BACKGROUND: One third of patients with schizophrenia do not achieve remission with current antipsychotic treatments. Converging data support an immune-mediated component in a subset of cases, overlapping with autoimmune CNS disorders. The B-cell-depleting monoclonal antibody rituximab is used in diseases such as multiple sclerosis and has been explored as an immunomodulatory strategy. We investigated plasma biomarkers, focusing on T-helper-related transcription factors, in relation to outcome after rituximab in schizophrenia.

METHODS: Nineteen severely ill, treatment-resistant patients (n = 9 with schizophrenia and n = 10 with obsessive-compulsive disorder [OCD]) included in an open-label pilot trial, received a single 1000 mg intravenous infusion of rituximab. Symptoms were assessed at baseline and week 12 using PANSS or Y-BOCS, global functioning with PSP, and improvement with CGI-I. Response was defined as "much" or "very much improved" on CGI-I at week 12. For the present analyses, we compared schizophrenia responders with a combined group of schizophrenia and OCD non-responders. Plasma and whole blood were collected at baseline and week 12. Multiplex cytokines and RT-qPCR for the expression of 13 genes coding for cytokines and T-cell-related transcription factors were analyzed, including Th1 and Th17 master regulators TBX21 (T-bet) and RORC (RORγt), respectively. We also constructed a composite rank score combining TBX21 and RORC expression (sum of their within-sample ranks).

RESULTS: Six out of eight schizophrenia patients were classified as responders and showed large symptomatic improvement (median PANSS change -70.1) and marked functional gain (median PSP +22.5). Within the analytic sample, schizophrenia responders (n = 6) had higher baseline TBX21 and RORC expression than non-responders (n = 8). Baseline TBX21 correlated with PSP improvement at week 12 (rs = 0.675, p < 0.01). The TBX21+RORC composite rank score showed the strongest association with outcome (higher in responders, p < 0.001; correlated with PSP gain, rs = 0.793, p < 0.001). Classical inflammatory markers, including IL-6, TNF-α and high-sensitivity C-reactive protein, did not differentiate responders.

DISCUSSION: Elevated baseline expression of the Th1- and Th17-associated transcription factors TBX21 and RORC - particularly their combined composite rank score - was associated with symptomatic and functional response to rituximab in treatment-resistant schizophrenia. The data suggest that a TBX21/RORC-defined, Th1/Th17-skewed T-cell signature may characterize a rituximab-responsive immunopsychiatric subtype of schizophrenia, in which B-cell depletion may secondarily modulate pathogenic T-cell response. These findings should be viewed as preliminary and hypothesis-generating for future controlled studies.

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.