| 1. |
- Hylén, Ulrika, 1977-
(författare)
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Immunopsychiatry from a transdiagnostic perspective : the immunometabolic interplay
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objective: Psychiatric disorders are common and they significantly impact quality of life. It has been proposed that inflammatory processescontribute to the emergence of psychiatric disorders. In addition to inflammation, disturbances in metabolic pathways have been seen in individuals with various psychiatric disorders. At the interface between inflammation and metabolism stands the Nod-like receptor 3 (NLRP3) inflammasome, which is anintracellular protein complex responsible for cleaving members of the interleukin-1(IL-1) to their active forms. The overall aim of this thesis project was tounderstand the interplay between metabolism and inflammation in a transdiagnostic cohort of individuals with severe psychiatric disorders.Methods: Patients with severe psychiatric disorder (n=39) and age- and sexmatched healthy controls (n=39) were included in the studies. Psychiatric diagnoses, comorbidities, severity, and functioning were measured using a numberof validated assessment scales. Biological parameters, such as circulating immune markers, gene expression, and metabolites were analyzed using electrochemiluminescence immunoassay, qPCR, and UHPLC-MSMS, respectively. Results: The results revealed that in individuals with psychiatric disorders, immune cells were primed in regard to the NLRP3 inflammasome, with elevatedinflammasome-related cytokine levels, regardless of diagnosis. In addition, positive metabolic inflammasome regulators, such as lactic acid, serine, and glutamine were significantly higher in the patients; the main metabolic pathwaysthat were affected included arginine and proline metabolism and tryptophan metabolism. A number of these parameters also correlated with the patients’ disease severity. Lastly, the patients as a group displayed transdiagnosticchanges in immune–lipid pathways. In particular, strong associations could beobserved between two triglycerides and one ether phospholipid, with the inflammatory markers osteopontin and IL-1Ra.Conclusion: Severe psychiatric disorders are associated with changes in the inflammasome system and its corresponding cytokines, as well as with metabolicdysregulation. The data indicate that, while these systems are known to be associated, their interplay seems limited to relatively few inflammatory mediatorsand metabolites in this patient group. Lastly, while large overlaps were seen between different primary diagnoses, unifying, transdiagnostic patterns of inflammatory and metabolic dysregulation were weak; further studies with a largercohort are needed to examine this issue.
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| 2. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder : Two open-label pilot studies on treatment-resistant patients
- 2023
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Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 158, s. 319-329
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Glans, Martin, 1985-
(författare)
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The relationship between generalised joint hypermobility and neurodevelopment disorders
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge about comorbidities is important since they often can affect the diagnoses, treatment and outcome of a patient. Moreover, it may provide an insight to biological underpinnings contributing to the association. Generalised joint hypermobility (GJH) has recently been suggested to be a common, yet unrecognized, comorbidity amongst individuals with NDDs. In the present thesis we aimed to evaluate the relationships between GJH and ADHD and GJH and ASD across the full clinical and non-clinical spectra. Moreover, we aimed to make available a simple screening tool for GJH for Swedish speakers.In study I we translated the five-part questionnaire on hypermobility (5PQ) into Swedish and tested psychometric properties in a non-clinical adult population (n=315). The Swedish 5PQ showed good psychometric properties in the general adult population with a sensitivity of 91%, a specificity of 75%, and an AUC of 0.87. Thus, it is a promising measure for GJH screening in adults. In studies II and III we measured GJH in large cohorts of adults with ADHD (n=431), ASD (n=199) and general population controls (n=419). We evaluated the associations between GJH and ADHD and GJH and ASD by using logistic regression models, while adjusting for age, sex and ethnicity. GJH was associated with ADHD and ASD with adjusted odds ratios of 4.7 and 3.1, respectively.In study IV a large cohort of adults from the general population (n=887) completed a survey form comprising the 5PQ and questions regarding symptoms and traits of ADHD, ASD and motor impairment. Responses were compared between GJH and non-GJH individuals. We found that sub-syndromal neurodevelopmental symptoms were not affected by GJH. Thus, the association between GJH and NDDs appears to be limited to clinical populations. However, the hypothesis needs to be tested with a physical assessment of GJH before any firm conclusions can be drawn.
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| 4. |
- Popiolek, Katarzyna, 1981-
(författare)
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Electroconvulsive therapy for bipolar disorder
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims This thesis aimed to investigate 1. the effectiveness of electroconvulsivetherapy (ECT) in bipolar depression and mania in real-life settings; 2. the prognostic factors of response to ECT; 3. readmission ratesand risk factors after the acute phase of bipolar disorder; and 4. the association between ECT and readmission rate in mania.Methods This thesis includes four nationwide register studies. Data came from several national registers linked by personal identity numbers.Results Response was achieved in 80.2% of ECT-treated patients with bipolardepression and 84.4% of ECT-treated patients with mania. Younger age was associated with a lower response rate to ECT in depressive episodes. Patients aged 16–30 years had a lower chance of responding than patients aged 31–40 years, 61–70, and 71–80 years. Response to ECT in mania was associated with the severity of symptoms. Patients who were markedly ill, severely ill, and among the most extremely ill had a higher chance of responding than patients with mild to moderate illness. Relapse within 3, 6, and 12 months after bipolar depression was reached by 29%, 41%, and 52% of patients, respectively. After manic episodes, 30%, 41%, and 55% of patients were readmitted within 3, 6, and 12 months, respectively. Treatment with ECT was not associated with a longer time to readmission after a manic episode than other treatments.Conclusions Over 80% of patients with bipolar depression and mania responded to ECT. In depressive episodes, patients at lower ages had a lower chance of achieving response after ECT, and in mania, patients with more severe symptoms had a higher chance of responding to ECT. The readmission rate after both manic and depressive episodes was high. There was no significant difference between time to readmission in patients treated with and without ECT during index admission for mania.
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