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- 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. |
- 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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| 3. |
- Bränn, Emma, 1988-
(författare)
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Biomarkers for Peripartum Depression : Focusing on aspects of the immune system and the metabolome
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripartum depression is a common, multifactorial, and potentially devastating disease among new mothers. A biological marker for peripartum depression would facilitate early detection, better understanding of the pathophysiology, and identification of targets for treatment. Evidence is growing for a potential role of the immune system in depression outside the peripartum period. Major adaptations of the immune system occur during pregnancy, justifying the search for immunological markers for peripartum depression. The immune system is very complex and dynamic during pregnancy, complicating the study of associations with depression. The metabolome is also affected by pregnancy and is linked to the immune system via, e.g., the microbiota. Hence, metabolomic profiling could increase the understanding of peripartum depression. This thesis aimed to explore inflammatory markers and metabolic profiles in the peripartum period, in order to discover possible biomarkers, and to increase the understanding of the pathophysiology of peripartum depression.All studies were conducted within the Biology, Affect, Stress, Imaging, and Cognition (BASIC) study. The Edinburgh Postnatal Depression Scale and the Mini International Neuropsychiatric Interview were used to assess depressive symptoms. Multiplex Proximity Extension assays were used to analyze inflammatory markers in pregnancy and postpartum. Luminex Bio-Plex Pro Human Cytokine Assays were used to analyze cytokine levels across the peripartum period, and gas chromatography-mass spectrometry metabolomics were used for metabolic profiling. No marker was discriminative enough to be used on its own as a biomarker for peripartum depression. However, several inflammatory markers (such as STAM-BP, TRANCE, HGF, IL-18, FGF-23, and CXCL1) were identified as possible candidates for more advanced diagnostic algorithms. The results further pointed towards the importance of adaptation of the immune system during pregnancy and postpartum, where levels of cytokines such as VEGF-A might have an important role in antenatal and postpartum depression. The results even highlight the importance of examination timing. Lastly, the metabolic profiling suggested different subgroups of women with postpartum depressive symptoms, supporting theories of peripartum depression being a heterogeneous disease in need of subgroup definition.
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| 4. |
- Sundberg, Isak
(författare)
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Exploring Links between Melatonin, Inflammation and Depression
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Major depressive disorder (MDD) is one of the leading global causes of disease burden. Worse yet, about one third of the patients with MDD do not experience a remission with current treatments. The symptoms of MDD likely represent a variety of underlying pathologic processes and more knowledge about these processes is needed to optimize treatment for MDD. The focus of this thesis was to study the relationship between inflammation, melatonin and symptoms of depression. In papers I-III a population of young adults seeking psychiatric care was examined for depressive symptoms, melatonin levels in saliva, gastrointestinal (GI) symptoms and inflammatory markers in blood. In paper IV a cohort of patients with hepatitis C receiving treatment with new direct-acting agents (DAAs) were prospectively followed during treatment for depressive symptoms and sleep.All patients were diagnosed by means of structured or semi-structured interviews and depressive symptoms were assessed with the self-rating version of the Montgomery Åsberg Depression Rating Scale. Sleep quality was measured by the Pittsburgh Sleep Quality Index, and GI symptoms were assessed with the Gastrointestinal Symptom Rating Scale-IBS. Melatonin in saliva was measured using enzyme-linked immunosorbent assay, and inflammatory markers in blood were analysed by proximity extension assay.In young adults seeking psychiatric care melatonin levels at bedtime were inversely correlated with depressive symptoms. In those patients with a current depressive episode low melatonin values at bedtime were a negative prognostic factor for response after 6 months (paper I). Postprandial melatonin levels were positively associated with GI symptoms of bloating and pain (paper II). Postprandial melatonin levels were also associated with the inflammatory markers vascular endothelial growth factor A (VEGF-A), monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1α (MIP-1α). Evening levels of melatonin did not correlate with the inflammatory markers. VEGF-A and MCP-1 as well as postprandial levels of melatonin correlated with a diagnosis of anxiety disorder, whereas MIP-1α correlated with MDD (paper III). Patients with hepatitis C underwent treatment with DAAs without experiencing pronounced psychiatric side effects in terms of depressive symptoms or sleep disturbances (paper IV).In summary, the findings confirm a relationship between bedtime melatonin levels and depressive symptoms. The findings also show a connection between daytime melatonin and GI-symptoms. In addition, the findings indicate an association between inflammation and daytime melatonin. Together these results demonstrate links between melatonin, inflammation and depression. Lastly, interferon-free treatment against hepatitis C did not induce depressive symptoms.
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