| 1. |
- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
- Malmqvist, Anna, et al.
(författare)
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Increased peripheral levels of TARC/CCL17 in first episode psychosis patients
- 2019
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Ingår i: Schizophrenia Research. - : ELSEVIER. - 0920-9964 .- 1573-2509. ; 210, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
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| 3. |
- Alenius, Malin, 1974-
(författare)
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Treatment Response in Psychotic Patients in a Naturalistic Setting : Classification, Genes, Drugs, Insight and Social Networks
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many patients with psychotic symptoms respond poorly to treatment. Various approaches have been made to classify these patients according to treatment response. However, existing classifications have been criticized for various reasons and a new classification system is needed. Further, no satisfactory explanation of the poor treatment response has been apparent. The general aim of this thesis was therefore to develop and validate a new classification method of functional remission in a naturalistic population of patients with psychosis and to utilize this classification to investigate the population from genetic, drug treatment, insight and social network points of view. Data for this cross-sectional study of patients (n=123) attending the Psychosis Outpatient Care clinic in the county of Jönköping, Sweden, were obtained from patient interviews, blood samples and information from patient files. The new classification method CANSEPT, which combines the CAN rating scale (CAN), the UKU side effect rating scale (SE) and the patient’s previous treatment history (PT), showed validity in discriminating the patients and was accepted well by the patients. CANSEPT was used to group the patients in the other studies in this thesis. The results indicated that the gene polymorphism ABCB1 3435T, was related to worse significant social and clinical needs for patients on olanzapine, while the polymorphism DRD2 Taq1 A1 was related to a greater risk of significant side effects; especially if male, or taking strong dopamine D2-receptor antagonistic drugs. Drug treatment factors were also related to treatment response; longer duration of untreated prodromal and early psychosis was seen for patients with current significant social and clinical needs and non-adherence to treatment was associated with worse significant side effects. Worse treatment outcomes also appeared to be associated with smaller social network groups, worse insight into illness, poorer knowledge of warning signs and worse coping strategies. In summary, CANSEPT was shown to be a useful valid, multidimensional tool for classification of treatment response. Gene polymorphisms, duration of untreated illness, non-adherence to treatment, social networks and knowledge should be taken into consideration when investigating inadequate treatment response.
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| 4. |
- Alnaes, Dag, et al.
(författare)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 5. |
- Becklén, Meneca, et al.
(författare)
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Plasma bilirubin levels are reduced in first-episode psychosis patients and associates to working memory and duration of untreated psychosis.
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a severe mental disorder and one of its characteristics is cognitive impairments. Findings regarding levels of the heme metabolite and plasma antioxidant bilirubin in schizophrenia are inconclusive. However, a recently published study indicate that low levels of bilirubin may be implicated in the memory impairments seen in the disorder. The aim of this cross-sectional study was to investigate the levels of bilirubin in individuals with a first-episode psychosis (FEP) and to examine if bilirubin levels were associated to cognitive impairments, symptoms and duration of untreated psychosis (DUP). Bilirubin levels were reduced in 39 individuals with FEP compared with 20 HC (median [IQR]: 11.0 [9.0-13.0] µM vs. 15.0 [11.5-18.5] µM). In individuals with FEP, bilirubin levels were also positively correlated to two working memory tests (r = 0.40 and r = 0.32) and inversely correlated to DUP (r = - 0.36). Findings were not influenced by confounding factors. The results confirm the antioxidant deficit previously seen in schizophrenia, but also indicate that these changes may be related to DUP. The study also confirms that bilirubin may be implicated in the cognitive deficits that accompanies the disorder, here for the first time presented in individuals with FEP.
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| 6. |
- Bodén, Robert, 1973-
(författare)
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Prognostic Factors in First-Episode Schizophrenia : Five-year Outcome of Symptoms, Function and Obesity
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Our knowledge of prognostic factors and optimal treatment organisation in schizophrenia is incomplete. The disparity of outcome measures used has been a major obstacle for research. Increasing evidence has shown that schizophrenia is associated with increased cardiovascular mortality, development of obesity and autonomic nervous system imbalance. Assertive community treatment (ACT) has been suggested as a promising direction for organising treatment services for first-episode schizophrenia, but its long-term effect has not been evaluated. One aim of the present thesis was to investigate prognostic factors for 5-year symptomatic and functional outcome and obesity development. A further aim was to evaluate a recently proposed definition of remission and examine the long-term effects of introducing a modified ACT programme (mACT). Thus, we performed a follow-up study of all consecutive first-episode psychosis patients in Uppsala County, Sweden during 1995-2000 (n=144). In the first study we investigated the changes in a broad 5-year outcome of symptoms and function among patients presenting first time ever to psychiatric health care during 3 years before and during 3 years after the implementation of mACT. This change in the psychiatric service, however, was not followed by any long-term clinical benefits. In the second study, we examined the association between remission of eight core schizophrenia symptoms and functional outcome. Remission was strongly associated with having good function and having a higher self-rated satisfaction with life. In the third study, we explored a set of biochemical markers as predictors of weight gain and development of obesity. Haemoglobin, red blood cell count, hematocrit, γ-glutamyltransferase and creatinine were associated with the development of obesity in first-episode schizophrenia. In the fourth and final study, we tested electrocardiographic measures of autonomic imbalance as predictors of symptomatic remission. Higher heart rate and high ST and T-wave amplitudes were related to symptomatic remission, indicating that cardiac autonomic imbalance at baseline may have a prognostic value in first-episode schizophrenia.
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| 7. |
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| 8. |
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| 9. |
- Comasco, Erika, 1982-, et al.
(författare)
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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
- 2017
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Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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| 10. |
- Eckerström, Joachim, 1982-, et al.
(författare)
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Brief admission (BA) for patients with emotional instability and self-harm : nurses’ perspectives - person-centred care in clinical practice
- 2019
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Taylor & Francis. - 1748-2623 .- 1748-2631. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Emotional instability and self-harm pose major problems for society and health care. There are effective interventions in outpatient care, but when patients need inpatient care, nurses often struggle meeting their patient’s needs. Brief admission (BA) is a newly implemented crisis intervention and novel form of inpatient care. The aim of this study is to describe nurses’ experiences working with BA related to patients with emotional instability and self-harm.Methods: Eight nurses were interviewed according to a semi-structured interview guide. The data was analysed using qualitative content analysis.Results: Four main categories emerged regarding nurses’ experiences with BA: provides security and continuity, fosters caring relationships, shifts focus towards patient’s health and empowers the patient. The nurse’s role shifted from “handling problems” to establishing caring relationships with a focus on the person’s health and possibilities for recovering instead of psychiatric symptoms.Conclusions: Previous studies on patients’ perspective of BA describe positive experiences such as increased autonomy and participation in the healthcare process. This study supports those findings, albeit from the perspective of nurses. Our findings suggest that BA may reduce work-related stress experienced by nurses while caring for persons with emotional instability and self-harm. BA may also support nurses in their ability to provide more meaningful and constructive psychiatric inpatient care.
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