| 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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| 11. |
- Eckerström, Joachim, et al.
(författare)
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Brief admission for patients with emotional instability and self-harm : A qualitative analysis of patients' experiences during crisis
- 2020
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Ingår i: International Journal of Mental Health Nursing. - : John Wiley & Sons. - 1445-8330 .- 1447-0349. ; 29:5, s. 962-971
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies report that individuals diagnosed with borderline personality disorder have been met by negative attitudes from healthcare professionals and their care needs have often been neglected during hospitalizations. When symptoms of emotional instability are combined with self-harm, the resulting crisis often becomes difficult to handle for patients and healthcare professionals. To meet their care needs during these crises, an intervention called 'brief admission' (BA) has been developed. The purpose of BA is to provide a timeout, in situations of increased stress and threat, in order to foster self-management in a safe environment. In the present study, we explored the following research questions: What are patients' experiences with BA? What do patients consider to be the key components of BA? What improvements are considered relevant by patients? A qualitative design was employed, and 15 patients (13 females, 2 males; mean age 38.5 ± 12.9, range 20-67 years) were interviewed using a semi-structured interview guide. Thematic analyses were performed, which yielded four themes related to the patients' experiences: 'a timeout when life is tough', 'it is comforting to know that help exists', 'encouraged to take personal responsibility', and 'it is helpful to see the problems from a different perspective'. Four themes also described the key components: 'a clear treatment plan', 'a smooth admission procedure', 'a friendly and welcoming approach from the staff', and 'daily conversations'. Lastly, three themes described areas for improvements: 'feeling guilty about seeking BA', 'room occupancy issues', and 'differences in staff's competence'. Collectively, the findings indicate that BA constructively supports patients with emotional instability and self-harm during a period of crisis.
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| 12. |
- Eckerström, Joachim, et al.
(författare)
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Patient-Initiated Brief Admission for Individuals with Emotional Instability and Self-Harm : An Evaluation of Psychiatric Symptoms and Health-Related Quality of Life
- 2022
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Ingår i: Issues in Mental Health Nursing. - : Taylor & Francis. - 0161-2840 .- 1096-4673. ; 43:7, s. 593-602
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Tidskriftsartikel (refereegranskat)abstract
- Patient-initiated brief admission (PIBA) was developed for patients with emotional instability and self-harm, to cope with crises. The hypothesis was that psychiatric symptoms would decrease, and health-related quality of life (HRQoL) increase, after 1-3 days at hospital. One hundred and thirteen patients were recruited from a psychiatric clinic in Stockholm during 2016-2020. At admission and discharge, the patients completed the Hospital Anxiety and Depression Scale (HADS) and the EuroQoL-5 Dimension Questionnaire (EQ-5D). The patients also evaluated PIBA as a crisis intervention. A significant decrease in symptoms of anxiety and depression was found. HRQoL increased significantly assessed with EQ-5D and 95.2% of the participants found PIBA to be a constructive intervention.
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| 13. |
- Fatouros-Bergman, Helena, et al.
(författare)
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Meta-analysis of cognitive performance in drug-naive patients with schizophrenia
- 2014
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 158:1-3, s. 156-162
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive deficits represent a significant characteristic of schizophrenia. However, a majority of the clinical studies have been conducted in antipsychotic drug treated patients. Thus, it remains unclear if significant cognitive impairments exist in the absence of medication. This is the first meta-analysis of cognitive findings in drug-na ve patients with schizophrenia. Cognitive data from 23 studies encompassing 1106 patients and 1385 controls published from 1992 to 2013 were included. Tests were to a large extent ordered in cognitive domains according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. Analysis was performed with STATA using the random-effects model and heterogeneity as well as Egger's publication bias was assessed. Overall the results show that patients performed worse than healthy controls in all cognitive domains with medium to large effect sizes. Verbal memory, speed of processing and working memory were three of the domains with the greatest impairments. The pattern of results is in line with previous meta-analytic findings in antipsychotic treated patients. The present meta-analysis confirms the existence of significant cognitive impairments at the early stage of the illness in the absence of antipsychotic medication.
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| 14. |
- Flyckt, Lena, et al.
(författare)
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Aberrant tyrosine transport across the fibroblast membrane in patients with schizophrenia : indications of maternal inheritance
- 2011
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Ingår i: Journal of Psychiatric Research. - : Pergamon Press. - 0022-3956 .- 1879-1379. ; 45:4, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- Background: In previous studies of the present patients with schizophrenia, aberrant tyrosine transport across the fibroblast membrane was found. A low K(m), a kinetic factor indicating high affinity between tyrosine and the binding site at the cell membrane, was found to be associated with poor cognitive functions in patients. The present study aimed at investigating possible relationships between patients with schizophrenia and their first-degree relatives in aberrant tyrosine transport indicating that it may be a biological marker for the genetic susceptibility. Methods: Thirty-three parents, 13 fathers and 20 mothers, from 23 families with a schizophrenic patient agreed to enter the study. They underwent skin biopsies for fibroblast cultivation, neuropsychological and psychiatric investigations and were classified as family history positive or negative. Tyrosine transport kinetics (K(m) and V(max)) were calculated from in vitro trials of gradients of extracellular tyrosine concentrations in fibroblast cultures. Results: An association between patients with schizophrenia and their mothers were found for a low K(m) indicating maternal inheritance. Mothers displaying a low K(m) performed worse on the neuropsychological tests compared to mothers with normal K(m). Corresponding relationships between a low K(m) and neurocognitive dysfunction had previously been found for the patients. Conclusions: An aberrant tyrosine transport across plasma membrane may constitute a biological marker for an endophenotype within the schizophrenia spectrum with low cognitive functioning. A plausible mode for genetic transmission is maternal inheritance. (C) 2010 Elsevier Ltd. All rights reserved.
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| 15. |
- Flyckt, Lena, et al.
(författare)
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Predicting 5-year outcome in first-episode psychosis: Construction of a prognostic rating scale
- 2006
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Ingår i: Journal of Clinical Psychiatry. - 0160-6689. ; 67:6, s. 916-924
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to construct a rating scale to predict long-term outcome on the basis of clinical and sociodemographic characteristics in patients with symptoms of psychosis who seek psychiatric help for the first time. Method: Patients (N = 153) experiencing their first episode of psychosis (DSM-IV schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic episode, delusional disorder, affective psychosis with mood-incongruent delusions, or psychotic disorder not otherwise specified or being actively psychotic) were consecutively recruited from 17 psychiatric clinics in Sweden from January 1996 through December 1997 (24 months). Baseline characteristics were assessed with an extensive battery of psychiatric rating scales; duration of untreated psychosis, premorbid characteristics, and cognitive functioning were also assessed. The relationship between baseline characteristics and the 5-year outcome was analyzed using a stepwise logistic regression model. Results: In the logistic regression analysis, 5 variables were found to have unique contributions in the prediction of outcome. In order of magnitude of the odds ratios, these variables were Global Assessment of Functioning (GAF) score during the year before first admission, education level, actual GAF score at first admission, gender, and social network. The sensitivity, i.e., correctly identified cases (poor outcome), was 0.84, and the specificity, i.e., the correctly identified non-cases (good outcome), was 0.77. Conclusion: To initiate adequate interventions, it is crucial to identify patients experiencing their first episode of psychosis who are likely to have an unfavorable long-term outcome. The predictive rating scale described here is a feasible tool for early detection of these patients.
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| 16. |
- Flyckt, Lena
(författare)
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Schizophrenia as a systemic disorder : studies of peripheral and central biological functions
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychiatric disturbances with an onset in adulthood may show subtle signs in childhood and school age. This is particularly applicable to patients with schizophrenia. A plasma membrane disturbance has been proposed as a common denominator responsible for both the central nervous system abnormalities and the changes in peripheral organs in patients with schizophrenia. The aim of the present thesis was to investigate central (neuropsychological, neurological and psychomotor) and peripheral (neuromuscular, tyrosine transport across the cell membrane) functions in schizophrenia with tyrosine kinetics as an indicator of membrane function. Another aim was to study possible familial transmission(s) of central and peripheral biological changes by investigating the occurrences of such abnormalities in unaffected first-degree relatives to the patients. Patients with schizophrenia (n = 39) their first degree- relatives (n = 44) and healthy controls (n = 55) were investigated according to the below listed studies. I. Clinical neurological investigation of neurological signs were performed. Psychomotor functions were investigated using the finger tapping, Purdue pegboard and pronation-supination tests, hand grasp strength, and gait. II. Histopathological examination of the skeletal muscle fibre was performed. The electrophysiological properties of the motor unit was studied in patients with schizophrenia and controls using the macro electromyographical (EMG) technique. III. Investigation of the muscle fibre histology and electrophysiology was performed as in study II in unaffected first-degree relatives to patients with schizophrenia. IV. Tyrosine transport (Km and Vmax) across the cell membrane was investigated in vitro using cultivated fibroblasts from patient with schizophrenia and healthy controls. V. Cognitive functions in patients with schizophrenia, their first-degree relatives and controls were assessed using an extensive battery of neuropsychological tests. Patients with schizophrenia exhibited neurological abnormalities and aberrant psychomotor performance to a significantly greater extent than healthy controls. Neuromuscular changes were found significantly more often in patients with schizophrenia and their unaffected first-degree relatives compared to controls. The most frequent histopathological finding in patients was muscle fibre atrophies, affecting both type I and type II fibres. Increased amplitude and area of the motor unit action potentials were found in the macro EMG recordings from patients and relatives but not in that from controls. The patients exhibited aberrant tyrosine transport kinetics with significantly lower Vmax (indicating lower tyrosine transport) and Km (indicating higher affinity) compared to controls. Finally, the patients performed significantly worse than their first-degree relatives and the controls in most of the neuropsychological tests and this significantly correlated with a lower level of functioning. Biological and clinical changes have been demonstrated deriving both from the central nervous system and peripheral organs indicating that schizophrenia is a systemic disease. Furthermore, the type of macro EMG findings and tyrosine transport aberrations indicate a membrane dysfunction. These results entail a different perspective on the ethiology of schizophrenia.
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| 17. |
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| 18. |
- Lee, Maria, et al.
(författare)
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No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis
- 2021
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Ingår i: NPJ SCHIZOPHRENIA. - : Springer Nature. - 2334-265X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [C-11]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (beta = 0.013-0.074, partial r= -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.
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| 19. |
- Lindgren, Timmy, et al.
(författare)
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Psychiatry Nurses' Experiences of Patient-Initiated Brief Admission from Inpatient and Outpatient Perspectives : A Qualitative Exploratory Study
- 2024
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Ingår i: Issues in Mental Health Nursing. - 1096-4673. ; 45:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Patient-initiated brief admission (PIBA) allows patients to decide when admission to psychiatric care is necessary. This may prevent long-term hospitalisation and promote patient participation. Research on psychiatric nurses' experiences with PIBA is lacking, therefore 11 nurses were interviewed and data analysed using content analysis. Prominent categories were: improved personal development for the patient, more equal nurse-patient relationship, rapid access to a safe environment and strengthened professional collaboration. PIBA is a helpful intervention for patients in crisis, giving both patients and nurses a sense of security. Future studies should explore how this impacts nurses' work environment and job satisfaction.
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| 20. |
- Lindkvist, Rose Marie, et al.
(författare)
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Brief admission by self-referral as an add-on to usual care for individuals with self-harm at risk of suicide : cost-effectiveness and 4-year health-economic consequences after a Swedish randomized controlled trial
- 2024
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Ingår i: Nordic Journal of Psychiatry. - 0803-9488.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brief Admission by self-referral (BA) is a crisis-management intervention standardized for individuals with self-harm at risk of suicide. We analyzed its health-economic consequences. Materials and methods: BA plus treatment as usual (TAU) was compared with TAU alone in a 12-month randomized controlled trial with 117 participants regarding costs for hospital admissions, coercive measures, emergency care and health outcomes (quality-adjusted life years; QALYs). Participants were followed from 12 months before baseline to up to five years after. Results: Over one year BA was associated with a mean annual cost reduction of 4800 or incremental cost of 4600 euros, depending on bed occupancy assumption. Cost-savings were greatest for individuals with >180 admission days in the year before baseline. In terms of health outcomes BA was associated with a QALY gain of 0.078. Uncertainty analyses indicated a significant QALY gain and ambiguity in costs, resulting in BA either dominating TAU or costing 59 000 euros per gained QALY. Conclusion: BA is likely to produce QALY gains for individuals living with self-harm and suicidality. Cost-effectiveness depends on targeting high-need individuals and comparable bed utilization between BA and other psychiatric admissions. Future research should elaborate the explanatory factors for individual variations in the usage and benefit of BA.
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| 21. |
- Lyle, Maria Smitmanis, et al.
(författare)
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What are the effects of implementing patient-controlled admissions in inpatient care? : A study protocol of a large-scale implementation and naturalistic evaluation for adult and adolescent patients with severe psychiatric conditions throughout Region Stockholm
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Patient-controlled admissions (PCAs) represent a change in psychiatric inpatient care where patients are allowed to decide for themselves when hospitalisation might be required. Prior research has demonstrated that PCA increase the number of admissions, but decrease days in inpatient care, while both the admissions to and days in involuntary care decrease. However, investigations have been restricted to specific patient groups arid have not examined other possible benefits, such as effects on symptoms, quality of life and autonomy. Methods and analysis This study explores the implementation process and effects of PCA in Region Stockholm, who is currently introducing PCA for all patients with severe psychiatric conditions and extensive healthcare utilisation. In total, the study comprises approximately 45 inpatient wards, including child and adolescent psychiatry. In a naturalistic evaluation, patients assigned PCA will be followed up to 36 months, both with regard to hospitalisation rates and self-reported outcomes. In addition, qualitative studies will explore the experiences of patients, caregivers of adolescents and healthcare providers. Ethics and dissemination Approval has been granted by the Swedish Ethical Review Authority (Dnr: 2020-06498). The findings from this study will be disseminated via publications in international peer-reviewed journals, at scientific conferences, as part of two doctoral theses, and through the Swedish Partnership for Mental Health.
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| 22. |
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| 23. |
- Skogh, Elisabeth, 1952-
(författare)
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Studies on Variability in Olanzapine Disposition
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Schizophrenia and schizoaffective disorders are chronic conditions with a significant impact on many functions. Positive, negative, cognitive and motor symptoms appear in different degrees and constellations. Antipsychotics are of fundamental importance to reduce symptoms. However, insufficient clinical effect and adverse drug reactions (ADRs) are important limitations of this drug therapy. Olanzapine (OLA) is a second-generation antipsychotic (SGA) drug widely used in the treatment of schizophrenia and schizoaffective disorder. The drug has well-documented effects against positive symptoms and has been claimed to be efficacious also against negative symptoms.This thesis comprises of two studies. The aim of study 1 was to investigate factors that may influence the inter- and intra-individual variability of steady-state trough concentrations of OLA and its N-desmethyl metabolite (DMO) in serum. This was done in a cohort of patients treated with oral OLA in a routine clinical setting. In study 2 steady-state trough serum OLA and DMO concentrations were studied in relation to cerebrospinal fluid (CSF) OLA and DMO concentrations in patients with schizophrenia or schizoaffective disorder, medicated with oral OLA as the only antipsychotic drug. We also analysed the effects of age, gender smoking and concomitant medication in both studies and in study 2 we also analysed polymorphisms in genes with suggested importance for OLA disposition. The drug metabolizing enzymes CYP1A2 and CYP2D6 have earlier been found to be of importance for OLA metabolism and one animal study has suggested a role for P-gp for the transport of OLA into the brain. Therefore we analysed the influence of single nucleotide polymorphisms in the CYP1A2 gene (-3860G>A, -2467T>delT, -739T>G, -729C>T, -163C>A, and in the CYP2D6 gene (*3, *4, *5,*6, and*41) and in the ABCB1 gene (1236C>T, 3435C>T, and 2677G>A/T).Study 1 started as a post-marketing surveillance project. In 1997 a high-performance liquid chromatography (HPLC)-based therapeutic drug monitoring (TDM) routine for serum OLA and DMO was established. During 1997–1999, a total of 753 TDM requests for a total of 545 Swedish patients were analysed. Additional patient information on certain clinical variables was collected on a specifically designed TDM request form. Samples from 194 patients were found to be eligible for further scrutiny. We found that the concentration-to-dose ratio (C/D) for OLA varied 25-fold and that of DMO 22-fold between individuals. The intraindividual variability over time was lower. Women had significantly higher median C/D ratio for OLA than men. However, the higher C/D ratio for OLA in women was statistically significant only in the non-smoking group. Non-smokers had significantly higher C/D ratio for OLA than smokers. Smokers received significantly higher daily doses of OLA than non-smokers. In the group with reported ADRs, the serum OLA concentration was 22% higher than in the group without ADRs. Patients co-medicated with carbamazepine had a 71% lower C/D ratio for OLA than patients who did not co-medicate with carbamazepine.Study 2 included 37 Caucasian outpatients (10 smokers and 27 non-smokers). CSF was collected from 29 out of them. Because of very low OLA and DMO concentrations in CSF, a new liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for determination of OLA and DMO in serum and CSF was developed. We found a strong correlation between serum and CSF concentrations of OLA and a somewhat weaker corresponding correlation regarding DMO. The median CSF concentrations of OLA and DMO were on an average 13% and 16% of the serum levels. Non-smokers had higher (P <0.01) C/D ratio for OLA in serum and in CSF than smokers. Extensive metabolizers (EM) of CYP2D6 had higher daily OLA dosages than poor metabolizers (PM) when the influence of smoking was taken into account. EM smokers also showed lower CSF C/D for DMO than PM smokers. The DMO/OLA ratio in CSF showed a similar pattern, with a statistically significant combined effect of smoking and CYP2D6 genotype, EM smokers having the lowest and PM smokers the highest ratio. The combination of smoking and CYP2D6 genotype also affected the CSF/serum DMO ratio, PM smokers having the highest and EM smokers the lowest ratio (mean 20%, vs 9.5%). Patients co-medicating with benzodiazepines also showed higher CSF DMO/OLA ratio than patients without benzodiazepines. Moreover, DMO concentrations in CSF in relation to serum were higher in benzodiazepine users than in patients not comedicating with benzodiazepines (mean 24% vs 14.4%). Smoking habits did not affect these results. Carriers of the ABCB1 1236T/2677T/3435T haplotype had higher serum and CSF OLA concentrations than patients without this haplotype. The C/D ratios for serum DMO decreased with increasing age (P < 0.05).In summary, smoking habits and co-medication with carbamazepine should be taken into consideration when dosing OLA. In study 1 we noted that women had higher serum C/D OLA ratio than men among non-smokers. This could not be confirmed in study 2, probably due to the small study population. Polymorphisms in genes of importance for OLA metabolism (CYP1A2 and CYP2D6) and transport (ABCB1) over membranes have some, but probably a minor, effect on serum and CSF concentrations. Larger studies are needed to confirm these observations. Smoking in combination with CYP2D6 polymorphism and the use of benzodiazepines affected the DMO metabolism in the brain in this study. However, because of low precision in the method at low DMO concentrations and a low number of patients, these results must also be confirmed in larger studies. The strong correlation between serum and CSF OLA concentrations established in study 2 indicates that factors influencing serum concentrations (such as smoking) also influence these concentrations in CSF. When patients are non-responsive to treatment, not compliant, vulnerable to ADRs on standard doses, or when drug interactions are suspected, TDM serum-OLA concentrations can be used as a diagnostic tool. Therapeutic drug monitoring is also of value to optimize long-term treatment of patients as environmental factors such as smoking and drug interactions may differ over time and could markedly interact with a patient´s metabolic capacity and thereby the therapeutic outcome.
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| 24. |
- Stålberg, Gabriella, 1969-
(författare)
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Vulnerability and Social Functioning in Schizophrenia
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis offers a broad approach in elucidating biological risk factors, as well as psychological and social functioning in schizophrenia. The aims are as follows: (I) investigate the association between birth characteristics and schizophrenia, (II) study the association between levels of neurotransmitter neuropeptide Y (NPY) in cerebrospinal fluid (CSF), social function and longitudinal outcome in schizophrenia, (III) compare social functioning of patients with schizophrenia with their biological siblings and (IV) explore how siblings to patients with schizophrenia perceive the sibling relationship and their role.Paper I was a cohort analysis of 11,360 same-sexed twins in which obstetric records were used. Low birth weight and small head circumference were associated with later development of schizophrenia. To some extent the results persisted in the within-pair analyses conducted on 82 pairs discordant for schizophrenia.Fifty-six patients with schizophrenia were included in paper II. Levels of NPY in CSF correlated to social competence at index admission. For each standard deviation increase in baseline NPY, there was a concomitant increased risk of being unemployed, having moderate or severe symptoms or recent hospitalization at the 3-year follow-up.In paper III, social functioning was investigated using the Swedish version of the videotaped test Assessment of Interpersonal Problem Solving Skills (AIPSS) in 70 participants (25 patients with schizophrenia, 20 siblings and 25 randomly selected controls). The patients presented severe deficits in social functioning. The siblings expressed subtle impairments in nonverbal language but did not generally differ from the controls.To explore the siblings’ perspective on schizophrenia a qualitative study was conducted with interviews of 16 siblings in paper IV. A unifying major theme was an emotional sibling bond. Siblings developed several coping patterns, including avoidance, isolation, normalization, care giving and grieving. A third major theme consisted of the fear of inheriting schizophrenia.In conclusion, fetal growth, altered levels of NPY in CSF and subtle impairments in nonverbal social behavior might be important risk factors in schizophrenia. Patients with schizophrenia revealed extensive impaired social functioning, and from the siblings’ perspective, a brother or sister’s diagnosis of schizophrenia seems to have a profound psychological impact on the siblings.
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| 25. |
- Tønnesen, Siren, et al.
(författare)
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Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder : A Multisample Diffusion Tensor Imaging Study
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 2451-9022 .- 2451-9030. ; 5:12, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts.METHODS: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.RESULTS: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics.CONCLUSIONS: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
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