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  • Annerbrink, Kristina, et al. (författare)
  • Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid.
  • 2010
  • Ingår i: Psychiatry research. - 0165-1781. ; 179:2, s. 231-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Haukvik, Unn Kristin, et al. (författare)
  • Cerebral cortical thickness and a history of obstetric complications in schizophrenia
  • 2009
  • Ingår i: Journal of Psychiatric Research. - Elsevier. - 1879-1379. ; 43:16, s. 1287-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have thinner brain cortices compared with healthy control subjects. Neurodevelopment is vulnerable to obstetric complications (OCs) such as hypoxia and birth trauma, factors that are also related to increased risk of developing schizophrenia. With the hypothesis that OCs might explain the thinner cortices found in schizophrenia, we studied patients with schizophrenia and healthy controls subjects for association between number and severity of OCs and variation in cortical thickness. Methods: MRI scans of 54 adults with schizophrenia or schizoaffective disorder and 54 healthy controls were acquired at Karolinska Institutet, Stockholm, Sweden. Measures of brain cortical thickness were obtained using automated computer processing (FreeSurfer). OCs were assessed from obstetric records and scored blindly according to the McNeil-Sjostrom scale. At numerous cortical locations, putative effects of OCs on cortical thickness variation were tested for each trimester, for labour, for composite OC scores, severe OC scores, and hypoxia scores among patients and controls separately. Results: Number and severity of OCs varied among both patient and control subjects but were not associated with cortical thickness in either of the groups. Patients demonstrated thinner brain cortices but there were no significant differences in number and severity of OC scores across groups. Conclusion: In the present study, number and severity of obstetric complications were not associated with brain cortical thickness, in patients with schizophrenia or in healthy control subjects. The thinner brain cortices found in patients with schizophrenia were not explained by a history of OCs. (C) 2009 Elsevier Ltd. All rights reserved.
  • Jonsson, Erik G., et al. (författare)
  • Use of antipsychotics - An analysis of lifetime treatment in 66 patients with psychoses
  • 2011
  • Ingår i: Psychiatry Research. - Elsevier. - 1872-7123. ; 187:1-2, s. 80-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Only a minority of patients treated with antipsychotics in clinical studies continue their treatments throughout a longer study period. Few studies address this issue from a lifetime perspective. In this naturalistic study, we aimed at analysing the prescription pattern of antipsychotic drugs among a sample of Swedish patients with a diagnosis of psychotic illness, from the first contact with psychiatry (typically between 1973 and 1997) until the last written note in the case history documents. A retrospective descriptive analysis was performed of all case history data of 66 patients diagnosed with schizophrenia or related psychotic disorders. Patients with schizophrenia were prescribed antipsychotic medication more than 90% of the time. Each patient generally had been prescribed several (up to 16) different antipsychotic drugs and a quarter of the patients had been prescribed two or more antipsychotics for a third of their prescription time. Patients with psychosis were exposed to a cumulatively growing number of antipsychotics. Various factors, including clinician and patient expectations, and specific strengths and limitations of available antipsychotics may account for frequent medication changes over time. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  • Olafsson, Sigurgeir, et al. (författare)
  • Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
  • 2017
  • Ingår i: npj Genomic Medicine. - Nature Publishing Group. - 2056-7944. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10-7, 4.3 × 10-9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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