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  • Meehan, A. D., et al. (författare)
  • Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management
  • 2018
  • Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 42:2, s. 415-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism. Methods Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations. Results The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years. Conclusion The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.
  • Najar, Hemen, 1979, et al. (författare)
  • Weight gain with add-on second-generation antipsychotics in bipolar disorder: a naturalistic study
  • 2017
  • Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X .- 1600-0447. ; 135:6, s. 606-611
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveOur aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. MethodsData were derived from the quality register for bipolar disorder in Sweden (BipolaR). Patients with bipolar disorder who started add-on treatment with a SGA (n=575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer (n=566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as 7% gain in body weight. ResultsThe group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. ConclusionWe found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting.
  • Nordanskog, Pia, et al. (författare)
  • Electroconvulsive Therapy in Sweden 2013 : Data From the National Quality Register for ECT
  • 2015
  • Ingår i: The Journal of ECT. - Philadelphia, USA : Wolters Kluwer. - 1095-0680 .- 1533-4112. ; 31:4, s. 263-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013.Methods: The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT.Results: We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series.Conclusions: In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.
  • Popiolek, K., et al. (författare)
  • Rehospitalization and suicide following electroconvulsive therapy for bipolar depression–A population-based register study
  • 2018
  • Ingår i: Journal of Affective Disorders. - : ELSEVIER SCIENCE BV. - 0165-0327 .- 1573-2517. ; 226, s. 146-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Electroconvulsive therapy (ECT) is effective in bipolar depression, but relapse is common. The aim of the study was (i) to identify prognostic factors (ii) and to determine the impact of pharmacological approaches on the risk for rehospitalization or suicide. Methods This register study analyzed data from individuals treated with inpatient ECT for bipolar depression. Subjects were identified using the Swedish National Patient Register between 2011 and 2014 and the Swedish National Quality Register for ECT. Other national registers provided data on psychopharmacotherapy, socio-demographic factors, and causes of death. The endpoint was the composite of rehospitalization for any psychiatric disorder, suicide attempt or completed suicide (RoS). Cox regression was used to calculate hazard ratios in univariate and multivariate models. Results Data from 1255 patients were analyzed. The mean period of follow-up was 346 days. A total of 29%, 41%, and 52% of patients reached RoS at 3, 6, and 12 months post-discharge. A history of multiple psychiatric admissions, lower age, and post-discharge treatment with antipsychotics or benzodiazepines was associated with RoS. Limitations Indication bias may have affected the results. Conclusions A history of multiple hospital admissions and lower age are key predictors of the composite of rehospitalization or suicide in patients treated with ECT for bipolar depression. Lithium might be effective. By contrast, antipsychotics and benzodiazepines were associated with increased risk, but possibly this finding was influenced by indication bias. © 2017 The Authors
  • Rolstad, Sindre, 1976, et al. (författare)
  • CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment.
  • 2015
  • Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - 1873-7862. ; 25:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent cognitive impairment in the euthymic state of bipolar disorder is increasingly recognized. Mounting evidence also suggests an association between neuroinflammation and cognitive dysfunction. The purpose of this study was to test if cerebrospinal fluid (CSF) markers of neuroinflammation could account for cognitive impairment in bipolar disorder. Hierarchical linear regression models were applied to account for performance in five cognitive domains using CSF neuroinflammatory biomarkers as predictors in patients with bipolar disorder type I and II (N=78). The associations between these biomarkers and cognition were further tested in healthy age- and sex-matched controls (N=86). In patients with bipolar disorder, the CSF biomarkers accounted for a significant proportion of the variance in executive functions (42.8%, p=<.0005) independently of age, medication, disease status, and bipolar subtype. The microglial marker YKL-40 had a high impact (beta=-.99), and was the only biomarker that contributed individually. CSF biomarkers were not associated with cognitive performance in healthy controls. The CSF neuroinflammation biomarker YKL-40 is associated with executive performance in euthymic bipolar disorder, but not in healthy controls.
  • Rundgren, S., et al. (författare)
  • Improvement of postpartum depression and psychosis after electroconvulsive therapy: A population-based study with a matched comparison group
  • 2018
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 235, s. 258-264
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Electroconvulsive therapy (ECT) is used to treat postpartum depression and psychosis based on clinical experience and small observational studies. Aims: The primary aim was to test the hypothesis that the response rate to ECT for depression and psychosis is higher during the postpartum period than outside this period. The secondary aim was to identify predictors of a response to ECT during the postpartum period. Materials and methods: Cases with postpartum depression and/or psychosis received ECT within 6 months of delivery. A matched comparison group with depression and/or psychosis (not within the postpartum period) was identified from the Swedish National Quality Register for ECT. The improvement 1 week after ECT was classified according to the Clinical Global Impressions Scale - Improvement scale (CGI-I) as responder (CGI-I score 1-2) or non-responder (CGI-I score 3-7). Results: 185 cases and 185 comparison group subjects were included (46% with psychosis in each groups). More cases (87.0%) than comparison group subjects (73.5%) responded to ECT (p = 0.001). Adjusted binary regression analysis revealed that more severe symptoms prior to treatment were the only statistically significant predictor of response. Conclusion: The response rate of those with postpartum depression and/or psychosis to ECT was high. The response rate of patients with psychosis or depression was higher during the postpartum period than outside it. This study supports the use of ECT for severe forms of postpartum depression and/or psychosis.
  • Sellgren, C. M., et al. (författare)
  • Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls
  • 2019
  • Ingår i: Translational Psychiatry. - 2158-3188. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.
  • Sparding, Timea, et al. (författare)
  • Classification of cognitive performance in bipolar disorder.
  • 2017
  • Ingår i: Cognitive neuropsychiatry. - 1464-0619. ; 22:5, s. 407-421
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls.Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques.A distinct subgroup (∼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics.Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.
  • van Hulzen, Kimm J E, et al. (författare)
  • Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.
  • 2017
  • Ingår i: Biological psychiatry. - 1873-2402. ; 82:9, s. 634-641
  • Tidskriftsartikel (refereegranskat)abstract
    • Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD.Genome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks.We found a significant single nucleotide polymorphism-based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull = .64, p = 3.13 × 10(-14); rGrestricted = .71, p = 4.09 × 10(-16)). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47 × 10(-8); prs11756438 = 4.36 × 10(-8)) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 = 2.11 × 10(-8)) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue.The single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.
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