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  • 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. - 0165-0327. ; 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.
  • Pålsson, Erik, 1975-, et al. (författare)
  • Cerebrospinal fluid monoamine metabolite profiles in bipolar disorder, ADHD, and controls.
  • 2017
  • Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - 1435-1463. ; 124:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Alterations in monoaminergic signaling are suggested as key aspects of the pathophysiology in bipolar disorder and ADHD, but it is not known if the monoamine metabolic profile differs between these disorders. One method to study monoaminergic systems in humans is to measure monoamine end-point metabolite concentrations in cerebrospinal fluid (CSF). Here, we analyzed CSF monoamine metabolite concentrations in 103 adults with bipolar disorder, 72 adults with ADHD, and 113 controls. Individuals with bipolar disorder had significantly higher homovanillic acid (HVA, 264 ± 112 nmol/L, p < 0.001) and 5-hydroxyindoleacetic acid (5-HIAA, 116 ± 42 nmol/L, p = 0.001) concentration, but lower 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG, 38 ± 8 nmol/L, p < 0.001) concentrations than controls (HVA, 206 ± 70 nmol/L; 5-HIAA, 98 ± 31 nmol/L; and MHPG, 42 ± 7 nmol/L). Higher HVA concentrations were associated with a history of psychosis in the bipolar disorder sample. Subjects with ADHD had higher HVA (240 ± 94 nmol/L, p < 0.001) concentrations compared with controls. In addition, SSRI treatment was associated with lower 5-HIAA concentrations in both patient groups. A power analysis indicated that for within-group comparisons, only large effects would be reliably detectable. Thus, there may be moderate-to-small effects caused by medication that were not detected due to the limited size of the sub-groups in these analyses. In conclusion, the present study suggests disorder-specific alterations of CSF monoamine metabolite concentrations in patients with bipolar disorder and ADHD compared with controls; these differences were independent of acute symptoms and medication effects.
  • Pålsson, Erik, 1975-, et al. (författare)
  • Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls
  • 2015
  • Ingår i: European Neuropsychopharmacology. - 0924-977X. ; 25:1, s. 133-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Goran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.
  • Rangan, Aaditya V, et al. (författare)
  • A loop-counting method for covariate-corrected low-rank biclustering of gene-expression and genome-wide association study data.
  • 2018
  • Ingår i: PLoS computational biology. - 1553-7358. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A common goal in data-analysis is to sift through a large data-matrix and detect any significant submatrices (i.e., biclusters) that have a low numerical rank. We present a simple algorithm for tackling this biclustering problem. Our algorithm accumulates information about 2-by-2 submatrices (i.e., 'loops') within the data-matrix, and focuses on rows and columns of the data-matrix that participate in an abundance of low-rank loops. We demonstrate, through analysis and numerical-experiments, that this loop-counting method performs well in a variety of scenarios, outperforming simple spectral methods in many situations of interest. Another important feature of our method is that it can easily be modified to account for aspects of experimental design which commonly arise in practice. For example, our algorithm can be modified to correct for controls, categorical- and continuous-covariates, as well as sparsity within the data. We demonstrate these practical features with two examples; the first drawn from gene-expression analysis and the second drawn from a much larger genome-wide-association-study (GWAS).
  • Rolstad, Sindre, 1976-, et al. (författare)
  • Cognitive Performance and Cerebrospinal Fluid Biomarkers of Neurodegeneration: A Study of Patients with Bipolar Disorder and Healthy Controls
  • 2015
  • Ingår i: Plos One. - 1932-6203. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (A beta) 1-42, ratios of A beta 42/40 and A beta 42/38, soluble amyloid precursor protein alpha and beta, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers. In patients, the CSF biomarkers explained a significant proportion of the variance (15-36%, p =. 002 -<. 0005) in all cognitive domains independently of age, medication, disease status, and bipolar subtype I or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain changes, i.e., P-tau and A beta 1-42, did not contribute significantly. In healthy controls, CSF biomarkers did not explain the variance in cognitive performance. Selected CSF biomarkers of neurodegenerative processes accounted for cognitive performance in persons with bipolar disorder, but not for healthy controls. Specifically, the ratios of A beta 42/40 and A beta 42/38 were consistently associated with altered cognitive performance.
  • Rolstad, Sindre, 1976-, et al. (författare)
  • Cognitive reserve lessens the burden of white matter lesions on executive functions in bipolar disorder
  • 2016
  • Ingår i: Psychological Medicine. - 0033-2917. ; 46:15, s. 3095-3104
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD. Method. We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains. Results. CR reduced the influence of total volumes of deep WMH (beta=-0.38, Q = 0.003) and ventricular CSF (beta = -41, Q = 006) on executive functions. Conclusions. The interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation.
  • Rolstad, Sindre, 1976-, et al. (författare)
  • Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.
  • 2016
  • Ingår i: Cognitive neuropsychiatry. - 1464-0619. ; 21:3, s. 271-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.
  • Rolstad, Sindre, 1976-, et al. (författare)
  • Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder
  • 2015
  • Ingår i: Bipolar disorders. - 1399-5618. ; 17:8
  • Tidskriftsartikel (refereegranskat)abstract
    • LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.
  • 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. - 0165-0327. ; 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.
  • Salarvan, Sara, et al. (författare)
  • Neuropsychological profiles of adult bipolar disorder patients with and without comorbid attention-deficit hyperactivity disorder.
  • 2019
  • Ingår i: International journal of bipolar disorders. - 2194-7511. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Comorbid attention-deficit/hyperactivity disorder (ADHD) is common in bipolar disorder and associated with worse outcomes. Cognitive testing might be a tool to identify this group. Here we compare the neuropsychological profiles of bipolar disorder patients with (BD + cADHD) and without (BD - cADHD) childhood attention-deficit hyperactivity disorder.Adult patients with BD  -  cADHD (n = 66), BD + cADHD (n = 32), and healthy controls (n = 112) were tested using a comprehensive battery of neuropsychological tests. Patients underwent rigorous diagnostic assessments for bipolar disorder and ADHD, as well as a parental interview to establish childhood ADHD.The neuropsychological profiles of the groups were similar, except that the BD + cADHD group performed significantly worse on working memory. Working memory did not differ between those in the BD + cADHD group who only had a history of childhood ADHD and those that still met criteria for ADHD in adulthood.Cognitive testing had limited power to differentiate between bipolar disorder adults with and without childhood ADHD. The BD + cADHD subgroup cannot explain the significant cognitive heterogeneity seen in bipolar disorder patients.
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