| 1. |
- Bergen, S. E., et al.
(författare)
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Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder
- 2012
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 17:9, s. 880-886
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case-control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 x 10(-8)). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.
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| 2. |
- Ruderfer, D M, et al.
(författare)
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Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.
- 2014
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:9, s. 1017-1024
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.Molecular Psychiatry advance online publication, 26 November 2013;
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| 3. |
- Johansson, Viktoria, et al.
(författare)
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Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. Methodology/Principal Findings: We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 mu m in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR = 48, 95% CL: 8.2-550, p<0.0001) and the co-twin-group (OR = 16, 95% CL: 2.0-218, p = 0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. Conclusion: Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder.
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| 4. |
- Kyaga, S., et al.
(författare)
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Mental illness, suicide and creativity: 40-Year prospective total population study
- 2013
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Ingår i: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956 .- 1879-1379. ; 47:1, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- We previously demonstrated that patients with schizophrenia or bipolar disorder and their relatives are overrepresented in creative occupations. Here, we use a new dataset with a considerably larger sample of patients (n = 1,173,763) to survey other psychiatric diagnoses and to validate previous findings. The specific aims of this study were to i) investigate if creativity is associated with all psychiatric disorders or restricted to those with psychotic features, and ii) to specifically investigate authors in relationship to psychopathology. We conducted a nested case-control study using longitudinal Swedish total population registries, where the occurrence of creative occupations in patients and their non-diagnosed relatives was compared to that of matched population controls. Diagnoses included were schizophrenia, schizoaffective disorder, bipolar disorder, unipolar depression, anxiety disorders, alcohol abuse, drug abuse, autism, ADHD, anorexia nervosa, and completed suicide. Creative professions were defined as scientific and artistic occupations. Data were analyzed using conditional logistic regression. Except for bipolar disorder, individuals with overall creative professions were not more likely to stiffer from investigated psychiatric disorders than controls. However, being an author was specifically associated with increased likelihood of schizophrenia, bipolar disorder, unipolar depression, anxiety disorders, substance abuse, and suicide. In addition, we found an association between creative professions and first-degree relatives of patients with schizophrenia, bipolar disorder, anorexia nervosa, and for siblings of patients with autism. We discuss the findings in relationship to some of the major components of creativity. (C) 2012 Elsevier Ltd. All rights reserved.
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| 5. |
- Mobarrez, F., et al.
(författare)
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Microparticles and microscopic structures in three fractions of fresh cerebrospinal fluid in schizophrenia: Case report of twins
- 2013
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 143:1, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a diagnosis with a set of symptoms of aberrant psychological phenomena. Here, we discuss that there may be an imbalance of proteostasis of neurons in the brain leading to increase in membrane shedding and buildup of microparticles (MPs) appearing in the cerebrospinal fluid. The number of MPs can be determined and their phenotypes verified by size and membrane expression with flow cytometry. This is the first report of specified MPs in cerebrospinal fluid (CSF) in schizophrenia. Two 56-year-old Swedish-born female monozygotic twins of Caucasian ethnicity with onset of schizophrenia more than 30 years ago were studied. Three fractions of fresh CSF were examined for microparticles by flow cytometry analysis, which measure the specific binding of antibodies to CD42a (platelet-MP; 33 GPIX), CD144 (endothelial-MP; Ve-cadherin), CD45 (leukocyte-MP; pan-leukocyte antigen) and of phosphatidylserine to lactadherin. The patients with schizophrenia displayed more phosphatidylserine-positive MPs in CSF compared with healthy control subjects. The scanning electron microscopic (SEM) structures in CSF studied over a 3-year period in twins with schizophrenia were of similar appearance at both time points. The increased number of MPs in fresh CSF may be a sign of enhanced membrane shedding in the central nervous system. Such MPs can be investigated for both human and non-human DNA, RNA and microRNA that may activate different immune signaling systems in patients with schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.
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| 6. |
- Sellgren, C, et al.
(författare)
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Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden.
- 2011
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Ingår i: Acta psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 124:6, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Sellgren C, Landén M, Lichtenstein P, Hultman CM, Långström N. Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden. Objective: Hospital discharge registers (HDRs) are frequently used in epidemiological research. However, the validity of several important psychiatric diagnostic entities, including bipolar disorder, remains uncertain. Hence, we aimed to develop an optimal algorithm for register-based identification of DSM-IV-TR bipolar disorder. Method: We identified potential cases in the Swedish national HDR using two separate discharge diagnoses of bipolar disorder according to ICD versions 8-10 during January 1, 1973 to December 31, 2004. In a randomly selected subsample of 135 cases from the county of Sörmland, two senior psychiatrists reassessed the diagnostic status based on patients' medical records. We scrutinized false-positive cases and modified the initial algorithm to improve positive predictive value while minimizing false negatives. Finally, we externally validated resulting caseness algorithms by linking HDR diagnostic data with best-estimate clinical diagnoses from the National Quality Assurance Register for Bipolar Disorder (BipoläR), dispensed lithium prescriptions from the National Prescribed Drug Register, and the ICD-10 diagnoses from the National Outpatient Register respectively. Results: The algorithm with two discharge diagnoses of bipolar disorder yielded a positive predictive value of 0.81. Modification by excluding individuals diagnosed with ICD-8 296.20 (manic-depressive psychosis, depressed type), and/or ICD-9 296.B (unipolar affective psychosis, melancholic form), gave a positive positive predictive value of 0.92. The modified algorithm also had statistically superior external validity compared with the original algorithm. Conclusion: Our findings suggest that DSM-IV-TR bipolar disorder caseness based on two inpatient episodes with a bipolar disorder diagnosis is sufficiently sensitive and specific to be used in further epidemiological study of bipolar disorder.
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