Publications (25)158.86 Total impact
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Article: Neuropeptide Y genes and suicidal behaviour among schizophrenic patients.
Psychiatric genetics 02/2013; · 2.33 Impact Factor -
Article: Core features of repeated suicidal behaviour
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ABSTRACT: BackgroundThe aim of this article was to study repeated suicidal behaviour in a low-incidence population to elucidate robust risk factors. MethodsA cohort of first-ever suicide attempters from 1960 to 1982 on the Faroe Islands was followed up for a minimum of 20 years. The cohort was initially characterized in psychiatric and social terms. ResultsThe incidence of suicidal behaviour for the cohort years (age 15 years and older) was 37.9 per 100,000 per year (95% confidence interval 31.5–45.1). It was associated, as expected, with gender, age, residence, marital status, occupation, diagnosis, previous psychiatric admission, alcohol intoxication and the method and planning of the act. Factors of the index episode predicting repetition at 5 years were gestures and alcohol intoxication and at 20 years were physical methods, suicide letter and alcohol intoxication. ConclusionsAlcohol intoxication and the level of determination behind the suicide attempt emerge as targets for prevention. Alcohol intoxication at the initial episode seems to be a strong long-term as well as short-term risk factor.Social Psychiatry and Psychiatric Epidemiology 04/2012; 41(2):103-107. · 2.70 Impact Factor -
Article: Preventing repetition of attempted suicide--II. The Amager project, a randomized controlled trial.
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ABSTRACT: Repetition after attempted suicide is high but only few effect studies have been carried out. The Baerum Model from Norway offers practical and affordable intervention for those not being offered psychiatric treatment. During a period from 2005-2007, all attempted suicide patients except those with major psychiatric diagnoses (schizophrenia, bipolar disorder, severe/psychotic depression), were offered participation. The intervention group received the OPAC programme (outreach, problem solving, adherence, continuity) and the control group received treatment as usual (TAU). The intervention period was 6 months. After this intervention period, all patients were followed passively for an extra 6 months. The design was an intent-to-treat one. The outcomes were: 1) repetition of attempted suicide or suicide, and 2) total number of suicidal acts. A total of 200 patients were offered participation, 67 refused. Of the 133 participants, 69 were randomized to the OPAC programme and 64 to the (non-intervention) control group. Four in each group dropped out after initial participation. There was a significant lower proportion who repeated a suicide attempt the intervention group (proportion 8.7%) than in the control group (proportion 21.9%) and the number of repetitive acts was also significant lower (eight repetitions in the intervention group vs. 22 in the control group). In conclusion, our findings suggest a protective effect of the OPAC programme on the proportion who repeated a suicide attempt and on the total number of repetitions during the follow-up.Nordic journal of psychiatry 10/2011; 65(5):292-8. · 0.99 Impact Factor -
Article: Genome-wide association study identifies five new schizophrenia loci.
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ABSTRACT: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).Nature Genetics 09/2011; 43(10):969-76. · 35.53 Impact Factor -
Article: A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene.
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ABSTRACT: Panic disorder (PD) is a mental disorder with recurrent panic attacks that occur spontaneously and are not associated to any particular object or situation. There is no consensus on what causes PD. However, it is recognized that PD is influenced by environmental factors, as well as genetic factors. Despite a significant hereditary component, genetic studies have only been modestly successful in identifying genes of importance for the development of PD. In this study, we conducted a genome-wide scan using microsatellite markers and PD patients and control individuals from the isolated population of the Faroe Islands. Subsequently, we conducted a fine mapping, which revealed the amiloride-sensitive cation channel 1 (ACCN1) located on chromosome 17q11.2-q12 as a potential candidate gene for PD. The further analyses of the ACCN1 gene using single-nucleotide polymorphisms (SNPs) revealed significant association with PD in an extended Faroese case-control sample. However, analyses of a larger independent Danish case-control sample yielded no substantial significant association. This suggests that the possible risk alleles associated in the isolated population are not those involved in the development of PD in a larger outbred population.European journal of human genetics: EJHG 08/2011; 20(1):84-90. · 3.56 Impact Factor -
Article: [Intersectorial co-operation in psychiatry].
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ABSTRACT: Critical intersectorial problems of co-operation are revealed through an organizational psychological analysis focusing on intergroup dynamics. The aim of the paper is to examine and improve the intersectorial co-operation in psychiatry and present a new trio-interview design that includes patients as well as staff. Results from a follow-up study investigating the co-operation between Psychiatric Center Amager (PCA) and socialpsychiatric institutions (SPI) in Copenhagen is presented and analysed. The study was based on data gathered via structured interviews with patients and staff from both sectors (n = 60 in 2005, n = 87 in 2007), employing quantitative as well as qualitative methods. The newly developed trio-interview design with informant-triads for studies of the quality of intersectorial co-operation in psychiatry was applied to the study. Quantitative data from the patients showed that the co-operation was generally considered to be unsatisfactory in 2005 and 2007. SPI satisfaction estimates concerning the latest hospitalization period were higher in 2007 than in 2005. Staff from both sectors estimated that co-operation was significantly higher during 2007 than during 2005. Qualitative data showed that in 2007, staff was the decisive factor. The co-operation was estimated to be unsatisfactory in 2005 and 2007. Measures to strengthen intersectorial co-operation were implemented in 2006, but had limited effect.Ugeskrift for laeger 11/2009; 171(48):3514-8. -
Article: Association of MCTP2 gene variants with schizophrenia in three independent samples of Scandinavian origin (SCOPE).
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ABSTRACT: The MCTP2 gene is involved in intercellular signal transduction and synapse function. We genotyped 37 tagging SNPs across the MCTP2 gene to study a possible association with schizophrenia in three independent Scandinavian samples. We report, for the first time, a possible involvement of MCTP2 as a potential novel susceptibility gene for schizophrenia.Psychiatry Research 03/2009; 168(3):256-8. · 2.52 Impact Factor -
Article: Large recurrent microdeletions associated with schizophrenia.
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ABSTRACT: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.Nature 10/2008; 455(7210):232-6. · 36.28 Impact Factor -
Article: Variation in the purinergic P2RX(7) receptor gene and schizophrenia.
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ABSTRACT: The purinergic receptor gene P2RX(7) is located in a major linkage hotspot for schizophrenia and bipolar disorders, 12q21-33. It has previously been associated with bipolar disorder but has never been analysed in relation to schizophrenia, although it is involved in several neuronal processes associated with schizophrenia. Nine functionally characterised variants in P2RX(7) were genotyped in 389 patients diagnosed with schizophrenia, each matched on sex, birth-year and month with two healthy controls. We did not find association between P2RX(7) and schizophrenia and stratification on gender did not change this result. The high ethnic and diagnostic homogeneity of the sample adds credibility to this finding. P2XR(7) was not associated with schizophrenia in this study.Biological Psychiatry 08/2008; 104(1-3):146-52. · 8.28 Impact Factor -
Article: The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples.
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ABSTRACT: Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness. We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects). Variants of the mitogen-activated protein kinase 14 gene (MAPK14) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender. Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the findings are weak and not resistant to correction for multiple testing, which may indicate that they are either spurious or may relate to a particular subtype or aspect of the illness.BMC Medical Genetics 02/2008; 9:39. · 2.33 Impact Factor -
Article: Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder: an association study.
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ABSTRACT: Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences. The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism and schizophrenia. Additional studies are warranted to shed further light on these relationships.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2008; 147B(6):976-82. · 3.70 Impact Factor -
Article: [Residents in the psychiatric institution Sundbygård. Comparison of two cross-sectional studies, from 1998 and 2004].
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ABSTRACT: The deinstitutionalization of psychiatric hospitals has triggered a development of social institutions for mentally ill persons. In 1987 the psychiatric institution Sundbygård was changed for this purpose, and in 2001 enlarged. A survey in 1998 showed that the residents were mainly people suffering from schizophrenia with need for intensive psychiatric treatment. The usage of psychiatric hospital beds for residents increased from an average of 7.7 beds per day in 1998 to 10.2 beds in 2003. It was necessary to repeat the survey from 1998, this time adding an analysis of predictive factors for readmission to psychiatric ward. In the following, we will present the results of such an analysis. The psychiatrist in charge of treatment evaluated the residents by the same methods as used in 1998 for demographic and clinical information in cooperation with the staff. While in 1998 there were 78 male and 69 female residents, in 2004 there were 90 males and 76 females. The median age of the residents declined from 1998 to 2004. The proportion of schizophrenics increased from 69 to 90%. Similar results were seen for alcohol and drug abusers, with an increase from 16 to 26%. Residents with forensic psychiatric sentences increased from 5 to 12 and residents with severe productive symptoms increased from 47 to 97. The median GAF score was 35. In 2004 the atypical antipsychotics were generally prescribed. Predictors for readmission to psychiatric ward were new residency, forensic psychiatric sentence and severity of productive symptoms. This study shows that from 1998 to 2004 the number and proportion of residents with a schizophrenia diagnosis and an active alcohol and drug abuse has increased. The need for psychiatric admissions also increased. Thus, reallocation of resources is needed.Ugeskrift for laeger 02/2007; 169(4):307-10. -
Article: Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects.
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ABSTRACT: Abnormality in neurodevelopment is one of the most robust hypotheses on the etiology of schizophrenia and has found substantial support from brain imaging and genetic studies. Neurodevelopmental processes involve several signaling pathways, including the Notch, but little is known at present regarding their possible involvement in schizophrenia. In the present study we investigated the link of non-synonymous variants of five genes of the Notch pathway (NOTCH2, NOTCH3, JAGGED2, ASCL1 and NUMBL) to schizophrenia in a group of 200 Brazilian patients and 200-paired controls. Also, we replicated the association of the NUMBL variant, our most promising finding, in an unrelated set of 684 Danish patients and controls. When the Brazilian and Danish cohorts were merged, a total of 1084 subjects, we found the allele 18 CAG of NUMBL (p=0.003, x2=8.88, OR=1.30, 95% CI 1.09-1.56) as well as the 18/18 CAG genotype (p=0.002, x2=9.46, OR=1.46, 95% CI 1.15-1.87) to be associated with schizophrenia. The consistency of this finding in two independent and unrelated populations reinforces the veracity of this association.Schizophrenia Research 01/2007; 88(1-3):275-82. · 4.75 Impact Factor -
Article: Brain expressed microRNAs implicated in schizophrenia etiology.
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ABSTRACT: Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation. We have studied the association between schizophrenia and genetic variants of miRNA genes associated with brain-expression using a case-control study design on three Scandinavian samples. Eighteen known SNPs within or near brain-expressed miRNAs in three samples (Danish, Swedish and Norwegian: 420/163/257 schizophrenia patients and 1006/177/293 control subjects), were analyzed. Subsequently, joint analysis of the three samples was performed on SNPs showing marginal association. Two SNPs rs17578796 and rs1700 in hsa-mir-206 (mir-206) and hsa-mit-198 (mir-198) showed nominal significant allelic association to schizophrenia in the Danish and Norwegian sample respectively (P = 0.0021 & p = 0.038), of which only rs17578796 was significant in the joint sample. In-silico analysis revealed that 8 of the 15 genes predicted to be regulated by both mir-206 and mir-198, are transcriptional targets or interaction partners of the JUN, ATF2 and TAF1 connected in a tight network. JUN and two of the miRNA targets (CCND2 and PTPN1) in the network have previously been associated with schizophrenia. We found nominal association between brain-expressed miRNAs and schizophrenia for rs17578796 and rs1700 located in mir-206 and mir-198 respectively. These two miRNAs have a surprising large number (15) of targets in common, eight of which are also connected by the same transcription factors.PLoS ONE 01/2007; 2(9):e873. · 4.09 Impact Factor -
Article: Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene.
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ABSTRACT: Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia.The American Journal of Human Genetics 10/2006; 79(3):586-92. · 10.60 Impact Factor -
Article: Genetics of panic disorder on the Faroe Islands: a replication study of chromosome 9 and panic disorder.
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ABSTRACT: The population of the Faroe Islands in the North Atlantic Ocean is likely to have the same ancestry as the Icelandic population. An Icelandic study on Panic Disorder has found some evidence for a loci on chromosome 9. On the Faroe Islands we have an ongoing genetic project concerning panic disorder among other psychiatric disorders. We searched for shared alleles and haplotypes in distantly related cases from the isolated and recently found population of the Faroe Islands, using 26 more or less evenly distributed microsatellite markers on chromosome 9, with emphasis on the candidate region identified in the Icelandic study. We have not been able to replicate the Icelandic results. Owing to the study design and sample size, we would not be able to detect areas with small impact.Psychiatric Genetics 07/2006; 16(3):99-104. · 2.58 Impact Factor -
Article: Highly discrepant proportions of female and male Scandinavian and British Isles ancestry within the isolated population of the Faroe Islands.
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ABSTRACT: The Faroe Islands in the North Atlantic Ocean are inhabited by a small population, whose origin is thought to date back to the Viking Age. Historical, archaeological and linguistic evidence indicates that the present population of the Faroe Islands may have a mixture of Scandinavian and British Isles ancestry. In the present study we used 122 new and 19 previously published hypervariable region I sequences of the mitochondrial control region to analyse the genetic diversity of the Faroese population and compare it with other populations in the North Atlantic region. The analyses suggested that the Faroese mtDNA pool has been affected by genetic drift, and is among the most homogenous and isolated in the North Atlantic region. This will have implications for attempts to locate genes for complex disorders. To obtain estimates of Scandinavian vs British Isles ancestry proportions, we applied a frequency-based admixture approach taking private haplotypes into account by the use of phylogenetic information. While previous studies have suggested an excess of Scandinavian ancestry among the male settlers of the Faroe Islands, the current study indicates an excess of British Isles ancestry among the female settlers of the Faroe Islands. Compared to other admixed populations of the North Atlantic region, the population of the Faroe Islands appears to have the highest level of asymmetry in Scandinavian vs British Isles ancestry proportions among female and male settlers of the archipelago.European Journal of HumanGenetics 05/2006; 14(4):497-504. · 4.40 Impact Factor -
Article: Association between the CCR5 32-bp deletion allele and late onset of schizophrenia.
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ABSTRACT: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset. Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher age at first admission. After age at first admission was analyzed as a continuous variable, it was dichotomized using 40 years as the cutoff. With this approach the authors found that genotype distributions of patients with age at first admission above the cutoff (possible cases of late-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation of the deletion allele in the latter subgroup of patients. These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without affecting the disease susceptibility.American Journal of Psychiatry 04/2006; 163(3):507-11. · 12.54 Impact Factor -
Article: No significant association of the 5' end of neuregulin 1 and schizophrenia in a large Danish sample.
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ABSTRACT: Neuregulin 1 has been implicated as a susceptibility gene in schizophrenia. Several research groups have reported association with the 5' end of the gene although no causative variant has been reported. We have investigated whether there is association with the 5' end of the gene in Danish schizophrenia patients. We found that the at-risk haplotype initially reported in the Icelandic population was not found in significant excess (or = 1.4, p = 0.12). The haplotype structure in the Danish sample was similar to that of other reported in other Caucasian populations and highly different from that of Chinese.Schizophrenia Research 04/2006; 83(1):1-5. · 4.75 Impact Factor -
Article: Core features of repeated suicidal behaviour: a long-term follow-up after suicide attempts in a low-suicide-incidence population.
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ABSTRACT: The aim of this article was to study repeated suicidal behaviour in a low-incidence population to elucidate robust risk factors. A cohort of first-ever suicide attempters from 1960 to 1982 on the Faroe Islands was followed up for a minimum of 20 years. The cohort was initially characterized in psychiatric and social terms. The incidence of suicidal behaviour for the cohort years (age 15 years and older) was 37.9 per 100,000 per year (95% confidence interval 31.5-45.1). It was associated, as expected, with gender, age, residence, marital status, occupation, diagnosis, previous psychiatric admission, alcohol intoxication and the method and planning of the act. Factors of the index episode predicting repetition at 5 years were gestures and alcohol intoxication and at 20 years were physical methods, suicide letter and alcohol intoxication. Alcohol intoxication and the level of determination behind the suicide attempt emerge as targets for prevention. Alcohol intoxication at the initial episode seems to be a strong long-term as well as short-term risk factor.Social Psychiatry and Psychiatric Epidemiology 03/2006; 41(2):103-7. · 2.70 Impact Factor
Top co-authors
Top Journals
Institutions
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2007–2008
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Psykiatrisk Center Sct. Hans
Roskilde, Zealand, Denmark -
University of Copenhagen
- Psychiatric Center
Copenhagen, Capital Region, Denmark
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2006
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Aarhus Universitetshospital
- Centre for Psychiatric Research
Århus, Central Jutland, Denmark
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