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Matias Brødsgaard Grynderup,
Henrik Albert Kolstad,
Sigurd Mikkelsen,
Johan Hviid Andersen,
Jens Peter Bonde,
Henriette Nørmølle Buttenschøn,
Anette Kærgaard,
Linda Kærlev,
Reiner Rugulies,
Jane Frølund Thomsen,
Marianne Agergaard Vammen, Ole Mors,
Ase Marie Hansen
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ABSTRACT: Stress is a suspected cause of depression. High cortisol concentration, a biomarker of an activated stress response, has been found in depressed patients. The aim of this study was to determine if a high level of salivary cortisol is a risk factor of depression. In 2007, we enrolled 4467 public employees. Morning and evening salivary cortisol concentration were measured for each participant. Participants reporting high levels of depressive, burnout, or stress symptoms, assessed by questionnaires were assigned to a psychiatric interview. In this interview 98 participants were diagnosed with depression and subsequently excluded. Two years later in 2009, 2920 participants who had provided at least one valid saliva cortisol measurement at baseline participated at follow up. The psychiatric interviews were repeated and 62 cases of newly onset depression were diagnosed. Odds ratios of depression were estimated for every 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration, as well as for the difference between morning and evening cortisol concentration. The risk of depression decreased by increasing daily mean cortisol concentration and by increasing difference between morning and evening concentrations, while morning and evening cortisol concentrations were not significantly associated with depression. The adjusted odds ratios for 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration were 0.69 (95% CI: 0.45, 1.05), 0.87 (95% CI: 0.59, 1.28), and 0.53 (95% CI: 0.32, 0.90), respectively. The adjusted odds ratio for 1.0nmol/l increase in difference between morning and evening concentration were 0.64 (95% CI: 0.45, 0.90). This study did not support the hypothesis that high salivary cortisol concentration is a risk factor of depression, but indicate that low mean salivary cortisol concentration and a small difference between morning and evening cortisol concentration may be risk factors of depression.
Psychoneuroendocrinology 04/2013; · 5.81 Impact Factor
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Matias Brødsgaard Grynderup, Ole Mors,
Ase Marie Hansen,
Johan Hviid Andersen,
Jens Peter Bonde,
Anette Kærgaard,
Linda Kærlev,
Sigurd Mikkelsen,
Reiner Rugulies,
Jane Frølund Thomsen,
Henrik Albert Kolstad
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ABSTRACT: OBJECTIVES: The aim of this study is to analyse if low justice at work, analysed as aggregated workplace means, increases the risk of depression. METHODS: A total of 4237 non-depressed Danish public employees within 378 different work units were enrolled in 2007. Mean levels of procedural and relational justice were computed for each work unit to obtain exposure measures that were robust to reporting bias related to depression. Two years later in 2009, 3047 (72%) participated at follow-up. Those reporting high levels of depressive, burn-out or stress symptoms were assigned to a psychiatric diagnostic interview. In the interview 58 cases of new onset depression were identified. Depression ORs by work unit level of procedural and relational justice were estimated by multivariable logistic regression accounting for established risk factors for depression. RESULTS: Working in a work unit with low procedural justice (adjusted ORs of 2.50, 95% CI 1.06 to 5.88) and low relational justice (3.14, 95% CI 1.37 to 7.19) predicted onset of depression. CONCLUSIONS: Our results indicate that a work environment characterised by low levels of justice is a risk factor for depression.
Occupational and environmental medicine 03/2013; · 3.64 Impact Factor
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ABSTRACT: INTRODUCTION: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other populations. METHOD: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Tryptophan Hydroxylase I and II (TPH1 and TPH2) genes. RESULTS: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory interaction test showed that the minor allele of rs1800532 in TPH1 has a protective effect for males younger than 35 years and females older than 50 years, whereas for the oldest male subjects, it tended to be a risk factor. We also observed a significant interaction between age-group and the 5-HTTLPR genotype (with and without rs25531) in SLC6A4. The long allele or high expression allele tends to have a protective effect in the middle age-group. LIMITATION: We only analysed a limited number of genetic variants. CONCLUSION: None of the analysed variants are strong risk factors. To reveal a better understanding of the genes involved in suicide, we suggest future studies should include both genetic and non-genetic factors.
Journal of affective disorders 01/2013; · 3.76 Impact Factor
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PLoS ONE 01/2013; 8(5). · 4.09 Impact Factor
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ABSTRACT: BACKGROUND: Severe unipolar depression can be classified as either psychotic depression (PD) or non-psychotic depression (non-PD). A number of biological and clinical differences have been detected between PD and non-PD, but it remains unknown whether risk factors for the two subtypes also differ. The aim of the present study was therefore to investigate whether a number of potential risk factors influenced the risk of developing PD and non-PD to different extents. METHODS: This is a register-based historical prospective cohort study following all 2.4 million individuals born in Denmark between 1955 and 1990. During follow-up 2183 and 9101 individuals were registered in the Danish Psychiatric Central Research Register with PD and non-PD respectively. The association between risk factors and the development of PD and non-PD was estimated by survival analysis (Poisson regression) and expressed as incidence rate ratios (IRR). RESULTS: The most consistent finding of the study was that of a general overlap in familial and environmental risk factors for PD and non-PD. However, a parental history of bipolar disorder was a risk factor for PD (mother, IRR=1.66, p=0.003. Father, IRR=1.56, p=0.040) and not for non-PD (mother, IRR=0.92, p=0.430. Father, IRR=1.08, p=0.552). Conversely, a positive family history of schizophrenia was associated with neither PD nor non-PD LIMITATIONS: Diagnoses were assigned as part of routine clinical practice. CONCLUSION: Our findings justify the distinction between PD and non-PD in the current diagnostic manuals. Furthermore, the fact that parental bipolar disorder and not schizophrenia was a risk factor for PD supports the Kraepelinian dichotomy.
Journal of affective disorders 12/2012; · 3.76 Impact Factor
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ABSTRACT: BACKGROUND: Psychotic and mixed affective episodes are prevalent in the course of bipolar disorder. Despite many studies on the implications of psychotic mania (PM), psychotic depression (PD) and mixed affective episodes (MAE), relatively little is known about the relationship between the three subtypes. The present study aimed to investigate whether the occurrence of PM, PD and MAE were associated with one another. METHODS: This is a nationwide register-based, historical prospective cohort study. Data was obtained from the Danish Psychiatric Central Research Register. Subjects were defined as all individuals assigned with an ICD-10 diagnosis of bipolar disorder between January 1st 1994 and December 31st 2010. Potential associations among psychotic and mixed affective episodes were tested by means of logistic regression. RESULTS: We identified 14,529 individuals with bipolar disorder with lifetime incidences of PM, PD and MAE of 19%, 15% and 17% respectively. We detected significant associations between PM and MAE (Adjusted Odds Ratio (AOR)=1.26, p=0.003), PD and MAE (AOR=1.24, p=0.001), and PM and PD (AOR=1.28, p=0.005). LIMITATIONS: Diagnoses were assigned as part of routine clinical practice. CONCLUSIONS: According to this register-based study, PD, PM and MAE are all associated with one another. This knowledge should be taken into consideration by clinicians when monitoring patients with bipolar disorder and by nosologists when defining the criteria and potential subtypes for mixed affective episodes for the upcoming DSM-5 and ICD-11.
Journal of affective disorders 10/2012; · 3.76 Impact Factor
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ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in metabolic pathways of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes a common polymorphism (rs1801133 or C677T), which is associated with enzyme activity. The T-allele of the C677T polymorphism has been associated with earlier age at onset of schizophrenia in a Scandinavian population, although no association was found in replication attempts in other populations. Extending the study to five Nordic samples consisting of 2,198 patients with schizophrenia, including the original Scandinavian samples, there was no significant association between MTHFR C677T polymorphism and age at onset in schizophrenia. The present results do not suggest that the investigated MTHFR polymorphism has any significant influence on age at onset of schizophrenia in the Nordic population. © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2012; · 3.70 Impact Factor
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Katherine E Tansey,
Michel Guipponi,
Nader Perroud,
Guido Bondolfi,
Enrico Domenici,
David Evans,
Stephanie K Hall,
Joanna Hauser,
Neven Henigsberg,
Xiaolan Hu, [......],
Anne Farmer,
Jens R Wendland,
Alain Malafosse,
Peter Holmans,
Glyn Lewis,
Cathryn M Lewis,
Tine Bryan Stensbøl,
Shitij Kapur,
Peter McGuffin,
Rudolf Uher
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ABSTRACT: It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.
The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.
No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.
PLoS Medicine 10/2012; 9(10):e1001326. · 16.27 Impact Factor
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ABSTRACT: BACKGROUND: It has been suggested that clinician-rated scales and self-report questionnaires may be interchangeable in the measurement of depression severity, but it has not been tested whether clinically significant information is lost when assessment is restricted to either clinician-rated or self-report instruments. The aim of this study is to test whether self-report provides information relevant to short-term treatment outcomes that is not captured by clinician-rating and vice versa. METHODS: In genome-based drugs for depression (GENDEP), 811 patients with major depressive disorder treated with escitalopram or nortriptyline were assessed with the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (HRSD), and the self-report Beck Depression Inventory (BDI). In sequenced treatment alternatives to relieve depression (STAR*D), 4,041 patients treated with citalopram were assessed with the clinician-rated and self-report versions of the Quick Inventory of Depressive Symptomatology (QIDS-C and QIDS-SR) in addition to HRSD. RESULTS: In GENDEP, baseline BDI significantly predicted outcome on MADRS/HRSD after adjusting for baseline MADRS/HRSD, explaining additional 3 to 4% of variation in the clinician-rated outcomes (both P < .001). Likewise, each clinician-rated scale significantly predicted outcome on BDI after adjusting for baseline BDI and explained additional 1% of variance in the self-reported outcome (both P < .001). The results were confirmed in STAR*D, where self-report and clinician-rated versions of the same instrument each uniquely contributed to the prediction of treatment outcome. CONCLUSIONS: Complete assessment of depression should include both clinician-rated scales and self-reported measures.
Depression and Anxiety 08/2012; · 4.18 Impact Factor
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Robert A Power,
Robert Keers,
Mandy Y Ng,
Amy W Butler,
Rudolf Uher,
Sarah Cohen-Woods,
Marcus Ising,
Nick Craddock,
Michael J Owen,
Ania Korszun, [......],
Elisabeth B Binder,
Katherine J Aitchison,
Federica Tozzi,
Pierandrea Muglia,
Gerome Breen,
Ian W Craig,
Anne E Farmer,
Bertram Müller-Myhsok,
Peter McGuffin,
Cathryn M Lewis
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ABSTRACT: Genome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P < 5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P = 0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder. © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2012; 159B(7):859-68. · 3.70 Impact Factor
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Matias Brødsgaard Grynderup, Ole Mors,
Ase Marie Hansen,
Johan Hviid Andersen,
Jens Peter Ellekilde Bonde,
Anette Kærgaard,
Linda Kærlev,
Sigurd Mikkelsen,
Reiner Rugulies,
Jane Frølund Thomsen,
Henrik Albert Kolstad
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ABSTRACT: OBJECTIVES: The aim of this study was to examine if high psychological demands and low decision latitude at work increase the risk of depression. METHODS: In 2007, 4237 non-depressed Danish public employees within 378 different work units were enrolled in the study. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were robust to reporting bias. In 2009, 3046 (72%) participated at follow-up, and those reporting high levels of depressive, burnout or stress symptoms went through a psychiatric interview by which 58 cases of new onset depression were diagnosed. Odds ratios (OR) of depression for different levels of work unit mean psychological demands and decision latitude were estimated by logistic regression taking established risk factors into account. RESULTS: The OR for depression according to psychological demands was 1.07 [95% confidence interval (95% CI) 0.42-2.49] for every unit of change on a 5-point scale. The corresponding OR for decision latitude was 1.85 (95% CI 0.55-6.26). No interactive effects of psychological demands and decision latitude were observed. CONCLUSION: These findings suggest that low decision latitude may predict depression, but confidence intervals are wide and findings are also compatible with no increased risk.
Scandinavian journal of work, environment & health 08/2012; · 3.12 Impact Factor
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ABSTRACT: Foldager L, Steffensen R, Thiel S, Als TD, Nielsen HJ, Nordentoft M, Mortensen PB, Mors O, Jensenius JC. MBL and MASP-2 concentrations in serum and MBL2 promoter polymorphisms are associated to schizophrenia. Objective: Causative relations between infections and psychosis, especially schizophrenia, have been speculated for more than a century, suggesting a hypothesis of association between schizophrenia and hereditary immune defects. Mannan-binding lectin (MBL) is a pattern-recognition molecule of the innate immune defence. MBL deficiency is the most common hereditary defect in the immune system and may predispose to infection and autoimmunity. Mannan-binding lectin serine protease-2 (MASP-2) is an MBL-associated serine protease mediating complement activation upon binding of MBL/MASP to microorganisms. The objective was to investigate if schizophrenia is associated with serum concentrations of MBL and MASP-2 or with genetic variants of the genes MBL2 and MASP2 encoding these proteins. Methods: The sample consisted of 100 patients with schizophrenia and 350 controls. Concentrations of MBL and MASP-2 in serum were measured and seven single nucleotide polymorphisms known to influence these concentrations were genotyped. Results: Significant association of disease with genetic markers was found in MBL2 but not in MASP2. Significant difference in MBL serum concentration was found between patients and controls when adjusting for MBL2 haplotypes. For concentrations of MASP-2, a significant interaction effect between a MASP2 variant and disease was found. Interestingly, MASP-2 levels also depended significantly on variants in MBL2 exon 1. Conclusion: This study supports previous studies showing increased complement activity in patients with schizophrenia, indicates aetiological heterogeneity among patients and underlines that multilocus genotypes have to be considered when investigating effects on MBL level. It appears that inclusion of additional components from the system of complement activation is warranted.
Acta Neuropsychiatrica 08/2012; 24(4):199-207. · 0.58 Impact Factor
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ABSTRACT: Most comparisons of the efficacy of antidepressants have relied on the assumption that missing data are randomly distributed. Dropout rates differ between drugs, suggesting this assumption may not hold true. This paper examines the effect of non-random dropout on a comparison of two antidepressant drugs, escitalopram and nortriptyline, in the treatment of major depressive disorder. The GENDEP study followed adult patients with major depressive disorder over 12 weeks of treatment, and the primary analysis found no difference in efficacy of the two antidepressants under missing at random assumption. By applying the recently developed Muthén-Roy model, we compared the relative efficacy of these two antidepressants taking into account non-random distribution of missing outcomes (NMAR). Individuals who dropped out of the study were those who were not responding to treatment. Based on the best fitting NMAR model, it was found that escitalopram reduced symptom scores by an additional 1.4 points on the Montgomery-Åsberg Depression Rating Scale (p = 0.02), equivalent to 5% of baseline depression severity, compared to nortriptyline. We conclude that association between dropout and worsening symptoms led to an overestimate of the effectiveness of treatment, especially with nortriptyline, in the primary analysis. These findings review the primary analysis of GENDEP and suggest that, when non-random dropout is accounted for, escitalopram is more effective than nortriptyline in reducing symptoms of major depression.
Journal of psychiatric research 07/2012; 46(10):1333-8. · 3.72 Impact Factor
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Betina Elfving,
Henriette N Buttenschøn,
Leslie Foldager,
Pia H P Poulsen,
Johan H Andersen,
Matias B Grynderup,
Åse M Hansen,
Henrik A Kolstad,
Linda Kaerlev,
Sigurd Mikkelsen,
Jane F Thomsen,
Anders D Børglum,
Gregers Wegener, Ole Mors
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ABSTRACT: Brain-derived neurotrophic factor (BDNF) has been suggested as a candidate gene for depression and numerous studies have investigated the possible association between genetic variants within BDNF and depression. Clinical studies have investigated the serum BDNF levels in individuals with depression. However, few studies have combined genetic association studies with serum BDNF measurements. The purpose of the present study was therefore to perform an investigation of BDNF using 162 individuals with depression and 289 healthy individuals. All individuals returned a completed questionnaire and participated in a semi-structured diagnostic interview. The major contribution of the present study is the integration of clinical assessment of cases and control individuals, simultaneous analyses of several genetic variants, serum BDNF measurements, and information on socio-demographic variables, lifestyle, and health indicators in a statistical model. In the present study the serum BDNF levels were increased in the depressive subjects compared to control individuals. Additionally, six SNPs were successfully analyzed, but did not associate with depression. Multiple linear regression models were applied and age, depression, gender, the Val66Met polymorphism, and the interaction between Val66Met and gender were identified as significant determinants of the serum BDNF level. In conclusion, our data demonstrate that other factors than a diagnosis of depression influence the serum BDNF level and the importance of these factors should be emphasized comparing different studies.
Journal of psychiatric research 06/2012; 46(9):1118-25. · 3.72 Impact Factor
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ABSTRACT: Depressive disorders represent a significant health concern as they are associated with high social and physical dysfunction and increased risk for suicide. Electroconvulsive therapy (ECT) is the most effective treatment for patients with drug-resistant severe depressive disorders. However, the underlying biological mechanisms of ECT are not well characterized. In particular, the regulation of transcription factors upon ECT has only just started to be unveiled. The schizophrenia and bipolar disorder associated bromodomain containing 1 (BRD1) gene is important for the acetylation of histone H3K14 and holds a key role in normal embryonic development and survival. In this study, we have measured Brd1 mRNA in the hippocampus and the frontal cortex of male Sprague-Dawley rats upon acute and repeated electroconvulsive seizures (ECS) over a period of 10 days. We found an increase in the general expression of Brd1 mRNA in the hippocampus after repeated ECS compared to sham (F = 8.108, P = 0.003). Furthermore, we provide evidence suggesting a decrease in the expression of the Brd1 mRNA variant comprising an extended version of exon 7 (Brd1-L) in the frontal cortex after repeated ECS compared to sham (F = 6.225, P = 0.023). These findings indicate that regulation of the Brd1 gene is part of the biological response to ECS and that splice variants are induced differentially in different brain regions.
Neuroscience Letters 05/2012; 516(1):110-3. · 2.11 Impact Factor
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Evangelos Vassos,
Stacy Steinberg,
Sven Cichon,
Gerome Breen,
Engilbert Sigurdsson,
Ole A Andreassen,
Srdjan Djurovic,
Gunnar Morken,
Maria Grigoroiu-Serbanescu,
Carmen C Diaconu, [......],
I Alex Rubino,
Vera Golimbet,
Lambertus A Kiemeney,
Leonard H van den Berg,
Barbara Franke,
Erik G Jönsson,
Anne Farmer,
Hreinn Stefansson,
Kari Stefansson,
David A Collier
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ABSTRACT: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia.
To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method.
In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 × 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21).
There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.
Biological psychiatry 05/2012; 72(8):645-50. · 8.93 Impact Factor
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Mette Nyegaard,
Ditte Demontis,
Britta Boserup Thestrup,
Anne Hedemand,
Karina Meden Sørensen,
Thomas Hansen,
Thomas Werge,
David Michael Hougaard,
Robert H Yolken,
Preben Bo Mortensen, Ole Mors,
Anders D Børglum
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ABSTRACT: The human endogenous retrovirus HERV-K18 is located within intron 1 of CD48 on chromosome 1q and is still active in the human genome. Genetic variation in HERV-K18 single-nucleotide polymorphisms (SNPs) has previously been associated with an increased risk of schizophrenia (SZ) and with type 2 diabetes (T2D) among individuals with SZ. Here, we present a replication study of association of two SNPs in HERV-K18 and 19 tagSNPs in CD48 with (a) SZ and (b) T2D in patients with SZ in two Danish samples (total number of cases=750 and controls=1214). No association was found with SZ or with T2D among individuals with SZ for any of the investigated SNPs. However, one HERV-K18 SNP showed a tendency toward an association with T2D in younger SZ patients, in agreement with previous findings, but due to a very low sample size, this result needs to be further investigated.
Psychiatric genetics 04/2012; 22(3):146-8. · 2.33 Impact Factor
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Psychotherapy and Psychosomatics 03/2012; 81(3):135-44. · 6.28 Impact Factor
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ABSTRACT: Recent genetic evidence has implicated the bromodomain containing 1 gene (BRD1) with brain development and susceptibility to Schizophrenia and Bipolar Disorder. The BRD1 protein, which is essential for acetylation of histone H3K14, is a putative regulator of transcription during brain development and in the mature CNS. However, several issues remain to be clarified for example regarding the regulation of the BRD1 gene upon environmental interventions. Chronic restraint stress (CRS) in rats represents an environmental method for induction of morphological and functional changes in the hippocampus and the prefrontal cortex. In order to investigate whether the expression of the rat Brd1 gene may be regulated during such conditions, Brd1 mRNA and protein levels in hippocampus and prefrontal cortex extracts from rats subjected to either 1/2 or 6h of CRS per day for 21days were measured. We found a significant 2-fold up-regulation of long exon 7 splice variants of the Brd1 gene (Brd1-L) in hippocampus in both groups of CRS rats compared to controls. Concomitantly, we found a similar up-regulation of the BRD1 protein. In prefrontal cortex, we found no significant differences in Brd1 mRNA or protein levels. As selective histone deacetylase (HDAC) inhibitors not only preserve stress-induced hyperacetylation of histone H3K14 but also have hippocampal-dependent antidepressant-like activity, we propose that BRD1 by its intrinsic acetylation activity towards histone H3K14 is a player in the regulatory processes underlying adaptation to stress in the mature CNS.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2012; 22(9):651-6. · 3.68 Impact Factor
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ABSTRACT: Mixed affective episode is a prevalent mood disorder characterized by the coexistence or rapid alternation of manic and depressive symptoms, which is associated with significant suffering and high risk of suicide. Unfortunately, the current diagnostic classification of mixed affective episodes in the ICD-10 lacks a detailed definition with relevant subtypes. This inconsistency has significant negative implications for both research into the disorders in the bipolar spectrum and for clinical practice. For this reason there is a need for special attention on this diagnosis in the revisions of the diagnostic manuals. In this manuscript we suggest a set of clear diagnostic criteria and exhaustive subtypes for the mixed affective episodes aimed at the upcoming ICD-11. The defined syndrome and its subtypes are in close congruence with the suggested DSM-5 "mixed episode specifier", which is an advantage for common understanding and for research across the ICD/DSM border.
Journal of affective disorders 01/2012; 138(1-2):170-2. · 3.76 Impact Factor
