ORCID Profile
0000-0001-7169-2620
Current Organisation
Charité Universitätsmedizin Berlin
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Publisher: SAGE Publications
Date: 08-12-2015
Abstract: It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Using a novel gene-based (statistical) approach, we aimed to identify in idual genes and pathways associated both with MA and MO. Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value ( p gene-based ≤ 0.05) in the MA subgroup, 107 also produced p gene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) ( p binomial-test = 1.5 × 10 –4 ). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes ( TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene ( NPFF) as a novel candidate risk gene for both types of migraine.
Publisher: SAGE Publications
Date: 09-2014
Abstract: There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) should be considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migraine cases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differ from male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, we examined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 population-matched controls. Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migraine subgroups was performed for the 12 independent SNP loci significantly associated ( p 5 × 10 −8 thus surpassing the threshold for genome-wide significance) with migraine susceptibility. Overall genetic overlap was assessed using SNP effect concordance analysis (SECA) at over 23,000 independent SNPs. Significant heterogeneity of SNP effects ( p het 1.4 × 10 −3 ) was observed between the MA and MO subgroups (for SNP rs9349379), and between the clinic- and population-based subgroups (for SNPs rs10915437, rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genome-wide SNP effects to be in the same direction across the subgroups. Any differences in common genetic risk across these subgroups are outweighed by the similarities. Meta-analysis of additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibility loci for migraine.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.EURONEURO.2011.08.008
Abstract: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7 anxiety disorders: €74.4 brain tumor: €5.2 child/adolescent disorders: €21.3 dementia: €105.2 eating disorders: €0.8 epilepsy: €13.8 headache: €43.5 mental retardation: €43.3 mood disorders: €113.4 multiple sclerosis: €14.6 neuromuscular disorders: €7.7 Parkinson's disease: €13.9 personality disorders: €27.3 psychotic disorders: €93.9 sleep disorders: €35.4 somatoform disorder: €21.2 stroke: €64.1 traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2016
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JPSYCHORES.2019.109884
Abstract: The objective was to evaluate the association between restless legs syndrome (RLS) with generalized anxiety disorder (GAD), major depression disorder (MDD), dysthymia, and GAD-depression comorbidity. Secondary aims were to examine the association between RLS with the cognitive-affective and somatic-vegetative disturbances experienced as part of depression and GAD. This was a cross-sectional study of 1493 elderly participants (median age 80.6 years, 64% women) from Dijon, France. Probable RLS was assessed using the minimal diagnostic criteria of the International Restless Legs Study Group and RLS symptom frequency and treatment. Participants underwent structured interviews for MDD, dysthymia, and GAD. Participants also completed the Center for Epidemiological Studies-Depression scale (CES-D). The association between RLS and psychiatric disorders, their criterion symptoms, or symptom factors was examined using logistic regression. The point prevalence of probable RLS in this s le was 8.2%. Probable RLS was associated with isolated GAD (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.01-4.68) and comorbid GAD-any depression disorder (OR 3.26, 95% CI 1.14-9.29), but not MDD or dysthymia. Probable RLS was also associated with the GAD criterion worry most days and feeling tense, and the CES-D factors representing depressed affect, somatic symptoms, and positive affect. Probable RLS was associated with GAD-depression comorbidity as well as isolated GAD. The findings challenge previous reports linking RLS solely with MDD, suggesting the association is partly driven by GAD-depression comorbidity.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2010
Abstract: Early identification of in iduals at risk of dementia will become crucial when effective preventative strategies for this condition are developed. Various dementia prediction models have been proposed, including clinic-based criteria for mild cognitive impairment, and more-broadly constructed algorithms, which synthesize information from known dementia risk factors, such as poor cognition and health. Knowledge of the predictive accuracy of such models will be important if they are to be used in daily clinical practice or to screen the entire older population (in iduals aged >or=65 years). This article presents an overview of recent progress in the development of dementia prediction models for use in population screening. In total, 25 articles relating to dementia risk screening met our inclusion criteria for review. Our evaluation of the predictive accuracy of each model shows that most are poor at discriminating at-risk in iduals from not-at-risk cases. The best models incorporate erse sources of information across multiple risk factors. Typically, poor accuracy is associated with single-factor models, long follow-up intervals and the outcome measure of all-cause dementia. A parsimonious and cost-effective consensus model needs to be developed that accurately identifies in iduals with a high risk of future dementia.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Elsevier BV
Date: 03-2012
Publisher: American Medical Association (AMA)
Date: 03-2019
Publisher: Springer Science and Business Media LLC
Date: 20-06-2016
DOI: 10.1038/NG.3598
Publisher: SAGE Publications
Date: 05-2006
DOI: 10.1111/J.1468-2982.2005.01076.X
Abstract: Patients with functional gastrointestinal disorders frequently report migraine. We aimed to determine the prevalence of idiopathic upper abdominal symptoms in patients with migraine and compare it with a control population of healthy blood donors. We assessed abdominal symptoms using the Bowel Disease Questionnaire in a series of 488 consecutive blood donors without migraine and 99 patients with migraine. Upper abdominal symptoms were reported by 38% [95% confidence interval (CI) 32, 44] of blood donors compared with 81% (67, 91, P 0.001) of migraine patients. Of the blood donors, 23% (18, 28) reported frequent dyspepsia compared with 60% (44, 74, P 0.001) of the migraine patients. Migraine was associated with frequent upper abdominal symptoms (odds ratio 2.7, 95% CI 1.2, 6.1) after adjusting for age, gender, smoking and consumption of analgesics and alcohol. Upper abdominal symptoms are significantly more frequent in patients with migraine compared with healthy controls. The association between migraine and idiopathic upper abdominal symptoms may suggest common pathophysio-logical mechanisms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2015
Publisher: Springer Science and Business Media LLC
Date: 06-07-2020
DOI: 10.1038/S41467-020-17002-0
Abstract: Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine ( N cases / N controls = 59,674/316,078) and BP ( N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, r g = 0.11, P = 3.56 × 10 −06 ) and systolic BP (SBP, r g = 0.06, P = 0.01), but not pulse pressure (PP, r g = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci ( P ≤ 5 × 10 −08 ), nine of which replicate ( P 0.05) in the UK Biobank. Five shared loci ( ITGB5 , SMG6 , ADRA2B , ANKDD1B , and KIAA0040 ) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg P = 5.57 × 10 −25 ) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg P = 2.60 × 10 −07 ) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg P = 3.65 × 10 −07 ). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.
Publisher: Elsevier BV
Date: 02-2015
Publisher: Public Library of Science (PLoS)
Date: 28-09-2017
Publisher: Georg Thieme Verlag KG
Date: 05-2021
DOI: 10.1055/A-1444-6302
Abstract: Die COVID-19-Pandemie stellt unsere Gesellschaft auf die Probe. Binnen kürzester Zeit mussten zahlreiche Herausforderungen adressiert werden, wie die Kontaktnachverfolgung durch die Gesundheitsämter, die Beschaffung von medizinischen Produkten, die intensivmedizinische und pflegerische Versorgung der Erkrankten und vieles mehr. Alle gesellschaftlichen Bereiche, wie Wirtschaft, Bildung, Kultur und das private Leben sind durch die gesundheitliche Bedrohung und die Maßnahmen zur Eindämmung massiv beeinträchtigt. Besonders stark betroffen sind dabei Kinder, alte Menschen, vulnerable Gruppen, Menschen in sozial bzw. wirtschaftlich prekären Situationen und Menschen mit gesundheitlichen Vorbelastungen. Dies unterstreicht die Erkenntnis, dass
Publisher: Springer Science and Business Media LLC
Date: 02-2022
DOI: 10.1038/S41588-021-00990-0
Abstract: Migraine affects over a billion in iduals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2 , CACNA1A and MPPED2 ), two that seem specific for migraine without aura (near SPINK2 and near FECH ) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide ( CALCA/CALCB ) and serotonin 1F receptor ( HTR1F ). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2016
DOI: 10.1038/NG1016-1296C
Publisher: Deutscher Universitätsverlag
Date: 2004
Publisher: Elsevier BV
Date: 05-2018
Publisher: Informa UK Limited
Date: 16-04-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-06-2018
Abstract: Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more than 200,000 patients for 25 brain-associated disorders and 17 phenotypes. Broadly, it appears that psychiatric and neurologic disorders share relatively little common genetic risk. However, different and independent pathways can result in similar clinical manifestations (e.g., psychosis, which occurs in both schizophrenia and Alzheimer's disease). Schizophrenia correlated with many psychiatric disorders, whereas the immunopathological affliction Crohn's disease did not, and posttraumatic stress syndrome was also largely independent of underlying traits. Essentially, the earlier the onset of a disorder, the more inheritable it appeared to be. Science , this issue p. eaap8757
Publisher: Wiley
Date: 09-11-2018
DOI: 10.1111/ENE.13840
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-07-2021
DOI: 10.1212/WNL.0000000000011986
Abstract: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women. We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type. During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR] migraine 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HR migraine aura 1.54 [1.04, 2.30], HR migraine no aura 1.32 [0.87, 2.02], p heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HR migraine 1.34 [1.27, 1.41]) than among never users (HR migraine 1.19 [1.11, 1.28]). Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.
Publisher: Public Library of Science (PLoS)
Date: 29-05-2012
Publisher: Elsevier BV
Date: 06-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
DOI: 10.1161/STROKEAHA.111.680728
Abstract: To determine the interrelationships between baseline Mini-Mental State Examination (MMSE) score and risk of overall dementia, post-recurrent stroke dementia, and dementia without recurrent stroke among patients with a history of stroke. Prospective cohort study among participants enrolled in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) for whom baseline MMSE score was available. Baseline MMSE score was ided into 4 categories: 30, 29–27, 26–24, and . Participants were followed for incident dementia and recurrent stroke. Logistic regression models were used to examine the association between MMSE score and dementia. Of the 6080 participants included in this analysis, 2493 had an MMSE score of 30, 1768 had a score of 29–28, 1369 had a score of 26–24, and 450 had a score of . Average follow-up time was 3.8 years. There were 407 cases of dementia, 106 of which were preceded by a recurrent stroke. The risk of overall dementia increased with decreasing MMSE score. However, the impact of MMSE score on the risk of dementia without recurrent stroke was much stronger than the impact of MMSE score on the risk of post-recurrent stroke dementia. For those with MMSE score , the risk of dementia without recurrent stroke was 47.89 (95% confidence interval, 28.57–80.26), whereas the risk of post-recurrent stroke dementia was only 7.17 (95% confidence interval, 3.70–13.89). Higher MMSE scores were even less strongly associated with the risk of post-recurrent stroke dementia. Patients with stroke with low MMSE scores are at high risk of dementia over time, even in the absence of a recurrent stroke, and should therefore be followed closely for further cognitive decline.
Publisher: Wiley
Date: 19-12-2011
DOI: 10.1111/J.1468-1331.2011.03590.X
Abstract: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries. One-year prevalence and annual cost per person of 19 major groups of disorders are based on 'best estimates' derived from systematic literature reviews by panels of experts in epidemiology and health economics. Our cost estimation model was populated with national statistics from Eurostat to adjust to 2010 values, converting all local currencies to Euros (€), imputing cost for countries where no data were available, and aggregating country estimates to purchasing power parity-adjusted estimates of the total cost of brain disorders in Europe in 2010. Total European 2010 cost of brain disorders was €798 billion, of which direct health care cost 37%, direct non-medical cost 23%, and indirect cost 40%. Average cost per inhabitant was €5.550. The European average cost per person with a disorder of the brain ranged between €285 for headache and €30 000 for neuromuscular disorders. Total annual cost per disorder (in billion € 2010) was as follows: addiction 65.7 anxiety disorders 74.4 brain tumor 5.2 child/adolescent disorders 21.3 dementia 105.2 eating disorders 0.8 epilepsy 13.8 headache 43.5 mental retardation 43.3 mood disorders 113.4 multiple sclerosis 14.6 neuromuscular disorders 7.7 Parkinson's disease 13.9 personality disorders 27.3 psychotic disorders 93.9 sleep disorders 35.4 somatoform disorder 21.2 stroke 64.1 and traumatic brain injury 33.0. Our cost model revealed that brain disorders overall are much more costly than previously estimated constituting a major health economic challenge for Europe. Our estimate should be regarded as conservative because many disorders or cost items could not be included because of lack of data.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2011
DOI: 10.1038/NG.856
Publisher: Springer Science and Business Media LLC
Date: 23-06-2013
DOI: 10.1038/NG.2676
Location: No location found
Location: United States of America
No related grants have been discovered for Tobias Kurth.