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15 Publications visible to you, out of a total of 15
Genome-wide association analysis of actigraphic sleep phenotypes in the LIFE Adult Study.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

The genetic basis of sleep is still poorly understood. Despite the moderate to high heritability of sleep-related phenotypes, known genetic variants explain only a small proportion of the phenotypical … variance. However, most previous studies were based solely upon self-report measures. The present study aimed to conduct the first genome-wide association (GWA) of actigraphic sleep phenotypes. The analyses included 956 middle- to older-aged subjects (40-79 years) from the LIFE Adult Study. The SenseWear Pro 3 Armband was used to collect 11 actigraphic parameters of night- and daytime sleep and three parameters of rest (lying down). The parameters comprised measures of sleep timing, quantity and quality. A total of 7 141 204 single nucleotide polymorphisms (SNPs) were analysed after imputation and quality control. We identified several variants below the significance threshold of P </= 5x 10(-8) (not corrected for analysis of multiple traits). The most significant was a hit near UFL1 associated with sleep efficiency on weekdays (P = 1.39 x 10(-8) ). Further SNPs were close to significance, including an association between sleep latency and a variant in CSNK2A1 (P = 8.20 x 10(-8) ), a gene known to be involved in the regulation of circadian rhythm. In summary, our GWAS identified novel candidate genes with biological plausibility being promising candidates for replication and further follow-up studies.

Authors: J. Spada, M. Scholz, H. Kirsten, T. Hensch, K. Horn, P. Jawinski, C. Ulke, R. Burkhardt, K. Wirkner, M. Loeffler, U. Hegerl, C. Sander

Date Published: 30th Apr 2016

Publication Type: Journal article

Tobacco use is associated with reduced amplitude and intensity dependence of the cortical auditory evoked N1-P2 component.
LIFE Adult

Abstract (Expand)

RATIONALE: Tobacco use is linked to cerebral atrophy and reduced cognitive performance in later life. However, smoking-related long-term effects on brain function remain largely uncertain. Previous … studies suggest that nicotine affects serotonergic signaling, and the intensity dependence (alias loudness dependence) of the auditory evoked N1-P2 potential has been proposed as a marker of serotonergic neurotransmission. OBJECTIVE: In the present study, we assesed the effects of chronic smoking on amplitude and intensity dependence of the auditory evoked N1-P2 potential. METHODS: Subjects underwent a 15-min intensity dependence of auditory evoked potentials (IAEP) paradigm. From N = 1739 eligible subjects (40-79 years), we systematically matched current smokers, ex-smokers, and never-smokers by sex, age, alcohol and caffeine consumption, and socioeconomic status. Between-group differences and potential dose-dependencies were evaluated. RESULTS: Analyses revealed higher N1-P2 amplitudes and intensity dependencies in never-smokers relative to ex- and current smokers, with ex-smokers exhibiting intermediate intensity dependencies. Moreover, we observed pack years and number of cigarettes consumed per day to be inversely correlated with amplitudes in current smokers. CONCLUSIONS: According to the IAEP serotonin hypothesis, our results suggest serotonin activity to be highest in current smokers, intermediate in ex-smokers, and lowest in never-smokers. To our knowledge, the present study is the first providing evidence for a dose-dependent reduction in N1-P2 amplitudes. Further, we extend prior research by showing reduced amplitudes and intensity dependencies in ex-smokers even 25 years, on average, after cessation. While we can rule out several smoking-related confounders to bias observed associations, causal inferences remain to be established by future longitudinal studies.

Authors: P. Jawinski, N. Mauche, C. Ulke, J. Huang, J. Spada, C. Enzenbach, C. Sander, U. Hegerl, T. Hensch

Date Published: 18th Mar 2016

Publication Type: Not specified

Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Recent genome-wide association studies identified a number of chromosomal risk loci for bipolar disorder (BD, 'manic-depressive illness'). According to the vigilance regulation … model, the regulation of brain arousal (referred to as 'vigilance') when assessed via EEG is an emerging biomarker linked to the pathogenesis of manic and depressive episodes. On this basis, the present study aimed to assess whether carriers of BD risk alleles differ in brain arousal regulation. METHODS: Healthy participants of the population-based Leipzig Health Care Study (LIFE) underwent a 20-min eyes-closed resting EEG paradigm. Brain arousal was assessed applying the computer-based Vigilance Algorithm Leipzig (VIGALL). The primary sample (n = 540) was genotyped for ten of the most reliable BD risk variants, of which two qualified for replication (n = 509). RESULTS: Primary sample analyses revealed Bonferroni-adjusted significance for rs1006737 in CACNA1C (encoding a calcium channel subunit), with risk allele carriers exhibiting relatively steep brain arousal declines. Further, carriers of two risk alleles of rs472913 at 1p32.1 showed generally lower brain arousal levels for the duration of the resting paradigm. However, both associations failed replication. CONCLUSION: Although our initial findings are in line with the vigilance regulation model and convincing in view of the previously reported notable role of ion channelopathies in BD, our results do not provide consistent evidence for a link between BD risk variants and brain arousal regulation. Several between-sample differences may account for this inconsistency. The molecular genetics of brain arousal regulation remain to be clarified.

Authors: P. Jawinski, C. Sander, N. Mauche, J. Spada, J. Huang, A. Schmidt, M. Hantzsch, R. Burkhardt, M. Scholz, U. Hegerl, T. Hensch

Date Published: 29th Oct 2015

Publication Type: Not specified

Human Diseases: bipolar disorder

First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression.
LIFE Adult

Abstract (Expand)

Minor depression is diagnosed when a patient suffers from 2 to 4 depressive symptoms for at least 2 weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. … To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). 27 subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE). Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index (BMI), and degree of white matter hyperintensities (score on Fazekas scale). S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (p = 0.10-0.66). NSE correlated with Fazekas score in patients with minor depression (rs = 0.436, p = 0.048) and in the whole sample (rs = 0.252, p = 0.019). S100B correlated with BMI (rs = 0.246, p = 0.031) and with age in healthy subjects (rs = 0.345, p = 0.002). Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

Authors: M. Polyakova, C. Sander, K. Arelin, L. Lampe, T. Luck, M. Luppa, J. Kratzsch, K. T. Hoffmann, S. Riedel-Heller, A. Villringer, P. Schoenknecht, M. L. Schroeter

Date Published: 27th Oct 2015

Publication Type: Not specified

Human Diseases: mental depression

Impact of chronic smoking on P3 components in a three-stimulus oddball paradigm
LIFE Adult

Abstract (Expand)

Background: The P3 is related to cognitive functions, psychopathology and effects of cognition-improving and -impairing drugs. Studies assessing the chronic effects of smoking on P3 mostly reported a … reduction of P3 amplitude for chronic and former smokers. To date, only a few studies have analyzed this impact by using a three-stimulus oddball paradigm. This study tries to replicate previous smoking associations applying an eyes-closed active three-stimulus oddball paradigm in a well-diagnosed population based sample of healthy elderly subjects who were allowed to smoke ad libitum. The study also tries to estimate whether smoking is a relevant confounder in P3 assessment within the analyzed sample. Methods: From the Leipzig Health Care Study (LIFE) current, former and non-smokers without mental or neurological disorders were matched by age, sex and qualification. Risky alcohol consumption was further exclusion criterion given the strong association between alcoholism and P3 amplitude reduction. Results: Smoking status was not associated with any P3 parameter, with exception of prolonged P3a latency at Fz in former smokers compared to never smokers. Also, there were no significant effects of smoking status on any of the behavioral measures or a correlation with smoking-related data. Discussion: This study indicates that smoking does not seem to relevantly impact the P3 components in non-abstaining healthy elderly subjects when confounders are controlled for.

Authors: N. Mauche, C. Sander, P. Jawinski, C. Enzenbach, S. Olbrich, P. Schonknecht, U. Hegerl, T. Hensch

Date Published: 1st Sep 2015

Publication Type: Not specified

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 … inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Authors: M. Loeffler, C. Engel, P. Ahnert, D. Alfermann, K. Arelin, R. Baber, F. Beutner, H. Binder, E. Brahler, R. Burkhardt, U. Ceglarek, C. Enzenbach, M. Fuchs, H. Glaesmer, F. Girlich, A. Hagendorff, M. Hantzsch, U. Hegerl, S. Henger, T. Hensch, A. Hinz, V. Holzendorf, D. Husser, A. Kersting, A. Kiel, T. Kirsten, J. Kratzsch, K. Krohn, T. Luck, S. Melzer, J. Netto, M. Nuchter, M. Raschpichler, F. G. Rauscher, S. G. Riedel-Heller, C. Sander, M. Scholz, P. Schonknecht, M. L. Schroeter, J. C. Simon, R. Speer, J. Staker, R. Stein, Y. Stobel-Richter, M. Stumvoll, A. Tarnok, A. Teren, D. Teupser, F. S. Then, A. Tonjes, R. Treudler, A. Villringer, A. Weissgerber, P. Wiedemann, S. Zachariae, K. Wirkner, J. Thiery

Date Published: 22nd Jul 2015

Publication Type: Not specified

Human Diseases: disease of mental health, mental depression, vascular disease, allergic hypersensitivity disease, sleep disorder, retinal degeneration

Genetic association of objective sleep phenotypes with a functional polymorphism in the neuropeptide S receptor gene
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. …. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genome-wide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep. METHODS The study included n = 393 white subjects (62-79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System. RESULTS The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p = .007 and p = .003, respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers. CONCLUSION The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application.

Authors: Janek Spada, Christian Sander, Ralph Burkhardt, Madlen Häntzsch, Roland Mergl, Markus Scholz, Ulrich Hegerl, Tilman Hensch

Date Published: 4th Jun 2014

Publication Type: Journal article

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