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Dive into the research topics where Philippe Jawinski is active.

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Featured researches published by Philippe Jawinski.


Journal of Sleep Research | 2016

Genome-wide association analysis of actigraphic sleep phenotypes in the LIFE Adult Study

Janek Spada; Markus Scholz; Holger Kirsten; Tilman Hensch; Katrin Horn; Philippe Jawinski; Christine Ulke; Ralph Burkhardt; Kerstin Wirkner; Markus Loeffler; Ulrich Hegerl; Christian Sander

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 ≤ 5× 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 × 10−8). Further SNPs were close to significance, including an association between sleep latency and a variant in CSNK2A1 (P = 8.20 × 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.


Bipolar Disorders | 2016

Early report on brain arousal regulation in manic vs depressive episodes in bipolar disorder

Dirk Alexander Wittekind; Janek Spada; Alexander Gross; Tilman Hensch; Philippe Jawinski; Christine Ulke; Christian Sander; Ulrich Hegerl

The arousal regulation model of affective disorders attributes an important role in the pathophysiology of affective disorders to dysregulation of brain arousal regulation. According to this model, sensation avoidance and withdrawal in depression and sensation seeking and hyperactivity in mania can be explained as auto‐regulatory attempts to counteract a tonically high (depression) or unstable (mania) arousal. The aim of this study was to compare brain arousal regulation between manic and depressive bipolar patients and healthy controls. We hypothesized that currently depressed patients with bipolar disorder show hyperstable arousal regulation, while currently manic patients show unstable arousal regulation.


World Journal of Biological Psychiatry | 2017

Sleep disturbances and upregulation of brain arousal during daytime in depressed versus non-depressed elderly subjects

Christine Ulke; Christian Sander; Philippe Jawinski; Nicole Mauche; Jue Huang; Janek Spada; Dirk Alexander Wittekind; Roland Mergl; Tobias Luck; Steffi G. Riedel-Heller; Tilman Hensch; Ulrich Hegerl

Abstract Objectives: Although patients with depression often suffer from sleep disturbances, most of them are not sleepy. Upregulation of brain arousal has been proposed as pathophysiological mechanism explaining sleep disturbances, inner tension, autonomic hyperarousal and anhedonia in depression. The aim of the current study was to examine the association between night-time sleep disturbances and brain arousal regulation the next day in depressed versus non-depressed subjects. Methods: Twenty-eight elderly subjects (21 female; age = 70.5 ± 4.4 years) with depressive syndromes without psychotropic medication, and 28 controls (22 female; age = 70.9 ± 4.5 years), underwent a 15-min resting electroencephalogram; the Vigilance Algorithm Leipzig (VIGALL 2.1) provided an objective measure of brain arousal regulation. Sleep disturbances were assessed by a validated and self-rated sleep questionnaire. Results: In the depressive group, but not in controls, more sleep disturbances were associated with a higher brain arousal stability score (high score corresponds to upregulation) the next day (sleep onset latency: rs = 0.69, P < .0001; sleep quality: rs = −0.59, P < .001). Conclusions: The data confirm the hypothesis that in persons with depressive syndromes sleep disturbances are related to upregulation of brain arousal the next day. This finding is in line with the concept that dysregulation of brain arousal is a central pathophysiological aspect in depression.


Chronobiology International | 2016

Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences, arousal regulation and sleep

Philippe Jawinski; Sophie Tegelkamp; Christian Sander; Madlen Häntzsch; Jue Huang; Nicole Mauche; Markus Scholz; Janek Spada; Christine Ulke; Ralph Burkhardt; Andreas Reif; Ulrich Hegerl; Tilman Hensch

ABSTRACT Dopamine has been implicated in the regulation of sleep–wake states and the circadian rhythm. However, there is no consensus on the impact of two established dopaminergic gene variants: the catechol-O-methyltransferase Val158Met (COMT Val158Met; rs4680) and the dopamine D4 receptor Exon III variable-number-of-tandem-repeat polymorphism (DRD4 VNTR). Pursuing a multi-method approach, we examined their potential effects on circadian preferences, arousal regulation and sleep. Subjects underwent a 7-day actigraphy assessment (SenseWear Pro3), a 20-minute resting EEG (analyzed using VIGALL 2.0) and a body mass index (BMI) assessment. Further, they completed the Morningness–Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). The sample comprised 4625 subjects (19–82 years) genotyped for COMT Val158Met, and 689 elderly subjects (64–82 years) genotyped for DRD4 VNTR. The number of subjects varied across phenotypes. Power calculations revealed a minimum required phenotypic variance explained by genotype ranging between 0.5% and 1.5% for COMT Val158Met and between 3.3% and 6.0% for DRD4 VNTR. Analyses did not reveal significant genotype effects on MEQ, ESS, PSQI, BMI, actigraphy and EEG variables. Additionally, we found no compelling evidence in sex- and age-stratified subsamples. Few associations surpassed the threshold of nominal significance (p < .05), providing some indication for a link between DRD4 VNTR and daytime sleepiness. Taken together, in light of the statistical power obtained in the present study, our data particularly suggest no impact of the COMT Val158Met polymorphism on circadian preferences, arousal regulation and sleep. The suggestive link between DRD4 VNTR and daytime sleepiness, on the other hand, might be worth investigation in a sample enriched with younger adults.


BMC Neuroscience | 2017

Evoked potentials and behavioral performance during different states of brain arousal

Jue Huang; Tilman Hensch; Christine Ulke; Christian Sander; Janek Spada; Philippe Jawinski; Ulrich Hegerl

BackgroundPrevious studies compared evoked potentials (EPs) between several sleep stages but only one uniform wake state. However, using electroencephalography (EEG), several arousal states can be distinguished before sleep onset. Recently, the Vigilance Algorithm Leipzig (VIGALL 2.0) has been developed, which automatically attributes one out of seven EEG-vigilance stages to each 1-s EEG segment, ranging from stage 0 (associated with cognitively active wakefulness), to stages A1, A2 and A3 (associated with relaxed wakefulness), to stages B1 and B2/3 (associated with drowsiness) up to stage C (indicating sleep onset). Applying VIGALL, we specified the effects of these finely differentiated EEG-vigilance stages (indicating arousal states) on EPs (P1, N1, P2, N300, MMN and P3) and behavioral performance. Subjects underwent an ignored and attended condition of a 2-h eyes-closed oddball-task. Final analysis included 43 subjects in the ignored and 51 subjects in the attended condition. First, the effect of brain arousal states on EPs and performance parameters were analyzed between EEG-vigilance stages A (i.e. A1, A2 and A3 combined), B1 and B2/3&C (i.e. B2/3 and C combined). Then, in a second step, the effects of the finely differentiated EEG-vigilance stages were further specified.ResultsComparing stages A versus B1 versus B2/3&C, a significant effect of EEG-vigilance stages on all behavioral parameters and all EPs, with exception of MMN and P3, was found. By applying VIGALL, a more detailed view of arousal effects on EP and performance was possible, such as the finding that the P2 showed no further significant increase in stages deeper than B1. Stage 0 did not differ from any of the A-stages. Within more fine-graded stages, such as the A-substages, EPs and performance only partially differed. However, these analyses were partly based on small sample sizes and future studies should take effort to get enough epochs of rare stages (such as A3 and C).ConclusionsA clear impact of arousal on EPs and behavioral performance was obtained, which emphasize the necessity to consider arousal effects when interpreting EPs.


Molecular Psychiatry | 2018

Human brain arousal in the resting state: a genome-wide association study

Philippe Jawinski; Holger Kirsten; Christian Sander; Janek Spada; Christine Ulke; Jue Huang; Ralph Burkhardt; Markus Scholz; Tilman Hensch; Ulrich Hegerl

Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6). The strongest hit was an expression quantitative trait locus (eQTL) of TMEM159 (lead-SNP: rs79472635, p = 5.49E-8). Importantly, at the gene-level, GWAS analyses revealed significant evidence for TMEM159 (p = 0.013, Bonferroni-corrected). By mapping our SNPs to the GWAS results from the Psychiatric Genomics Consortium, we found that all corresponding markers of TMEM159 showed nominally significant associations with Major Depressive Disorder (MDD; 0.006 ≤ p ≤ 0.011). More specifically, variants associated with high arousal levels have previously been linked to an increased risk for MDD. In line with this, the MetaXcan database suggests increased expression levels of TMEM159 in MDD, as well as Autism Spectrum Disorder, and Alzheimer’s Disease. Furthermore, our pathway analyses provided evidence for a role of sodium/calcium exchangers in resting state arousal. In conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms. Our results also encourage the elaboration of the previously reported interrelations between ion-channel modulators, sleep-wake behavior, and psychiatric disorders.


Neuropsychiatric Electrophysiology | 2015

Test-retest reliability of brain arousal regulation as assessed with VIGALL 2.0

Jue Huang; Christian Sander; Philippe Jawinski; Christine Ulke; Janek Spada; Ulrich Hegerl; Tilman Hensch


Neuropsychobiology | 2015

Brain Arousal Regulation in Carriers of Bipolar Disorder Risk Alleles.

Philippe Jawinski; Christian Sander; Nicole Mauche; Janek Spada; Jue Huang; Anna Schmidt; Madlen Häntzsch; Ralph Burkhardt; Markus Scholz; Ulrich Hegerl; Tilman Hensch


Sleep | 2017

Recorded and Reported Sleepiness: The Association Between Brain Arousal in Resting State and Subjective Daytime Sleepiness

Philippe Jawinski; Jennifer Kittel; Christian Sander; Jue Huang; Janek Spada; Christine Ulke; Kerstin Wirkner; Tilman Hensch; Ulrich Hegerl


Psychopharmacology | 2016

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

Philippe Jawinski; Nicole Mauche; Christine Ulke; Jue Huang; Janek Spada; Cornelia Enzenbach; Christian Sander; Ulrich Hegerl; Tilman Hensch

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