Summary: 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 theLIFEAdult 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 ofP ≤ 5× 10⁻⁸(not corrected for analysis of multiple traits). The most significant was a hit nearUFL1associated with sleep efficiency on weekdays (P = 1.39 × 10⁻⁸). FurtherSNPs were close to significance, including an association between sleep latency and a variant inCSNK2A1(P = 8.20 × 10⁻⁸), a gene known to be involved in the regulation of circadian rhythm. In summary, ourGWASidentified novel candidate genes with biological plausibility being promising candidates for replication and further follow‐up studies.

The aim of this study was to assess cognitive differences between male and female adults with Attention Deficit Hyperactivity Disorder (ADHD). Patients with an ADHD diagnosis according to the DSM-IV guidelines were included in a cross-sectional study evaluating cognitive measures. 28 women and 41 men from ages 19 to 56 completed self-report questionnaires and performed a computer-based test of attentional performance (TAP). The TAP assesses cognitive functions highly affected in ADHD patients, including working memory, alertness and attention as well as behavioral control and response inhibition. There were no measurable differences in self-report scales assessing current symptomology between the sexes, however men scored higher on the scale for childhood symptoms. Performance measures for general wakefulness were comparable between men and women, while working memory and behavioral control test results differed. Females reacted significantly slower and more unstable for both the TAP Go/NoGo paradigm and working memory subtest, while also making more errors in the latter. We found gender-specific effects regarding working memory and behavioral control in this sample of adult patients with ADHD. Further studies are warranted, examining whether these differences relate to differences in clinical presentation and comorbidity patterns between men and women.

Different levels of brain arousal can be delineated not only during sleep but also during wakefulness. Electroencephalography (EEG) is the gold standard to assess different levels of brain arousal. A novel EEG- and electrooculography (EOG)-based tool, the Vigilance Algorithm Leipzig (VIGALL 2.0), allows determining the level of EEG-vigilance (indicating brain arousal). Considering the frequency patterns and LORETA-based cortical distribution of electroencephalic activity, VIGALL 2.0 automatically attributes one out of seven vigilance stages to each EEG segment (1-sec EEG segments by default), ranging from high alertness (stage 0), to relaxed wakefulness (stage A1 to A3), to drowsiness (stage B1 to B2/3) up to sleep onset (stage C). Building on the time series of these seven vigilance stages across 20 min, two parameterizations of the temporal dynamic (brain arousal regulation) are calculated: the lability score and the slope index. 27 healthy participants (age = 22.93 ± 3.44 years, 18 females) underwent two sessions (7 days apart) of a twenty-minute eyes-closed resting EEG paradigm. The test-retest reliability coefficients for the EEG-vigilance stages were between rho = .53 and .86 (all p < .01). For the temporal dynamic of the stages across 20 min, the test-retest reliability coefficients were rho = .70 (lability score, p < .001) and .71 (slope index, p < .001). This study demonstrated some trait aspects of brain arousal regulation by confirming the stability of temporal dynamic of EEG-vigilance stages as assessed with VIGALL 2.0. Considering the “first day in lab” effect identified in the present study, more adaptation to the lab surrounding and a stricter control of other state factors should be taken into account, which might improve reliability. Additionally, in a clinical context, a broader range of brain arousal regulation patterns might be found, possibly leading to higher test-retest reliability than was found in this homogenous healthy sample. This would be desirable, as parameters of brain arousal regulation are promising diagnostic and prognostic biomarkers for diseases with arousal disturbances, such as affective disorders, ADHD and fatigue.

The norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[¹¹C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right:F_1,25 = 12.30,p = .002; regions on the left:F_1,41 = 6.80,p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.

Daytime sleepiness is a significant public health concern. Early evidence points toward the computerized VIGALL (Vigilance Algorithm Leipzig) as time-efficient tool to assess sleepiness objectively. In the present study, we investigated the association between VIGALL variables of EEG vigilance (indicating brain arousal in resting state) and subjective daytime sleepiness in the LIFE cohort study. Additionally, we validated VIGALL against the self-rated likelihood of having fallen asleep during the conducted resting EEG and against heart periods. Participants of the primary sample LIFE 60+ (N = 1927, 60–79 years) and replication sample LIFE 40+ (N = 293, 40–56 years) completed the Epworth Sleepiness Scale (ESS). After an average interval of 3 weeks (LIFE 60+) and 65 weeks (LIFE 40+), respectively, participants underwent a single 20-minute resting EEG, analyzed using VIGALL 2.1. Analyses revealed significant associations between ESS and EEG vigilance in LIFE 60+ (rho = −0.17, p = 1E–14) and LIFE 40+ (rho = −0.24, p = 2E-5). Correlations between EEG vigilance and self-rated sleep likelihood reached rho = −0.43 (p = 2E-91) in LIFE 60+ and rho = −0.50 (p = 5E–20) in LIFE 40+. Overall, strongest correlations were obtained for EEG vigilance variable “slope index.” Furthermore, lower EEG vigilance was consistently associated with longer heart periods. The present study contributes to the validation of VIGALL. Despite the considerable interval between ESS and EEG assessment dates, the strength of ESS-VIGALL association approximates prior ESS–Multiple Sleep Latency Test results. In this light, VIGALL might constitute an economical choice for the objective assessment of daytime sleepiness in large cohort studies. The discriminative power to identify disorders of hypersomnolence, however, remains to be addressed.