Wakefulness Regulation Research Articles

EEG wakefulness regulation in transdiagnostic patients after a recent suicide attempt

ObjectiveDecades of research have not yet produced statistically reliable predictors of preparatory behavior eventually leading to suicide attempts or deaths by suicide. As the nature of suicidal behavior is complex, it is best investigated in a transdiagnostic approach, while assessing objective markers, as proposed by the Research Domain Criteria (Cuthbert, 2013). MethodsA 15-min resting-state EEG was recorded in 45 healthy controls, and 49 transdiagnostic in-patients with a recent (<6 months) suicide attempt. Brain arousal regulation in eyes-closed condition was assessed with the Vigilance Algorithm Leipzig (VIGALL) (Sander et al., 2015). ResultsA significant incline of median vigilance and vigilance slope was observed in patients within the first 3-min of the EEG recording. Additionally, a significant positive correlation of self-reported suicidal ideation with the vigilance slope over 15-min recording time, as well as a significant negative correlation with EEG vigilance stage A1 during the first 3-min was found. ConclusionsTransdiagnostic patients with a recent suicide attempt show a distinct vigilance regulation pattern. Further studies including a control group consisting of patients without life-time suicide attempts are needed to increase the clinical utility of the findings. SignificanceThese findings might serve as potential objective markers of suicidal behavior.

Effort during prolonged wakefulness is associated with performance to attentional and executive tasks but not with cortical excitability in late-middle-aged healthy individuals.

Sleep loss negatively affects brain function with repercussion not only on objective measures of performance but also on many subjective dimensions, including effort perceived for the completion of cognitive processes. This may be particularly important in aging, which is accompanied by important changes in sleep and wakefulness regulation. We aimed to determine whether subjectively perceived effort covaried with cognitive performance in healthy late-middle-aged individuals. We assessed effort and performance to cognitive tasks in 99 healthy adults (66 women; 50-70 years) during a 20-hr wake extension protocol, following 7 days of regular sleep and wake times and a baseline night of sleep in the laboratory. We further explored links with cortical excitability using transcranial magnetic stimulation coupled to electroencephalography. Perceived effort increased during wake extension and was highly correlated to subjective metrics of sleepiness, fatigue, and motivation, but not to variations in cortical excitability. Moreover, effort increase was associated with decreased performance to some cognitive tasks (psychomotor vigilance and two-back working memory task). Importantly, effort variations during wakefulness extension decreased from age 50 to 70 years, while more effort is associated with worse performance in older individuals. In healthy late-middle-aged individuals, more effort is perceived to perform cognitive tasks, but it is not sufficient to overcome the performance decline brought by lack of sleep. Entry in the seventh decade may stand as a turning point in the daily variations of perceived effort and its link with cognition. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The role of brain wakefulness regulation, depressive symptoms, and SSRI side effects in patients with major depressive disorder

The role of brain wakefulness regulation, depressive symptoms, and SSRI side effects in patients with major depressive disorder

Kinase signalling in excitatory neurons regulates sleep quantity and depth.

Progress has been made in the elucidation of sleep and wakefulness regulation at the neurocircuit level1,2. However, the intracellular signalling pathways that regulate sleep and the neuron groups in which these intracellular mechanisms work remain largely unknown. Here, using a forward genetics approach in mice, we identify histone deacetylase 4 (HDAC4) as a sleep-regulating molecule. Haploinsufficiency of Hdac4, a substrate of salt-inducible kinase 3 (SIK3)3, increased sleep. By contrast, mice that lacked SIK3 or its upstream kinase LKB1 in neurons or with a Hdac4S245A mutation that confers resistance to phosphorylation by SIK3 showed decreased sleep. These findings indicate that LKB1-SIK3-HDAC4 constitute a signalling cascade that regulates sleep and wakefulness. We also performed targeted manipulation of SIK3 and HDAC4 in specific neurons and brain regions. This showed that SIK3 signalling in excitatory neurons located in the cerebral cortex and the hypothalamus positively regulates EEG delta power during non-rapid eye movement sleep (NREMS) and NREMS amount, respectively. A subset of transcripts biased towards synaptic functions was commonly regulated in cortical glutamatergic neurons through the expression of a gain-of-function allele of Sik3 and through sleep deprivation. These findings suggest that NREMS quantity and depth are regulated by distinct groups of excitatory neurons through common intracellular signals. This study provides a basis for linking intracellular events and circuit-level mechanisms that control NREMS.

Impact of different classes of antidepressants on sleep and wakefulness regulation in depression

Sleep disturbances are common in patients with mental disorders. Sleep disturbances, in particular insomnia, are widespread in depression. Depressed patients have a lot of sleep complaints that are often confirmed by polysomnography. Most antidepressants impair sleep, so drugs that help to restore sleep are of particular value in clinical practice. Agomelatine (valdoxan) rapidly improves sleep in depressed patients by making it easier to fall asleep, increasing total sleep time, duration of rapid eye movement (REM), and slow-wave sleep (SWS), and improving functioning during the day.

NeuroPharm study: EEG wakefulness regulation as a biomarker in MDD

While several electroencephalogram (EEG)-based biomarkers have been proposed as diagnostic or predictive tools in major depressive disorder (MDD), there is a clear lack of replication studies in this field. Markers that link clinical features such as disturbed wakefulness regulation in MDD with neurophysiological patterns are particularly promising candidates for e.g., EEG-informed choices of antidepressive treatment. We investigate if we in an independent MDD sample can replicate abnormal findings of EEG-vigilance regulation during rest and as a predictor for antidepressive treatment response. EEG-resting state was recorded in 91 patients and 35 healthy controls from the NeuroPharm trial. EEG-vigilance was assessed using the Vigilance Algorithm Leipzig (VIGALL). We compared the vigilance regulation during rest between patients and healthy controls and between remitters/responders and non-remitters/non-responders after eight weeks of SSRI/SNRI treatment using two different sets of response criteria (NeuroPharm and iSPOT-D). We replicated previous findings showing hyperstable EEG-wakefulness regulation in patients in comparison to healthy subjects. Responders defined by the iSPOT-D criteria showed a higher propensity toward low vigilance stages in comparison to patients with no response at pretreatment, however, this did not apply when using the NeuroPharm criteria. EEG-wakefulness regulation patterns normalized toward patterns of healthy controls after 8 weeks of treatment. This replication study supports the diagnostic value of EEG-vigilance regulation and its usefulness as a biomarker for the choice of treatment in MDD.

Changes in EEG permutation entropy in the evening and in the transition from wake to sleep.

Quantifying the complexity of the EEG signal during prolonged wakefulness and during sleep is gaining interest as an additional mean to characterize the mechanisms associated with sleep and wakefulness regulation. Here, we characterized how EEG complexity, as indexed by Multiscale Permutation Entropy (MSPE), changed progressively in the evening prior to light off and during the transition from wakefulness to sleep. We further explored whether MSPE was able to discriminate between wakefulness and sleep around sleep onset and whether MSPE changes were correlated with spectral measures of the EEG related to sleep need during concomitant wakefulness (theta power-Ptheta: 4-8 Hz). To address these questions, we took advantage of large datasets of several hundred of ambulatory EEG recordings of individual of both sexes aged 25-101 years. Results show that MSPE significantly decreases before light off (i.e. before sleep time) and in the transition from wakefulness to sleep onset. Furthermore, MSPE allows for an excellent discrimination between pre-sleep wakefulness and early sleep. Finally, we show that MSPE is correlated with concomitant Ptheta. Yet, the direction of the latter correlation changed from before light-off to the transition to sleep. Given the association between EEG complexity and consciousness, MSPE may track efficiently putative changes in consciousness preceding sleep onset. An MSPE stands as a comprehensive measure that is not limited to a given frequency band and reflects a progressive change brain state associated with sleep and wakefulness regulation. It may be an effective mean to detect when the brain is in a state close to sleep onset.

Quality of life and procrastination in post-H1N1 narcolepsy, sporadic narcolepsy and idiopathic hypersomnia, a Swedish cross-sectional study

Objective/BackgroundA cross-sectional study of health-related quality of life (HRQoL), procrastination and the relation to sleepiness, depression and fatigue in post-H1N1 narcolepsy type 1 (NT1), sporadic NT1 and idiopathic hypersomnia (IH). Patients/MethodsParticipants with NT1 and IH were enrolled from the Department of Neurology, Sahlgrenska University Hospital in Gothenburg (Sweden). All participants completed questionnaires about medication, employment, studies, transfer income, sleepiness, HRQoL, depression, fatigue and three questionnaires for procrastination. ResultsPost-H1N1, sporadic NT1 and IH all scored higher than healthy controls on Epworth Sleepiness Scale (ESS), Patient Health Questionnaire (PHQ-9) and Fatigue Severity Scale (FSS), whereas EQ-5D-5L index and VAS was lower than for healthy individuals, but with no difference between groups. Post-H1N1 NT1 had a larger proportion of participants prescribed with sodium oxybate (44% vs. 9%, p = 0.003) and dexamphetamine (62% vs. 17%, p = 0.03) compared to sporadic NT1. The latter also in significantly higher doses than in sporadic NT1 (46 ± 12 vs. 25 ± 10 and 47.5 ± 21 mg, p < 0.0001). Post-H1N1 NT1 also had significantly higher scores on Pure Procrastination Scale (PPS), Irrational Procrastination Scale (IPS) and Susceptibility to Temptation Scale (STS), indicating a higher degree of procrastination. Multivariate analysis showed that depression, and to some extent fatigue, were predictors in NT1 for both HRQoL and procrastination. ConclusionsThe results show that health-related quality of life is impaired and tendency to procrastinate is higher in patients suffering from NT1 and both attributes can in part be explained by depressive symptoms. These findings highlight the impact of symptoms other than sleep and wakefulness regulation in patients with NT1.

FV 14 Dynamic modulation of vigilance states during affective stimulation

Background To investigate the interplay between affective information processing and functional brain states, differences in arousal regulation after stimulation with affective narratives were investigated. Based on EEG acquisitions at resting state, it is possible to differentiate stages of wakefulness regulation. The temporal evolution of these vigilance stages sheds light on individual variations in arousal level in reaction to preceding affective stimulation ( Olbrich et al., 2009 ). Methods Resting state EEG was recorded from eighteen healthy subjects for 10 min each with eyes closed: first at baseline and then after passive listening to three emotional narratives about experiences in early childhood of strangers (securely attached, insecure-dismissing, insecure-preoccupied) ( Borchardt et al., 2015 ). Using the VIGALL 2.0 algorithm, vigilance stages (high: A1, A2, A3, low: B2/3) in consecutive EEG segments (duration: 2.4 s) were classified and their dynamic profile was analyszed ( Sander et al., 2015 ). Additionally, the Temperament and Character Inventory (TCI) was assessed ( Cloninger et al., 1993 ). Results At baseline, the percentage of subjects in low vigilance stages was continuously high and stable over time, while in conditions after emotional stimulation the percentage of subjects was first highest in high vigilance stages but quickly decreased over time. A difference between narrative conditions was revealed in the insecure-dismissing condition, in which the decrease of the percentage of subjects in high vigilance stages was highest compared to the other two conditions. Analyzing dynamics of vigilance stages, only in the insecure-dismissing condition, the number of EEG segments in high vigilance stages in the first 160 s (interval 1) was significantly higher compared to the last 160 s (interval 4) after normalization to the subject-specific baseline level (p = 0.008). In a subgroup of the participants (N = 14), we found a significant, strong negative correlation (r = −0.82, p = 0.0003) between individual dynamic of slope in high vigilance stages at baseline and harm avoidance, a temperament trait of personality, whose characteristics are elevated tiredness, weakness, and a prolonged recovery after emotional stress. Discussion At resting state, a continuous decrease of vigilance is a physiological finding ( Olbrich et al., 2009 ). So far, an effect of preceding auditory stimulation with affective content on regulation of wakefulness has not been investigated and provides evidence for dynamic influences of emotions and mood on brain states ( Borchardt et al., 2015 , Bola and Borchardt, 2016 ).

P 127 Vigilance regulation in adult ADHD

Background Functional regulation of vigilance or wakefulness is crucial for interaction with the environment and can be described as a unique, situation-dependent characteristic. Disorders of wakefulness regulation manifest themselves as delayed or rash declines in vigilance under calm settings. The vigilance model of affective disorders and ADHS postulate that unstable regulation of vigilance (“CNS arousal”) is observed not only in overtired children, but also in patients with mania and ADHS. Moreover, sensation and novelty seeking, hyperactivity and impulsivity observed in such persons should be interpreted as an autoregulatory attempt to stabilise vigilance by creating a stimulus incentive environment. As in mania, also in ADHD several EEG-based studies indicate an unstable regulation of wakefulness. Using an EEG-based algorithm (Vigilance Algorithm Leipzig, VIGALL) to assess the transition from high wakefulness to drowsiness until sleep onset, paediatric ADHD as well as manic patients showed an unstable vigilance regulation with rapid declines to lower vigilance stages or sleep onset. We investigated whether the vigilance regulation in adult patients with ADHD is less stable than that of healthy controls by exploring the frequency of EEG-vigilance regulation patterns. Methods Resting EEG recordings of unmedicated adult ADHD patients and healthy controls were analysed. The diagnosis was provided based on the DSM-IV criteria. EEG recordings of 15 min under quiet rest with eyes closed were performed. The computer-based Vigilance Algorithm Leipzig (VIGALL) was used to classify 1-s EEG segments into stages on the continuum ranging from full wakefulness to sleep onset. Results/conclusions Patients with ADHD showed an unstable vigilance regulation and spent more time in the less vigilance stages compared to the healthy controls. The investigated vigilance regulation model in ADHD could establish new insights into the neurophysiology of ADHD in adulthood and should be the subject of further investigations. An additional pre-post-treatment investigation with view on the suitability of the vigilance regulation as a predictor for response after a treatment with psychostimulants appears also useful.

CNS- and ANS-arousal predict response to antidepressant medication: Findings from the randomized iSPOT-D study

Arousal systems are one of the recently announced NIMH Research Domain Criteria to inform future diagnostics and treatment prediction. In major depressive disorder (MDD), altered central nervous system (CNS) wakefulness regulation and an increased sympathetic autonomic nervous system (ANS) activity have been identified as biomarkers with possible discriminative value for prediction of antidepressant treatment response. Therefore, the hypothesis of a more pronounced decline of CNS and ANS-arousal being predictive for a positive treatment outcome to selective-serotonin-reuptake-inhibitor (SSRI) treatment was derived from a small, independent exploratory dataset (N = 25) and replicated using data from the randomized international Study to Predict Optimized Treatment Response in Depression (iSPOT-D). There, 1008 MDD participants were randomized to either a SSRI (escitalopram or sertraline) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI-venlafaxine) arm. Treatment response was established after eight weeks using the 17-item Hamilton Rating Scale for Depression. CNS-arousal (i.e. electroencephalogram-vigilance), ANS-arousal (heart rate) and their change across time were assessed during rest. Responders and remitters to SSRI treatment were characterized by a faster decline of CNS-arousal during rest whereas SNRI responders showed a significant increase of ANS-arousal. Furthermore, SSRI responders/remitters showed an association between ANS- and CNS-arousal regulation in comparison to non-responders/non-remitters while this was not the case for SNRI treatment arm. Since positive treatment outcome to SSRI and SNRI was linked to distinct CNS and ANS-arousal profiles, these predictive markers probably are not disorder specific alterations but reflect the responsiveness of the nervous system to specific drugs.

Vigilance regulation in adult ADHD

Background Functional regulation of vigilance or wakefulness is crucial for interaction with the environment and can be described as a unique, situation-dependent characteristic. Disorders of wakefulness regulation manifest themselves as delayed or rash declines in vigilance under calm settings. The vigilance model of affective disorders and ADHS postulate that unstable regulation of vigilance (“CNS arousal”) is observed not only in overtired children, but also in patients with mania and ADHS. Moreover, sensation and novelty seeking, hyperactivity and impulsivity observed in such persons should be interpreted as an autoregulatory attempt to stabilise vigilance by creating a stimulus incentive environment. As in mania, also in ADHD several EEG-based studies indicate an unstable regulation of wakefulness. Using an EEG-based algorithm (Vigilance Algorithm Leipzig, VIGALL) to assess the transition from high wakefulness to drowsiness until sleep onset, paediatric ADHD as well as manic patients showed an unstable vigilance regulation with rapid declines to lower vigilance stages or sleep onset. We investigated whether the vigilance regulation in adult patients with ADHD is less stable than that of healthy controls by exploring the frequency of EEG-vigilance regulation patterns. Methods EEG recordings of 15 min under quiet rest with eyes closed were performed. The computer-based Vigilance Algorithm Leipzig (VIGALL) was used to classify 1-s EEG segments into stages on the

Neurophysiological Mechanism of Sleep and Wakefulness Regulation

Neurophysiological Mechanism of Sleep and Wakefulness Regulation

P135. EEG-based assessment of wakefulness regulation in different mood states in bipolar disorder – A retrospective analysis

Background According to the vigilance theory of affective disorders, unipolar depression is characterised by a hyperstable wakefulness regulation, meaning that patients suffering from depression show a high alertness and a less distinct and later decline into lower vigilance and sleep states. Mania on the other hand is associated with an unstable wakefulness regulation with a rapid decline into sleep states and quickly alternating wakefulness states ( Hegerl and Hensch, 2012 ). This theory has been backed up for unipolar depression in recent years ( Hegerl et al., 2012 ). However, so far EEG-based assessment of wakefulness regulation has not been performed for bipolar patients in different mood states. Objective The aim of this study is to assess and to compare wakefulness regulation in bipolar depression, mania and euthymia. This will be done both for diagnostic groups as well as for individual patients for whom EEG-recordings in all mood states are available. Methods This is going to be a retrospective, cross-sectional analysis. In the department of psychiatry at the university hospital in Leipzig, inpatients suffering from bipolar mania/depression and bipolar outpatients in euthymia undergo a 15-min resting EEG. Strict inclusion and exclusion criteria were defined to ensure comparability of results. So far, we have included 23 manic, 13 hypomanic and 51 depressive patients suffering from bipolar disorder. Mood at the time of EEG-recording is assessed via the Young Mania Rating Scale (YMRS) and the 17-item Hamilton rating scale for depression (HAMD-17). EEG-vigilance regulation will be determined with a computer-based vigilance classification algorithm (VIGALL, Vigilance Algorithm Leipzig), allowing a classification of vigilance stages A (with substages A1, A2 and A3), B (with substages B1 and B2/3) and C. Hypothesis We hypothesize that currently depressive bipolar patients will show hyperstable wakefulness, while currently manic patients will show an unstable wakefulness regulation. Furthermore, we hypothesize that this is a state – rather than a trait – dependent regulation.

The stimulating impact of light on brain cognition function

Light regulates multiple non-visual circadian, neuroendocrine, and neurobehavioral functions, and conveys a strong stimulating signal for alert-ness and cognition. This review summarizes a series of neuroimaging studies investigating the brain mechanisms underlying the latter stimulating impact of light. Results of these studies are compatible with a scenario where light would first hit subcortical areas involved in arousal regulation before affecting cortical areas involved in the ongoing non-visual cognitive process, and then cognitive performance. Recent data demonstrated that the non-visual impact of light is most likely triggered via outputs from intrinsically photosensitive retinal ganglion cells (ipRGC) expressing the photopigment melanopsin, which are maximally sensitive to blue light. In addition, the stimulating impact of light is intimately related to wakefulness regulation as it changes with circadian phase and sleep pressure. Finally, markers of inter-individual difference have also been described: age, PERIOD3 genotype, and psychiatric status. This review emphasizes the importance of light for human brain cognitive function and for cognition in general.

Positive allosteric modulation of mGlu7 receptors by AMN082 affects sleep and wakefulness in the rat

Evidence indicates that metabotropic glutamate receptors (mGlu) are involved in the regulation of physiological and behavioral processes, and glutamate has been implicated in several pathologies of the Central Nervous System. Pharmacological evidence suggests the therapeutic potential of targeting mGlu7 receptor in a number of pathological conditions; and previous research has shown the involvement of glutamate on sleep and wakefulness regulation. Here, the effects of mGlu7 receptor selective modulation on sleep and wake states are explored. 32 male Wistar rats were implanted with electrodes for recording sleep and wakefulness. N,N′-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) (5, 10, and 20mg/kg, i.p.), a potent, selective and systemically active mGlu7 receptor positive allosteric modulator, or vehicle was administered 1hour after the beginning of the light period. AMN082 (5 and 10mg/kg) significantly increased total time of sleep; and time spent on Slow Wave Sleep (SWS) was increased. AMN082 at 10mg/kg specifically affected Light SWS, increasing time spent on Light SWS. The highest dose of AMN082, 20mg/kg, significantly reduced time spent in Rapid Eye Movement (REM) sleep, decreasing the number of REM sleep episodes and their mean duration. Total time spent awake was increased and mean episode duration of wakefulness was prolonged. The present results suggest that mGlu7 receptors might be involved in sleep regulation and drugs targeting these receptors could affect sleep and wakefulness architecture.

Poster #121 PROTEIN PROFILING OF PATIENTS WITH ACUTE PSYCHOSIS VS PSYCHIATRIC CONTROLS: A PROTEOMIC APPROACH

Arousal systems are one of the recently announced NIMH Research Domain Criteria to inform future diagnostics and treatment prediction. In major depressive disorder (MDD), altered central nervous system (CNS) wakefulness regulation and an increased sympathetic autonomic nervous system (ANS) activity have been identified as biomarkers with possible discriminative value for prediction of antidepressant treatment response. Therefore, the hypothesis of a more pronounced decline of CNS and ANS-arousal being predictive for a positive treatment outcome to selective-serotonin-reuptake-inhibitor (SSRI) treatment was derived from a small, independent exploratory dataset (N = 25) and replicated using data from the randomized international Study to Predict Optimized Treatment Response in Depression (iSPOT-D). There, 1008 MDD participants were randomized to either a SSRI (escitalopram or sertraline) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI-venlafaxine) arm. Treatment response was established after eight weeks using the 17-item Hamilton Rating Scale for Depression. CNS-arousal (i.e. electroencephalogram-vigilance), ANS-arousal (heart rate) and their change across time were assessed during rest. Responders and remitters to SSRI treatment were characterized by a faster decline of CNS-arousal during rest whereas SNRI responders showed a significant increase of ANS-arousal. Furthermore, SSRI responders/remitters showed an association between ANS- and CNS-arousal regulation in comparison to non-responders/non-remitters while this was not the case for SNRI treatment arm. Since positive treatment outcome to SSRI and SNRI was linked to distinct CNS and ANS-arousal profiles, these predictive markers probably are not disorder specific alterations but reflect the responsiveness of the nervous system to specific drugs.

P-514 - Wakefulness regulation and the prediction of antidepressant treatment in major depression

The vigilance regulation model of affective disorders suggests that tonically high vigilance (i.e. brain arousal) in patients with major depression (MD) induces social withdrawal and sensation avoidance as autoregulatory reactions to decrease external stimulation. A computer based algorithm (VIGALL) has been developed that allows the classification of EEG-vigilance time series. Validation studies revealed a close association of EEG-vigilance stages and autonomous nervous system (ANS) activity and proved the discriminative power of VIGALL by showing that patients with MD reveal a more stable EEG-vigilance regulation compared to healthy controls. Before this background the question raises, whether vigilance regulation patterns could also be used for treatment prediction in MD. The predictive power of three different pre-treatment EEG-vigilance regulation patterns was analyzed in 33 previously unmedicated patients with MD. Results will be presented that show differences of frequency distribution of vigilance regulation patterns in responders and non-responders, defined by a reduction more or less than 30% in Hamilton Depression Rating Scale after two weeks of treatment with an SSRI or mirtazapine. Additionally, differences of ANS activity by means of heart rate variability between responders and non-responders will be shown. The results will be discussed within the light of a possible dysregulation of cortical and autonomous arousal in MD. Also the usage of EEG-vigilance regulation patterns as a biomarker for antidepressant treatment outcome in MD will be adressed.

Régulation de la veille et du sommeil : les acteurs moléculaires

By combining brain section/lesion studies and sleep analysis, neurophysiologists have identified the brain areas responsible for regulating sleep and wakefulness during the first half of the 20th century. Identification of the phenotypic nature of the neurons underlying the regulation of vigilance, as well as their anatomical and functional connections led to a theoretical model based on mutual inhibitory interactions between sleep-on neurons (namely GABAergic neurons of the hypothalamic preoptic region) and wake-on neurons (mainly monoaminergic and cholinergic neurons). In addition to the corresponding neurotransmitters (serotonin, acetylcholine and GABA), other neuroactive molecules that play key roles in sleep and wakefulness regulation have recently been discovered, leading to an updated model. Hypocretin, also known as orexin, is a key neuropeptide involved in the sleep disorder narcolepsy. Extensive characterization of the respective roles of these neurotransmitters has led to the identification of novel therapeutic targets for the treatment of sleep disorders. For example, blockade of hypocretin receptors has hypnotic effects.

Mania and attention-deficit/hyperactivity disorder: common symptomatology, common pathophysiology and common treatment?

Attention-deficit/hyperactivity disorder (ADHD) and mania show broad symptom overlap, and high comorbidity exists between ADHD and bipolar disorder. This raises the question concerning common neurobiological pathomechanisms and concerning common treatments. On genetic, biochemical, electrophysiological, brain morphological and neuropsychological levels, the commonalities of ADHD and mania and the commonalities between ADHD and bipolar disorder (independent of manic state) are outlined. An intriguing finding is that both ADHD and mania are characterized by an unstable wakefulness regulation assessed by EEG measures of vigilance, by ratings of sleepiness and by deficits in sustained attention tasks. In both mania and ADHD, this unstable wakefulness regulation is supposed to be a central pathogenetic factor leading to attention deficits and inducing the hyperactive, impulsive and sensation-seeking behavior as an autoregulatory attempt to stabilize wakefulness by increasing external stimulation. Evidence is accumulating to suggest that psychostimulants do not have a high risk of triggering or aggravating mania, but might even be a treatment option in acute mania. ADHD and mania share many symptoms and several pathogenetic aspects. The common belief that stimulants are contraindicated in mania has been challenged, and controlled trials to study the possible antimanic effects of vigilance-stabilizing drugs such as stimulants are justified and necessary.