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Ulrich Hegerl - One of the best experts on this subject based on the ideXlab platform.

  • Is brain Arousal Regulation a predictor of response to psychostimulant therapy in adult ADHD patients?
    European Archives of Psychiatry and Clinical Neuroscience, 2019
    Co-Authors: Maria Strauß, Christine Ulke, Ulrich Hegerl, Christian Sander, Madlen Paucke, Andreas Reif, Heike Weber, Julia Heupel, Juliane Kopf, Sarah Kittel-schneider
    Abstract:

    We investigated whether baseline brain Arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An Arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of Arousal decline. In logistic regression analysis, Arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0–1.65); p  = 0.027]. In this pilot study, we demonstrated that Arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable Arousal Regulation during a 15-min EEG at rest increases the chance of treatment response.

  • Brain Arousal Regulation in SSRI-medicated patients with major depression.
    Journal of psychiatric research, 2018
    Co-Authors: Christine Ulke, Janek Spada, Philippe Jawinski, Tilman Hensch, Dirk Alexander Wittekind, K Franik, Ulrich Hegerl
    Abstract:

    Abstract EEG measures of Arousal have been suggested as diagnostic and predictive biomarkers for major depression. The aim of the present study was to examine whether self-rated depression severity in SSRI-medicated patients with major depression (MD) is associated with EEG measures of brain Arousal. Based on previous studies, we expected that a higher level of brain Arousal and a slower Arousal decline during a 15-min EEG recording are associated with higher symptom severity as assessed with the Beck Depression Inventory (BDI) at the time of the EEG recording. EEGs of 78 MD patients and 46 healthy controls were analyzed. Brain Arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). Based on automatically classified 1-s segments (EEG-vigilance Stages 0, A1, A2, A3, B1, B2/3 or C) we computed indices to assess the level (mean EEG-vigilance) and the decline of Arousal (slope index) during the 15-min resting state EEG under eyes-closed condition. We found that a higher Arousal level and a slower Arousal decline corresponded to higher severity of depressive symptoms (rho = 0.238, p = .018; and rho = 0.236; p = .019). Self-rated non-remitters (BDI>12) had a higher Arousal level (mean EEG-vigilance: t76 = −2.19, p = .016) and slower Arousal decline (slope index: Z = −2.08, p = .019) during the 15-min recording as compared to remitters. Similar results were obtained between non-remitters and healthy controls (mean EEG-vigilance: t102 = −2.75, p = .004; slope index: Z = −1.92, p = .028), but not between remitters and controls (p > .260). The findings support the model that brain Arousal Regulation plays an important role in the pathophysiology and treatment of MD.

  • brain Arousal Regulation in adults with attention deficit hyperactivity disorder adhd
    Psychiatry Research-neuroimaging, 2018
    Co-Authors: Maria Straus, Christine Ulke, Jue Huang, Christian Sander, Madlen Paucke, Nicole Mauche, Tetyana Stark, Ulrich Hegerl
    Abstract:

    Abstract The main aim of the current study was to test the hypothesis that adult patients with attention-deficit/hyperactivity disorder (ADHD) have less stable brain Arousal Regulation than healthy controls. We objectively assessed brain Arousal Regulation using the Vigilance Algorithm Leipzig (VIGALL 2.1) to analyze 15-min resting EEG data of thirty-three ADHD patients and thirty-five matched controls. Based on automatically classified 1-s segments we computed mean EEG-vigilance (indexing Arousal level) and Arousal stability score (indexing Arousal Regulation). Adult ADHD patients showed significantly lower Arousal levels and significantly less stable brain Arousal Regulation than controls. Multiple regression analysis indicated that Arousal Regulation (i.e., Arousal stability score) predicted the retrospectively-assessed severity of childhood ADHD symptoms, supporting the trait aspect of brain Arousal Regulation. Our findings support the Arousal Regulation model of ADHD, which interprets hyperactivity and sensation seeking as an autoregulatory reaction to an unstable Regulation of brain Arousal. EEG-based Arousal parameters may be candidate biomarkers for adult ADHD.

  • p 131 association between clinical depressive symptomatology and brain Arousal Regulation in medicated patients with major depression
    Clinical Neurophysiology, 2017
    Co-Authors: Dirk Alexander Wittekind, Janek Spada, Tilman Hensch, K Franik, C Sander, Ulrich Hegerl
    Abstract:

    Background According to the Arousal Regulation model of affective disorders, typical depressive symptoms like sensation avoidance and withdrawal in depression can partly be explained as an auto-regulatory attempt to counteract a tonically high brain Arousal, which has repeatedly been shown in unmedicated patients with Major Depression (MDD). Brain Arousal has so far not been studied in medicated MDD patients and it is unclear to what extent depressive symptomatology is associated with brain Arousal Regulation. The aim of this study was to compare Arousal Regulation in medicated MDD patients with healthy controls and to investigate the association between self-rated depressive symptomatology and brain Arousal Regulation. We hypothesized that despite drug treatment depressed patients would still show a hyperstable brain Arousal compared to healthy controls and that depressive symptomatology will be positively associated with the stability of brain Arousal Regulation. Methods Between 2006 and 2014, 130 currently depressed MDD patients treated with a Selective Serotonine Reuptake Inhibitor (SSRI) and 130 age- and sex-matched healthy controls received a 15 min resting EEG. Depressive symptomatology was assessed with the Beck Depression Inventory (BDI; self-assessment) and sleep quality and duration was measured with the “Allgemeiner Schlaffragebogen” (SF-A). Brain Arousal was assessed with the Vigilance Algorithm Leipzig (VIGALL), which classifies 1-s EEG segments as one of seven EEG-vigilance sub-stages. Results No difference in the Regulation of brain Arousal/wakefulness between medicated MDD patients and healthy controls was found. Also, there was neither a clear association between depression severity nor individual items of the BDI and Arousal Regulation. Conclusion Our results are in line with a recent longitudinal study, showing a less stable Arousal Regulation in MDD patients after treatment with SSRI, suggesting a labilizing effect of SSRI on brain Arousal Regulation. Limitations are the retrospective design and the heterogenity of the group with respect to depression severity.

  • p 161 coupling of brain Arousal and autonomic Regulation in the transition from wakefulness to sleep onset during an auditory oddball task in the resting state
    Clinical Neurophysiology, 2017
    Co-Authors: Christine Ulke, Ulrich Hegerl, Jue Huang, G. Surova, Roland Mergl, Justus T C Schwabedal, Tilman Hensch
    Abstract:

    Background Simultaneous downRegulation of the autonomic and central nervous system activity enables the gradual physiological state change from wakefulness to sleep onset. DysRegulation of central or autonomic Arousal has been found in neurological ( Silvani et al., 2016 ) and psychiatric disorders ( Hegerl and Hensch, 2014 , Hegerl et al., 2012 , Schulz et al., 2016 , Schwabedal et al., 2016 ), often associated with dysregulated sleep-wake patterns. Aim We investigated the hypothesis that brain-autonomic co-Regulation affects the attentive process in the transition from wakefulness to sleep onset. We propose that the degree to which autonomic and brain dynamics are correlated predicts the level of cortical excitability or inhibition and sleep onset behavior in this transition. To test our hypothesis, we explored electroencephalogram (EEG), electrocardiogram (ECG) and skin conductance data recorded during a 2-h resting state oddball experiment. Methods 39 healthy study participants underwent a 2-h resting EEG with eyes closed including ECG-derived heart rate (HR) and measurement of skin conductance level (SCL). The Vigilance Algorithm Leipzig (VIGALL 2.1) was used to assess brain Arousal Regulation based on automatic EEG-vigilance stage classification of 1-s EEG segments. These vigilance stages (=vigilance; V) were scored and cross-correlated with HR and SCL over a range of ±100 s, and a mean period of vigilance fluctuations was estimated from the frequency of maxima after low-pass filtering. Mean amplitudes of event-related potentials N100 and P200 to standard and deviant stimuli at Cz were calculated as indices of cortical excitability (N100) and cortical inhibition (P200) ( Cortoos et al., 2014 ). Results In all subjects, higher max cross-correlation coefficients (V-HR mean: r = 0.362, range: −0.069 to 0.762; SD = 0.192; V-SCL mean: r = 0.277, range: −0.299 to 0.629; SD = 0.211) were associated with longer mean periods of cortico-autonomic signals (V-HR: r = 0.462, p = .003; V-SCL: r = 0.516, p = .001). The cross-correlation of V with either HR and SCL partitioned the subjects into two groups (group no lag: n0 = 20, τ  = 0; group lag: n1 = 19, τ (range) = −98 to −87) dependent on the time lag of maximal correlation. Subjects in n0, who fell asleep more often (indexed by the frequency of falling asleep: t37 = 2.49, p = .018) during the 2-h EEG compared to subjects in n1, had higher max cross-correlation coefficients (V-HR: t37 = 4.24, p = 1.43E−4; V-SCL: t37 = 5.02, p = 1.35E−5) and displayed an increased standard (t30.235 = 3.19, p = .003) and deviant P200 amplitude (t37 = 3.63, p = .001) compared to subjects in n1. No significant group differences were found for N100 amplitudes and KSS score either before or after the recording. Conclusion Healthy individuals with no time lag between cortical and autonomic signals showed a stronger brain-autonomic coupling and increased P200 amplitudes (indicating a higher level of cortical inhibition) compared to individuals with a temporal misalignment. This may explain differences in sleep-onset behavior between groups. Present results indicate possible diagnostic value in the assessment of brain-autonomic Regulation, for example in disorders with sleep-related symptoms such as insomnia, dementia or depression.

Nicholas D. Schiff - One of the best experts on this subject based on the ideXlab platform.

John D Herrington - One of the best experts on this subject based on the ideXlab platform.

  • brief report emotion Regulation and respiratory sinus arrhythmia in autism spectrum disorder
    Journal of Autism and Developmental Disorders, 2014
    Co-Authors: Margaret C Souders, Lauren E Bradstreet, Christine Delussey, John D Herrington
    Abstract:

    Emotion Regulation (ER) may be an important transdiagnostic factor for understanding mental and behavioral health given its association with several psychiatric disorders, including autism spectrum disorder (ASD). However, there is limited research on ER in ASD, particularly using biomarkers such as respiratory sinus arrhythmia (RSA). The aim of the current study was to examine RSA among school-aged children with ASD in relation to symptoms of anxiety, executive functioning, and adaptive socialization skills. Results showed decreased RSA in children with ASD (relative to typically developing controls), reflecting decreased parasympathetic nervous system activity. In addition, decreased RSA was associated with increased symptoms of anxiety and lower socialization skills. These findings emphasize the need for interventions targeting emotional and Arousal Regulation in ASD.

Christine Ulke - One of the best experts on this subject based on the ideXlab platform.

  • Is brain Arousal Regulation a predictor of response to psychostimulant therapy in adult ADHD patients?
    European Archives of Psychiatry and Clinical Neuroscience, 2019
    Co-Authors: Maria Strauß, Christine Ulke, Ulrich Hegerl, Christian Sander, Madlen Paucke, Andreas Reif, Heike Weber, Julia Heupel, Juliane Kopf, Sarah Kittel-schneider
    Abstract:

    We investigated whether baseline brain Arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An Arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of Arousal decline. In logistic regression analysis, Arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0–1.65); p  = 0.027]. In this pilot study, we demonstrated that Arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable Arousal Regulation during a 15-min EEG at rest increases the chance of treatment response.

  • brain Arousal Regulation and depressive symptomatology in adults with attention deficit hyperactivity disorder adhd
    BMC Neuroscience, 2019
    Co-Authors: Jue Huang, Christine Ulke, Maria Strauß
    Abstract:

    The aim of the present study was to evaluate the stability of brain Arousal in adult attention-deficit/hyperactivity disorder (ADHD) outpatients with and without depressive symptomatology, and its association with depressive symptom severity and absolute electroencephalogram (EEG) power in different frequency bands. We included 31 outpatient adults (45.16% females), who were diagnosed according to DSM-IV and received no medication. Their Arousal stability score (index of the steepness of Arousal decline during a 15-min EEG under resting conditions), the absolute EEG power and self-reports, including depressive and ADHD-related symptoms, were analyzed. Participants were split into an unstable and stable Arousal group based on the median (= 6) of the Arousal stability score. ADHD patients in the stable group reported more severe depressive symptoms (p = 0.018) and showed reduced absolute EEG power in the delta (0.002 ≤ p ≤ 0.025) and theta (0.011 ≤ p ≤ 0.034) bands compared to those in the unstable group. There was no correlation between the Arousal stability score and self-report-scales concerning ADHD-related symptoms (0.214 ≤ p ≤ 0.989), but a positive association with self-reported depressive severity (p = 0.018) and negative association with powers in the EEG delta and theta bands (0.001 ≤ p ≤ 0.033). In view of high comorbidity of depression and ADHD in adult patients, these findings support the assumption that brain Arousal Regulation could be considered as a helpful marker for the clinical differentiation between ADHD and depression.

  • Brain Arousal Regulation in SSRI-medicated patients with major depression.
    Journal of psychiatric research, 2018
    Co-Authors: Christine Ulke, Janek Spada, Philippe Jawinski, Tilman Hensch, Dirk Alexander Wittekind, K Franik, Ulrich Hegerl
    Abstract:

    Abstract EEG measures of Arousal have been suggested as diagnostic and predictive biomarkers for major depression. The aim of the present study was to examine whether self-rated depression severity in SSRI-medicated patients with major depression (MD) is associated with EEG measures of brain Arousal. Based on previous studies, we expected that a higher level of brain Arousal and a slower Arousal decline during a 15-min EEG recording are associated with higher symptom severity as assessed with the Beck Depression Inventory (BDI) at the time of the EEG recording. EEGs of 78 MD patients and 46 healthy controls were analyzed. Brain Arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). Based on automatically classified 1-s segments (EEG-vigilance Stages 0, A1, A2, A3, B1, B2/3 or C) we computed indices to assess the level (mean EEG-vigilance) and the decline of Arousal (slope index) during the 15-min resting state EEG under eyes-closed condition. We found that a higher Arousal level and a slower Arousal decline corresponded to higher severity of depressive symptoms (rho = 0.238, p = .018; and rho = 0.236; p = .019). Self-rated non-remitters (BDI>12) had a higher Arousal level (mean EEG-vigilance: t76 = −2.19, p = .016) and slower Arousal decline (slope index: Z = −2.08, p = .019) during the 15-min recording as compared to remitters. Similar results were obtained between non-remitters and healthy controls (mean EEG-vigilance: t102 = −2.75, p = .004; slope index: Z = −1.92, p = .028), but not between remitters and controls (p > .260). The findings support the model that brain Arousal Regulation plays an important role in the pathophysiology and treatment of MD.

  • brain Arousal Regulation in adults with attention deficit hyperactivity disorder adhd
    Psychiatry Research-neuroimaging, 2018
    Co-Authors: Maria Straus, Christine Ulke, Jue Huang, Christian Sander, Madlen Paucke, Nicole Mauche, Tetyana Stark, Ulrich Hegerl
    Abstract:

    Abstract The main aim of the current study was to test the hypothesis that adult patients with attention-deficit/hyperactivity disorder (ADHD) have less stable brain Arousal Regulation than healthy controls. We objectively assessed brain Arousal Regulation using the Vigilance Algorithm Leipzig (VIGALL 2.1) to analyze 15-min resting EEG data of thirty-three ADHD patients and thirty-five matched controls. Based on automatically classified 1-s segments we computed mean EEG-vigilance (indexing Arousal level) and Arousal stability score (indexing Arousal Regulation). Adult ADHD patients showed significantly lower Arousal levels and significantly less stable brain Arousal Regulation than controls. Multiple regression analysis indicated that Arousal Regulation (i.e., Arousal stability score) predicted the retrospectively-assessed severity of childhood ADHD symptoms, supporting the trait aspect of brain Arousal Regulation. Our findings support the Arousal Regulation model of ADHD, which interprets hyperactivity and sensation seeking as an autoregulatory reaction to an unstable Regulation of brain Arousal. EEG-based Arousal parameters may be candidate biomarkers for adult ADHD.

  • p 161 coupling of brain Arousal and autonomic Regulation in the transition from wakefulness to sleep onset during an auditory oddball task in the resting state
    Clinical Neurophysiology, 2017
    Co-Authors: Christine Ulke, Ulrich Hegerl, Jue Huang, G. Surova, Roland Mergl, Justus T C Schwabedal, Tilman Hensch
    Abstract:

    Background Simultaneous downRegulation of the autonomic and central nervous system activity enables the gradual physiological state change from wakefulness to sleep onset. DysRegulation of central or autonomic Arousal has been found in neurological ( Silvani et al., 2016 ) and psychiatric disorders ( Hegerl and Hensch, 2014 , Hegerl et al., 2012 , Schulz et al., 2016 , Schwabedal et al., 2016 ), often associated with dysregulated sleep-wake patterns. Aim We investigated the hypothesis that brain-autonomic co-Regulation affects the attentive process in the transition from wakefulness to sleep onset. We propose that the degree to which autonomic and brain dynamics are correlated predicts the level of cortical excitability or inhibition and sleep onset behavior in this transition. To test our hypothesis, we explored electroencephalogram (EEG), electrocardiogram (ECG) and skin conductance data recorded during a 2-h resting state oddball experiment. Methods 39 healthy study participants underwent a 2-h resting EEG with eyes closed including ECG-derived heart rate (HR) and measurement of skin conductance level (SCL). The Vigilance Algorithm Leipzig (VIGALL 2.1) was used to assess brain Arousal Regulation based on automatic EEG-vigilance stage classification of 1-s EEG segments. These vigilance stages (=vigilance; V) were scored and cross-correlated with HR and SCL over a range of ±100 s, and a mean period of vigilance fluctuations was estimated from the frequency of maxima after low-pass filtering. Mean amplitudes of event-related potentials N100 and P200 to standard and deviant stimuli at Cz were calculated as indices of cortical excitability (N100) and cortical inhibition (P200) ( Cortoos et al., 2014 ). Results In all subjects, higher max cross-correlation coefficients (V-HR mean: r = 0.362, range: −0.069 to 0.762; SD = 0.192; V-SCL mean: r = 0.277, range: −0.299 to 0.629; SD = 0.211) were associated with longer mean periods of cortico-autonomic signals (V-HR: r = 0.462, p = .003; V-SCL: r = 0.516, p = .001). The cross-correlation of V with either HR and SCL partitioned the subjects into two groups (group no lag: n0 = 20, τ  = 0; group lag: n1 = 19, τ (range) = −98 to −87) dependent on the time lag of maximal correlation. Subjects in n0, who fell asleep more often (indexed by the frequency of falling asleep: t37 = 2.49, p = .018) during the 2-h EEG compared to subjects in n1, had higher max cross-correlation coefficients (V-HR: t37 = 4.24, p = 1.43E−4; V-SCL: t37 = 5.02, p = 1.35E−5) and displayed an increased standard (t30.235 = 3.19, p = .003) and deviant P200 amplitude (t37 = 3.63, p = .001) compared to subjects in n1. No significant group differences were found for N100 amplitudes and KSS score either before or after the recording. Conclusion Healthy individuals with no time lag between cortical and autonomic signals showed a stronger brain-autonomic coupling and increased P200 amplitudes (indicating a higher level of cortical inhibition) compared to individuals with a temporal misalignment. This may explain differences in sleep-onset behavior between groups. Present results indicate possible diagnostic value in the assessment of brain-autonomic Regulation, for example in disorders with sleep-related symptoms such as insomnia, dementia or depression.

Christian Sander - One of the best experts on this subject based on the ideXlab platform.

  • Is brain Arousal Regulation a predictor of response to psychostimulant therapy in adult ADHD patients?
    European Archives of Psychiatry and Clinical Neuroscience, 2019
    Co-Authors: Maria Strauß, Christine Ulke, Ulrich Hegerl, Christian Sander, Madlen Paucke, Andreas Reif, Heike Weber, Julia Heupel, Juliane Kopf, Sarah Kittel-schneider
    Abstract:

    We investigated whether baseline brain Arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An Arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of Arousal decline. In logistic regression analysis, Arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0–1.65); p  = 0.027]. In this pilot study, we demonstrated that Arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable Arousal Regulation during a 15-min EEG at rest increases the chance of treatment response.

  • brain Arousal Regulation in adults with attention deficit hyperactivity disorder adhd
    Psychiatry Research-neuroimaging, 2018
    Co-Authors: Maria Straus, Christine Ulke, Jue Huang, Christian Sander, Madlen Paucke, Nicole Mauche, Tetyana Stark, Ulrich Hegerl
    Abstract:

    Abstract The main aim of the current study was to test the hypothesis that adult patients with attention-deficit/hyperactivity disorder (ADHD) have less stable brain Arousal Regulation than healthy controls. We objectively assessed brain Arousal Regulation using the Vigilance Algorithm Leipzig (VIGALL 2.1) to analyze 15-min resting EEG data of thirty-three ADHD patients and thirty-five matched controls. Based on automatically classified 1-s segments we computed mean EEG-vigilance (indexing Arousal level) and Arousal stability score (indexing Arousal Regulation). Adult ADHD patients showed significantly lower Arousal levels and significantly less stable brain Arousal Regulation than controls. Multiple regression analysis indicated that Arousal Regulation (i.e., Arousal stability score) predicted the retrospectively-assessed severity of childhood ADHD symptoms, supporting the trait aspect of brain Arousal Regulation. Our findings support the Arousal Regulation model of ADHD, which interprets hyperactivity and sensation seeking as an autoregulatory reaction to an unstable Regulation of brain Arousal. EEG-based Arousal parameters may be candidate biomarkers for adult ADHD.

  • brain Arousal Regulation as response predictor for antidepressant therapy in major depression
    Scientific Reports, 2017
    Co-Authors: Frank M. Schmidt, Christian Sander, Roland Mergl, Marieelisa Dietz, Claudia Nowak, Thomas Schroder, Peter Schonknecht, Hubertus Himmerich, Ulrich Hegerl
    Abstract:

    A tonically high level of brain Arousal and its hyperstable Regulation is supposed to be a pathogenic factor in major depression. Preclinical studies indicate that most antidepressants may counteract this dysRegulation. Therefore, it was hypothesized that responders to antidepressants show a) a high level of EEG-vigilance (an indicator of brain Arousal) and b) a more stable EEG-vigilance Regulation than non-responders. In 65 unmedicated depressed patients 15-min resting-state EEGs were recorded off medication (baseline). In 57 patients an additional EEG was recorded 14 ± 1 days following onset of antidepressant treatment (T1). Response was defined as a ≥50% HAMD-17-improvement after 28 ± 1 days of treatment (T2), resulting in 29 responders and 36 non-responders. Brain Arousal was assessed using the Vigilance Algorithm Leipzig (VIGALL 2.1). At baseline responders and non-responders differed in distribution of overall EEG-vigilance stages (F2,133 = 4.780, p = 0.009), with responders showing significantly more high vigilance stage A and less low vigilance stage B. The 15-minutes Time-course of EEG-vigilance did not differ significantly between groups. Exploratory analyses revealed that responders showed a stronger decline in EEG-vigilance levels from baseline to T1 than non-responders (F2,130 = 4.978, p = 0.005). Higher brain Arousal level in responders to antidepressants supports the concept that dysRegulation of brain Arousal is a possible predictor of treatment response in affective disorders.

  • Early report on brain Arousal Regulation in manic vs depressive episodes in bipolar disorder
    Bipolar disorders, 2016
    Co-Authors: Dirk Alexander Wittekind, Christine Ulke, Janek Spada, Philippe Jawinski, Tilman Hensch, Christian Sander, Alexander Gross, Ulrich Hegerl
    Abstract:

    Objectives 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. Methods Twenty-eight patients with bipolar disorder received a 15-min resting electroencephalogram (EEG) during a depressive episode and 19 patients received the same during a manic/hypomanic episode. Twenty-eight healthy control subjects were matched for age and sex. The Vigilance Algorithm Leipzig (VIGALL), which classifies 1-s EEG segments as one of seven EEG-vigilance substages, was used to measure brain Arousal Regulation. Results Manic patients showed more unstable EEG-vigilance Regulation as compared to the control sample (P = .004) and to patients with a depressive episode (P ≤ .001). Depressive patients had significantly higher mean vigilance levels (P = .045) than controls. Conclusions A clear difference was found in the Regulation of brain Arousal of manic patients vs depressive patients and controls. These data suggest that brain Arousal might depend on the current mood state, which would support the Arousal Regulation model of affective disorders.

  • Time to wake up: No impact of COMT Val158Met gene variation on circadian preferences, Arousal Regulation and sleep
    Chronobiology international, 2016
    Co-Authors: Philippe Jawinski, Christine Ulke, Janek Spada, Jue Huang, Christian Sander, Nicole Mauche, Markus Scholz, Sophie Tegelkamp, Madlen Häntzsch, Ralph Burkhardt
    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.