Reported and Recorded Sleepiness in Obesity and Depression.

BACKGROUND: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known. OBJECTIVES: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements. METHODS: Healthy controls (HC, NHC = 66), normal-weighted depressed (DEP, NDEP = 16), non-depressed obese (OB, NOB = 68), and obese depressed patients (OBDEP, NOBDEP = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses. RESULTS: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not. CONCLUSION: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.

Why some obese people become depressed whilst others do not: exploring links between cognitive reactivity, depression and obesity.

Obesity and depression are two major public health concerns, particularly when they co-occur. To date, mechanisms underlying this association have not been established and it is unclear why some obese people become depressed whilst others do not. However, considering the strong association between depression and cognitive reactivity (CR), the present study explores possible associations between obesity, depression and CR in light of the scarce and conflicting nature of past literature. 254 participants were included for measures of depression, CR and obesity. Multivariate analyses of covariance examined the effects of depression and obesity as well as interaction effects of depression x obesity controlling for age and gender. Directions of effects were analysed by means of regression analyses and group contrasts. Linear analyses revealed (1) a significant effect of obesity on the rumination (RUM) and control/perfectionism subscales of CR, (2) a significant effect of depression on CR and all of its subscales, and (3) a significant interaction effect between obesity x depression on RUM. Results may support the 'Jolly Fat Hypothesis' and the existence of a psychologically protected subgroup of obese patients characterised by a lower ruminative thinking style and fewer depressive symptoms. Thus, incorporating anti-rumination therapy into treatment for obese individuals may be beneficial to prevent the development of comorbid depression.

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls.

BACKGROUND: In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups. METHODS: In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-x03B3; and IL-2 were measured prior to the EEG. RESULTS: Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant. CONCLUSIONS: The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.

Inflammatory cytokines in general and central obesity and modulating effects of physical activity.

CONTEXT: Chronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date. OBJECTIVE: To characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers. MAIN OUTCOMES MEASURES: Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR). RESULTS: General obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants. CONCLUSIONS: Results confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.

Cytokine levels in depressed and non-depressed subjects, and masking effects of obesity.

In major depressive disorder, changes in cytokine levels have been reported to play a role in pathogenesis. Therefore, we sought to investigate a broad range of cytokines in depression. We compared serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (INF-γ) and tumor necrosis factor (TNF)-α in 64 subjects with current depression and 206 non-depressed subjects. Depressed patients had higher levels of IL-2, IL-5, IL-12, IL-13, GM-CSF, INF-γ and TNF-α, compared to non-depressed subjects. Splitting groups into non-obese (BMI < 30) and obese (BMI ≥ 30), the non-obese depressed patients (n = 40) showed elevated IL-5, IL-12, IL-13, GM-CSF, INF-γ and TNF-α levels compared to non-obese and non-depressed subjects (n = 85). The obese and depressed patients (n = 24) showed elevated levels of IL-5, IL-12 and INF-γ compared to obese but not depressed subjects (n = 121). Levels of several cytokines were found to be associated with physical activity, employment status and presence of daily naps. The results support over-expression of pro-inflammatory cytokines in depression and extend the range of cytokines potentially associated with depression to include GM-CSF, IL-5 and IL-13. Changes in these cytokines may contribute to co-morbidity between depression and allergic and asthmatic diseases. The results also suggest inflammatory processes associated with obesity, and support an interaction between cytokine serum concentrations and behavioral aspects of both obesity and depression.

Functional connectivity in major depression: increased phase synchronization between frontal cortical EEG-source estimates.

Structural and metabolic alterations in prefrontal brain areas, including the subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have been shown in major depressive disorder (MDD). Still it remains largely unknown how brain connectivity within these regions is altered at the level of neuronal oscillations. Therefore, the goal was to analyze prefrontal electroencephalographic phase synchronization in MDD and its changes after antidepressant treatment. In 60 unmedicated patients and 60 healthy controls (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at baseline and in a subgroup of patients after 2 weeks of antidepressant medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was assessed with eLORETA (low resolution brain electromagnetic tomography) by means of lagged phase synchronization. At baseline, patients revealed increased prefrontal connectivity at the alpha frequency between the SGPFC and the left DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation was found for baseline beta connectivity and reduction in scores on the Hamilton depression rating scale. MDD is characterized by increased EEG functional connectivity within frontal brain areas. These EEG markers of disturbed neuronal communication might have potential value as biomarkers.

Separation of low-voltage EEG-activity during mental activation from that during transition to drowsiness.

When dealing with electroencephalograms (EEGs) recorded under resting conditions, periods of low-voltage activity might indicate drowsiness, but mental activation as well. Thus, low-voltage EEG retrieves a notorious source of confusion. The simultaneous occurrence of drowsiness related slow horizontal eye movements (SEM) allow to assign low-voltage EEG-activity to a brain state of reduced vigilance instead of mental activation. The aim of this study was to investigate, whether under resting conditions with eyes closed low-voltage EEG with SEM (B1+) and without SEM (B1-) differ in spectral and spatial distribution of EEG-activity. EEGs of 35 healthy subjects where analyzed, each containing at least 10 s of low-voltage EEG recorded during a calculation task (calc, as control condition), as well as 10 s of each B1- and B1+, recorded during following about 20 min of rest. Using standardized, low resolution brain electromagnetic tomography, cortical current density was computed in four individually adapted frequency bands (delta, theta, alpha, beta) for calc, B1- and B1+. Paired test comparison of cortical current densities revealed significant differences for B1- compared to B1+. In detail, B1- exhibited lower delta- and theta band activity, especially in the cingulate- and adjacent medial portions of the frontal, parietal and occipital cortices, as well as higher beta band activity in temporal cortices. Similar results where found in calc versus B1+. These findings support the association of B1- to a higher level of vigilance compared to B1+, thus justifying the separation of low-voltage EEG-activity by means of SEM.

EEG vigilance regulation patterns and their discriminative power to separate patients with major depression from healthy controls.

BACKGROUND/AIM: Recently, a framework has been presented that links vigilance regulation, i.e. tonic brain arousal, with clinical symptoms of affective disorders. Against this background, the aim of this study was to deepen the knowledge of vigilance regulation by (1) identifying different patterns of vigilance regulation at rest in healthy subjects (n = 141) and (2) comparing the frequency distribution of these patterns between unmedicated patients with major depression (MD; n = 30) and healthy controls (HCs; n = 30). METHOD: Each 1-second segment of 15-min resting EEGs from 141 healthy subjects was classified as 1 of 7 different vigilance stages using the Vigilance Algorithm Leipzig. K-means clustering was used to distinguish different patterns of EEG vigilance regulation. The frequency distribution of these patterns was analyzed in independent data of 30 unmedicated MD patients and 30 matched HCs using a χ² test. RESULTS: The 3-cluster solution with a stable, a slowly declining and an unstable vigilance regulation pattern yielded the highest mathematical quality and performed best for separation of MD patients and HCs (χ² = 13.34; p < 0.001). Patterns with stable vigilance regulation were found significantly more often in patients with MD than in HCs. CONCLUSION: A stable vigilance regulation pattern, derived from a large sample of HCs, characterizes most patients with MD and separates them from matched HCs with a sensitivity between 67 and 73% and a specificity between 67 and 80%. The pattern of vigilance regulation might be a useful biomarker for delineating MD subgroups, e.g. for treatment prediction.

State Effects of Two Forms of Meditation on Prefrontal EEG Asymmetry in Previously Depressed Individuals.

We investigated state effects of two forms of meditation on electroencephalography prefrontal α-asymmetry, a global indicator of approach versus withdrawal motivation and related affective state. A clinical series of previously depressed individuals were guided to practice either mindfulness breathing meditation (N = 8) or a form of meditation directly aimed at cultivating positive affect, loving kindness or metta meditation (N = 7). Prefrontal asymmetry was assessed directly before and after the 15-min meditation period. Results showed changes in asymmetry towards stronger relative left prefrontal activation, i.e., stronger approach tendencies, regardless of condition. Further explorations of these findings suggested that responses were moderated by participants' tendencies to engage in ruminative brooding. Individuals high in brooding tended to respond to breathing meditation but not loving kindness meditation, while those low in brooding showed the opposite pattern. Comparisons with an additionally recruited "rest" group provided evidence suggesting that changes seen were not simply attributable to habituation. The results indicate that both forms of meditation practice can have beneficial state effects on prefrontal α-asymmetry and point towards differential indications for offering them in the treatment of previously depressed patients.

Cognitive reactivity mediates the relationship between neuroticism and depression.

Although neuroticism has long been established as an important risk factor for depression, the mechanisms through which this temperamental predisposition translates into the occurrence of symptoms are still relatively unclear. This study investigated cognitive reactivity, i.e. the ease with which particular patterns of negative thinking are reactivated in response to mild low mood, as a potential mediator. Individuals with (N = 98) and without a previous history of depression (N = 83) who had provided neuroticism scores six years previously were assessed for cognitive reactivity and current symptoms of depression using self-report questionnaires. Tendencies to respond to mild low mood with ruminative thinking mediated the relation between neuroticism and current symptoms of depression in both groups. Reactivation of hopelessness and suicidal thinking occurred as an additional mediator only in those with a history of previous depression. The results suggest that neuroticism predisposes individuals to depression by generally increasing the likelihood of ruminative responses to low mood. In those with a history of depression in the past, neuroticism additionally increases risk of recurrence by facilitating reactivation of previously associated patterns such as suicidal thinking and hopelessness. These findings suggest potential targets for interventions to help preventing the occurrence, or recurrence of depression in those who due to their temperamental predisposition are at an increased risk.