[Atypical depression as a risk factor for obstructive sleep apnea syndrome in young adults]. / La dépression majeure à caractéristique atypique comme facteur de risque du syndrome d'apnées obstructives du sommeil chez le jeune adulte.

OBJECTIVES: In the literature, several studies have investigated the particular relationship between major depression and obstructive sleep apnoea syndrome (OSAS). However, most of these studies have focused primarily on middle-aged to elderly individuals (≥40 years) which means that this problem has been little studied in young adults (<30 years). Nevertheless, in young adults the prevalence of major depression (particularly its atypical subtype) is not negligible, which seems to justify carrying out additional investigations in order to allow a better understanding of the potential role played by major depression in the pathophysiology of OSAS in this particular subpopulation. The aim of this study was therefore to empirically investigate the prevalence of OSAS in young adults and to study the risk of OSAS associated with major depression in this particular subpopulation. METHODS: Polysomnographic and demographic data from 264 young adults were collected from the Erasme Hospital Sleep Laboratory (Brussels, Belgium) database to enable our analyses. During their two-night stay (including a first night of habituation and a night of polysomnography) at the Sleep Laboratory, these individuals underwent a complete somatic assessment (including blood test, electrocardiogram, daytime electroencephalogram and urinalysis), a systematic psychiatric assessment by a unit psychiatrist and an assessment of their complaints related to sleep. These different steps made it possible to systematically diagnose all somatic pathologies, psychiatric disorders according to the diagnostic criteria of the DSM-IV-TR and sleep pathologies according to the diagnostic criteria of the AASM. This allowed the selection of young adults included in our study based on our inclusion and exclusion criteria. Polysomnographic recordings from our Sleep Laboratory were visually scored according to AASM criteria. An obstructive sleep apnoea-hypopnoea index ≥5/hour was used for the diagnosis of OSAS. At the statistical level, in order to allow our analyses, we subdivided our sample of young adults into two groups: a control group without OSAS (n=215) and a patient group with OSAS (n=49). After checking the normal distribution of our data, normally distributed data were analysed with t-tests whereas asymmetrically or dichotomously distributed data were analysed with Wilcoxon tests or Chi2 tests. Univariate regression models were used to study the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults and potential confounding factors. In multivariate regression models, the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults was adjusted only for confounding factors significantly associated with OSAS during univariate analysis. These confounding factors were introduced in a hierarchical manner in the various multivariate regression models constructed. RESULTS: The prevalence of OSAS in our population of young adults was 18.6 %. During univariate analyses, atypical depression [OR 2.51 (95% CI 1.18-5.32), p-value=0.014], male gender [OR 4.53 (95% CI 2.20-9.34), P-value <0.001], presence of snoring [OR 2.51 (95% CI 1.33-4.75), P-value=0.005], presence of at least one cardio-metabolic alteration [OR 2.26 (95% CI 1.19-4.28), P-value=0.012], body mass index>30 kg/m2 [OR 4.55 (95% CI 2.07-10.03), P-value <0.001] and ferritin ≥150 µg/L [OR 3.28 (95% CI 1.69-6.36), P-value<0.001] were associated with increased risk of OSAS in our population of young adults. After adjusting for these major confounding factors associated with OSAS (gender, body mass index, cardio-metabolic alterations, ferritin level, and snoring) in the four models studied, multivariate regression analyses confirmed that unlike typical depression, atypical depression [OR 3.09 (95% CI 1.26-7.54), P-value=0.019] was a risk factor for OSAS in young adults. CONCLUSIONS: In our study, we demonstrated that the prevalence of OSAS was 18.6 % in young adults referred to the Erasme Hospital Sleep Laboratory. In addition, we have shown that unlike typical depression, atypical depression was associated with an increased risk of OSAS in young adults, which seems to justify more systematic research of this pathology in young adults suffering from atypical depression in order to allow the establishment of adapted therapeutic strategies and avoid the negative consequences associated with the co-occurrence of these two pathologies.

Decreased neuroautonomic complexity in men during an acute major depressive episode: analysis of heart rate dynamics.

Major depression affects multiple physiologic systems. Therefore, analysis of signals that reflect integrated function may be useful in probing dynamical changes in this syndrome. Increasing evidence supports the conceptual framework that complex variability is a marker of healthy, adaptive control mechanisms and that dynamical complexity decreases with aging and disease. We tested the hypothesis that heart rate (HR) dynamics in non-medicated, young to middle-aged males during an acute major depressive episode would exhibit lower complexity compared with healthy counterparts. We analyzed HR time series, a neuroautonomically regulated signal, during sleep, using the multiscale entropy method. Our results show that the complexity of the HR dynamics is significantly lower for depressed than for non-depressed subjects for the entire night (P<0.02) and combined sleep stages 1 and 2 (P<0.02). These findings raise the possibility of using the complexity of physiologic signals as the basis of novel dynamical biomarkers of depression.

Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD), which is associated with altered neuroplasticity and increased relative cardiac sympathic activity, enhances the risk of cardiovascular pathologies. Interaction between cardiac sympatho-vagal indexes and delta sleep power is probably altered in MDD. METHOD: Sleep characteristics and cardiac sympatho-vagal indexes of 10 depressive patients were compared to 10 control men across the first three non-rapid eye movement (NREM)-REM cycles. Interaction between normalized high frequency (HF) and delta power bands was studied using coherence analysis. RESULTS: Patients showed increased sleep latency, stage 1 and wake durations. No differences in heart rate variabilities were observed: Total power, HF and RR-interval decreased from NREM to REM sleep and wakefulness in both groups. Gain value was lower in patients while coherence and phase shift were similar between groups. Modifications in HF appear 8 min before modifications in delta. CONCLUSION: Major depressive disorder is related to an altered link between cardiac vagal influence and delta sleep, suggesting disorders in cardiovascular controls and an altered neuroplasticity.

The impact of chronic primary insomnia on the heart rate--EEG variability link.

OBJECTIVE: To determine if chronic insomnia alters the relationship between heart rate variability and delta sleep determined at the EEG. METHODS: After one night of accommodation, polysomnography was performed in 14 male patients with chronic primary insomnia matched with 14 healthy men. ECG and EEG recordings allowed the determination of High Frequency (HF) power of RR-interval and delta sleep EEG power across the first three Non Rapid Eye Movement (NREM)-REM cycles. Interaction between normalized HF RR-interval variability and normalized delta sleep EEG power was studied by coherency analysis. RESULTS: Patients showed increased total number of awakenings, longer sleep latency and wake durations and shorter sleep efficiency and REM duration than controls (p<.01). Heart rate variability across first three NREM-REM cycles and sleep stages (NREM, REM and awake) were similar between both groups. In each group, normalized HF variability of RR-interval decreased from NREM to both REM and awake. Patients showed decreased linear relationship between normalized HF RR-interval variability and delta EEG power, expressed by decreased coherence, in comparison to controls (p<.05). Gain and phase shift between these signals were similar between both groups. CONCLUSIONS: Interaction between changes in cardiac autonomic activity and delta power is altered in chronic primary insomniac patients, even in the absence of modifications in heart rate variability and cardiovascular diseases. SIGNIFICANCE: This altered interaction could reflect the first step to cardiovascular disorders.

The modifications of the long-range temporal correlations of the sleep EEG due to major depressive episode disappear with the status of remission.

OBJECTIVE: The aim of the present study is to investigate the scaling properties of the sleep electroencephalogram (EEG) in remitted depressed men, and to evaluate if a past history of major depressive disorder (MDD) could modify significantly and definitively, as a "scar marker," the dynamics of the sleep EEG time series. METHODOLOGY: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated depressed men in full to partial remission (42.43+/-5.62 years) and 14 healthy subjects (42.8+/-8.55 years). Scaling properties in these time series were investigated with detrended fluctuation analysis (DFA) (time range: 0.16-2.00 s). The scaling exponent alpha was determined in stage 2, in slow wave sleep (stages 3 and 4), and during rapid eye movement (REM) sleep. Forty-five epochs of 20 s were chosen randomly in each of these stages for each subject in both groups. RESULTS: We did not observe a significant difference and deviation of the scaling exponents between the two groups during the three sleep stages of interest. CONCLUSION: In this study, we do not observe any functional sequelae of a past history of one or more unipolar major depressive episode on the fluctuation properties of the sleep EEG. This finding is a sign of similar underlying neuronal dynamics in healthy controls and patients with a lifetime history of MDD. This study gives an additional argument to the theory that depression does not modify definitively the dynamics of the neuronal networks and is therefore against the "depressive scar hypothesis," in which permanent residual deficit is created by the acute state of the depressive disease.

Characterization of the sleep EEG in acutely depressed men using detrended fluctuation analysis.

OBJECTIVE: The aim of the present paper is to study the fluctuations of the sleep EEG over various time scales during a specific pathological condition: major depressive episode. Focus is made on scaling behaviour, which is the signature of the absence of characteristic time scale, and the presence of long-range correlations associated to physiological constancy preservation, variability reduction and mostly adaptability. METHODS: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated patients with a major depressive episode (41.70+/-8.11 years) and 14 healthy subjects (42.43+/-5.67 years). Scaling in these time series was investigated with detrended fluctuation analysis (time range: 0.16-2.00s). Scaling exponents (alpha) were determined in stage 2, slow wave sleep (stages 3 and 4) and during REM sleep. Forty-five epochs of 20s were chosen randomly in each of these stages. RESULTS: The median values of alpha were lower in patients during stage 2 and SWS. CONCLUSIONS: Major depressive episodes are characterized by a modification in the correlation structure of the sleep EEG time series. The finding which shows decreasing rate of the temporal correlations being different within the two groups in stage 2 and SWS provides an electrophysiologic argument that the underlying neuronal dynamics are modified during acute depression. SIGNIFICANCE: The observed modifications in scaling behaviour in acutely depressed patients could be an explanation of the sleep fragmentation and instability found during major depressive episode.

The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome.

We hypothesize that sleep apnea-hypopnea alters interaction between cardiac vagal modulation and sleep delta EEG. Sleep apnea-hypopnea syndrome (SAHS) is related to cardiovascular complications in men. SAHS patients show higher sympathetic activity than normal subjects. In healthy men, non-rapid eye movement (NREM) sleep is associated with cardiac vagal influence, whereas rapid eye movement (REM) sleep is linked to cardiac sympathetic activity. Interaction between cardiac autonomic modulation and delta sleep EEG is not altered across a life span nor is the delay between appearances of modifications in both signals. Healthy controls, moderate SAHS, and severe SAHS patients were compared across the first three NREM-REM cycles. Spectral analysis was applied to ECG and EEG signals. High frequency (HF) and low frequency (LF) of heart rate variability (HRV), ratio of LF/HF, and normalized (nu) delta power were obtained. A coherency analysis between HF(nu) and delta was performed, as well as a correlation analysis between obstructive apnea index (AI) or hypopnea index (HI) and gain, coherence, or phase shift. HRV components were similar between groups. In each group, HF(nu) was larger during NREM, while LF(nu) predominated across REM and wake stages. Coherence and gain between HF(nu) and delta decreased from controls to severe SAHS patients. In SAHS patients, the delay between modifications in HF(nu) and delta did not differ from zero. AI and HI correlated negatively with coherence, while HI correlated negatively with gain only. Apneas-hypopneas affect the link between cardiac sympathetic and vagal modulation and delta EEG demonstrated by the loss of cardiac autonomic activity fluctuations across shifts in sleep stages. Obstructive apneas and hypopneas alter the interaction between both signals differently.

QRS artifact elimination on full night sleep EEG.

Spectral analysis is now a standard procedure for analyzing the electroencephalograms (EEG) obtained by polysomnographic recordings. These numerical methods assume an artifact-free EEG since artifacts create spurious spectral components. Our aim was the development of a QRS artifact removal technique that might be applied to full night EEG with a minimal human intervention. This technique should handle one EEG channel, with or without use of one ECG channel. Variance minimization, independent component analysis (ICA), morphological filters (MF) have been implemented. Careful attention has been given to define the MF structuring element. The tests on artifact-simulated and real data were checked on the residual ECG spectral components present in the cleaned EEG. The best results are obtained by the MF when the structuring element is an artifact template defined either directly on the EEG or on the ICA ECG component. Further developments are required to identify and subtract the T-wave artifacts.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men.

OBJECTIVE: We investigated the interactions between heart rate variability and sleep electroencephalogram power spectra. METHODS: Heart rate and sleep electroencephalogram signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. Spectral components of RR intervals were studied across sleep stages. The cross-spectrum maximum was determined as well as coherencies, gains and phase shifts between normalized high frequency of RR intervals and all electroencephalographic frequency bands, calculated over the first 3 NREM-REM cycles. RESULTS: RR intervals increased from awake to NREM and decreased during REM. Normalized low frequency decreased from awake to NREM and increased during REM while normalized high frequency evolved conversely. Low to high frequency ratio developed in opposition to RR intervals. Coherencies between normalized high frequency and power spectra were high for all bands. The gain was highest for delta band. Phase shift between normalized high frequency and delta differed from zero and modifications in normalized high frequency preceded changes in delta by 41+/-14 degrees. CONCLUSIONS: Our study demonstrates that: (1) all electroencephalographic power bands are linked to normalized high frequency; (2) modifications in cardiac vagal activity show predominantly parallel changes and precede changes in delta band by a phase shift corresponding to a lead of 12+/-5 min.

Characteristics of spontaneous sleep with varying NREMS Episodes in healthy men: implication for delta activity homeostasis.

STUDY OBJECTIVES: We investigated the effects of the variation in the number of NREMS episodes on human sleep, in particular on delta activity distribution. PARTICIPANTS: Forty-one medication-free healthy men without personal or family history of psychiatric disorders. INTERVENTIONS: Subjects slept four consecutive nights, the last three were analyzed. Sleep was undisturbed and uninterrupted following self-selected schedule. RESULTS: With the exception of one night out of 123, subjects slept at least four NREMS episodes with 80% presenting five or six episodes per night. Yet, only 24% slept the same number of NREMS episodes across three nights. Shorter first NREMS episode was associated with greater number of NREMS episodes, and the total number of NREMS episodes was significantly predicted by the duration of the first one. Whether subjects slept four, five or six NREMS episodes, the proportion of TST spent in REMS, total delta power, total spectral power and the rate of delta power in the first NREMS episode did not differ between subjects. In each night, the distribution of delta activity across the first four NREMS episodes was not modified by the total number of NREMS episodes. CONCLUSION: When spontaneous sleep is allowed, healthy men mostly sleep beyond the fourth NREMS episode. Based on delta activity distribution across the first four episodes, we have demonstrated that the number of NREMS episodes does not modify delta sleep homeostasis. Only duration of first NREMS episode predicts the number of NREMS episodes slept. These results suggest that sleep homeostasis and NREMS-REMS alternation may be two independent processes.

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants.

OBJECTIVE: Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. STUDY DESIGN: Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. RESULTS: More intense auditory stimuli were needed to induce arousals in newborns (P =.002) and infants (P =. 044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P =.002) than of nonsmokers. CONCLUSIONS: Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth.

Contribution to the definition of the power bands limits of sleep EEG by linear prediction.

The linear prediction method has been applied to compute the power spectra distribution in 10 healthy young men (aged 17 to 26). For each subject, the local extrema positions have been detected and grouped as a function of their frequency. The computation of a mean frequency distribution for the extrema position, on the 10 subjects, allowed for the definition of eight frequency power bands. The time evolution of these power bands during the first NREM episode has been computed and averaged for the 10 subjects. The cross-correlation analysis demonstrated the relevance of three bands in the range 0-8.10 Hz: delta ]0-2.78] Hz, theta 1 ]2.78-5.42] Hz, theta 2 ]5.42-8.10] Hz. Our extrema study leads to the division of the beta range ]16.25-25.00] Hz into three bands. However, their time evolution does not support the usefulness of the partitioning of the beta range, probably resulting from our too low sampling frequency.

Distribution of delta activity across nonrapid eye movement sleep episodes in healthy young men.

The distribution of delta activity across successive nonrapid eye movement (NREM) sleep episodes and its night-to-night stability across three consecutive nights were investigated by studying delta power with spectral analysis in 31 healthy young men. Repeated-measures analysis of variance (ANOVA) with polynomial contrast was applied to grouped data of absolute delta power and three indexes: (1) the rate of delta power per NREM episode to its duration, 2) the standardized rate for the last NREM episode, and 3) the logarithm of the standardized rate. A significant linear decrease across NREM episodes was observed for each variable in each successive night. In addition, using night as a second within-subjects factor, no night effect was observed. Yet, the subsequent analysis of the logarithmic data yielded greater F values in all three nights' data as well as a linear function that accounted for a greater proportion of total variance than the analysis of the nonlogarithmic data. Since a linear decline for the logarithm of a variable implies an exponential distribution for that variable, we conclude that delta activity is distributed exponentially across NREM episodes, and this finding shows a remarkable night-to-night stability.

Sleep EEG analysis by linear prediction: frequency changes of slow-wave activity within NREM and REM sleep episodes in healthy men.

The linear prediction method was applied to obtain a power spectra estimate of sleep EEG in 10 healthy young men. In order to analyze frequency changes of the slow-wave activity (EEG power in the delta band, 0.05-2.88 Hz), the delta mean frequency was computed for each 20-second sleep epoch. A mean delta mean frequency was calculated for each sleep stage in each individual. Our observations indicate that the delta mean frequency decreases during NREM periods and increases mainly at the onset of the REM episodes. This finding, in parallel with the detailed analysis of slow-wave power variations, leads to an additional description of sleep characteristics during transitions between the NREM-REM sleep episodes.