A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness

ObjectiveTo explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA).MethodsEight patients with moderate–severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified.ResultsDFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (r = 0.738, p = 0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls.ConclusionsThe DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss.SignificanceDFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness.     

Electroretinography in seasonal affective disorder.

Retinal mechanisms have been hypothesized in the pathophysiology of seasonal affective disorder (SAD). Electroretinography (ERG) is a noninvasive electrophysiologic test that provides an objective measure of photoreceptor and retinal function. We conducted dark-adapted ERG examinations with a bright white light stimulus in a group of depressed, drug-free patients with seasonal affective disorder (6 men, 18 women) diagnosed by DSM-III-R criteria, and a group of sex- and age-matched control subjects (6 men, 16 women) during the winter. A significant difference was found between SAD patients and controls, but female SAD patients had lower ERG b-wave amplitudes than female controls, while male SAD patients had higher amplitudes than the matched controls. The ERG b-wave implicit times (times from onset of stimulus to peak of b-wave) were significantly longer in the left eyes of the male control subjects. These data may indicate subtle retinal changes in patients with SAD, but the results must be considered preliminary because of the small number of subjects studied and the large intersubject variability in the ERG procedure.     

A circadian signal of change of season in patients with seasonal affective disorder.

BACKGROUND: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. METHODS: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. RESULTS: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0 +/- 1.3 vs 8.4 +/- 1.3 hours; P=.001) but in healthy volunteers there was no change (9.0 +/- 1.6 vs 8.9 +/- 1.2 hours; P=.5). CONCLUSIONS: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder.     

Increased vagal tone during winter in subsyndromal seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent winter depression with summer remissions and/or hypomania. Further symptoms include hypersomnia, increased appetite, weight gain, fatigue, and social withdrawal, which may indicate autonomic changes during winter. METHODS: Measurements of respiratory sinus arrhythmia, heart rate (HR), and skin conductance level (SCL) were taken from 32 participants in subsyndromal SAD and control groups (eight male and eight female subjects in each group) in autumn and winter to determine any change in autonomic function. Measures were taken at baseline and during two stressor tasks. Single determinations of blood pressure, sublingual temperature, depression, aerobic fitness, and body mass index were also measured at each session. Replication in a second data collection period over subsequent winter and spring periods was conducted with an additional 32 participants to extend the findings and to counterbalance order effects in testing. Data were combined to produce "winter" and "nonwinter" test periods and statistically corrected for testing order. RESULTS: Respiratory sinus arrhythmia differences indicated that SAD subjects have increased vagal tone in winter. Both groups show a decrease for HR and increases for SCL and diastolic blood pressure in winter. CONCLUSIONS: Seasonal affective disorder may show similarities with hibernation, and the results may indicate mechanisms different from those of nonseasonal depression.     

Alcoholism and seasonal affective disorder

Seasonal changes in mood and behavior (seasonality) may be closely related to alcoholism. Some patients with alcoholism have a seasonal pattern to their alcohol misuse. They may be self-medicating an underlying seasonal affective disorder (SAD) with alcohol or manifesting a seasonal pattern to alcohol-induced depression. Both genetic and environmental factors play a role in the etiology and pathogenesis of alcoholism and SAD, operating, at least in part, through the brain serotonergic system. Family and molecular genetic studies suggest that there may be a genetic link between seasonality and alcoholism. Certain environmental and social factors may contribute to the development of seasonality in patients with alcoholism. The fact that SAD and alcoholism may be comorbid shows the importance of a thorough diagnostic interview. Both mental health and drug and alcohol professionals should be provided with education to assist with appropriate identification, management, and referral of patients presenting with comorbid alcoholism and SAD.     

Insight in seasonal affective disorder

Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P < .05). In conclusion, SAD patients possess a moderate amount of insight into depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.     

Prevalence of seasonal affective disorder in Alaska.

OBJECTIVE: The goals of this study are to provide estimates of the prevalence of seasonal affective disorder in Alaska, to examine sociodemographic correlates, and to evaluate the relation between seasonal affective disorder and general depression. METHOD: A random sample of 283 residents of Fairbanks who had lived in Alaska for 3 years or more were interviewed with the Seasonal Pattern Assessment Questionnaire and the Center for Epidemiologic Studies Depression Scale (CES-D Scale). RESULTS: Twenty-six (9.2%) of the subjects met diagnostic criteria for seasonal affective disorder, one of the highest figures yet reported. These cyclic winter affective disorders occurred more often in women than men (ratio = 3:2) and were less prevalent among residents who were older than 40 years of age. Assessment of depression with the CES-D Scale supported the diagnostic classification of respondents and the differentiation of seasonal affective disorder from other depression. CONCLUSIONS: This study supports the conclusions that seasonal affective disorder is prevalent in northern populations and that sex and age may represent the major risk factors that differentiate it from the general experience of depression in northern communities.     

Cocaine addiction: relationship to seasonal affective disorder.

We report a 25 year-old patient with seasonal affective disorder (SAD) and cocaine abuse who experienced cyclical fluctuations in cocaine craving which were concomitant with seasonal alterations in mood. The temporal association of both disorders in this patient suggests that they may share a common underlying pathophysiology. Since disturbances in circadian rhythms and pineal melatonin functions may in part underlie the pathophysiology of SAD and the psychomimetic effects of cocaine are mediated in part through the pineal gland, we propose that dysfunction of circadian rhythms and pineal melatonin functions may partly mediate the association of SAD with cocaine abuse. This hypothesis may have potential clinical and therapeutic implications for a subgroup of cocaine abusers with SAD since light therapy, which is efficacious in the therapy of SAD, may also prove to be beneficial in reducing cocaine addiction. Furthermore, the report illustrates the need for investigations of environmental cues for cocaine abuse with specific attention given to the effects of light on circadian mood changes.     

EEG spectral power and sleepiness during 24 h of sustained wakefulness in patients with obstructive sleep apnea syndrome.

OBJECTIVE: This study investigated if obstructive sleep apnea syndrome (OSAS) may be associated with higher activity in different frequency bands of the EEG during a sustained wakefulness paradigm. METHODS: Twelve OSA patients and 8 healthy controls were studied with the Karolinska Drowsiness Test (KDT) and subjective ratings of sleepiness (VAS and KSS) conducted every hour during 24 h of sustained wakefulness. RESULTS: The waking EEG activity, mainly in the low (0.5-7.8 Hz) and fast (12.7-29.2 Hz) frequency band, increased as time awake progressed in both groups but more obviously in OSA patients. A similar pattern was observed for rated sleepiness in both groups. Moreover, VAS ratings of alertness were closely related to the awake theta, fast alpha and beta bands in controls but not in OSA patients. CONCLUSIONS: OSAS was associated with a wake-dependent increase in low (0.5-7.8 Hz) and fast (12.7-29.2 Hz) frequency range activity. Variations in behavioural sleepiness measured by VAS ratings closely reflect most of the waking EEG parameters in controls but not in OSA patients. SIGNIFICANCE: In a sustained wakefulness paradigm, higher activity in delta, theta and beta bands associated with OSAS indicates that OSA patients show marked signs of higher sleepiness and stronger efforts than controls to stay awake, even though they tend to underestimate their sleepiness.     

Differential EEG patterns in affective disorder and schizophrenia.

We analyzed the EEGs of 27 schizophrenic patients and 132 patients with affective disorder who received diagnoses according to rigorous research criteria. The proportion of abnormal EEGs was twice as great among schizophrenics as among affectives, and when the groups were compared for localized cortical differences, schizophrenics had more temporal abnormalities and affectives more parieto/occipital abnormalities. There was also a trend toward different hemispheric lateralization for the two groups, with a reversal of the relative proportions of left- and right-sided abnormalities. These differences were unrelated to age, sex, severity of illness, or past or present drug administration. These findings are complementary to those of other workers, lend support to the validity of our diagnostic research criteria, and provide additional evidence for neurophysiological differences between schizophrenics and patients with affective disorder.     

Seasonal panic disorder: a possible variant of seasonal affective disorder.

The present communication concerns a 30 year-old female patient with panic disorder in whom panic attacks appeared to be seasonally-related. Characteristically, attacks were more frequent and severe during the months of October to May with spontaneous remissions during the months of June to September. Since 70% of patients with seasonal affective disorder (SAD), a variant of affective illness characterized by recurrent winter depressions with remissions in summer, suffer from anxiety disorders, we propose that seasonal panic disorder may be a variant of SAD. Since SAD is associated with phase delay of circadian rhythms, some forms of panic disorder may be related to phase instability of circadian rhythms. Moreover, since administration of artificial bright light therapy is currently the most effective treatment for SAD, it is suggested that patients with panic disorder should be questioned as to whether their symptoms are seasonally related. If a positive association is established, these patients should be offered treatment with light therapy prior to or coincident with the institution of pharmacotherapy.     

Association between seasonal affective disorder and subjective quality of the sleep/wake cycle in adolescents

The relationship between seasonal affective disorder (SAD) and subjective quality of sleep/wake cycle in adolescents was explored. The Seasonal Pattern Assessment Questionnaire for Children and Adolescents (SPAQ-CA) and Mini Sleep Questionnaire (MSQ) were administered to 345 adolescents living in the city of Cesena (Emilia-Romagna region, Italy) (299 females; age range: 14–18 years), to determine SAD and perceived quality of the sleep/wake cycle. The response rate was 92% for females and 90.2% for males. The MSQ includes two factors, sleep and wake, with lower scores corresponding to a lower quality of sleep and wake. The MSQ includes cut-off criteria to detect a good or bad sleep and wake quality. Adolescents with SAD (16±5.7) scored significantly lower than those not affected on wake factor (19.5±4.3), while no effect has been observed on sleep factor. SAD was the only one significant predictor of good/bad wake quality, while it did not reach significant level with reference to good/bad sleep quality. Present results are indications of a possible influence of SAD on wake quality and further studies are necessary to confirm them.     

Pathophysiology of seasonal affective disorder: a review

The study of the pathophysiology of seasonal affective disorder (SAD, also known as winter depression) has historically been intimately linked to investigations into the mechanisms of action of light therapy. This paper reviews the studies on the pathophysiology of SAD with emphasis on circadian, neurotransmitter, and genetic hypotheses. There is substantial evidence for circadian phase shift and serotonergic hypotheses, but conflicting results may indicate that SAD is a biologically heterogeneous condition. Recent progress in defining the molecular mechanisms of the human circadian clock and retinal phototransduction of light will provide important new directions for future studies of the etiology and pathophysiology of SAD.     

Seasonality of birth in seasonal affective disorder

BACKGROUND: Season of birth or seasonal changes in putative etiologic factors are thought to influence the development of several psychiatric illnesses. The aim of this investigation was to examine seasonal differences in the frequency of birth in a clinical sample of patients with seasonal affective disorder (SAD). METHOD: 553 outpatients suffering from SAD-DSM-IV-defined depressive disorder with winter-type seasonal pattern-who had been diagnosed and treated at the Department of General Psychiatry (University of Vienna, Austria) between 1994 and 2003, were included in this evaluation. We compared the observed number of births in our sample with expected values calculated from the general population. RESULTS: There was a significant deviation of the observed number of births from the expected values calculated on a monthly basis (p = .009). When comparing quarters (periods of 3 months), we found fewer births than expected in the first quarter of the year and a slight excess of births in the second and third quarters (p = .034). There were also more births in the spring/summer season and fewer than expected in fall and winter (p = .029). Interestingly, patients with melancholic depression were more frequently born in fall/winter and less often in spring/summer compared with patients with atypical depression (p = .008). CONCLUSION: Besides genetic factors, season of birth or seasonal changes in environmental factors also could influence the development of SAD. In addition, birth effects seem to be dependent on the symptom profile of the patients, but further studies are needed to elucidate the underlying mechanisms of these observations.