Patricia A. Coble

The Pittsburgh Sleep Diary

SUMMARY  Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two‐week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle‐aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12–31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n= 39, P < 0.001).

The effects of prenatal alcohol and marijuana exposure: disturbances in neonatal sleep cycling and arousal.

ABSTRACT: Neonatal EEG and sleep findings are presented from a longitudinal study of the effects of maternal alcohol and marijuana use during pregnancy. Infant outcome has been examined relative to the trimester(s) of pregnancy during which use occurred. Disturbances in sleep cycling, motility, and arousals were noted that were both substance and trimester specific. Alcohol consumed during the first trimester of pregnancy was associated with disruptions in sleep and arousal, whereas marijuana use affected sleep and motility regardless of the trimester in which it was used. Although these findings are preliminary and based on a small sample of women exhibiting only moderate substance use during pregnancy, they do suggest that specific neurophysiological systems may be differentially affected by prenatal alcohol or marijuana exposure even in the absence of morphological abnormalities.

EEG sleep in outpatients with generalized anxiety: A preliminary comparison with depressed outpatients

To develop further perspective on the psychophysiology of generalized anxiety disorder and primary depression, all-night electroencephalographic (EEG) sleep measures in outpatients with diagnoses of generalized anxiety disorder and primary (nondelusional) depression were compared. Both groups had difficulty initiating and maintaining sleep, and diminished amounts of slow-wave sleep. Compared to patients with generalized anxiety disorder, depressives had a shorter rapid eye movement (REM) latency, greater REM sleep percent and eye movement activity, and a different temporal distribution of REM sleep. Anxious patients showed few changes from first to second night, whereas depressives showed increases in several REM sleep indexes. The combination of REM sleep latency and REM percent correctly classified 86.7% of patients. These data may provide a more direct measure of central nervous system arousal and sleep/wake function than previous studies in the psychophysiology of anxiety. They also lend support to the clinical distinction between generalized anxiety disorder and primary depression and to the classification of anxiety states as disorders of initiating and maintaining sleep.

Sleep, gender, and depression: An analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients

Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21-69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph preamplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by-age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non-rapid-eye-movement (NREM) periods does not support gender differences in slow-wave sleep regulation.

Application of automated REM and slow wave sleep analysis: II. Testing the assumptions of the two-process model of sleep regulation in normal and depressed subjects

Abnormalities in a two-process model of sleep regulation (a sleep-dependent process, termed Process S, and a sleep-independent circadian process, termed Process C) have been proposed to account for sleep abnormalities in depressive states. The major tenets of the two-process model of sleep regulation as applied to depression are: the level of process S, as reflected by the electroencephalographic (EEG) slow-wave activity, corresponds to the sleep-dependent facet of sleep propensity; the pathognomonic changes of sleep in depressives are a consequence of a deficiency in the build-up of process S. The application of automated rapid eye movement (REM) and delta wave analyses in normal subjects and younger depressed patients supports the model to some extent: The time spent asleep is positively correlated with total delta waves (normals and depressives) and average delta waves (depressives); delta sleep is lower in depressives than in normals; the average delta wave count is significantly reduced in younger depressives over the total night and in non-REM period 1. The model also postulates that measures of phasic REM activity are inversely related to process S, suggesting that process S can be regarded as exerting an inhibitory influence on phasic REM activity.

Amitriptyline plasma levels and clinical response in primary depression.

Sixteen patients with primary depression were treated for 4 wk with amitriptyline. After clinical diagnoses were determined, patients entered a double‐blind protocol (amitriptyline or placebo) and their clinical status was determined with the Hamilton Depression Rating Scale by raters blind to the drug type, its dosage and plasma levels. Amitriptyline (AT) and nortriptyline (NT) plasma levels were assayed twice weekly by gas chromatography‐mass spectrometry. In the 16 patients, a negative correlation between the Hamilton Score and the mean total tricyclic level (p < 0.01), as well as with individual plasma levels, was found at the end of the treatment period. When the group was divided into clinical responders and nonresponders, the mean total tricyclic (AT + NT) levels discriminated the two groups by day 12 (p < 0.001) as well as at the end of the protocol (day 26, 88% of the patients were classified correctly if an arbitrary level of200 ng/ml total tricyclic plasma level was chosen). These results strongly suggest the presence of a positive correlation between plasma levels and clinical improvement in patients with primary depression.

Application of automated REM and slow wave sleep analysis: I. Normal and depressed subjects.

Computerized analysis of rapid eye movement (REM) and delta electroencephalographic (EEG) sleep patterns in normal and depressed subjects offers opportunities to examine sleep more precisely than previously possible. In the present study, automated REM analyses demonstrated good reliability with traditional manual procedures in both normal and depressed subjects. However, automated delta analyses correlated well with traditional scoring in normal subjects, but not in depressed patients. These findings suggest the use of automated delta techniques similar to those employed in this report or spectral analytic techniques in the following types of studies: specificity of delta sleep in various psychiatric syndromes, changes in delta sleep produced by the administration of psychotropic agents, relationships between delta sleep and sleep-related neuro-endocrine patterns, and, finally, relationships between delta sleep patterns and other biological rhythms such as activity and temperature.

Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients

Despite their widespread use, there are few data concerning the effects of tricyclic antidepressants on EEG sleep in depression. The present study documented the effects of desipramine (DMI, n=17) and amitriptyline (AT, n=16) upon EEG sleep in hospitalized depressed patients as part of a double-blind protocol involving 28 days of active treatment. Compared to placebo, patients receiving DMI showed somewhat worsened sleep continuity, particularly after 1 week of administration when the dose was 150 mg/day. On the other hand, sleep architecture and REM measures showed a rapid suppression of REM sleep, and then partial tolerance for this effect was observed with continued administration of DMI for 3 weeks. DMI was a more potent suppressor of REM sleep, while AT was more sedative. Based on these differences in effects upon EEG sleep, a discriminant function was derived and resulted in a correct classification of 87.5% of AT cases and 76.5% of DMI cases. These results are discussed in terms of the differences in pharmacological profiels for uptake blockade and anticholinergic potency for these two compounds.

Application of the multiple sleep latency test in disorders of excessive sleepiness

Multiple sleep latency tests were performed in 42 drug-free outpatients with excessive sleepiness: 12 narcoleptics, 9 sleep apneics, 7 primary depressives, and 14 patients with miscellaneous disorders. Among-group comparisons were made by one-way ANOVA for each nap (time-of-day effect) and using four-nap means of EEG sleep variables. Four-nap means were significantly different among groups for percent awake, percent time spent asleep, stage 1 latency, and REM latency. Of 22 significant pairwise comparisons (P less than 0.05, LSD test), 77.3% occurred at 12.00 and 14.00. Depressives showed lower sleep percentage (more arousal) and fell asleep later than narcoleptics or apneics. Patients with miscellaneous disorders occupied a middle position. Sleep percentage was gradually reduced during the day in depressives but remained high or rose further in apneics, narcoleptics, and miscellaneous patients. Naps were SOREMP-positive (sleep onset REM) 60.4% of the time in narcoleptics, 25.0% in apneics, 3.5% in depressives, and 5.4% in miscellaneous patients. SOREMP distribution across naps (10.00, 12.00, 14.00 and 16.00) was 19%, 31%, 19% and 31%, respectively. REM latency was significantly shorter in narcolepsy than in apnea. In summary, results show a continuum of excessive daytime sleepiness (EDS), demonstrating MSLT application in the differential diagnosis of EDS and significant diurnal variation in sleep measures.

EEG sleep, depression, and aging

To date little attention has been paid to the possible age-dependent relationships of EEG sleep measures in depression or to the implications of such relationships for diagnostic sensitivity and specificity. In a study of 108 patients with major depressive disorders (67 inpatients, 41 outpatients), age was shown to be a very powerful determinant of electroencephalographic (EEG) sleep patterns. Thus, among other sleep variables, sleep efficiency, delta sleep percent, and REM latency all showed significant linear declines with increasing age. Similar trends were seen in both inpatients and outpatients. Some variables were without age trends (age-stable), including sleep latency, REM sleep percent, and REM activity. These findings confirm those of an earlier report from our laboratory [45] and suggest that age-corrected sleep variables can be developed for clinical diagnostic application. Thus, using normative data from Gillin et al. [19] for comparison, a sensitivity level of 65% for age-corrected REM latency was demonstrated, together with a specificity of 95% and a diagnostic confidence of 92%. Data from a pilot study comparing EEG sleep measures in depression and dementia are also presented; these data suggest the potential utility of EEG sleep measures in the differential diagnosis of these two disorders, especially in patients with mixed symptoms. Additional areas for further research are reviewed with enumeration of specific testable hypotheses.