Polly Moore

Predictors of mood response to acute tryptophan depletion: A reanalysis

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled (‘mega-analysis’) in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode.

Association between polysomnographic sleep measures and health-related quality of life in obstructive sleep apnea

Many facets of health‐related quality of life are diminished in obstructive sleep apnea (OSA) as they are in other chronic medical conditions. We speculated that impairment in health‐related quality of life (HRQoL) might result from the fatigue and daytime somnolence associated with the sleep disorder, as an indirect result from the fragmentation of night‐time sleep in OSA. Our hypothesis was that sleep fragmentation measures would correlate with poorer HRQoL measured by medical outcomes study (MOS) subscales. Thirty‐nine patients with polysomnographically‐confirmed OSA participated in this study. Pearson’s correlations were performed with the following sleep architecture variables: wake after sleep onset, the total number of brief arousals, the number of respiratory‐related arousals, the rate of respiratory events per hour, and total sleep time. To our surprise, although the total number of arousals was associated with health distress (r=–0.481, P < 0.005), it did not correlate with any other subscales indicating poorer physical and mental health. The relatively insensitive measure of total sleep time (TST) correlated in the expected direction with most subscales. However, after controlling for age and gender, respiratory disturbance indices (RDI) and/or number of arousals emerged as significantly associated with mobility, cognitive functioning, social functioning, energy and fatigue, and health distress. Our findings suggest that polysomnographic indicators of sleep quality and sleep continuity may be an important influence determining many aspects of HRQoL in OSA patients.

Does obstructive sleep apnea confound sleep architecture findings in Subjects with depressive symptoms

BACKGROUND Compared with normal subjects, depressed patients have shorter rapid eye movement sleep latency (REML), increased REM and decreased slow wave sleep as a percentage of total sleep time (REM%, SWS%), and longer sleep latency (SL). Obstructive sleep apnea (OSA) patients experience longer REML, decreased REM% and SWS%, and shorter SL. We examined the interplay of depressive symptoms, OSA, and sleep architecture. METHODS Subjects (n = 106) were studied with polysomnography. OSA was defined as a Respiratory Disturbance Index > or = 15. Subjects were divided into Hi/Lo groups using a Center for Epidemiological Studies-Depression (CES-D) score of 16. RESULTS OSA patients had shorter SL than non-OSA patients (14.5 vs. 26.8 min, p <.001); Hi CES-D subjects showed a trend toward longer SL than Lo CES-D subjects (23.7 vs. 17.5 min, p =.079). Significant OSA x CES-D interactions emerged, however, for REM% (p =.040) and SL (p =.002): OSA/Hi CES-D subjects had higher REM% than OSA/Lo CES-D subjects (19.3% vs. 14.3%, p =.021); non-OSA/Hi CES-D subjects had SL (35.3 min) 2-3 times as long as other subjects (p =.002-.012). CONCLUSIONS Because of the high prevalence of OSA and depression, findings suggest that OSA must be considered in studies of mood and sleep architecture. Conversely, depressive symptoms must be considered in studies of OSA and sleep architecture.

Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.

Human plasma DSIP decreases at the initiation of sleep at different circadian times

Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.

Assessing the trade‐offs between crossover and parallel group designs in sleep research

Sleep researchers invariably struggle with decisions regarding the optimal design for their studies. Whether such studies involve treatment for insomnia, obstructive sleep apnea, or any other sleep disorder, questions arise regarding the respective trade‐offs between a parallel group and a crossover design. This study analyzed the variance structure of commonly measured polysomnographic variables in an effort to describe the statistical impact of these alternate designs. The study examined the effects of opioids on sleep and employed multiple crossovers between placebo, MS‐contin, and methadone using a double‐blind, randomized crossover design. Thirty‐seven healthy subjects were studied. Four of the subjects were unable to complete the protocol for a variety of reasons, and polysomnogram data was unavailable for one subject. Data from 37 subjects provide the basis for this analysis. Despite dropouts, the crossover study was approximately four times as efficient as the parallel group design in terms of being able to recognize differences in deep sleep across these conditions. Other polysomnographic variables also favored the crossover design to varying extents. Despite the operational complexity of a crossover design, the statistical efficiency of this approach makes it a preferable approach for designing intervention studies in sleep research.