Christine Cherry

Electroencephalographic sleep correlates of episode and vulnerability to recurrence in depression

The study of electroencephalogram (EEG) sleep in depressed patients before and after treatment with psychotherapy can distinguish episode-related and persistent biological features. With longitudinal follow-up, we can also assess whether EEG sleep measures are associated with recurrence of depression. In the current study, we examined EEG sleep during the depressed state and during symptomatic remission after treatment with interpersonal psychotherapy in 42 outpatients with major depression. Analyses included both visually-scored and computer-analyzed measures. Patients showed significant increases in sleep latency (p = .01) and rapid eye movement (REM) latency (p = .04) from baseline to remission, as well as a decrease in REM sleep percent (p = .03). Total delta EEG counts decreased from baseline to remission (p = .03), specifically in the second nonrapid eye movement (NREM) period (p = .03); as a result, the relative distribution of delta activity shifted toward sleep onset (i.e., increased delta sleep ratio; p = .03). Automated REM counts also decreased from depression to remission (p = .006). Compared to patients who remained well through one year of follow-up, those who suffered a recurrence of depression had less delta EEG activity at baseline and remission (p = .01), particularly in the lowest delta frequency band of 0.5-1.0 Hz. Specific components of sleep (total delta activity, delta ratio, REM activity) constitute episode-related biological features. Other components (slowest delta activity) may represent vulnerability factors for recurrence.

Pretreatment REM sleep and subjective sleep quality distinguish depressed psychotherapy remitters and nonremitters

BACKGROUND We compared pretreatment subjective and electroencephalographic sleep measures among depressed patients who remitted with psychotherapy alone and those who did not remit. METHODS Patients were 111 midlife women with recurrent major depressive disorder. Baseline psychiatric ratings and sleep studies were conducted prior to treatment with weekly interpersonal psychotherapy. Remission was defined as a score of < or = 7 for 3 consecutive weeks on the Hamilton Depression Rating Scale. Clinical and sleep measures were compared between remitters (n = 62) and nonremitters (n = 49) using t tests and random regression. Linear discriminant function analyses were used to categorize remitters and nonremitters on the basis of sleep measures. RESULTS Treatment nonremitters had significantly worse subjective sleep quality and significantly elevated phasic REM sleep as measured by multivariate and univariate analyses. The linear accumulation of REM activity during sleep occurred at a significantly higher rate in nonremitters than in remitters. Linear discriminant function analyses based on subjective sleep quality and REM activity correctly identified 68.3% of nonremitters and 68.5% of remitters. CONCLUSIONS These findings highlight the role of subjective and REM sleep measures as correlates of short-term psychotherapy treatment response in major depressive disorder. Disturbed sleep may be a physiological indicator of increased limbic and brain stem arousal.

Sleep and treatment response in depression: new findings using power spectral analysis

This study examined quantitative measures of sleep electroencephalogram (EEG) and phasic rapid eye movements (REM) as correlates of remission and recovery in depressed patients. To address correlates of remission, pre-treatment EEG sleep studies were examined in 130 women outpatients with major depressive disorder treated with interpersonal psychotherapy (IPT). To address correlates of recovery, baseline and post-treatment EEG sleep studies were examined in 23 women who recovered with IPT alone and 23 women who recovered with IPT+fluoxetine. Outcomes included EEG power spectra during non-rapid eye movement (NREM) sleep and REM sleep and quantitative REMs. IPT non-remitters had increased phasic REM compared with remitters, but no significant differences in EEG power spectra. IPT+fluoxetine recoverers, but not IPT recoverers, showed increases in phasic REM and REM percentage from baseline to recovery. In NREM sleep, the IPT+fluoxetine group showed a decrease in alpha power from baseline to recovery, while the IPT group showed a slight increase. The number of REMs was a more robust correlate of remission and recovery than modeled quantitative EEG spectra during NREM or REM sleep. Quantitative REMs may provide a more direct measure of brainstem function and dysfunction during REM sleep than quantitative sleep EEG measures.

Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking.

Little research has examined the association of tobacco dependence with nicotine tolerance or reinforcement in a clinical sample. Smokers preparing to quit smoking participated in laboratory sessions to assess nicotine tolerance on subjective, cardiovascular, and performance measures and to assess nicotine reinforcement using a choice procedure. Participants were then provided with individual counseling (but no medication), made a quit attempt, and were followed for 1 year to determine clinical outcome, as determined by postquit withdrawal and days to relapse. Nicotine tolerance was unrelated to either withdrawal or relapse. However, acute nicotine reinforcement was significantly related to both greater withdrawal and faster relapse. Results challenge the common assumption that nicotine tolerance is closely related to dependence but suggest that nicotine reinforcement may have theoretical and clinical significance for dependence.

Insulin-like growth factor 1 and growth hormone binding protein in depression: a preliminary communication.

This study was undertaken in order to advance our understanding of the distal growth hormone axis in depression. Insulin-like growth factor 1 (IGF-1) and growth hormone binding protein (GHBP) were measured in a group of 19 depressed women and a group of 16 healthy women. Using a generalized linear model, IGF-1 levels were negatively correlated with age (p = 0.0001), influenced by menstrual phase (p = 0.016), and significantly increased in the depressed group (p = 0.02). Using the same type of analysis, GHBP was significantly related to menstrual phase (p = 0.0001) and body mass index (p = 0.0001), but was not significantly different in patients and controls. IGF-1 and GHBP were positively correlated among healthy subjects (r = 0.46, p = 0.08), but not among depressed patients (r = -0.16, p = 0.51), although these correlation coefficients were not statistically significantly different from each other. These findings confirm the importance of several physiological factors in the regulation of IGF-1 and GHBP, and suggest that depression further influences this regulation.

Latent structure of EEG sleep variables in depressed and control subjects: descriptions and clinical correlates

In this study, we aimed to determine the latent structure of multiple EEG sleep variables in patients with major depressive disorder (MDD) and in healthy control subjects and to examine associations between sleep factors and clinical variables. Subjects included 109 women with MDD and 54 healthy control women. EEG sleep data were collected prior to any treatment. Principal components analysis (PCA) was conducted on a set of 24 sleep variables. Separate PCAs were run for patients with MDD, control subjects, and a matched group of patients and controls. Other analyses included correlations, t-tests and MANOVA. Each PCA identified four sleep factors that explained 70% of the total variance in individual sleep variables: slow wave sleep, REM sleep, sleep continuity and REM latency/delta sleep ratio (RL/DSR). Patients with MDD and healthy controls differed on the mean value of the sleep continuity factor, and a multivariate analysis of variance based on the PCA identified MDD-control differences in REM sleep and sleep continuity. In the MDD group, slow wave sleep correlated inversely with age and personality disorder symptoms; sleep continuity correlated with subjective sleep quality and anxiety; and RL/DSR correlated inversely with age. The mean value of the REM factor was higher among treatment non-responders than responders. EEG sleep variables have a similar latent structure in women with MDD and in healthy controls. These sleep factors are supported conceptually and empirically, and correlate with clinical measures in women with MDD. Multivariate statistical techniques decrease the risk of Type I and Type II errors when using a large number of collinear sleep measures, and can clarify conceptual issues related to sleep and depression.

Effects of Prior Fluoxetine Treatment on EEG Sleep in Women with Recurrent Depression

We examined whether fluoxetine treatment has persistent effects on electroencephalographic sleep after drug discontinuation in patients with recurrent major depression. Age-matched groups of 23 women were treated with interpersonal psychotherapy alone (IPT) or fluoxetine plus interpersonal psychotherapy (IPT + FLU). Sleep studies were conducted when patients were depressed, and again at remission, at least four weeks after fluoxetine discontinuation. The groups did not differ in depression ratings pre- to post-treatment. Significant group*time interaction effects were noted for REM sleep (p = .04) and slow wave sleep (p = .02). REM percentage and phasic REM activity increased in the IPT + FLU group but decreased in the IPT group. The effects of fluoxetine treatment on electroencephalographic sleep can be observed for at least four weeks after drug discontinuation and appear to represent both drug discontinuation and neuroadaptation effects.