Research report
Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

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Abstract

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.

Introduction

Electroencephalographic (EEG) sleep variables of adult patients with major depressive episode(s), including unipolar and bipolar depression, have been intensively studied (for a review, see Benca et al., 1992, Reynolds and Kupfer, 1987). There is evidence to suggest that polysomnography profiles may help to distinguish these two subtypes of depression (Duncan et al., 1979, Feinberg et al., 1982, Fossion et al., 1998, Giles et al., 1986, Jernajczyk, 1986, Jovanovic, 1977, Kupfer et al., 1972, Thase et al., 1989). The most consistent EEG sleep variables associated with depression include sleep continuity disturbances, earlier onset of the first rapid eye movement (REM) sleep, higher phasic activity during REM sleep, altered temporal distribution of REM sleep, and diminished slow-wave sleep (Benca et al., 1992). Some data suggest that bipolar patients, specifically those with bipolar II subtype, may manifest hypersomnia (Feinberg et al., 1982, Fossion et al., 1998, Giles et al., 1986, Kupfer et al., 1972). Also, reduced REM latency may be less prevalent in bipolar depression (Giles et al., 1986, Jernajczyk, 1986, Jovanovic, 1977, Thase et al., 1989).

In contrast to the well-replicated EEG sleep findings in adult depression, controlled studies of child and adolescent cohorts with major depressive disorder have shown relatively few EEG sleep changes. Of four controlled investigations in children (Dahl et al., 1991, Emslie et al., 1990, Puig-Antich et al., 1982, Young et al., 1982), only one study, comprising an inpatient sample, reported prolonged sleep latency and reduced REM latency compared with controls (Emslie et al., 1990). Among 10 adolescent studies, five reported sleep continuity disturbances, six observed shortened REM latency, and two studies found higher REM density (Appelboom-Fondu et al., 1988, Dahl et al., 1990, Dahl et al., 1996, Emslie et al., 1994, Goetz et al., 1987, Goetz et al., 1991, Khan and Todd, 1990, Kutcher et al., 1992, Lahmeyer et al., 1983, Riemann et al., 1995). Reduction in slow-wave sleep was not observed in any of these investigations.

Taken together, these data suggest that sleep changes associated with depression appear to show maturational variations (Benca et al., 1992, Knowles and MacLean, 1990, Lauer et al., 1991). In addition to developmental influences on these sleep alterations, clinical course might play a role in the manifestation of EEG sleep changes. At the time of enrollment into studies, child and adolescent subjects, including controls, would not have passed through the major period of risk for onset of depression or for other psychiatric disorders. Previously, we reported that adolescent control subjects who subsequently developed depression showed evidence of depression-related EEG sleep changes, suggesting that vulnerability to depression in healthy volunteers may be a confounding factor in interpreting EEG sleep findings in youngsters (Rao et al., 1996). Since adult studies have found some polysomnographic differences between unipolar and bipolar individuals, it is also possible that latent bipolar disorder might mask some EEG sleep differences. There is evidence that early-onset depression is associated with a higher likelihood of switching to bipolar disorder than the adult form of the illness (Geller et al., 1994, Strober and Carlson, 1982, Strober et al., 1993).

Previously, we presented data on the association between EEG sleep measures performed during adolescence and clinical outcome in early adult life (Rao et al., 1996). These analyses focused on group comparisons among adolescents originally diagnosed with unipolar depression who had recurrent or non-recurrent unipolar course at follow-up, as well as subjects initially classified as controls but developed depression subsequently. All three depressed groups had reduced REM latency and higher REM density compared with controls who had no evidence of psychiatric disorder at follow-up (see Rao et al., 1996). In this report, we present data examining EEG sleep characteristics in relation to unipolar versus bipolar course among adolescents originally diagnosed as having unipolar depression.

Section snippets

Clinical assessments during adolescence

The methods for the initial study have been described in detail elsewhere (Dahl et al., 1990), and are reviewed here briefly. The study was approved by the University of Pittsburgh Institutional Review Board. Prior to all research assessments, the parents signed the informed consent form and the adolescents signed the assent form. The assessments for the depressed cohort included present episode and lifetime diagnosis versions of the Schedule for Affective Disorders and Schizophrenia for

Relationship between prospective clinical course and adolescent EEG sleep measures

Mean values of selected EEG sleep measures for the three groups are presented in Table 1. With respect to sleep architecture variables, percent of stage 1 sleep and REM sleep showed significant group effects. After Bonferroni correction, subjects with bipolar disorder had significantly more stage 1 sleep compared with the unipolar group (P≤0.05). Also, there was a non-significant trend for subjects with bipolar disorder to have reduced stage 4 sleep compared to both unipolar depression and

Discussion

The results from this pilot investigation suggest that depressed adolescents with a subsequent unipolar clinical course manifest REM sleep changes that are similar to those seen in adult unipolar depression. However, unlike adult depressed patients, no slow-wave sleep deficits were observed. In contrast to this, depressed adolescents with latent bipolar illness demonstrated a relatively normal REM sleep profile, but showed some non-REM sleep changes. Specifically, more stage 1 sleep and reduced

Acknowledgements

This study was supported in part by the NIMH Scientist Development Award MH01419 (to UR), and by grants MH30915, AA08746 and MH41712.

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