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JAMES McCRACKEN

Adolescents At High Risk For Depression Show Sleep Eeg Abnormalities: Effects Of Scopolamine

JAMES T. McCRACKEN
RUSSELL E. POLAND
Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, CA
Department of Psychiatry, UCLA Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA, 90024-1759, USA

Introduction
Sleep abnormalities associated with depression in adults frequently persist beyond recovery, and may convey risk for subsequent depression. Some reports in adults support this contention, but few data exist from younger at-risk subjects. Given that the majority of new onsets of depression occur in the second decade of life, it is crucial to test whether vulnerability markers exist in adolescents prior to the development of depression. Believing that sleep vulnerability markers do exist even prior to the development of the disorder and are likely related to identified cholinergic sensitivity differences found in adults, we assessed the sleep of a high risk adolescent sample of adolescents at elevated risk for major depression by virtue of having a parental history of major depression.
Methodology
We studied polysomnographic sleep in a group of adolescents at high familial risk for developing depression (being offspring of at least one parent with a history of mood disorder) and normal controls under both baseline conditions and after acute scopolamine (SCOP) administration, a challenge hypothesized to elict differential responses in normals and high- risk subjects. In this study, the EEG sleep of a sample of 11 adolescents with a history of parental major depressive episodes and 13 low-risk normal control adolescents was obtained on two separate two-night sessions. On either of the sessions, saline or SCOP (4.5 mg/kg) were administered at 11:00 PM on the second night. Prior to participation, all subjects were verified to be healthly, on no medications, and without current psychopathology. Sleep EEG data was obtained from two, two-night sessions spaced approximately one week apart. Data from the second nights (following placebo or SCOP) were visually scored.
Results
High-risk adolescents showed a statistically significant increase (54%) in baseline (placebo) phasic REM sleep measures especially during the first REM period and for the total recording period as well, and a trend toward reduced slow-wave sleep, but baseline REM latency values did not differ. Scopolamine robustly suppressed REM sleep in both groups, with high risk adolescents showing a greater suppression of phasic REM activity in the first REM period. High risk adolescents also demonstrated a shorter sleep latency on the SCOP night. High risk adolescents displayed more frequent arousals on the baseline night, but the two groups showed a significant differential response to SCOP, with SCOP elicting more frequent arousals in the normal controls, while reducing mean arousals in the high risk group.
Conclusions
These findings provide support for the hypothesis that some sleep abnormalities associated with depression may be present prior to the onset of disorder, and may represent vulnerability markers for one pathway to depression. These data, while preliminary, also suggest that these vulnerability markers of depression may be associated with alterations of cholinergic neurotransmission, especially in the altered regulation of the sleep-onset transition and first REM-NREM period.