SLEEP 2011 Abstract Supplement

B. Clinical Sleep Science IX. Psychiatric and Behavioral Disorders and Sleep
0710
HIGH-FREQUENCY SLEEP EEG IN ABSTINENT
ALCOHOLICS COMPARED TO HEALTHY CONTROLS
Arnedt J, Hoffmann RF, Conroy DA, Armitage R, Brower K
Psychiatry, University of Michigan, Ann Arbor, MI, USA
Introduction: The underlying neurophysiological mechanisms of sleep
disturbances in recovering alcoholics and their relationship to relapse
are poorly understood. We tested the hypothesis that high-frequency
sleep EEG would be increased in alcohol-dependent (AD) participants
compared with healthy controls (HC), particularly among those who relapsed.
We also examined sex and race differences in high-frequency
sleep EEG.
Methods: Fifty-three ADs (36.6 ± 10.8 years, 10 women, 12 African
American, 34 Caucasian) in early recovery (39.8 ± 19.1 days abstinent)
and 19 age-matched HCs (35.6 ± 10.0 years, 4 women) participated.
Following a 2300 - 0600 hours at-home sleep schedule and screening,
participants underwent a baseline (2300 - 0600 hours) sleep night with
polysomnography (PSG). Power spectral analyses were conducted on
all 30-second artifact-free epochs and averaged by hour of the night in
the beta frequency band (β=16-30 Hz). We examined raw and relative
beta power (beta power/total power) across the entire night and by hour
of the night. Alcoholic participants returned after 12 weeks to assess
abstinence vs. any drinking with the Time Line Follow Back interview.
Results: Relative beta power across the night was significantly higher
in AD compared to HC participants (4.1 ± 0.7% vs. 3.7 ± 0.7%, p <
.05) and in African American compared to Caucasian subjects (4.6 ±
0.8% vs. 3.9 ± 0.6%, p < .04). AD men had higher relative beta power
than HC men (p < .05), but no differences were found among women.
AD participants who relapsed during the 12-week follow-up had higher
relative beta power than abstinent AD and HC participants (p < .05). No
other demographic, sleep, or alcohol-related variables were associated
with relapse.
Conclusion: High-frequency sleep EEG was increased in AD vs. HC
subjects, particularly among relapsers. CNS hyperactivity may be one
mechanism of sleep disturbance in AD subjects that predicts relapse during
recovery.
Support (If Any): NIH R01 AA016117 & K24 AA00304 (K Brower)
0711
THE EFFECT OF QUETIAPINE ON SLEEP DURING
ALCOHOL ABSTINENCE
Chakravorty S 1,2 , Kuna ST 1,2 , Ross RJ 1,2 , Witte L 1 , Oslin D 1,2
1
Philadelphia VAMC, Philadelphia, PA, USA, 2 University of
Pennsylvania School of Medicine, Philadelphia, PA, USA
Introduction: Insomnia is highly prevalent in the recovering alcoholic
patient, and has been shown to be a risk factor for relapse. Quetiapine,
a novel antipsychotic medication with hypnotic properties, is frequently
prescribed on an “off-label” basis for insomnia in these patients. The
effect of quetiapine on objective and subjective sleep in the recovering
alcoholics is currently unknown.
Methods: Male alcoholics (N = 24), within the first year of recovery
were recruited in an 8-week, double-blind, placebo-controlled trial. Participants
were randomized to receive either 400 mg/day at bedtime, of
quetiapine (N = 12), or placebo (N = 12). Two baseline polysomnograms
were conducted before and after 8 weeks of treatment. The primary
outcome measure was Sleep Efficiency on an in-laboratory polysomnogram.
The principal secondary outcome measure for subjective sleep
was the Insomnia Severity Index (ISI) total score. In addition, during
this treatment trial, participants were evaluated for neuro-behavioral
assays, addiction, and psychiatric variables using standardized instruments.
They also received the standardized psychotherapy called Medical
Management to help them cope with their urge to use alcohol.
Results: We report the preliminary study results on the participants who
completed the study [quetiapine (N = 10), and placebo (N = 10)]. Sleep
Efficiency, on an in-laboratory polysomnogram, before and after the
treatment showed a trend for the effect of Time, F(1, 19) = 3.99; p =
0.06; no effect of Medication status was seen. In addition, there were
significant effects of time, without any effect of medication status, for
the following variables: Insomnia Severity Index, PHQ-9 scores, Beck’s
Anxiety Inventory, and the Penn Alcohol Craving Scale. There were no
differences between the groups for the number of Lapses, or the 10%
Fastest Reaction Time scores on the psycho-motor vigilance task. Analysis
of the participants with baseline insomnia [ISI total score ≥ 8, quetiapine
(N = 10), placebo (N = 7)] showed a differential improvement
in insomnia (ISI total score) over time with quetiapine as compared to
placebo [Drug F(1,13) = 7.77, p = 0.015, Time F(8,101) = 20.35, p <
.001, Drug * Time F (8, 101) = 1.90, p = .06; AIC = 653].
Conclusion: Quetiapine was associated with improvement in subjective
insomnia ratings only in the alcohol dependent participants with
baseline insomnia.
Support (If Any): This study was funded by the MIRECC, VISN-4,
Department of Veterans Affairs.
0712
DIM LIGHT MELATONIN ONSET (DLMO) IN ALCOHOL-
DEPENDENT (AD) MEN AND WOMEN VS. HEALTHY
CONTROLS
Conroy DA, Hairston IS, Arnedt J, Hoffmann RF, Armitage R,
Brower K
Psychiatry, University of Michigan, Ann Arbor, MI, USA
Introduction: Sleep disturbances in AD patients may persist for years
despite abstinence from alcohol. Although the mechanisms are not well
understood, dysregulation of circadian rhythms has been suggested. One
study in African-American men showed a delay in peak melatonin volumes
in AD vs. healthy control (HC) subjects (Kühlwein et al., 2003),
but DLMO has not been assessed in either Caucasians or women with
alcoholism.
Methods: Forty-four AD participants (AD, mean age 36.8 ± 10.5 years,
10 women) in early recovery (mean abstinence 57.7 ± 19.5 days) and
19 age- and sex-matched controls (HC, mean age 34.8 ± 10.7 years,
5 women) participated. Following a 2300 - 0600 hours at-home sleep
schedule, a screening and a baseline night of polysomnography, participants
underwent a 3-hr extension of wakefulness (0200 - 0900 hours)
during which salivary melatonin samples were collected every 30 minutes
beginning at 1930 hours. The time of DLMO was the primary variable.
Other variables included area under the curve (AUC) and course of
melatonin values across time points.
Results: No significant differences between the AD and HC groups were
found for any outcome variable, analyzing men and women together.
Likewise, no significant differences were seen in women with and without
AD. In men, however, DLMO was significantly delayed in AD vs.
HC subjects [21:17 (0:44) vs. 20:51 (0:28) hr; t=-2.4, p=.025]; the AUC
was higher in HC than AD subjects [111.5 (61.7) vs. 78.4 (43.4) pg/ml;
t=2.1, p=.046]; and repeated measures ANOVA revealed a main effect
for diagnosis on mean melatonin volume [F(1, 38)=6.3, p=.016]. When
analyzing Caucasian men only (30 AD & 17 HC), DLMO remained significantly
delayed in AD subjects.
Conclusion: These results extend the findings of Kühlwein et al. to
Caucasian men. Further research should consider sex differences in the
mechanisms underlying sleep disturbances in AD.
Support (If Any): Grants AA016117 & AA00304 (K Brower)
A245
SLEEP, Volume 34, Abstract Supplement, 2011