Psychiatric Sequalae of Sleep
Disorders
Mark Brown, M.D.
Stanford Sleep Disorders Center
A.W.A.K.E. Meeting
Presentation Overview



Introduction
Primary Sleep
Disorders 
Psychiatry
Summary
Introduction

Epidemiology



Common
Psychiatric Morbidity
Sleep and Psychiatry



Comorbid
Difficult to separate
Etiology,
consequence, or
both?
Primary Sleep Disorders


Insufficient Sleep
Sleep Fragmenting
Disorders



SDB
RLS/PLMD
Disorders of
Hypersomnolence

Narcolepsy
Insufficient Sleep

Very common in
today’s society


20% of 1.1 million
Americans sleep less
than 6.5 hrs/night
Basal Sleep Need

Epi studies indicate
mean need of 8.16
hrs/night
Principles and Practice of Sleep Medicine, 4th Ed. 2005
Insufficient Sleep

Neuropsychiatric
Effects


Cognitive,
psychomotor,
memory
Subjective vs.
Objective
Balkin et al. Sleep Loss and Sleepiness. Chest. 134(3):653-660, 2008 Sep.
Insufficient Sleep

Individual
differences


Stable within
individuals
Varies between
individuals

Need vs. Resilience?
Van Dongen et al. “The cumulative cost of additional wakefulness: doseresponse effects on neurobehavioral functions and sleep physiology from
chronic sleep restriction and total sleep deprivation.” Sleep. 2003 Mar
15;26(2):117-26.
Sleep Disordered Breathing
(SDB)


Obstructive Sleep
Apnea/Hypopnea
Syndrome (OSAHS)
Apnea/Hypopnea
Index (AHI)





<5 normal
5-15 mild
15-30 moderate
>30 severe
Common

OSA: 4% of men and 2%
of women

Screening

Symptoms

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Snoring
Witnessed apneas
Choking arousals
Spouse report
Signs
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BMI
Neck Circumference
HTN
SDB and Depression

Multiple Studies
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Guilleminault et al
Reynolds et al
Millmann et al
Mosko, S et al
Aikens et al
Schroder et al. Depression and Obstructive Sleep Apnea (OSA). Annals of General Psychiatry
2005, 4:13, 1-8.
SDB and Depression

Review Harris et al

Large prevalence
studies
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
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
Sleep-EVAL
VA database
Hordaland Health
Study

Prospective
longitudinal Studies


Peppard et al
Treatment studies
Correlational studies

Cross-sectional
studies
Harris et al. Clinical Review: Obstructive sleep apnea and depression. Sleep
Medicine Reviews 13 (2009) 437-444.
SDB and Depression

Review
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1995-2006
OSA and
Depression/Anxiety
203 total articles
Rigorous exclusion
criteria
Final total of 55
articles
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Results
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Age 44-69 yrs
Median N 54
Median male sex
83%
Median AHI 48
Assessment of Mood

Beck, Zung, CES-D,
HADS, STAI, POMS,
MMPI, SCL-90, SCID,
interview, etc…
Saunamaki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea
syndrome: a review. Acta Neurol Scand 2007:116:277-288.
SDB and Depression (cont)

Pretreatment
Prevalence
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

Depression 7-63%
Anxiety 11-70%
CPAP Treatment

7 rigorous studies


Depression decreased
in 4/7 studies
Anxiety decreased in
2/4 studies
Saunamaki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea
syndrome: a review. Acta Neurol Scand 2007:116:277-288.
SDB and Depression

Sleep Heart Health
Study (SHHS)
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
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Results

6,441  3,078 subjects
2 PSG’s, 5 yrs apart
Quality of Life

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Mental Component
Summary Scale (MCS)


Sample

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Age 62
55% female
75% Caucasian

Very small changes over
5 years in RDI, BMI, ESS,
PCS, and MCS.
Minimal change in PCS
and no change in MCS
Significant association
between subjective sleep
quality and PCS/MCS.
Not clinically significant
changes over 5 years
Silva et al, Sleep Disordered Breathing and Quality of Life. Sleep, 32(8), 1049-1057.
SDB and Cognitive
Dysfunction

Review Aloia et al


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
1985-2002
Initial 187 articles
Final analysis 37
articles
Limitations

Results
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Impairment > 60%



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Attention/Vigilance
Exec Functioning
Memory
Impairment >80%


Construction
Motor Functioning
Aloia et al. Neuropsychological sequelae of obstructive sleep apnea-hypopnea
syndrome: A Critical Review. JINS, 2004, 10, 772-785.
SDB and Cognitive
Dysfunction (cont)

Treatment



Attention/vigilance
(11/17)
Global functioning,
executive
functioning, and
memory (6/10, 7/15,
8/15)
Psychomotor
functioning failed to
improve (0/6)
Aloia et al. Neuropsychological sequelae of obstructive sleep apnea-hypopnea
syndrome: A Critical Review. JINS, 2004, 10, 772-785.
SDB in Children

Introduction
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ADHD comorbidity
Prospective Study
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Adenotonsillectomy (AT)
cohort and surgical
control
N=78, 5-12.9(8.4)yrs
Mild-Moderate severity
57% male
95% f/u rate
Measurements

Results
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AT group


Higher scores for
hyperactivity,
inattention, MSLT,
and ADHD at baseline
and improved to
control rate 1 yr after
surgery
However, only
sleepiness correlated
with PSG
Chervin et al. Sleep disordered breathing, behavior, and cognition in children
before and after adenotonsillectomy. Pediatrics. 117(4) 2006 e769-e778.
SDB Summary

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
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Complex relationship
20+ year history of
studies
Comorbid
Treatment
implications


Lack of response
ADHD overlap in
children
RLS/PLMD

RLS
Definition/Criteria

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“Unpleasant” Limb
Sensations
Motor Restlessness
Precipitated by REST
and Relieved by
Activity
Worse in
Evening/Night

PLMD
Definition/Criteria


Repetitive,
stereotypic
dorsiflexions of the
big toe with fanning
of the small toes
with flexion of the
ankles, knees, &
thighs
Recur in intervals
RLS/PLMD

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Primary RLS
Secondary RLS



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Iron Deficiency
Renal Failure
Pregnancy
Medications

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TCA, SSRI, Dopamine
antagonists
(compazine,
metaclopramide)
Caffeine

PLMD



Any cause of RLS
Withdrawal of
anticonvulsants,
barbiturates,
hypnotics
Associated with SDB,
CPAP titration, and
Narcolepsy
RLS and QoL
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SHHS
2821 men and
women
RLS dx by 8-item
questionnaire and
correlated with PSG
findings
Health Related
Quality of Life SF-36


Decrements in ALL
physical domains
Decrements in
Psychiatric domains
of ‘Mental Health’
and ‘Vitality’

Dose-response
relationship
Winkelman et al. Polysomnographic and Health-related Quality of Life Correlates of
Restless Legs Syndrome in the Sleep Heart Health Study. SLEEP 32(6) 2009 772-778.
RLS and Psychiatric Disorders
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RLS in community
sample of Korean
Adults
6,509 subjects
Age 18-64
Face-to-face
interview, K-CIDI,
CES-D-K and EQ-5D

Prevalence



Women (1.3%)
Men (0.6%)
Increased with age
Cho et al. Restless Legs Syndrome in a Community Sample of Korean Adults:
Prevalence, Impact on Quality of Life, and Association with DSM-IV Psychiatric Disorders.
SLEEP. 32(8) 2009 1069-1076.
RLS and Psychiatric Disorders
(cont)

Results
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Psychotropics
(12.5% vs. 3%)
Anxiety or
depression (21.1%
vs. 12.6%)
Mean CES-D score
(10.8 vs. 6.4)

Lifetime Prevalence
of DSM-IV Disorders



40.3% vs. 27.7%
MDD most common
(15.3% vs. 8.3%)
Anxiety disorders
increased as well
(13.9% vs. 6.7%)
Cho et al. Restless Legs Syndrome in a Community Sample of Korean Adults:
Prevalence, Impact on Quality of Life, and Association with DSM-IV Psychiatric Disorders.
SLEEP. 32(8) 2009 1069-1076.
RLS, PLMD and Depression



Review
Depression more
common in RLS
RLS/PLMD
exacerbated in those
on SSRI’s/SNRI’s

RLS/PLMD improved
or similar to control
for buproprion and
trazodone
Picchietti and Winkelman. Restless Legs Syndrome, Periodic Limb Movements in Sleep,
and Depression. SLEEP. 28(7) 2005 891-898.
Narcolepsy



REM Disorder
Onset late childhood
to 20’s
Signs/Symptoms



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EDS
Sleep Attacks
Cataplexy
Hypnagogic
Hallucinations
Sleep Paralysis

Secondary Causes

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Head trauma
Stroke
MS
Brain Tumors
NG Disorders
CNS infections
Diagnosis



PSG with MSLT
HLA antigens
CSF
Narcolepsy and Psychiatry

Psychosocial
Morbidity Study



Cross-sectional
questionnaire survey
Children aged 4-18
Narcolepsy,
Behavior, Mood,
QoL. And
Educational
Assessments

Subjects



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42 subjects with
Narcolepsy
18 with EDS without
cataplexy
23 control group
No demographic
differences between
groups
Stores et al. The Psychosocial Problems of Children with Narcolepsy and those with
Excessive Daytime Sleepiness of Uncertain Origin. Pediatrics. 118(4) 2006 e1116-e1123.
Narcolepsy and Psychiatry
(cont.)

Results


Significant
differences for peer
problems, conduct,
emotional symptoms
and total problems
Prosocial and
hyperactivity not
different from
controls




CDI increased in
Narcolepsy and EDS
group
Mental Health QoL
affect but not
physical or global
Greater educational
difficulties
Increased
psychosocial
morbidity
Narcolepsy and Schizophrenia




Case Series (5)
All female, mean
age 39+/-6.8
Tx refractory
schizophrenia and
EDS
All selected had
narcolepsy tetrad


SANS, SAPS, BPRS
Patients 2-5 (not
avail for pt 1) had
statistically and
clinically significant
improvement of
SANS, SAPS, and
BPRS on stimulants.
Douglas et al. Florid Refractory Schizophrenias that turn out to be Treatable Variants of
HLA-Associated Narcolepsy. J Nerv Ment Dis. 179:012-017, 1991, 12-17.
Summary



Sleep disorders are
common
Sleep disorders have
associated
morbidity/mortality
Sleep disorders are
under-appreciated


The relationship
between sleep
disorders and
psychiatric disorders
appears bidirectional
Identification and
treatment of Primary
Sleep disorders may
improve psychiatric
comorbidity
Questions