Understanding the Pathogenesis of
Insomnia
Dr. Jason Ellis
Starting at the end….
Cognitive Behaviour Therapy for Insomnia is:
• Longer lasting than pharmacotherapy
• More efficacious and is more effective than pharmacotherapy
• Cheaper (in the long run) compared to pharmacotherapy
• Just as effective with complex cases as with ‘pure’ cases
So what’s the problem….?
Cognitive Behaviour Therapy for Insomnia is:
• Hampered by very few clinicians
• Prone to high levels of attrition (50%) and non-adherence
• Time and labour intensive for the client
Why is Addressing Acute Insomnia
Important?
• It is the single biggest predictor of chronic insomnia
• Acute insomnia is a symptom of many other disorders (e.g. MDD)
• 10M prescriptions annually in the UK for sleep medications (£15m)
• Persistence of chronic insomnia (mean 2 years) and associated issues
• Delivery of preventative intervention would most likely be cheaper than CBT-I
• Intervention would most likely be less burdensome on the patient
(attrition and non-adherence)
How do we Conceptualize Acute Insomnia?
Spielman et al (1987)
How do we Conceptualize Acute Insomnia?
Spielman et al (1987)
What is Acute Insomnia?
Acute Insomnia
Significant Life Event
Insomnia
Threshold
Stress
Response
Trigger
Time
Accumulation of Daily Hassles
Insomnia
Threshold
Stress
Response
Minimum
Frequency
Duration
Time
Course
1) Any life event or train of life
events which results in a
significant reduction in QoL
from the individuals Ideal
2) Distress at current situation
3 or more nights per week
3 days -3 months
3 - 14 days Subacute
2 - 4 Weeks Transient
1 - 3 Months Subchronic
Chronic Stressor
Insomnia
Threshold
Stress
Response
Time
Qualitative
Severity
Quantitative
Severity
Ellis, Gehrman, Espie, Riemann & Perlis (2012)
mild / moderate / severe as
defined by the patient
(+30 Minutes SOL; +30
Minutes WASO)
Prevalence of Acute Sleep Disturbance
70.00%
60.00%
50.00%
40.00%
USA
UK
30.00%
N = 2,861
N = 1095
66.85% F
Mean Age 32.72 (SD 13.81)
20.00%
10.00%
0.00%
Good Sleepers
Acute Sleep
Disturbance
Chronic Sleep
Disturbance
Unsure
USA = 9.47% Acute Sleep Disturbance – Age Category 29-45
UK = 7.85% Acute Sleep Disturbance – Mean Age 31.82 (SD 10.82)
Ellis, Perlis et al (under review)
Prevalence of Acute Insomnia
First-Onset Acute Insomnia
20.00%
Episode of Intermittent Acute Insomnia
18.00%
First-Onset Acute Sleep Disorders
Chronic Insomnia
16.00%
Other Chronic Sleep Disorders
14.00%
12.00%
10.00%
8.00%
First Onset Acute Insomnia = 2.65%
6.00%
Recurrent/ Intermittent Episode = 3.84%
4.00%
First Onset Acute Sleep Disorder = 1.37%
2.00%
0.00%
First-Onset
Acute
Insomnia
Episode of
Intermittent
Acute
Insomnia
First-Onset
Acute Sleep
Disorders
Chronic
Insomnia
Other
Chronic
Sleep
Disorders
Ellis, Perlis et al (under review)
Incidence of Acute Insomnia
412 Normal Sleepers from General Population
Met all criteria for Acute Insomnia:
1 month assessment (N = 412) – 3.39% - 2.67% First episode (57% F)
3 month assessment (N = 295) – 7.80% - 4.75% First episode (61% F)
75% remission from First-episode cases by 3 months
50% remission from Recurrent cases by 3 months
= 33% transition rate from Acute to Chronic Insomnia
Ellis, Perlis et al (under review)
Question: Are there any differences between normal sleepers
and people with acute insomnia in how they sleep?
Sample
• 54 Participants (36 Females / 18 Males; Mean age 33.6 SD 13.09)
• Either no-episode (n = 21 NS) or first-episode insomnia (n = 33 AI)
• Acute Insomnia (DSM-V Insomnia Disorder + 3 days – 3 months)
• No self-reported chronic illness or psychiatric illness
• No gender differences between groups (Chi 2.08, df = 2, p = .35)
• No age differences between groups (t(52) = -.3, p = .77)
Screening / Measures
• 48hour Urinary Melatonin (aMT6s) – circadian abnormalities
• Actigraphy (14 days)
• Sleep Diaries (14 days)
• Polysomnography (2 nights – 1st Night full screen / adaptation night)
• Life Events (LES); Stress (PSS); Psychological Adjustment (HADS)
Characterising Sleep Continuity in Acute Insomnia
Spontaneous Arousals
(number per hour of sleep)
SL (minutes)
Acute Insomnia (n = 33)
Normal Sleepers (n = 21)
WASO (minutes)
SEI (%)
0
20
No significant differences
40
60
80 100
Characterising Sleep Architecture in Acute Insomnia
Latency REM
Latency N3
Acute Insomnia (n = 33)
Normal Sleepers (n = 21)
Latency N2
Latency N1
0
20
No significant differences
40
60
80
100
Characterising Sleep Architecture in Acute Insomnia
% REM
% N3
Acute Insomnia (n = 33)
% N2
Normal Sleepers (n = 21)
% N1
% WAKE
0
20
40
% N2 (t(52) = 2.22, p<.05)
% N3 Significant (t(52) = -2.94, p<.005)
60
Architectural Differences Between
Sleeper Groups
REM Latency (minutes)
120
* p<.05
* p<.05
100
F(2,51) = 4.75, p<.01
80
60
REM Latency…
40
20
0
Normal Sleeper
(n = 21)
Acute to
Remission
(n = 19)
Acute to Chronic
(n = 14)
Architectural Differences Between
Sleeper Groups
Percentage Slow Wave Sleep
20
* p<.05
18
16
F(2,51) = 5.68, p<.001
14
12
10
Percentage Slow…
8
6
4
2
0
Normal Sleeper
(n = 21)
Acute to
Remission
(n = 19)
Acute to Chronic
(n = 14)
Is this a ‘level of stress’ response issue?
Life Event Scale Scores
Perceived Stress Scale Scores
46
250
* p<.05
* p<.05
45
* p<.05
* p<.05
44
200
43
42
150
41
Perceived Stress
Scores
Life Events…
40
100
39
38
50
37
36
0
Normal
Sleeper
(n = 21)
Acute to Acute to
Remission Chronic
(n = 19)
(n = 14)
Normal
Sleeper
(n = 21)
Acute to Acute to
Remission Chronic
(n = 19)
(n = 14)
Is this a ‘sleep propensity’ issue?
Is this a ‘sleep propensity’ issue?
Time in Bed
% Time in Bed (Day)
Time in Bed (Diary) Minutes
60
540
530
50
520
40
510
30
% Time in Bed
Time in Bed
500
20
490
10
480
0
470
Normal
Acute to
Sleeper (n = Remission
21)
(n = 19)
Acute to
Chronic (n =
14)
Normal
Sleeper (n =
21)
Acute to
Remission
(n = 19)
Acute to
Chronic (n =
14)
What is this pattern also seen in?
% Slow Wave Sleep
REM Latency (minutes)
20
120
* p<.05
* p<.05
* p<.05
18
100
16
14
80
12
10
60
REM…
40
Percentage
Slow Wave…
8
6
4
20
2
0
0
Normal
Sleeper
(n = 21)
Acute to
Remission
(n = 19)
Acute to
Chronic
(n = 14)
Normal
Sleeper
(n = 21)
Acute to
Acute to
Remission Chronic (n
(n = 19)
= 14)
Psychological Adjustment
12
* p<.05
10
* p<.05
8
6
Depression Scores
Anxiety Scores
4
2
0
Normal Sleeper
(n = 21)
Acute to
Remission
(n = 19)
Acute to Chronic
(n = 14)
New Approaches to Address Attrition in CBT-I?
Combining CBT-I with a stimulant
Decrease Slow Wave Sleep
Combining CBT-I with a hypnotic
Question: Are there any relevant daytime
factors which relate to this poor psychological adjustment
in acute insomnia?
Sleep Preoccupation
A tendency to be overly preoccupied about sleep during the day, with
catastrophic interpretations and counterproductive actions across the 24h cycle.
Affective = + worry about short and long-term consequences / anxious at night
Behavioural = + drink more coffee / go to bed earlier
Cognitive = + concentration difficulties / memory deficiencies
Are People With Insomnia Preoccupied with
their sleep?
722 participants completed the Sleep Preoccupation Scale
•
Poor sleeper (“a current sleep disruption which is negatively affecting the
quality, quantity, or timing of your sleep and/or having sleep which is
unrefreshing, and occurs at least three nights per week”)
•
Average sleeper (“a current sleep pattern which is sometimes disrupted
and/or unrefreshing but occurs less than three nights a week”)
•
Good sleeper (“a current sleep pattern which is not disrupted in its quality,
quantity, and timing, and is refreshing”)
Ellis et al (2007)
Levels of Daytime Sleep Preoccupation
Good Sleepers
Preoccupation
Average Sleepers
Poor Sleepers
0
10
20
30
40
50
60
Aim to examine the relationship between the Sleep Preoccupation Scale (SPS)
and sleep parameters over the course of a semi-natural stressor.
The sample was four classes of student nurses and midwives from a West London
Teaching Hospital.
Students filled in the SPS and a sleep diary every day over the course of their two
week exam period (one week before, over the two days of exams as well as three
days afterward). All scores are averaged across number of nights.
Of the initial sample of 103 students, 92 agreed to take part and returned the
questionnaires. Mean age 29.4 (SD 8.3) 80 (86.7%) females, 12 (13.3%) males.
BASELINE
EXAM
RECOVERY
SPS
40.57 (17.1)
58.67 (21.35)
45.97 (24.98)
SEI
71.28 (14.68)
59.39 (18.87)
64.18 (15.64)
0.2 (n.s)
-0.4 (p<0.05)
0.18 (n.s)
Correlation
Coefficient
BASELINE
EXAM
RECOVERY
SPS
40.57 (17.1)
58.67 (21.35)
45.97 (24.98)
SEI
71.28 (14.68)
59.39 (18.87)
64.18 (15.64)
0.2 (n.s)
-0.4 (p<0.05)
0.18 (n.s)
Correlation
Coefficient
Levels of Daytime Sleep Preoccupation
Good Sleepers
Average Sleepers
Preoccupation
Poor Sleepers
Exam Stress
Baseline
0
10
20
30
40
50
60
Conclusions
Acute Insomnia is:
Highly prevalent (7.9%)
Annual incidence (31.2%)
Increased Stage 2 Sleep
Decreased SWS
Increased Daytime Preoccupation
The transition to Chronic Insomnia is:
and associated with:
Highly likely (25-50%)
Increased REM Latency
Decreased SWS
Increased Anxiety and Depression
and which looks very similar to:
The onset of an Affective Disorder
How early is early prevention?
1020
* p<.05
1000
Milliseconds (Standard Error)
980
960
940
Control Group (N = 51)
Children of Parents with Insomnia (N = 38)
920
900
880
860
Neutral Words
Sleep-Related Words
Ellis, Thomson, Gregory & Sterr (2012)
University of Surrey
University of Everywhere Else in the World
Professor Annette Sterr
Dr. Michael Perlis (U Penn)
Professor Celyne Bastien (U Laval)
Dr. Phil Gehrman (U Penn)
Professor Dieter Riemann (U Freiberg)
University of London
Dr. Alice Gregory
And the people who fund this work
University of Glasgow
Professor Colin Espie
Dr. Maria Gardani
Dr. Amy Thomson
jason.ellis@northumbria.ac.uk