1. Ecological Momentary Assessment in Primary Insomnia Ecological Momentary Assessment Conference Pittsburgh, PA July 10, 2006 Daniel J. Buysse, M.D. Professor of Psychiatry University of Pittsburgh School of Medicine

2. Research diagnostic criteria for insomnia disorder Edinger, SLEEP 2004; 27:1567-96 A.The individual reports one or more of the following sleep related complaints: 1.difficulty initiating sleep 2.difficulty maintaining sleep 3.waking up too early, or 4.sleep that is chronically nonrestorative or poor in quality B.The above sleep difficulty occurs despite adequate opportunity and circumstances for sleep.

3. Research diagnostic criteria for insomnia disorder Edinger, SLEEP 2004; 27:1567-96 C.At least one of the following forms of daytime impairment related to the nighttime sleep difficulty is reported by the individual: 1.Fatigue/ malaise; 2.Attention, concentration, or memory impairment; 3.Social/ vocational dysfunction or poor school performance; 4.Mood disturbance/ irritability; 5.Daytime sleepiness; 6.Motivation/energy/initiative reduction; 7.Proneness for errors/accident at work or while driving; 8.Tension headaches, and/or GI symptoms in response to sleep loss; 9.Concerns or worries about sleep.

4. Consequences of insomnia Buysse, Primary Psychiatry, 2005;12(8):50-57  Decreased quality of life  Difficulty concentrating  Memory problems  Increased absenteeism  Decreased job performance  Increased incidence of psychiatric disorders, pain, poor health  Increased risk of falls and hip fractures  Increased healthcare utilization

5. Ecological momentary assessment of daytime symptoms in insomnia  Ecological: Subjects studied in the environment they typically inhabit  Momentary: Data collection in near- immediate state avoids retrospective bias  Assessment: Multiple assessments per day allow representative characterization of phenomena under study and permit assessment of temporal variation

6. Examples of EMA for one week in insomnia patients Concentration Mood Energy Alertness Overall Day number Rating

7. Goals  Characterize waking symptoms in subjects with Primary Insomnia (PI), using statistical techniques to analyze EMA data  Compare PI and Good Sleeper Controls (GSC)  Compare PI and GSC on “standard” retrospective clinical scales and sleep diary  Examine relationships between EMA ratings, standard scales, sleep diary

8. Subjects  General  PI and GSC, 3:1 ratio  Age 20-50 years, men and women  Medical history, psychiatric history (SCID), sleep disorders history, screening PSG (AHI, PLMAI < 15)  PI (n = 47)  DSM-IV Primary Insomnia  PSQI ≥ 7  No specific quantitative criteria  GSC (n = 18)  No sleep disorder  PSQI ≤ 5

9. Measures  Retrospective questionnaires  Inventory of Depressive Symptomatology (IDS) – sleep items  Beck Anxiety Inventory (BAI)  Penn State Worry Questionnaire (PSWQ)  Hyperarousal Scale (HAS)  Multidimensional Fatigue Inventory (MFI), general fatigue  Pittsburgh Sleep Quality Inventory (PSQI)  Epworth Sleepiness Scale (ESS)

10. Measures  Pittsburgh Sleep Diary (PghSD)  Total sleep time  Sleep latency  Wake after sleep onset  Sleep efficiency  Daytime Insomnia Symptom Scale (DISS)  20 visual analog scales  Presented 4 times per day: Wake up, noon, 6 p.m., bed time  Presented on personal data assistant

11. Statistics  Wilcoxon rank-sum test for retrospective, diary, and DISS data  Spearman rank-order correlations  Functional principal components analysis (FPCA) for DISS data  Individual subjects’ data smoothed over time with mixed-model B-spline regressions (3 quadratic B- spline functions with equally-spaced knots)  FPCA  Varimax rotation

12. Functional principal components analysis of DISS scales  Four eigenvectors  67% of variance  Factors  Alert Cognition  Negative Mood  Positive Mood  Sleepiness-Fatigue

13. Retrospective scales MeasureControl(n=18)Insomnia(n=47)p* Inventory of Depressive Symptomatology 3.4 (5.8) 10.3 (5.4) <.0001 Penn State Worry Questionnaire 16.3 (11.9) 30.1 (14.1).0002 Hyperarousal Scale 22.4 (7.3) 30.0 (6.2).0004 Multidimensional fatigue Inventory 6.9 (1.9) 13.2 (3.4) <.0001 Self-report sleep measures Pittsburgh Sleep Quality Index 1.9 (1.1) 11.0 (3.5) <.0001 Epworth Sleepiness Scale 4.4 (3.5) 7.4 (3.8).002

14. Sleep diary MeasureControl(n=18)Insomnia(n=47)p* Total sleep time (minutes) 464.9 (60.1) 370.1 (66.4) <.0001 Sleep latency (minutes) 8.2 (5.4) 30.9 (24.5) <.0001 Wake after sleep onset (minutes) 3.3 (3.7) 38.9 (29.5) <.0001 Sleep efficiency, % 97.7 (1.4) 83.7 (10.4) <.0001

15. Functional principal component loading values for items on the daytime symptoms in insomnia (DISS) scale in primary insomnia subjects Alert Cognition Forgetful-0.792 Clear-headed0.742 Concentrate0.742 Effort-0.677 Alert0.457 Positive Mood Relaxed0.808 Energetic0.706 Calm0.687 Happy0.658 Efficient0.427 Negative Mood Anxious0.750 Stressed0.703 Tense0.698 Sad0.696 Irritable0.581 Sleepiness/FatigueFatigued0.948 Sleepy0.880 Exhausted0.841

16. Functional principal components analysis of time series self-report data - - - - Primary Insomnia (n=47) Good Sleeper Controls (n=18) *p<.001 for each Alert Cognition Negative Mood Sleepiness/Fatigue Positive Mood

17. Correlations between DISS factor scores, retrospective psychological scales, and self-report sleep measures in insomnia patients (n=47) Measure Alert cognition Negative mood Positive mood Sleepiness/ fatigue Retrospective psychological scales Inventory of Depressive Symptomatology *-.32**.43*-.30.25 Multidimensional Fatigue Inventory -.26.25*-.35***.53 Sleep diary Sleep latency (minutes) *-.35*.30-.23.26 Sleep Efficiency (%).16-.09*.30**-.39 * p<.05 ** p<.01 ***p<.001

18. Conclusions  EMA scales correspond to commonly-reported waking symptom dimensions in PI  EMA indicates differences between PI and GSC  Level of symptoms  Diurnal patterns of symptoms  May provide clues to pathophysiology of daytime dysfunction in insomnia

19. [ 18 F] deoxyglucose PET during a.m. and p.m. wakefulness in healthy adults Buysse, Sleep, 2004; 27:1245-54 Midbrain reticular formation/ Raphe Pontine reticular formation Posterior hypothalamus L Locus coeruleus R Locus coeruleus

20. Correlations between regional glucose metabolism and DISS factors A. Alert cognition positive correlations B. Sleepiness/Fatigue negative correlations

21. Correlations between regional glucose metabolism and DISS factors A. Positive Affect positive correlations B. Positive Affect positive correlations C. Negative Affect negative correlations