1. Sleep and Health (or, Why should we bother to think about sleep in the context of mind-body research? Martica Hall, Ph.D. Associate Professor of Psychiatry University of Pittsburgh School of Medicine hallmh@upmc.edu Pittsburgh Mind-Body Center Summer Institute Pittsburgh, PA June 8, 2007

2. SLEEP  What is it?  How is it measured?  What affects it?  Is it related to health?  What can we do about it?  Where do we go from here?

3. Overview: Description of sleep What is sleep?  behavioral state of relative quiescence  reversible changes in consciousness and physiology  seen in all mammals  essential to health and functioning What drives sleep?  prior wakefulness  circadian rhythms  Habit  Circumstance

4. Overview: Functions of sleep  Ecological/ environmental advantage  Improves the quality of wakefulness –Alertness –Mood –Cognitive (especially frontal lobe) functions  Integration of experience; learning  Resensitization of receptors (e.g., norepinephrine, serotonin)  Metabolic, inflammatory effects  Longevity

5. Assessment of sleep-wake states  Self-report questionnaires  Sleep-wake diaries: Daily recording of sleep times and characteristics  Observer ratings: Unreliable  Actigraphy: Motion-sensitive accelerometer worn on wrist  Polysomnography (PSG): Modification of electroencephalography (EEG) –EEG –Eye movements –Muscle tone

6. Actigraphy Daytime activity peaks Nighttime inactivity Actigraph taken off

7. Polysomnography: Relaxed wakefulness (Stage w) C3-REF C4-REF O1-REF O2-REF LOC-REF ROC-REF EMG A REMs

8. Wakefulness, NREM, and REM WakeNREMREM ArousabilityHighLowestLow EEG amplitude LowHighLow EEG frequency FastSlow Mixed fast Muscle tone VariableLowAbsent Eye movements VoluntaryInfrequentRapid Heart Rate, Blood Pressure, Respiratory Rate Variable Slow/ low, regular Variable O2, CO2 response FullLowerLowest Thermoregulation Behavioral/ Physiological Physiological Reduced physiological Mental activity Full None/ limited Story-like dreams

9. PSG: Stage 1 sleep A B C EMG ROC-REF LOC-REF C3-REF C4-REF O1-REF O2-REF

10. PSG: Stage 2 sleep C3-REF C4-REF LOC-REF O1-REF 02-REF ROC-REF EMG SK

11. PSG: Stage 3 sleep

12. PSG: Stage 4 sleep LOC-REF C3-REF C4-REF O1-REF O2-REF ROC-REF EMG

13. PSG: Rapid-eye-movement (REM) sleep C3-REF C4-REF O1-REF 02-REF LOC-REF ROC-REF EMG

14. Factors that affect sleep  Age –Increased wakefulness during sleep period –Decreased Stage 3/4 NREM –Earlier timing –Greater daytime sleepiness  Sex (women have longer sleep, more Stage 3/4 NREM)  Timing: Sleep is best at night!  Illnesses, medications

15. Sleep in healthy young and older adults 20 year old woman 71 year old woman

16. Sleep stages across the life span Ohayon et al., SLEEP 2004; 27: 1255-73 Minutes Age (years)

17. Be mindful of circadian rhythms! Examples of human circadian rhythms Czeisler and Khalsa, 2000 Core body temperature Urine volume Thyroid Stimulating Hormone Growth Hormone Prolactin Parathyroid Hormone Motor activity Cortisol Time

18. HEALTH SLEEP SLEEP Sleep Restriction/Deprivation Sleep Duration Sleep Continuity Sleep Architecture Sleep/Wake Rhythms Sleep Disorders Mind-Body Sleep Research: Bridging the Gap Between Behavioral Medicine and Sleep Medicine

19. Sleep Restriction: Sleepiness & Performance (n= 16, sleep restriction to 33% below habitual sleep duration) Dinges et al., SLEEP. 20:267-77 (1997).

20. Sleep deprivation effects on cognitive function Drummond et al., Neuroreport, 1999 Normal sleep – Activation of PFC, parietal, pre-motor cortex Following sleep deprivation – Decreased activation fMRI during serial subtraction task

21. The effects of 53 hours of sleep deprivation on moral judgment (n = 26, 20 – 35 years of age) Kilgore et al., SLEEP, 30:345-52, 2007

22. © American Academy of Sleep Medicine  Surgery: 20% more errors and 14% more time required to perform simulated laparoscopy post-call (two studies) Taffinder et al, 1998; Grantcharov et al, 2001  Internal Medicine: efficiency and accuracy of ECG interpretation impaired in sleep-deprived interns Lingenfelser et al, 1994  Pediatrics: time required to place an intra-arterial line increased significantly in sleep-deprived Storer et al, 1989 Sleep deprivation in medical trainees

23. Sleep Restriction & Glucose Metabolism Glucose Effectiveness 30 – 40% decrease Sympathovagal Balance (trend) increase Spiegel et al., Lancet, 354:1435-9 (1999). Ghrelin : Leptin 70% increase Carbohydrate Craving 30% Increase Spiegel et al., Ann Intern. Med, 141:846-50 (2004). GLUCOSE(mg/dL)LEPTIN(ng/ml)

24. Sleep and the Metabolic Syndrome  U-Shaped curvilinear relationship: Metabolic Syndrome: odds of meeting criteria increased by 60 - 70% Glucose: odds of meeting criteria increased by 60 - 70%  Unique to Short Sleepers: Abdominal Obesity: odds of meeting criteria increased by 50 – 60% Triglycerides: odds of meeting criteria increased by 40%  Unique to Long Sleepers: n/a  Not Significant: Blood pressure, HDL  Results are similar to those found for sleep quality (Jennings, Muldoon, Hall, Buysse, Manuck, Sleep, 2007).

25. AHI SE Beta AHI SE Beta Sleep Problem Sleep Problem 60%50%40%30%20%10% Metabolic Syndrome (percent) 21.6% 24.6% Prevalence of the Metabolic Syndrome by Type of Sleep Problem Hall et al., APSS, 2007 55.6% 38.5% 22.3% 40.6%

26. 0 1 2 or more Number of Sleep Problems Number of Sleep Problems 50%40%30%20%10% Metabolic Syndrome (percent) 12.8% 32.1% 48.3% Prevalence of the Metabolic Syndrome by Number of Sleep Problems Hall et al., APSS, 2007

27. Sleep Duration and All-Cause Mortality Heslop et al., Sleep Medicine, 3:305-314, 2002. Kripke et al., Arch Gen Psychiatry, 59:131-136, 2003. Patel et al., Sleep, 27:440-4, 2004. Tamakoshi & Ohno, Sleep, 27:51-4,. Wingard & Berkman, Sleep, 6:102-7, 1983. Mid- to Late-life Men and Women Urban and Rural US and non-US Sleep Duration and Mortality

28. Survival as a Function of PSG-Assessed Sleep Latency Latency, < 30 min. Latency, > 30 min. 0 100 200 300 400 500 600 700 800 900 1000 Weeks 1.0 0.8 0.6 0.4 0.2 0.0 Cumulative Survival Log rank test = 9.63 p =.002 Dew et al., Psychosomatic Medicine, 2003

30. Insomnia disorder: ICSD-2 American Academy of Sleep Medicine, 2005 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.

31. Insomnia disorder: ICSD-2 American Academy of Sleep Medicine, 2005 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.

32. Insomnia Epidemiology Ohayon, Sleep Med Rev, 2002 Insomnia symptoms + daytime consequences 9-15% Insomnia symptoms -Overall prevalence 30-48% -Often or always: 16-21% -Moderate to extreme: 10-28% Insomnia diagnosis 6%

33. Insomnia Severity and QOL Good Sleepers (n = 391)Mild Insomniacs (n = 422) Severe Insomniacs (n = 240) Axes represent subscales of the SF-36. All P values <.05 (range.000-.023). Léger D et al. Psychosom Med. 2001;63:49-55.

34. Insomnia Is a Risk Factor for Psychiatric Disorders 0 2 4 6 8 10 12 14 16 18 Depression*Anxiety*AlcoholDrug* Incidence (%) More Than 3.5 Years Insomnia (n = 240) No Insomnia (n = 739) *95% CI for odds ratio excludes 1.0. Breslau N et al. Biol Psychiatry. 1996;39:411-418.

35. Shiftwork and Ulcers Drake et al., SLEEP, 2004 2036 174 360 N = 2,570 18 – 65 52% Male

36. Association of insomnia and CHD events Schwartz, J Psychosom Res, 1999; 47:313-33 Combined estimate Individual studies Meta-analysis of seven cohort and longitudinal studies

37. Family Conflict in Childhood and Later Insomnia Gregory et al., SLEEP, 2006 N = 1037, 52% male

38. Dose-Response Relationship Between Chronicity of Family Conflict and Later Insomnia Gregory et al., SLEEP, 2006 Number of assessments at which family scores in top quartile for family conflict

39. Treatment for insomnia BehavioralPharmacologic

40. Classes of pharmacologic agents used to treat insomnia  Benzodiazepine receptor agonists –True benzodiazepine –“Non-benzodizepines”  Melatonin and melatonin receptor agonists  Sedating antidepressants (trazodone, doxepin)  Antihistamines (diphenhydramine, doxylamine)  Valerian, “natural” agents  Sedating second generation antipsychotics  Miscellaneous: gabapentin, tiagabine

41. Behavioral treatments for insomnia  A diverse set of behavioral prescriptions… –All involve some change in the patient’s behavior –Of the patient, by the patient, for the patient –Use voluntary, waking behavior to influence sleep-wake balance  …designed to improve the quality of nocturnal sleep –Reduce sleep onset latency, intermittent wakefulness –Increase sleep duration (?), sleep efficiency –Regularize sleep timing, increase predictability A diverse set of behavioral prescriptions designed to improve the quality of nocturnal sleep

42. Behavioral treatments for insomnia TechniqueAim Sleep hygiene education Promote habits that help sleep; eliminate habits that hurt sleep Stimulus control Strengthen bed/bedroom as sleep stimulus Sleep restriction therapy Restrict time in bed to improve sleep depth/consolidation Cognitive behavior therapy Address maladaptive thoughts and beliefs Relaxation training Reduce physical/psychological arousal

43. RCT of Cognitive Behavioral Therapy for Insomnia Espie et al., SLEEP, 30:574-84, 2007 N = 201 5 Sessions Nurse-Administered Small Group DIARY MEAURES

44. Brief Behavioral Treatment for Insomnia (BBTI) vs. Information Control in Older Adults with Insomnia Pittsburgh Sleep Quality Index** Hamilton Depression Rating (Minus Sleep Items)* U test *p<.05, **p<.01 n = 13 (BBTI), n = 12 (Information Control) Pre-treatment baseline 4-weeks

45. NIA AgeWise Study Time Line 6-Month and 12- Month Intervals consent Medical Exam & Psychiatric Assessment Data Collection Session Data Collection Session & Brief Medical Exam sleep diary sleep study Intervention Stress Management + Healthy Sleep Practices Control sleep study sleep diary Data Collection Session & Brief Medical Exam