Sleep Biology and Consequences: Understanding Circadian Rhythms and Sleep Disruption

1. Sleep Biology and the Consequences of Sleep Disruption Tuesday 16th October 2018 1.20 – 1.40pm Russell G. Foster CBE, FRSB, FMedSci, FRS Professor of Circadian Neuroscience Head, Nuffield Laboratory of Ophthalmology Director, Sleep and Circadian Neuroscience Institute Fellow, Brasenose College E-mail: russell.foster@eye.ox.ac.uk

2. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?

3. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?

4. Core Body Temperature °C Growth Hormone Sleep Sleep 28 37.5°C 14 36.75°C 0 36°C 02 14 14 02 14 14 Systolic Pressure mm Hg Cortisol µg/100ml 200 150 100 100 24h Circadian Rhythms 0 50 02 14 14 02 14 14 Sleep Alertness 100 100 50 75 0 50 02 14 14 02 14 14

5. The Circadian System adjusts or “Fine-Tunes” Physiology and Behaviour to the profound changes of the 24h Day/Night Cycle Implications

6. Circadian Changes in Blood Pressure Stroke Stroke 12.00 06.00 SLEEP Stroke 130 mmHg ~50% increased chance of a stroke between 06.00 – 12.00 70 mmHg 10pm 6am • When to take stroke medication? • How to prepareour health services? Oxford Vascular Study (Peter M Rothwell )

7. Drug Timing: anti-cancer Ann Palliat Med. 2016 Oct;5(4):267-279. doi: 10.21037/apm.2016.09.05. Impact of radiotherapy at different times on survival in patients with multiple brain metastases Time of Day Matters!

8. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?

9. Time use on an average work day for employed persons ages 25 to 54 with children Other 6.6% Caring for Others 5% Eating and Drinking 4.2% Household activities 4.2% Sleep 32 – 36% Leasure and Sports 10.5% 24h Day Thomas Edison: “Sleep is a criminal waste of time and a heritage from our cave days” Work and related activities 37% Bureau of Labor Statistics, American Time Use Survey http://www.bls.gov/tus/charts/)

10. What Critical Processes Occur in the Sleeping Brain? Emotional Processing Developing Memories Processing Information

11. Wagner et. al. (2004) Nature Vol 427 P = 0.014 80 60 Sleep promotes the ability to come-up with novel solutions to complex problems! % Successful in Problem Solving 40 20 0 Morning - Intro Afternoon - Testing Morning - Intro Next Afternoon – Testing No Sleep Morning - Intro Next Afternoon – Testing With Sleep

12. Acetylcholine Noradrenaline Orexin Histamine Serotonin Dopamine What Critical Processes Occur in the Sleeping Brain? GABA Galanin Brain Regulates Growth & Repair Glutamate Removal of Waste Products Emotional Processing Replacing Energy Reserves Rebuilding Metabolism Developing Memories Processing Information The quality of our wake performance is defined by the quality of our sleep

13. The quality of our sleep is greatly influenced by when we sleep and how long we sleep Circadian Timing Sleep Pressure Societal Pressures

14. Circadian Timing & Sleep Pressure Sleep Pressure Sleepiness Circadian Clock Wake Sleep

15. Societal Pressures Sleep Pressure WAKE-UP SLEEP Circadian Clock Wakefulness Wake Sleep

16. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?

17. Sleep & Circadian Rhythm Disruption (SCRD) • Loss of Attention • High level of Micro-Sleeps • Failure to Process Information • Impulsivity, Loss of Empathy, Negative Focus • Memory Impairment, Increased Mistakes • Reduced Cognition and Creativity Short-Term • Immune Suppression • Increased Infection/Cancer Risk • Increased Cardiovascular Disease • Risk of Diabetes II • Metabolic Syndrome • Increased Stimulant/Sedative Use Long-Term “Mental Illness Vulnerability” • Mood Instability • Anxiety, Paranoia, Hallucinations • Exacerbation of symptoms in BPD & SCZ

18. In USA 100,000 crashes every year are related to sleepiness. Microsleeps

19. 2010 - Air India Express

20. Effect of sleep deprivation on brain activation while performing mathematical tasks (fMRI) Rested

21. Effect of sleep deprivation on brain activation while performing mathematical tasks (fMRI) Rested Sleep Deprived

23. Appetite - + Ghrelin Leptin Stomach Sleep Disruption Adipose Tissue

24. The majority of psychiatric inpatients experience clinically significant insomnia > 80% Haynes et al., (2011). Examination of insomnia and insomnia treatment in psychiatric inpatients. Int J Mental Health Nursing, 20:130-136.

25. “Conceptual Framework” Early Detection Mental Illness Overlapping Brain Circuits & Neurotransmitters Sleep Disruption Therapeutic Target Mechanistic Understanding Foster, R.G. et. Al. (2010) Nature Reviews Neuroscience 11(8), 589-599.

26. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?

27. What Could We Do Now For Those “At Risk” in the Home or Workplace? Few Brief Examples:

28. 1. Higher Frequency Health Checks Its all about catching problems early! • Long-Term Shiftwork • Increased Cardiovascular Disease • Cancer • Obesity • Risk of Diabetes II • Metabolic Syndrome • Gastro-intestinal problems

29. 1. Higher Frequency Health Checks 5 Year Cancer Relative Survival Rates by Stage at Detection Higher frequency health checks for those “at risk” of sleep disruption!

30. 2. Correct Lighting Light in the Nursing Home ~ 20 lux • Major improvement of sleep/wake timing • Increased cognition by 10% • Slowed cognitive decline • Reduced levels of depression • Improved capacity for daily living ~ 2000 lux • JAMA. 2008;299(22):2642-2655

31. 3. Technology to help vigilance More than half of trainee hospital doctors have had an accident or near miss on their way home after a night shift due to sleep deprivation Blue – Yes; Red – No; Green – Prefer not to say

32. 3. Technology to help vigilance Drowsiness Detection “Duty of care” by employer to provide such devices? Driver drowsiness detection is a car safety technology which helps prevent accidents caused by the driver getting drowsy

33. 4. Appropriate Nutrition • Shift workers are more vulnerable to: • Increased Cardiovascular Disease • Obesity • Risk of Diabetes II • Metabolic Syndrome • Gastro-intestinal problems Food on the Night Shift - Ideally Food on the Night Shift - Currently

34. 5. Sleep Education Teenagers – The “TeenSleep” Project Sleep Hygiene Lifestyle factors which impact sleep and how to promote sleep Science of Sleep What is sleep, why is it important and how sleep changes in adolescence Stress Management Techniques such as thought management, putting the day to rest and relaxation Sleep and Wellbeing 8 x 30 min sessions that teachers deliver Dr. Gaby Illingworth Dr. Rachel Sharman Prof. Colin Espie Prof. Russell Foster

35. 5. Sleep Education Pilot Study - Does sleep quality improve in teenagers? 20 *** 18 16 14 12 10 The Sleep Condition Indicator Score 8 6 4 2 Dr. Gaby Illingworth Dr. Rachel Sharman Prof. Colin Espie Prof. Russell Foster 0 Pre-Intervention Post-Intervention A score of 16 and below on the SCI indicates probable insomnia

36. 5. Sleep Education NOT JUST TEENAGERS Sleep education could play a potentially important role in helping individuals get better sleep and for partners to understand the negative changes in behaviour. For shift work couples with children under 19-years old, the risk of divorce increased up to six times when one of the spouses worked between midnight and 8 a.m. as compared to daytime hours.

37. 6. Care with the use of digital devices Reinforcement Weight Loss Behavioural Change

38. 6. Care with the use of digital devices Reinforcement Sleep Better Behavioural Change • Not Validated • Misleading • Stress Inducing!

39. Sleep Biology and the Consequences of Sleep Disruption • Circadian Rhythms - Impact • The Biology of Sleep • Impact of Sleep Disruption • What to do?