1. Sleep Disorders MedicineIn Psychiatry Alan B. Douglass MD, FRCPC, Dip. ABPN, Dip. Amer. Board of Sleep Medicine Asst. Professor, Dept of Psychiatry, University of Ottawa Medical Director, Sleep Disorders Service, Royal Ottawa Hospital

2. Introduction • Financial Disclosure: Nothing to declare • Today we will cover: • Basic sleep physiology • Narcolepsy – a disorder of the REM control system • Periodic Limb Movement Disorder • Obstructive Sleep Apnea • Insomnia – diagnosis & treatment

3. DSM-IV-TR

4. Great clinical textbook: (Mayo Clinic, 2004)

5. Sleep waveform schematic

6. Sleep Stage % by Age

7. Stg%

8. EEG Frequencies

9. 10-20 The “10 – 20” system of EEG electrode placement (C3 / C4 in yellow – where sleep is scored). 10 – 20 electrodes

10. Wake => Sleep Transition Wake => Sleep Transition R & K 1968

11. Stage 2 Sleep R & K 1968

12. Stage 4 Sleep

13. REM sleep onset Onset of REM R & K 1968

14. Sleep Histogram RL

15. 24-hr Sleepiness Profile

16. Multiple Sleep Latency Test (MSLT)

17. Sleep Restriction MSLT

18. Narcolepsy: MSLT, SOREMs

19. Whole Brain mid-saggital section. Netter / CIBA

20. Neurotransmitters in Sleep REM: only time of day when monoamines not firing !

21. REM Control Nuclei “Biological Clock” OREXIN REM induces muscle paralysis

22. Monoamines controlled by Orexin SCNclock DA(+) ~ Orexin / Hypocretin Histamine (+) 5HT(+) NA (+)

23. REM Trigger: nucleus reticularis pontis oralis REM Control

24. Orexin-Hypocretin projections

25. Narcolepsy -- Cataplexy

26. Narcolepsy: night sleep

27. Narcolepsy “Tetrad” (4 symptoms) • True sleep attacks • Falls asleep without warning, unusual situations • Cataplexy • Flaccid muscle paralysis; eyes and diaphragm OK; pt. remains awake but paralyzed. • Hypnagogic / Hypnopompic hallucinations • “Multimodal” – visual, tactile, auditory, smell. Often highly emotional, sexual, frightening • Sleep Paralysis • Awakes unable to move anything but eyes. Can’t breathe voluntarily or talk. HH often occur here too.

28. Narcolepsy: age of onset Silber 2004, p.97.

29. Narcolepsy Biology

30. Narcolepsy Treatments: • SLEEPINESS: • Stimulants (noradrenalin receptor agonists): amphetamine, methylphenidate, modafinil. • CATPLEXY: • Antidepressants that increase serotonin and or noradrenaline and block ACh, i.e. clomipramine, venlafaxine.

31. Narcolepsy versus Schizophrenia Apparent “Schizophrenic” Hallucinations Actually Daytime REM sleep intrusion Narcolepsy • 90% aassociation of narcolepsy with an HLA antigen DNA fragment (DQB1*0602) allows “inverse” screening of schizophrenics for narcolepsy • Narcolepsy is detectable in sleep lab (MSLT) but pt. must be medication-free for at least 3 weeks.

32. Worm in lateral hypothalamus causing narcolepsy.(neurocysticercosis)J. Clin. Sleep Med. 1(1) 2005, p. 41.

33. Obstructive Sleep Apnea

35. Normal

36. Sleep Apnea

37. OSA Clinical Symptoms

38. Clinical Applicability – Apnea • Sleep apnea and depression share clinical features; apnea can produce secondary depression. • Serious sleep apnea can cause sufficient impairment to suggest dementia; severe snoring in a “demented” patient could be a treatable illness. • Apnea or PLMD can cause sleep deprivation which can cause relapse of mania or depression.

39. Restless Legs Syndrome / Periodic Limb Movement Disorder(RLS-PLMD)

40. Periodic Limb Movement Disorder

41. RLS – PLMD: neurochemistry • Likely due to iron deficiency in basal ganglia (Fe++ is co-factor for enzymes that synthesize DA). • May predict onset of “syn-nuclein-opathies” (REM behaviour disorder, PSP, Parkinson’s, Lewy Body dementia).

42. SYMPTOMS Late evening / night Legs cramp, squirm, move by themselves Multiple awakenings “Charley Horses” Can’t tolerate legs being immobilized Worse in elderly TREATMENT Check Fe, ferritin, B12, folate Dopamine agonists (L-DOPA, ropinirole, pramipexole) Benzodiazepines or opiates now 2nd line Quinine obsolete RLS – PLMD: Sx and Tx

43. Polysomnographic Abnormalities In Psychiatric Patients

44. Sleep Abnormalities in Psychiatry Benca, 1992 • Meta-analysis of sleep in all major psychiatric disorders showed affective disorders had the largest and most consistent differences from controls. Kaneko, 1981 • Extremely short nocturnal REM latency is common to both psychiatric disorders and narcolepsy

45. Psychiatric Sleep Measurements • Sleep Latency (SL) – sleep onset defined as first 3 contiguous 30-sec. pages of Stage 1 sleep • REM Latency (RL) – time from sleep onset to first epoch of REM sleep • REM Latency Minus Awake (RLMA) – subtract any interposed pages of waking from the RL • Eye Movement Density in REM Sleep(REM Density, RD) – the actual number of eye movements divided by minutes spent in REM

46. REM Latency (RL & RLMA) • RL varies inversely with age & is highly prevalent in affective disorders. • RLMA has statistical properties that are superior to RL (smaller variance, more normal distribution). • RL is shortened by cholinergic agonists (arecoline, pilocarpine, physostigmine). • Prolonged by anticholinergics (benztropine, trihexyphenidyl, diphenhydramine).

47. MDD: sleep features • Long initial insomnia, early morning wakening • Shallow sleep, easily awakened • Non-refreshing sleep • Short RL & RLMA; normalized by SSRI (antidepressants are REM suppressants because they increase neurotransmission in serotonergic and adrenergic pathways). • High REM density (also a good predictor of eventual depression in a never-ill person)

48. MDD (cont.) • Some powerful sleep mechanism underlies the expression of depression • Total sleep deprivation or selective REM deprivation dramatically improves mood of severely depressed patients (benefit is lost after one night’s sleep or even short nap) • Amount of Non-REM sleep in nap predicts worsening of mood

49. Bipolar Disorder vs. MDD • MDD patients typically have reduced total night sleep, but normal day alertness • Depressed bipolar patients in often have excess sleep (up to 18 hours/day), crushing fatigue when awake, ravenous appetite, & weight gain: “atypical depression”. • “Switch process” in bipolars often occurs during sleep.

50. Bipolar Disorder vs. MDD Excessive sleeping Crushing fatigue Extreme appetite Actually Depressed Phase of Bipolar Disorder “Atypical Depression” DDx: Narcolepsy, Idiopathic Hypersomnolence