Winter Is Coming - PDF Document

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  1. Winter Is Coming How to Recognize and Treat Seasonal Affective Disorder Karl Lanocha, MD November 8, 2017

  2. Objectives • Clinical presentation, epidemiology, and pathophysiology of seasonal affective disorder (SAD), winter type • Light therapy as treatment for SAD • Mechanism of action of light therapy • Optimum dosing and timing based on chronotype and circadian rhythm • Recognize and limit side effects

  3. Definition • Depression that occurs during a specific season, usually winter • At least two episodes of seasonal mood disorder • Seasonal episodes outnumber non-seasonal episodes • Unclear if a discreet diagnostic entity

  4. Clinical Features • Sadness, irritability, mood reactivity • Lethargy, increased sleep • Social withdrawal • Carbohydrate craving, weight gain • Cognitive problems, psychomotor slowing

  5. Epidemiology • Female > Male (4:1) • Incidence correlates with latitude

  6. Tropic of Cancer 30° N Lat No SAD Tropic of Capricorn 30° S Lat Scientific American Mind, Vol 16, Nr 3, 2005

  7. NH 10% Portland 10% NY 7% 45° N Lat MD 5% Halfway Between Equator and North Pole San Francisco 5% 38° N Lat San Diego 2% FL 1% 30° N Lat AK >10% HI 0% 54-71° N Lat 18-28° N Lat

  8. Vitamin D synthesis

  9. Etiology • Neurotransmitters • Genetic polymorphisms • Hormonal factors • Psychological factors • Circadian rhythm dysregulation

  10. Neurotransmitter Factors • Serotonin turnover decreases during winter • Light therapy reverses tryptophan depletion • SSRIs shown to be effective

  11. Genetic Factors • Serotonin transporter promoter region (5- HTTLPR) • Serotonin 2A receptor (5-HT2A-1483G/A) • Dopamine-4 receptor gene (DRD4) seven- repeat allele • Neuronal PAS domain protein 2 (NPAS2) • P10L missense mutation in Opn4 melanopsin gene

  12. Hormonal Factors • Prolonged nocturnal melatonin release during winter months • Analogous to hibernating animals • SAD may be a vestigial form of hibernation

  13. Psychological Factors • Physiological vulnerability to vegetative symptoms and psychological vulnerability to affective and cognitive symptoms in response to vegetative symptoms • Behavioral disengagement in fall decreased potential for enjoyment decreased positive reinforcement in winter

  14. Chronobiological Factors: Photon Count Hypothesis • Vulnerability to shorter photoperiods or decreased light intensity • Symptom severity correlated to minutes of sunshine and global radiation • Dose response relationship between light intensity and symptom improvement

  15. Chronobiological Factors: Phase Shift Hypothesis • Sleep-wake phase delay • Longer sleep phase • Magnitude of antidepressant response to light therapy correlates to degree of phase advance

  16. 12916_2012_744_MOESM3_ESM.tiff 2,835×1,658 pixels Normal Phase vs. SAD Phase Delays 11/3/17, 2(33 PM

  17. Assessment • SIGH-SAD (Structured Interview Guide for Hamilton Depression Rating Scale—Seasonal Affective Disorder Version) • SPAQ (Seasonal Pattern Assessment Questionnaire)

  18. SIGH-SAD: Atypical Symptoms • Increased eating • Social withdrawal • Carbohydrate craving • Fatiguability • Weight gain • Hypersomnia • Reverse diurnal variation (afternoon slump) • Increased appetite

  19. SPAQ: Global Seasonality Score (GSS)

  20. SPAQ: Symptom Severity GSS >11 + moderate symptoms = SAD GSS 9-10 + mild symptoms = s-SAD

  21. Treatment • Light therapy • Dawn simulation • Bright light therapy • Antidepressant medication • SSRIs, bupropion • Other • Exercise, CBT

  22. Phototherapy • Definition: Use of ultraviolet radiation or visible light for therapeutic purposes • UV B (290-320 nm) is absorbed by epidermis and superficial dermis • UV A (320-400 nm) can reach mid or lower dermis • Visible light: (350-800 nm) can reach deep layers of dermis

  23. Phototherapy Uses • Ultraviolet: psoriasis, vitiligo, acne, atopic dermatitis • Visible: • neonatal jaundice • circadian rhythm disorders • jet lag • mood disorders

  24. Electromagnetic Spectrum

  25. Human Circadian Rhythms 1024px-Biological_clock_human.svg.png 1,024×529 pixels 10/28/17, 10)38 AM cortisol

  26. SUPRACHIASMATIC NUCLEUS • Extremely small, only about 10,000 neurons • Primary Zeitgeber (“time giver”) • All living creatures have analogous pacemakers • Light entrainment to photoperiod of 23 h 56 m 4.1 s

  27. Photoperiod 23 h 56 m 4.1 sec

  28. 400-700 nm (ipRGCs)

  29. Retinohypothalamic Pathway Suprachiasmatic Nuclei Lateral Geniculate Nucleus Right Retina Optic Chiasm Left Retina

  30. Human Melanopsin

  31. Photoactive Tetrapyrrole Chromophores

  32. Humoral Phototransduction via CO and NO

  33. Timing is Important • Circadian rhythm phase advance is necessary for clinical effect • SCN is most sensitive in early morning • 7.5-9.5 hr after DLMO • ~1 hr after cTmin • Less sensitive window 3-5 hours before DLMO

  34. SAD Phase Advances 12916_2012_744_MOESM3_ESM.tiff 2,835×1,658 pixels 11/3/17, 2(33 PM

  35. MORNINGNESS-EVENINGNESS QUESTIONNAIRE Self-Assessment Version (MEQ-SA)1 Name: _____________________________ Date: ________________________ For each question, please select the answer that best describes you by circling the point value that best indicates how you have felt in recent weeks. 1.Approximately what time would you get up if you were entirely free to plan your day? [5] 5:00 AM–6:30 AM (05:00–06:30 h) [4] 6:30 AM–7:45 AM (06:30–07:45 h) [3] 7:45 AM–9:45 AM (07:45–09:45 h) [2] 9:45 AM–11:00 AM (09:45–11:00 h) [1] 11:00 AM–12 noon (11:00–12:00 h) 2.Approximately what time would you go to bed if you were entirely free to plan your evening? [5] 8:00 PM–9:00 PM (20:00–21:00 h) [4] 9:00 PM–10:15 PM (21:00–22:15 h) [3] 10:15 PM–12:30 AM (22:15–00:30 h) [2] 12:30 AM–1:45 AM (00:30–01:45 h) [1] 1:45 AM–3:00 AM (01:45–03:00 h) 3.If you usually have to get up at a specific time in the morning, how much do you depend on an alarm clock? [4] Not at all [3] Slightly [2] Somewhat [1] Very much 1Some stem questions and item choices have been rephrased from the original instrument (Horne and Östberg, 1976) to conform with spoken American English. Discrete item choices have been substituted for continuous graphic scales. Prepared by Terman M, Rifkin JB, Jacobs J, White TM (2001), New York State Psychiatric Institute, 1051 Riverside Drive, Unit 50, New York, NY, 10032. January 2008 version. Supported by NIH Grant MH42931. See also: automated version (AutoMEQ) at www.cet.org. Horne JA and Östberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. International Journal of Chronobiology, 1976: 4, 97-100.

  36. Timing of Morning Light Therapy Based on MEQ Score MEQ Score Start Time (hours) 16-18 19-22 23-26 27-30 31-34 35-38 39-41 42-45 46-49 50-53 54-57 58-61 62-65 66-68 69-72 73-76 77-80 81-84 85-86 0845 0830 0815 0800 0745 0730 0715 0700 0645 0630 0615 0600 0545 0530 0515 0500 0445 0430 0415

  37. Dawn Simulator

  38. Technical Considerations •Lamp type (output and spectrum), filter, ballast frequency (for fluorescent lamps), size and positioning of radiating surface, heat emission, etc. •Lux meters vary in sensitivity across the visible spectrum and the size of the illuminated field •Lamps vary in spectral distribution and photoreceptors are differentially sensitive to discrete wavelength bands •Alternative measure of intensity is the irradiance or power (in μw/cm2)

  39. Apparatus details: downward-tilted, smoothly diffusing, ultraviolet absorbing, polycarbonate screen; high-frequency- ballasted soft-white fluorescent lamps at 5,000 Kelvin color temperature (same as sky on a clear day 2 h after sunrise or 2 h before sunset); 10,000 lux (same as sky at noon on overcast day) at 60 cm (24 in)

  40. Radiant Energy Source Temperatures Overcast Sky Coals Candle 100 W bulb Sunrise 2 hr after sunrise or 2 hr befor sunset 4,000 K 1,400 K 1,900 K 2,900 K 3,100 K 7,000 K

  41. Light Therapy Protocol • 30 min per day • Early morning required, late afternoon optional • Daily treatment until response, then every other day • Spontaneous remission in early May • Treatment may be discontinued abruptly (no tapering necessary)

  42. Side Effects • Headache • Eye strain • Restlessness/agitation • Hypomania • Photosensitivity reactions • Possible menstrual effects

  43. Ocular Safety • No acute or long term adverse effects in unmedicated patients with normal oculoretinal status • Potential damage to lens, cornea, retina, and pigment epithelium with • blue light < 450 nm • infrared (700 nm-1 mm)—90% of incadenscent bulb output