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SAD Presentation Copy Winter Is Coming How to Recognize and Treat Seasonal Affective Disorder Karl Lanocha, MD November 8, 2017 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 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 Clinical Features • Sadness, irritability, mood reactivity • Lethargy, increased sleep • Social withdrawal • Carbohydrate craving, weight gain • Cognitive problems, psychomotor slowing Epidemiology • Female > Male (4:1) • Incidence correlates with latitude Tropic of Cancer 30° N Lat No SAD Tropic of Capricorn 30° S Lat Scientific American Mind, Vol 16, Nr 3, 2005 NH 10% Portland 10% NY 7% 45° N Lat Halfway Between Equator and North Pole MD 5% 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 52bc835a15d22daeadf44fd316dd2a25.jpg 800×720 pixels 10/28/17, 1)18 PM Vitamin D synthesis https://i.pinimg.com/originals/52/bc/83/52bc835a15d22daeadf44fd316dd2a25.jpg Page 1 of 1 Etiology • Neurotransmitters • Genetic polymorphisms • Hormonal factors • Psychological factors • Circadian rhythm dysregulation Neurotransmitter Factors • Serotonin turnover decreases during winter • Light therapy reverses tryptophan depletion • SSRIs shown to be effective 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 Hormonal Factors • Prolonged nocturnal melatonin release during winter months • Analogous to hibernating animals • SAD may be a vestigial form of hibernation 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 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 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 Normal Phase vs. SAD Phase Delays 12916_2012_744_MOESM3_ESM.tiff 2,835×1,658 pixels 11/3/17, 2(33 PM https://static-content.springer.com/esm/art%3A10.1186%2F1741-7015-11-79/MediaObjects/12916_2012_744_MOESM3_ESM.tiff Page 1 of 1 Assessment • SIGH-SAD (Structured Interview Guide for Hamilton Depression Rating Scale—Seasonal Affective Disorder Version) • SPAQ (Seasonal Pattern Assessment Questionnaire) SIGH-SAD: Atypical Symptoms • Social withdrawal • Increased eating • Fatiguability • Carbohydrate craving • Hypersomnia • Weight gain • Increased appetite • Reverse diurnal variation (afternoon slump) SPAQ: Global Seasonality Score (GSS) SPAQ: Symptom Severity GSS >11 + moderate symptoms = SAD GSS 9-10 + mild symptoms = s-SAD Treatment • Light therapy • Dawn simulation • Bright light therapy • Antidepressant medication • SSRIs, bupropion • Other • Exercise, CBT 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 Phototherapy Uses • Ultraviolet: psoriasis, vitiligo, acne, atopic dermatitis • Visible: • neonatal jaundice • circadian rhythm disorders • jet lag • mood disorders Electromagnetic Spectrum Human Circadian Rhythms 1024px-Biological_clock_human.svg.png 1,024×529 pixels 10/28/17, 10)38 AM cortisol https://upload.wikimedia.org/wikipedia/commons/thumb/3/30/Biological_clock_human.svg/1024px-Biological_clock_human.svg.png Page 1 oF 1 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 Photoperiod 23 h 56 m 4.1 sec 12916_2012_744_MOESM1_ESM.tiff 2,835×4,169 pixels 11/3/17, 2(02 PM https://static-content.springer.com/esm/art%3A10.1186%2F1741-7015-11-79/MediaObjects/12916_2012_744_MOESM1_ESM.tiff Page 1 of 1 F1.large.jpg 1,280×812 pixels 10/28/17, 10)34 AM 400-700 nm (ipRGCs) http://www.neurology.org/content/71/8/594/F1.large.jpg Page 1 of 1 Retinohypothalamic Pathway Suprachiasmatic Nuclei Lateral Geniculate Nucleus Right Retina Optic Chiasm Left Retina Human Melanopsin Photoactive Tetrapyrrole Chromophores Humoral Phototransduction via CO and NO 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 SAD Phase Advances 12916_2012_744_MOESM3_ESM.tiff 2,835×1,658 pixels 11/3/17, 2(33 PM https://static-content.springer.com/esm/art%3A10.1186%2F1741-7015-11-79/MediaObjects/12916_2012_744_MOESM3_ESM.tiff Page 1 of 1 MORNINGNESS-EVENINGNESS QUESTIONNAIRE Self-Assessment Version (MEQ-SA)1 Name: _____________________________ Date: ________________________ For each question, please select the answer that best describes you by cir cling 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. Timing of Morning Light Therapy Based on MEQ Score MEQ Score Start Time (hours) 16-18 0845 19-22 0830 23-26 0815 27-30 0800 31-34 0745 35-38 0730 39-41 0715 42-45 0700 46-49 0645 50-53 0630 54-57 0615 58-61 0600 62-65 0545 66-68 0530 69-72 0515 73-76 0500 77-80 0445 81-84 0430 85-86 0415 Dawn Simulator 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) 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) Radiant Energy Source Temperatures Overcast Sky Coals Candle100 W bulbSunrise 2 hr after sunrise or 1,400 K 1,900 K 2,900 K 3,100 K 2 4,000hr befor K sunset7,000 K 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) Side Effects • Headache • Eye strain • Restlessness/agitation • Hypomania • Photosensitivity reactions • Possible menstrual effects 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 Beneficial vs. Harmful Light Memory Mood brain1.png 595×439 pixels 10/28/17, 10)33 AM http://circadianlight.com/images/icons/brain1.png Page 1 of 1 How-smartphone-light-affects-your-body-and-brain-full-infographic.jpg 1,200×1,282 pixels 10/28/17, 10)30 AM http://passwordincorrect.com/wp-content/uploads/2016/11/How-smartphone-light-affects-your-body-and-brain-full-infographic.jpg Page 1 of 1 Medication • Bupropion and SSRIs shown to augment effects of light therapy • Consider
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