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““Bright Nights”Bright Nights”
Seasons and Reasons:Seasons and Reasons:New Perspectives on Seasonal New Perspectives on Seasonal
Affective Disorder (S.A.D.)Affective Disorder (S.A.D.)
John F. Greden, M.D.John F. Greden, M.D.Rachel Upjohn Professor of Psychiatry and Clinical Rachel Upjohn Professor of Psychiatry and Clinical
NeurosciencesNeurosciencesChair, Department of PsychiatryChair, Department of Psychiatry
Executive Director, Comprehensive Depression CenterExecutive Director, Comprehensive Depression CenterResearch Professor, Molecular and Behavioral Research Professor, Molecular and Behavioral
Neurosciences InstituteNeurosciences Institute
January 30, 2007January 30, 2007Depression Center and Depression Center and Ambulatory Psychiatry Ambulatory Psychiatry
Disclosure StatementDisclosure StatementJohn F. Greden, M.D.John F. Greden, M.D.
Scientific Advisory Functions During Past Two Years– Cyberonics– Eli Lilly and Co.– GSK– Neuronetics– Pfizer – Wyeth
Society Advisory Boards and Foundations– DBSA (Depression and
Bipolar Support Alliance)
– American Foundation for Suicide Prevention
No corporate contracts or research projects supported by pharmaceutical companies
Stock Holding: Originus
There are no perceived conflicts of interest in this presentation
Agenda and TimetableAgenda and Timetable
Chronobiological Rhythms: What are they?
Symptoms of S.A.D. Treatments How to tell S.A.D. from other
disorders New Research Discussion with panel
The University of MichiganComprehensive
Depression Center
ParticipantsParticipants
John F. Greden, M.D. Neera Ghaziuddin, M.D. Todd Arnedt, Ph.D. Bruce Gimbel, M.D. The Ann Arbor District Library Melvin McInnis, M.D. Trish Meyer YOU!
Other names for S.A.D.Other names for S.A.D.
Winter DepressionSeasonal DepressionMajor Depression with a Seasonal
PatternChronobiological abnormality
OverviewOverview
We have biological clocks– Influenced by rotation of earth and tilting of earth
Our biological clocks are not perfect, and sometimes get “broken” – Our day is 24 hours and 11 minutes (Czeisler, 1999)
Some of us get clinical symptoms (Seasonal Affective Disorder or S.A.D.)
“Broken clocks” can be more serious, linked with depression and bipolar (manic-depression) disorders
Simple illustration of our clocksSimple illustration of our clocks
Suprachiasmatic Nucleus of Hypothalamus in Suprachiasmatic Nucleus of Hypothalamus in the brain is the major biological clock for the brain is the major biological clock for mammals, set by our genes and environmentmammals, set by our genes and environment
Symptoms of S.A.D. (Seasonal Symptoms of S.A.D. (Seasonal Affective Disorder)Affective Disorder)
Predictable onset (September-October) and offset (March-April) with absence of symptoms in summer
Carbohydrate/sweet craving, weight gain Hypersomnia (sleeping too much) Fatigue, “heavy limbs,” no energy Sadness, loss of pleasure, depression Irritability, more alcohol use Decreased libido, interest in sex
Features and Mechanisms of S.A.D. Features and Mechanisms of S.A.D. BMJ 1998;317:1704-1707 Hastings: The brain, circadian rhythms, and clock genes
How common?– 4 - 6 % with “full-blown”
SAD– 10 – 20 % of Americans
have some symptoms– 75% are women– Peak between ages 18 –
30; can occur in children and adolescents
Where?– More frequent as we get
closer to the poles– Rare within 30 degrees of
equator – Light exposure is
important
Features and Mechanisms of S.A.D. Features and Mechanisms of S.A.D. Hastings: The brain, circadian rhythms, and clock genes BMJ 1998:317:1704-1707
Decreased exposure to sunlight makes biological clocks run more slowly
Sleep and hormone cycles may get delayed, run more slowly in winter– Neurotransmitters
(chemical messengers) changed by light
• Serotonin• Norepinephrine• Dopamine
– Explains why both light and medications help
Features and Mechanisms of S.A.D.:Features and Mechanisms of S.A.D.:Special ProblemsSpecial Problems
Travel across time zonesChanging from day to night shiftsCo-occurring disorders
– Alzheimer’s – Bipolar Disorder– Diabetes?
TreatmentsTreatments
Phototherapy (Bright Lights)Antidepressant MedicationsExerciseMoving?
Phototherapy Treatment of S.A.D.Phototherapy Treatment of S.A.D.
Phototherapy: White fluorescent light tubes – Plastic screen blocks ultraviolet rays– Light intensity at least 10,000 Lux for 30 minutes in the
morning– Don’t look directly at light– 1 to 2 feet away– No tanning booths!– Improvements in 4 to 21 days– Symptoms come back if phototherapy stopped
Get Ophthalmology consult if you have eye problems
Minor side effects and precautions of Minor side effects and precautions of PhototherapyPhototherapy Eye strain Headache Irritability Insomnia Rarely, hypomania
or mania
Phototherapy Treatment and Phototherapy Treatment and Prevention of S.A.D.Prevention of S.A.D. Start using light box in October Go outside! Sit by windows when possible Regular sleep pattern Limit alcohol Ask your family or friends to help monitor
severity of your symptoms– If more severe than S.A.D. and into episode of
depression or mania, see your clinician
Antidepressant medication Rx for Antidepressant medication Rx for S.A.D.S.A.D. Sertraline [Zoloft] (N = 187) and fluoxetine
[Prozac] (N = 68) both shown effective Bupropion XL [Wellbutrin] (N = 1042) shown
effective and approved by F.D.A. in 2006– Allows use for the prevention of major depressive
episodes in adult patients with a history of seasonal affective disorder (SAD).
– 3 placebo-controlled clinical trials– 150-mg once daily in the morning and titrated to
300 mg/day (target dose) after 1 week if tolerated. Start in autumn
Major Depressive Disorder (MDD) Major Depressive Disorder (MDD) and S.A.D.and S.A.D. MDD often gets worse in winter
– This is NOT just S.A.D.
M.D.D. should be treated with medications and C.B.T or I.P.T.– Phototherapy may be used to help seasonal
flare-ups but light therapy should not replace other needed treatments
Consult your clinician
Consider light therapy as first-line Consider light therapy as first-line whenwhen
Depression is mildAntidepressants failGood compliance, able to make time
commitmentMedications not wanted, e.g.,
pregnancy, breast feedingCost variables: Greater initial cost but
insurance may be a variable
Consider medications as first-line Consider medications as first-line whenwhen
More severe depression Depression episodes during summer, don’t
end in spring Suicidal No response to light therapy Relative contraindications to light therapy
(e.g., retinal disease, photosensitizing drug) Cost variables
Bipolar Disorder, disturbed rhythms, Bipolar Disorder, disturbed rhythms, and S.A.D.and S.A.D. Bipolar patients with S.A.D. should receive mood
stabilizers Lithium (and valproic acid) likely fixes broken
body clocks in bipolar disorder– Blocks an enzyme (GSK-3ß) and stabilizes a
receptor( Rev-erbα) that leads to the rhythmic turning-on of the protein Bmal1, which fixes the clock cycle
– A version of the GSK-3ß gene has been linked to a milder, more easily treatable form of bipolar disorder.
Yin l, Wang J, Klein PS, Lazar MA, Nuclear receptor rev-erbα is a critical lithium-sensitive component of the circadian clock. Science, Vol. 311. no. 5763, pp. 1002 - 1005.
New Advances in S.A.D.New Advances in S.A.D.
We have learned a great deal Treatments are available Be persistent New “Advances”
– Clock Genes– Possible linkage between genes, weight gain,
and season of birth– Mechanisms of mood stabilizers– We can discuss if time permits
Your QuestionsYour Questions
Additional SlidesAdditional Slides
“Advances”– We can discuss if time permits
Selected ReferencesSample questions
New Advances in S.A.D.New Advances in S.A.D.
Clock Genes– Explain many things
• E.g., “Larks” vs. “Owls”
– Effects of lithium and mood stabilizers in bipolar disorder
Possible linkage between genes, weight gain, and season of birth
Are S.A.D., Weight Gain, Insulin Receptors, Are S.A.D., Weight Gain, Insulin Receptors, and Spring Birth Related Genetically? and Spring Birth Related Genetically? (Levitan et al, 2006)(Levitan et al, 2006)
When periodic famine and loss of food supply occur, weight gain improves survival– Seasonal famines once an issue
When food is constantly available, weight gain produces obesity– Periodic weight gain once adaptive, no
longer!
Are S.A.D., Weight Gain, Insulin Are S.A.D., Weight Gain, Insulin Receptors, DRD4 Gene and Spring Receptors, DRD4 Gene and Spring Birth Related Genetically? (Levitan et al, Birth Related Genetically? (Levitan et al, 2006)2006)Spring birth interacts with DRD4
gene– Linked to anticipation of seasonal
famines for those in northern latitudes?DRD4 x Insulin Gene x Birth season
interact to promote weight gain, and possibly S.A.D.
Vision: A National Network of Depression Vision: A National Network of Depression Centers will help us study large samples to better Centers will help us study large samples to better understand S.A.D. and other disordersunderstand S.A.D. and other disorders
Cancer Center Network
A National Network of Depression Centers:
Founding Members to Date
University of Michigan (Organizing Center)University of Texas Southwestern Duke UniversityJohns Hopkins UniversityUniversity of California San FranciscoUniversity of WashingtonUniversity of CincinnatiStanford UniversityCornell UniversityMassachusetts General Hospital(Brown University)(Columbia University)
Topics for discussionTopics for discussion
Where can I get lights? How can I better regulate my sleep? Can bright lights be used for children and
adolescents? Do bright lights help Major Depressive
Disorder? Bipolar Disorders? When should medications and bright
lights be used together?
Topics for discussionTopics for discussion
What about chocolate? Caffeine?Can I build my own light box?Will we ever have gene therapy to
treat S.A.D.Do mood stabilizers help S.A.D. or
seasonal flare-ups of depression or bipolar?
ReferencesReferences Rosenthal NE, Sack DA, Gillin JC, et al: Seasonal affective disorder: a description of the
syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 1984; 41:72-80.
Bauer MS, Dunner DL: Validity of seasonal pattern as a modifier for recurrent mood disorders for DSM-IV. Compr Psychiatry 1993;34:159-70.
Eastman CI, Young MA, Fogg LF, et al: A placebo-controlled trial of bright light treatment for winter seasonal affective disorder. Arch Gen Psychiatry 1998; 883-9.
Gallin PF, Terman M, Reme CE, et al: Opthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Am J Ophthalmol 1995; 119:202-10.
Kogan AO, Guilford PM: Side effects of short-term l0,000-lux light therapy. Am J Psychiatry 1998; 155:293-294.
Lam RW (ed.): Seasonal Affective Disorder and Beyond. Light Treatment for SAD and Non-SAD Conditions. Washington DC, American Psychiatric Press, 1998.
Lam RW, Gorman CP, Michalon M, et al: Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry 1995; 152:1765-70.
ReferencesReferences Lewy AJ, Bauer VK, Cutler NL, et al: Morning vs. evening light treatment of patients with winter depression. Arch Gen Psychiatry
1998;55:890-6.
Moscovitch A, Blashko C, Wiseman R, et al: A double-blind, placebo-controlled study of sertraline in patients with seasonal affective disorder. New Research Abstracts, 151st Meeting of the American Psychiatric Association, 1995.
Tam EM, Lam RW, Levitt AJ: Treatment of seasonal affective disorder: a review. Can J. Psychiatry 1995; 40:457-66.
Terman M, Terman JS, Ross DC: A controlled trial of timed bright light and negative air ionization for treatment of seasonal affective disorder. Arch Gen Psychiatry 1998; 55:875-82.
Terman M, Terman JS, Quitkin FM, McGrath PJ, Stewart JW, Rafferty B: Light therapy for seasonal affective disorder. A review of efficacy. Neuropsychopharmacology 1989; 2: 1-22.
INFORMATION RESOURCES FOR SAD Society for Light Treatment and Biological Rhythms (SLTBR). SLTBR is an international, not-for-profit society dedicated to fostering
research, professional development and clinical applications in the fieldsof light therapy and biological rhythms.
Contact: Stephanie Argraves, Executive Director, SLTBR842 Howard Avenue, New Haven, CT, USA 06519e-mail: [email protected] site: http://www.websciences.org/sltbr/(includes a list of Corporate Members that manufacture and distribute lightSevices)
University of Michigan Depression Center www.mail.med.umich.edu