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The Role of Diet in Sleep and Depression
Makena Dyer, B.Sc. and Joannie Dobbs, PhD, CNSHuman Nutrition, Food & Animal Sciences
University of Hawai‘i at MānoaPCCHA Annual Conference, October 13-15, 2014, Seattle, WA
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Learning Objectives
• Describe the relationship between sleep difficulty and depression
• Discuss research relating essential nutrients to sleep difficulty and depression
• Identify biomarkers linked to sleep difficulty and depression
• Identify appropriate/helpful questions regarding a patient’s diet that could indicate a role in sleep and depression issues
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The Partnerships in Mental Health
• Dr Alan Hawk, M.D.
– Psychiatrist for University Health Services at Mānoa triggered the initial exploration into the diet / mind relationship
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The Partnerships in Mental Health
• Discussions with Dr. Hawk and Sue Myhre – nurse practitioner led to the development of a nutrition assessment tool. This tool incorporated many of the health conditions that are seen by multiple practitioners but could have a link to subclinical malnutrition.
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The Role of Diet in Mental Health
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The Role of Diet in Mental Health
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Common Nutritional Issues in College Students
• Nutritional deficiencies– Iron– Potassium– Protein– Vitamin C
• Calorie restriction
Shams et al. Singapore Med J. 2010; 51(2): 116-119Ouellette et al. J Am Coll Nutr. 2012; 31(5): 301-10Kolodinsky et al. J Am Diet Assoc. 2007; 107(8): 1409-13Johnston et al. J Am Coll Health. 1998; 46(5): 209-13Butler et al. Am J Health Behav. 2004; 28(1): 24-32
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DSM-5 Criteria for Insomnia • “Dissatisfaction with sleep quantity or quality”
– Difficulty falling asleep– Difficulty staying asleep– Waking up early
• Disrupts work and social functioning• Occurs at least 3 nights per week for at least 3 months• Occurs even if circumstances permit sleep• Not related to other medical conditions or psychiatric
drug use
Adapted from The Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition.: DSM-5 by American Psychiatric Association
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Estimated Prevalence of Insomnia• Other diagnostic criteria for insomnia
– International Classification of Diseases-10
• Overall prevalence of 10-40% in the U.S.• Prevalence in younger adults (Kessler 2011)
– 23.9% of adults 18-29– 24.2% of adults 30-44
Mai and Buysse. Sleep Med Clin. 2008; 3(2): 167-164 Unbehaun et al. Nat Sci Sleep. 2010; 2: 127-138 Kessler et al. Sleep. 2011; 34(9): 1161–1171
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Sleep Difficulty in College Students
• 38% of students had poor quality sleep (Lund et al. 2010)
• 9.5% of students had chronic insomnia (Taylor et al. 2013)
Lund et al. J Adolesc Health. 2010; 46(2): 124-32Taylor et al. Behav Ther. 2013; 44(3): 339-48
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DSM-5 Criteria for Major Depressive Disorder
At least five of the following symptoms
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DSM-5 Criteria for Major Depressive Disorder
• Occurs in the same two-week period• Impairs work and social functioning• Not related to other medical conditions or
drug use
Adapted from The Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition.: DSM-5 by American Psychiatric Association
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Estimated Prevalence and Incidence of Major Depressive Disorder
• Lifetime prevalence in the U.S.: 16.2% of adults (about 34 million) (Kessler 2003)– 34 million individuals is almost equal to entire
population of Canada
• Major depressive episode in past year in young adults (SAMHSA 2013)– 8.9% of adults 18-25 (21.5 million)– 7.6% of adults 26-49 (18.4 million)
Kessler et al. JAMA. 2003; 289(23): 3095-105http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo02a-eng.htmSubstance Abuse and Mental Health Services Administration, NSDUH Series H-47, HHS Publication No. (SMA) 13-4805. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.
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Depression in College Students• Healthy Minds Study (2007 and 2009)
– 17% had signs of depression– 9% had major depressive disorder– 8.5% had taken antidepressants in past year
• Lifetime prevalence of suicidal thoughts in college students (Drum et al. 2009)– 18% of undergraduates– 15% of graduate students
Hunt and Eisenberg. J Adolesc Health. 2010; 46(1): 3-10Eisenberg et al. J Nerv Ment Dis. 2011; 199: 301-308Drum et al. Prof Psychol-Res Pr. 2009; 40(3): 213-222
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• Medical spending– Prescription medication
• $1.6 billion nationwide for prescription sleep aids in 2011 (Willyard 2012)
• $2.3 billion in Medicaid spending for antidepressants in 2004 (Chen et al. 2008)
– Over-the-counter drugs• $326 million for OTC sleep aids in 1995
(Martin 2004)
Costs of Sleep Difficulty and Depression
Willyard. Nat Med. 2012; 18(7): 996Chen et al. Res Social Adm Pharm. 2008; 4(3): 244-57Martin et al. Sleep Med Rev. 2004; 8(1): 63-72
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Costs of Sleep Difficulty and Depression
• Economic losses (lost productivity)– Up to $41 billion for insomnia
(Martin 2004)– Up to $33 billion for depression
(Wang 2003)
Martin et al. Sleep Med Rev. 2004; 8(1): 63-72Wang et al. Int J Methods Psychiatr Res. 2003; 12(1): 22-33
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Costs of Sleep Difficulty and/or Depression
• Increased risk of illnesses– Cardiovascular disease– Type 2 diabetes mellitus– Fibromyalgia– Headache– Hypothyroid
Shankar et al. PLoS One. 2010; 5(11): e14189Ariyo et al. Circulation. 2000; 102(15): 1773-9Knol et al. Diabetologia. 2006; 49(5): 837-45Hakkarainen et al. J Epidemiol Community Health 2007; 61: 53-58
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Relationship Between Sleep Difficulty and Depression
• Frequently observed together in patients
• Cause-and-effect relationship not yet determined– Which comes first?– Other causes?
Nutt et al. Dialogues Clin Neurosci. 2008; 10(3): 329-36Wiebe et al. Nat Sci Sleep. 2012; 4: 63-71
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Is There a Connection to Nutrition?
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Role of Nutrients in Sleep and Mood
• Nutrients are involved in biochemical processes
• Important process for sleep and mood is neurotransmitter synthesis
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Neurotransmitters
http://www.macalester.edu/academics/psychology/whathap/ubnrp/meth08/biochemistry/neurotransmitter.htm
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Neurotransmitter Synthesis
Hare 2004
Amino acid
Cofactor: Vitamin B-6
Kuhn et al. J Biol Chem. 1980; 255(9): 4137-4143Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9Hare and Loer. BMC Evol Biol. 2004; 4:24
Cofactors: BH4 (requires folate) and iron
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Hickman 1999
Neurotransmitter Synthesis
Acetyl CoA from pantothenic acid
Methyl group from SAM (requires folate and Vitamin B-12)
Hickman et al. Mol Cell. 1999; 3: 23-32Axelrod and Weissbach. Science. 1960; 131(3409): 1312Bottiglieri. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(7):1103-12.
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Neurotransmitter Synthesis
Amino acid
Hare 2004
Cofactors: BH4 (requires folate) and iron
Cofactor: Vitamin B-6
Cotter and O’Keeffe. Ther Clin Risk Manag. 2006; 2(4): 465-475Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9Hare and Loer. BMC Evol Biol. 2004; 4:24
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Neurotransmitter Synthesis
Cofactor: Copper
Vitamin C keeps copper in
reduced state
Methyl group from SAM (requires folate
and Vitamin B-12) Goridis 2002
Goridis and Rohrer. Nat Rev Neurosci. 2002; 3(7): 531-41Levine et al. J Biol Chem. 1985; 260(24): 12942-7.
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Other Issues with Neurotransmitters and Diet
• Bioavailability is also important– Role of carbohydrates
Benton and Donohoe. Public Health Nutr. 1999; 2(3A): 403-9
↑ Carbohydrate intake
↑ Insulin release
↑ Tryptophan available relative to other amino acids
↑ Tryptophan delivery to the
brain via albumin transport proteins
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Nutrients with Special Importance for Neurotransmitters
MACRO-NUTRIENTS ProteinCarbohydrateFat (omega-3 & 6 fatty acids)Water Micro-NutrientsVitamins Water Soluble B1, B2, Niacin, B6, Folate, B12 Biotin, Pantothenate, C, Choline Fat Soluble A, D, E, K Minerals (Ash) Major Minerals Calcium, Chloride Magnesium, Phosphorus Potassium, Sodium, Sulfur
Trace Minerals Chromium, Cobalt, Copper, Fluoride, Iron, Iodine, Manganese, Molybdenum Selenium, Zinc
Other Trace Minerals Appear to be essential: Arsenic, Boron, Nickel, Silicon
Possibly essential: Cadmium, Lead, Lithium, Aluminium, Bromine, Rubidium, Vanadium Other Food SubstancesCaffeineCholesterolDietary FiberOther Phytochemicals
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Summary of Nutrients with Special Importance to Sleep and Depression
MACRO-NUTRIENTS ProteinCarbohydrateFat (omega-3 & 6 fatty acids)Water Micro-NutrientsVitamins Water Soluble B1, B2, Niacin, B6, Folate, B12 Biotin, Pantothenate, C, Choline Fat Soluble A, D, E, K Minerals (Ash) Major Minerals Calcium, Chloride Magnesium, Phosphorus Potassium, Sodium, Sulfur
Trace Minerals Chromium, Cobalt, Copper, Fluoride, Iron, Iodine, Manganese, Molybdenum Selenium, Zinc
Other Trace Minerals Appear to be essential: Arsenic, Boron, Nickel, Silicon
Possibly essential: Cadmium, Lead, Lithium, Aluminium, Bromine, Rubidium, Vanadium Other Food SubstancesCaffeineCholesterolDietary FiberOther Phytochemicals
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We Wanted to See if the Relationship Between Depression and Insomnia Could be Seen in the
NHANES Studies
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National Health and Nutrition Examination Survey (NHANES)
• Nationwide study on health and nutrition
• 5,000 individuals each year from 15 counties
• Two-year studies since 1999
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NHANES Mobile Exam Center
www.cdc.gov
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NHANES Datasets
Adapted from wwwn.cdc.gov
• NHANES 2005-2006– Demographics Data– Dietary Data– Examination Data– Laboratory Data– Questionnaire Data
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Insomnia and Depression Research Objectives
• Compare nutritional statuses– Individuals with both insomnia and depression– Individuals with neither insomnia nor depression
• Determine what nutrients and biomarkers are most important to understanding these conditions
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Study Sample
• NHANES 2005-2006 and 2007-2008 datasets– Complete sleep and depression data
• Ages 18-35 years• n=2,744
– 1,307 females– 1,437 males
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Dietary Data• 24-hour diet recall
– Multiple pass method– USDA’s Food and Nutrient Database
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Questionnaire Data: Prescription Medications
Antidepressant drug use in past month
http://www.theguardian.com/society/2008/feb/26/mentalhealth.medicalresearch
http://www.webmd.com/drugs/2/drug-35-8095/zoloft-oral/sertraline-oral/details#images/00049490030
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Questionnaire Data: Insomnia
• Sleep Disorders questionnaire– Length of sleep– Sleep disorder diagnosis– Frequency of sleep complaints– Severity of daytime impairment
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Insomnia Criteria for This Research
• Based on DSM criteria• Frequency of “Often” (5-15 times) or
“Almost always” (16-30 times) in past month for one or more of the following:• Trouble falling asleep• Waking up during night• Waking up too early in the morning
Vozoris. J Hypertens. 2013; 31(4): 663-71
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Depression Criteria for This Research
• Patient Health Questionnaire-9 (PHQ-9)– Based on DSM criteria
• Depression = PHQ-9 ≥ 10– Sensitivity of 88% in detecting depression
(Kroenke 2001)
Kroenke et al. J Gen Intern Med. 2001; 16(9): 606-13
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Questionnaire Data: Depression
www.phqscreeners.com
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Data Analysis
• JMP Pro 11– Data mining
software
beckerinfo.net
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NHANES Data in JMP
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Females
Males
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What else did we find about Insomnia and Depression?
• Females are not like males– Greater prevalence in females than males
• May persist even with antidepressant use
• For females, antidepressant use with persistent symptoms is associated with lower intakes of certain nutrients
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TOTAL FEMALESNo
SymptomsInsomnia
onlyDepression
onlyInsomnia and
Depression
(n= 1307) 871 319 54 63
% 66.6% 24.4% 4.1% 4.8%
Antidepressant drug use
No 96.2% 34.3% 6.0% 6.1%
Yes 3.8% 2.3% 0.2% 1.1%
Insomnia and Depression in Females
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TOTAL MALE
No Symptoms Insomnia only
Depression only
Insomnia and Depression
(n = 1437) 1102 262 32 41
% 76.7% 18.2% 2.2% 2.9%
Antidepressant drug use
No 98.3% 23.3% 2.9% 3.5%
Yes 1.7% 0.5% 0.0% 0.2%
Insomnia and Depression in Males
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Body Wt., BMI, Symptoms and Antidepressant Use in Female Subjects
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The following Contour Graphs
present proportional
representations of data density – regardless of the
total n
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The following Contour Graph shows that the group with depression and
insomnia and taking anti-depressants consumed less calories
as a percent of their sedentary energy needs.
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Relationship of Energy Intake to Insomnia and Depression
Antidepressant Drug Use?
No
Yes
n=33n=837 n=52 n=10 2 outliers excluded
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The following Contour Graph shows that the depression and
insomnia group for all ethnicities was abnormal compared to the
other groups.
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Relationship of Energy Intake (by Ethnicity) to Insomnia and Depression
Antidepressant Drug Use?
No
Yes
Mexican-American
Non-Hispanic Black
Other Hispanic
Other Race
Non-Hispanic White
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The following Protein Contour graph shows a similar profile to
inadequate caloric intake. Most depressed females did not consume protein at the 0.8 grams protein/Kg
B.Wt RDA level nor met the 1.6 grams associated with a lower BMI
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Relationship of Insomnia and Depression to Protein Intake
n=33 n=10n=52n=828
Antidepressant Drug Use?
No
Yes
11 outliers excluded
RDA for Protein = 0.8 gm/kg body weight
Recommended Protein Intake for Some Individuals =
1.6 gm/kg body weight
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Foods That Provide Protein
• Animal products– Meats– Fish– Cheese
• Beans*• Nuts*
*Incomplete protein (missing essential amino acids); lower digestibility and higher calories
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Average Protein per Typical Food Serving
Food SourcesNLEA
Serving Size (g)
NLEA Volume per
Serving
Energy (kcal)
Protein (g)Kcal/ g protein
Fish / Chicken / Beef 85 ~ 3 oz. ckd 170 8
2% Cottage Cheese 110 ~ 0.5 oz. cup 100 8
Cheese 30 1 thin slice 110 16Legumes /
Beans 90 ~ 0.5 oz. cup 120 16
Beans - Processed 130 ~ 0.5 oz. cup 150 20
Grains 140 0.6 -1 cup 160 32Nuts 30 ~ 3.5 Tbsp. 190 36
http://www.fda.gov/iceci/inspections/inspectionguides/ucm074948.htm
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The following Contour Graph shows that the depression and
insomnia group for all ethnicities was abnormal compared to the
other groups.
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Relationship of Magnesium Intake to Insomnia and Depression
Antidepressant Drug Use?
No
Yes
n=52 n=10n=32n=836 4 outliers excluded
RDA for Magnesium = 400 mg
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Foods That Provide Magnesium
• Nuts• Beans• Spinach
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The following DHA Contour Graph shows that the depression and insomnia group on an average
consumes less DHA compared to the other groups.
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Relationship of DHA Intake Insomnia and Depression
Antidepressant Drug Use?
No
Yes
n=10n=33 n=51n=815 26 outliers excluded
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Foods That Provide DHA
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Summary of Nutrients with Special Importance to Sleep and Depression
MACRO-NUTRIENTS ProteinCarbohydrateFat (omega-3 & 6 fatty acids)Water Micro-NutrientsVitamins Water Soluble B1, B2, Niacin, B6, Folate, B12 Biotin, Pantothenate, C, Choline Fat Soluble A, D, E, K Minerals (Ash) Major Minerals Calcium, Chloride Magnesium, Phosphorus Potassium, Sodium, Sulfur
Trace Minerals Chromium, Cobalt, Copper, Fluoride, Iron, Iodine, Manganese, Molybdenum Selenium, Zinc
Other Trace Minerals Appear to be essential: Arsenic, Boron, Nickel, Silicon
Possibly essential: Cadmium, Lead, Lithium, Aluminium, Bromine, Rubidium, Vanadium Other Food SubstancesCaffeineCholesterolDietary FiberOther Phytochemicals
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Questions to Ask in Clinic
• Are you restricting calories?– Concerned about weight?
• What drives your food choices?– Avoiding certain foods can lead to essential
nutrient imbalances?• Vegan diet• “Clean” eating
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Summary
• Insomnia and depression can be due to any of several factors
• Neurochemicals and antidepressants are just part of the picture
• Diet and nutrition may address factors not addressed by antidepressants
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Acknowledgement
This work is supported in part by
USDA Smith Lever Funding
for Project 289H.
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Questions?
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References (continued)Knol et al. Diabetologia. 2006; 49(5): 837-45Kolodinsky et al. J Am Diet Assoc. 2007; 107(8): 1409-13Kuhn et al. J Biol Chem. 1980; 255(9): 4137-4143Levine et al. J Biol Chem. 1985; 260(24): 12942-7.Lund et al. J Adolesc Health. 2010; 46(2): 124-32Mai and Buysse. Sleep Med Clin. 2008; 3(2): 167-164Martin et al. Sleep Med Rev. 2004; 8(1): 63-72Nutt et al. Dialogues Clin Neurosci. 2008; 10(3): 329-36Ouellette et al. J Am Coll Nutr. 2012; 31(5): 301-10Shams et al. Singapore Med J. 2010; 51(2): 116-119Shankar et al. PLoS One. 2010; 5(11): e14189Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3Taylor et al. Behav Ther. 2013; 44(3): 339-48Unbehaun et al. Nat Sci Sleep. 2010; 2: 127-138 Vozoris. J Hypertens. 2013; 31(4): 663-71Wang et al. Int J Methods Psychiatr Res. 2003; 12(1): 22-33Wiebe et al. Nat Sci Sleep. 2012; 4: 63-71Willyard. Nat Med. 2012; 18(7): 996
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ImagesSlide 17: [Venn diagram of neurotransmitters]. Retrieved September 11th, 2014 from: http://www.macalester.edu/academics/psychology/whathap/ubnrp/meth08/biochemistry/neurotransmitter.htmSlide 25: [logo of NHANES]. Retrieved August 31st, 2014 from: http://www.cdc.gov/nchs/nhanes.htmSlide 25: [logo of CDC]. Retrieved August 31st, 2014 from: http://www.cdc.gov/nchs/nhanes.htmSlide 26: [photograph of NHANES MEC]. Retrieved August 31st, 2014 from: http://www.cdc.gov/nchs/features/nhanes_mec_collects_health_data.htmSlide 27: [screen capture of NHANES 2005-2006 menu]. Retrieved September 13th, 2014 from: http://wwwn.cdc.gov/nchs/nhanes/search/nhanes05_06.aspxSlide 30: [picture of Prozac pill]. Retrieved October 9th, 2014 from: http://www.theguardian.com/society/2008/feb/26/mentalhealth.medicalresearchSlide 30: [picture of Zoloft pills]. Retrieved October 9th, 2014 from: http://www.webmd.com/drugs/2/drug-35-8095/zoloft-oral/sertraline-oral/details#images/00049490030Slide 34: [screen capture of PHQ-9 questions]. Retrieved September 13th, 2014 from: http://www.phqscreeners.com/instructions/instructions.pdfSlide 37: [logo of JMP]. Retrieved September 14th, 2014 from: http://beckerinfo.net/bioinformatics/jmp-genomics-training/All other images are from journal articles, Microsoft Clip Art, or original work.