the role of diet in sleep and depression makena dyer, b.sc. and joannie dobbs, phd, cns human...

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

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

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

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.

The Role of Diet in Mental Health

The Role of Diet in Mental Health

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

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

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

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

DSM-5 Criteria for Major Depressive Disorder

At least five of the following symptoms

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

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.

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

• 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

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

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

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

Is There a Connection to Nutrition?

Role of Nutrients in Sleep and Mood

• Nutrients are involved in biochemical processes

• Important process for sleep and mood is neurotransmitter synthesis

Neurotransmitters

http://www.macalester.edu/academics/psychology/whathap/ubnrp/meth08/biochemistry/neurotransmitter.htm

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

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.

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

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.

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

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

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

We Wanted to See if the Relationship Between Depression and Insomnia Could be Seen in the

NHANES Studies

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

NHANES Mobile Exam Center

www.cdc.gov

NHANES Datasets

Adapted from wwwn.cdc.gov

• NHANES 2005-2006– Demographics Data– Dietary Data– Examination Data– Laboratory Data– Questionnaire Data

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

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

Dietary Data• 24-hour diet recall

– Multiple pass method– USDA’s Food and Nutrient Database

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

Questionnaire Data: Insomnia

• Sleep Disorders questionnaire– Length of sleep– Sleep disorder diagnosis– Frequency of sleep complaints– Severity of daytime impairment

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

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

Questionnaire Data: Depression

www.phqscreeners.com

Data Analysis

• JMP Pro 11– Data mining

software

beckerinfo.net

NHANES Data in JMP

Females

Males

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

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

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

Body Wt., BMI, Symptoms and Antidepressant Use in Female Subjects

The following Contour Graphs

present proportional

representations of data density – regardless of the

total n

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.

Relationship of Energy Intake to Insomnia and Depression

Antidepressant Drug Use?

No

Yes

n=33n=837 n=52 n=10 2 outliers excluded

The following Contour Graph shows that the depression and

insomnia group for all ethnicities was abnormal compared to the

other groups.

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

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

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

Foods That Provide Protein

• Animal products– Meats– Fish– Cheese

• Beans*• Nuts*

*Incomplete protein (missing essential amino acids); lower digestibility and higher calories

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

The following Contour Graph shows that the depression and

insomnia group for all ethnicities was abnormal compared to the

other groups.

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

Foods That Provide Magnesium

• Nuts• Beans• Spinach

The following DHA Contour Graph shows that the depression and insomnia group on an average

consumes less DHA compared to the other groups.

Relationship of DHA Intake Insomnia and Depression

Antidepressant Drug Use?

No

Yes

n=10n=33 n=51n=815 26 outliers excluded

Foods That Provide DHA

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

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

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

Acknowledgement

This work is supported in part by

USDA Smith Lever Funding

for Project 289H.

Questions?

ReferencesAmerican Psychiatric Association 2013 DSM-5 The Diagnostic and Statistical Manual for Mental Disorders, Ariyo et al. Circulation. 2000; 102(15): 1773-9Axelrod and Weissbach. Science. 1960; 131(3409): 1312Benton and Donohoe. Public Health Nutr. 1999; 2(3A): 403-9 Bottiglieri. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(7):1103-12.Butler et al. Am J Health Behav. 2004; 28(1): 24-32Chen et al. Res Social Adm Pharm. 2008; 4(3): 244-57Cotter and O’Keeffe. Ther Clin Risk Manag. 2006; 2(4): 465-475Drum et al. Prof Psychol-Res Pr. 2009; 40(3): 213-222Eisenberg et al. J Nerv Ment Dis. 2011; 199: 301-308Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9Goridis and Rohrer. Nat Rev Neurosci. 2002; 3(7): 531-41Hakkarainen et al. J Epidemiol Community Health 2007; 61: 53-58Hare and Loer. BMC Evol Biol. 2004; 4:24Hickman et al. Mol Cell. 1999; 3: 23-32Hunt and Eisenberg. J Adolesc Health. 2010; 46(1): 3-10Johnston et al. J Am Coll Health. 1998; 46(5): 209-13Kessler et al. JAMA. 2003; 289(23): 3095-105Kessler et al. Sleep. 2011; 34(9): 1161–1171

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

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.