The Role of Diet in Sleep and
Depression
Makena Dyer, B.Sc. and Joannie Dobbs, PhD, CNS
Human Nutrition, Food & Animal Sciences
University of Hawai‘i at Mānoa
PCCHA 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): 116-119
Ouellette et al. J Am Coll Nutr. 2012; 31(5): 301-10
Kolodinsky et al. J Am Diet Assoc. 2007; 107(8): 1409-13
Johnston et al. J Am Coll Health. 1998; 46(5): 209-13
Butler 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): 124-32
Taylor 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): 3095-105
http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo02a-eng.htm
Substance 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): 3-10
Eisenberg et al. J Nerv Ment Dis. 2011; 199: 301-308
Drum et al. Prof Psychol-Res Pr. 2009; 40(3): 213-222
Costs of Sleep Difficulty and Depression
• 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)
Willyard. Nat Med. 2012; 18(7): 996
Chen et al. Res Social Adm Pharm. 2008; 4(3): 244-57
Martin 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): 63-72
Wang 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): e14189
Ariyo et al. Circulation. 2000; 102(15): 1773-9
Knol et al. Diabetologia. 2006; 49(5): 837-45
Hakkarainen 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): 329-36
Wiebe 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
Amino acid
Hare 2004
Cofactors: BH4 (requires
folate) and iron
Kuhn et al. J Biol Chem. 1980; 255(9): 4137-4143
Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3
Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9
Hare and Loer. BMC Evol Biol. 2004; 4:24
Cofactor:
Vitamin B-6
Neurotransmitter Synthesis
Hickman 1999
Acetyl CoA from
pantothenic acid
Methyl group from SAM (requires
folate and Vitamin B-12)
Hickman et al. Mol Cell. 1999; 3: 23-32
Axelrod and Weissbach. Science. 1960; 131(3409): 1312
Bottiglieri. 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): 465-475
Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3
Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9
Hare 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 and Rohrer. Nat Rev Neurosci. 2002; 3(7): 531-41
Levine et al. J Biol Chem. 1985; 260(24): 12942-7.
Goridis 2002
Other Issues with
Neurotransmitters and Diet
• Bioavailability is also important
– Role of carbohydrates
↑ Carbohydrate
intake
↑ Insulin
release
↑ Tryptophan
available relative to
other amino acids
Benton and Donohoe. Public Health Nutr. 1999; 2(3A): 403-9
↑ Tryptophan
delivery to the
brain via albumin
transport proteins
Nutrients with Special Importance for
Neurotransmitters
MACRO-NUTRIENTS
Protein
Carbohydrate
Fat (omega-3 & 6 fatty acids)
Water
Micro-Nutrients
Vitamins
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 Substances
Caffeine
Cholesterol
Dietary Fiber
Other Phytochemicals
Summary of Nutrients with Special
Importance to Sleep and Depression
MACRO-NUTRIENTS
Protein
Carbohydrate
Fat (omega-3 & 6 fatty acids)
Water
Micro-Nutrients
Vitamins
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 Substances
Caffeine
Cholesterol
Dietary Fiber
Other 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
• NHANES 2005-2006
– Demographics Data
– Dietary Data
– Examination Data
– Laboratory Data
– Questionnaire Data
Adapted from wwwn.cdc.gov
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/zoloftoral/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
Insomnia and Depression in Females
No
TOTAL FEMALES Symptoms
Insomnia
only
Depression
only
Insomnia and
Depression
(n= 1307)
871
319
54
63
%
66.6%
24.4%
4.1%
4.8%
No
96.2%
34.3%
6.0%
6.1%
Yes
3.8%
2.3%
0.2%
1.1%
Antidepressant
drug use
Insomnia and Depression in Males
TOTAL
MALE
No
Depression
Symptoms Insomnia only
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%
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 antidepressants 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=837
n=33
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
MexicanAmerican
Non-Hispanic
Black
Non-Hispanic
White
Other Hispanic
Other Race
Antidepressant
Drug Use?
No
Yes
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
Antidepressant
Drug Use?
No
Yes
Recommended Protein
Intake for Some Individuals =
1.6 gm/kg body weight
RDA for Protein =
0.8 gm/kg body weight
n=828
n=33
n=52
n=10
11 outliers excluded
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
NLEA
NLEA
Energy
Food Sources
Serving
Volume per
(kcal)
Size (g)
Serving
Protein (g)
Fish / Chicken /
85
~ 3 oz. ckd
170
Beef
2% Cottage
110
~ 0.5 oz. cup
100
Cheese
Cheese
30
1 thin slice
110
Legumes /
~ 0.5 oz.
90
120
Beans
cup
Beans 130
~ 0.5 oz. cup
150
Processed
Grains
140
0.6 -1 cup
160
Nuts
30
~ 3.5 Tbsp.
190
Kcal/ g
protein
8
8
16
16
20
32
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
RDA for Magnesium = 400 mg
n=836
n=32
n=52
n=10
4 outliers excluded
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=815
n=33
n=51
n=10
26 outliers excluded
Foods That Provide DHA
Summary of Nutrients with Special
Importance to Sleep and Depression
MACRO-NUTRIENTS
Protein
Carbohydrate
Fat (omega-3 & 6 fatty acids)
Water
Micro-Nutrients
Vitamins
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 Substances
Caffeine
Cholesterol
Dietary Fiber
Other 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?
References
American Psychiatric Association 2013 DSM-5 The Diagnostic and Statistical Manual for Mental Disorders,
Ariyo et al. Circulation. 2000; 102(15): 1773-9
Axelrod and Weissbach. Science. 1960; 131(3409): 1312
Benton 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): 24-32
Chen et al. Res Social Adm Pharm. 2008; 4(3): 244-57
Cotter and O’Keeffe. Ther Clin Risk Manag. 2006; 2(4): 465-475
Drum et al. Prof Psychol-Res Pr. 2009; 40(3): 213-222
Eisenberg et al. J Nerv Ment Dis. 2011; 199: 301-308
Elsworth and Roth. Exp Neurol. 1997; 144(1): 1-9
Goridis and Rohrer. Nat Rev Neurosci. 2002; 3(7): 531-41
Hakkarainen et al. J Epidemiol Community Health 2007; 61: 53-58
Hare and Loer. BMC Evol Biol. 2004; 4:24
Hickman et al. Mol Cell. 1999; 3: 23-32
Hunt and Eisenberg. J Adolesc Health. 2010; 46(1): 3-10
Johnston et al. J Am Coll Health. 1998; 46(5): 209-13
Kessler et al. JAMA. 2003; 289(23): 3095-105
Kessler et al. Sleep. 2011; 34(9): 1161–1171
References (continued)
Knol et al. Diabetologia. 2006; 49(5): 837-45
Kolodinsky et al. J Am Diet Assoc. 2007; 107(8): 1409-13
Kuhn et al. J Biol Chem. 1980; 255(9): 4137-4143
Levine et al. J Biol Chem. 1985; 260(24): 12942-7.
Lund et al. J Adolesc Health. 2010; 46(2): 124-32
Mai and Buysse. Sleep Med Clin. 2008; 3(2): 167-164
Martin et al. Sleep Med Rev. 2004; 8(1): 63-72
Nutt et al. Dialogues Clin Neurosci. 2008; 10(3): 329-36
Ouellette et al. J Am Coll Nutr. 2012; 31(5): 301-10
Shams et al. Singapore Med J. 2010; 51(2): 116-119
Shankar et al. PLoS One. 2010; 5(11): e14189
Stahl. J Clin Psychiatry. 2008; 69(9): 1352-3
Taylor et al. Behav Ther. 2013; 44(3): 339-48
Unbehaun et al. Nat Sci Sleep. 2010; 2: 127-138
Vozoris. J Hypertens. 2013; 31(4): 663-71
Wang et al. Int J Methods Psychiatr Res. 2003; 12(1): 22-33
Wiebe et al. Nat Sci Sleep. 2012; 4: 63-71
Willyard. Nat Med. 2012; 18(7): 996
Images
Slide 17: [Venn diagram of neurotransmitters]. Retrieved September 11th, 2014 from:
http://www.macalester.edu/academics/psychology/whathap/ubnrp/meth08/biochemistry/neurotransmitter.htm
Slide 25: [logo of NHANES]. Retrieved August 31st, 2014 from: http://www.cdc.gov/nchs/nhanes.htm
Slide 25: [logo of CDC]. Retrieved August 31st, 2014 from: http://www.cdc.gov/nchs/nhanes.htm
Slide 26: [photograph of NHANES MEC]. Retrieved August 31st, 2014 from:
http://www.cdc.gov/nchs/features/nhanes_mec_collects_health_data.htm
Slide 27: [screen capture of NHANES 2005-2006 menu]. Retrieved September 13th, 2014 from:
http://wwwn.cdc.gov/nchs/nhanes/search/nhanes05_06.aspx
Slide 30: [picture of Prozac pill]. Retrieved October 9th, 2014 from:
http://www.theguardian.com/society/2008/feb/26/mentalhealth.medicalresearch
Slide 30: [picture of Zoloft pills]. Retrieved October 9th, 2014 from: http://www.webmd.com/drugs/2/drug-358095/zoloft-oral/sertraline-oral/details#images/00049490030
Slide 34: [screen capture of PHQ-9 questions]. Retrieved September 13th, 2014 from:
http://www.phqscreeners.com/instructions/instructions.pdf
Slide 37: [logo of JMP]. Retrieved September 14th, 2014 from: http://beckerinfo.net/bioinformatics/jmpgenomics-training/
All other images are from journal articles, Microsoft Clip Art, or original work.