Diet and Mental Health
Erik Messamore, MD, PhD
Consider
• The brain operates at a very high metabolic rate
• 2% of body weight, but consumes 20% of its
oxygen (and calories).
• High oxygen consumption creates high oxidative
stress – and demand for antioxidants.
• High metabolic activity requires amino acids,
fats, vitamins and minerals and trace elements.
• Brain is 20% protein and 80% fat (dry weight)
• 25 % of the body’s cholesterol is in the brain
• DHA (an omega-6 fatty acid) comprises 35% of
the fatty acid content of nerve terminals
Outline of Topics
1. Current Diagnosed Illnesses (depression,
schizophrenia, bipolar, etc) probably have
multiple causes.
2. Understand the various types of fats, fatty acids
3. Review relationship of fatty acids to mental
illness
4. Correlations between diet and mental illness
5. Obesity as a cause of inflammation/depression
6. Gluten and schizophrenia
Heterogeneity
•
•
•
•
Mental Illnesses are HETEROGENEOUS
Hetero = ‘not the same’
Opposite of ‘homogenous’
What gets called [Insert psychiatric diagnosis
here] may actually consist of many different
disease states the produce similar symptoms.
• Examples: headache, fever
Proof of Heterogeneity: drug responses
• Schizophrenia is at least 4 different diseases,
based on medication response to first-line
antipsychotic medication
1. Rapid response
2. Delayed response
3. Non-response (but does respond to clozapine)
4. Non-response (and non-responding to
clozapine)
Proof of Heterogeneity: drug responses
• Possibly at least 7 types of depression based on
medication response
1. SSRI fully responsive
2. SSRI partially responsive
3. SSRI non-responsive
4. SSRI adverse responsive
5. “atypical depression” responds to MAO inhibtor
6. “atypical depression” MAO-I non-responsive
7. Lithium responsive
Proof of heterogenity: brain waves
Quantitative electroencephalography reveals
6 distinct abnormal patterns in patients with
schizophrenia
John ER et al. (2007) Electrophysiological subtypes of
psychotic states. Acta Psychiatrica Scandinavica.
116:17-35
Proof of Heterogeniety: genetics
• Eight types of schizophrenia are suggested –
based on a combination of symptom expression
pattern and genetic variations.
• http://www.medicalnewstoday.com/articles/2880
51.php
Fats
80
46% of total calories in
the sailors diets came
from saturated fats
60
40
20
0
O
th
er
O
cc
up
at
io
ns
Sa
ilo
rs
Cases per 10,000 per year
New cases of schizophrenia in Norway: 1926 - 1950
Sundby P & Nyhus P (1963) Major and minor psychiatric disorders
in males in Oslo. An epidemiological study. Acta Psychiatrica
Scandinavica. 39:519-47.
Christensen O & Christensen O (1988) Fat consumption and
schizophrenia. Acta Psychiatrica Scandinavica. 78: 587-91.
Fats explained
• Fats and oils generally contain fatty acids
• Fatty acids are long chains of carbon atoms
• Carbon atoms form 4 chemical bonds
Carbon can form double-bonds and keep its
‘4-bond rule’
Methane
Carbon Dioxide
Butane
Butene
Fatty acids are long chains of carbon
Stearic acid, an 18-carbon-long fatty acid
“Saturated” means that all carbon atoms
contain the maximum amount of hydrogen
– or that all carbon atoms (in the ‘tail’) are
fully saturated with hydrogen
Stearic acid,
18 carbons,
fully saturated
Oleic acid,
18 carbons,
Mono-unsaturated
Trans fat
Hydrogen atoms on the same
side of the double-bond
- Hydrogen atoms on
opposite sides of the
double-bond
- Associated with increased
risk of heart disease
- May increase behavioral
effects of stimulants,
possibly leading to
addiction
- High levels in rodents are
transgenerational
Essential fatty acids
• Many highly unsaturated fatty acids cannot be
made by the body.
• These are “essential” fatty acids – because they
must be obtained from the diet.
Fatty acids form triglycerides and
phospholipids
A triglyceride
A phospholipid
Triglycerides and Phospholipids form the
cell membrane
Outer layer
Inner layer
Fatty acid composition affects membrane
fluidity
Saturated fats stack tightly
together
Membrane approaches solid
(like lard, butter, etc)
Polyunsaturated fats stack
much more loosely
Increases fluidity (like olive oil)
Proteins exist within the cell membrane
All neurotransmitter receptors are
transmembrane proteins
- Neurotransmitters or drugs bind
to receptor proteins in the cell
membrane.
- Receptor proteins do not
function properly if the
surrounding membrane is too
rigid.
- Fatty acids themselves can act as
signaling molecules.
- The wrong types of fatty acids
lead to wrong messages in the
cell.
Implications of Fatty Acid Derangements
• Changes in cell membrane fatty acid
composition can profoundly impact the
sensitivity of membrane proteins
• These include the receptors for serotonin,
norepinephrine, dopamine, GABA, acetylcholine,
and glutamate
• If the optimal fatty acids are not available (from
the diet, or from metabolism), the body will
substitute with suboptimal fatty acids.
Evidence for fatty acids importance to
mental health
• Depression is less prevalent and less severe in
countries where fish is a dietary staple (Japan,
Iceland).
• Schizophrenia is less debilitating in countries
with lower intake of saturated fats.
• Many (but not all) patients with mood disorders,
anxiety disorders, and psychotic disorders have
deficits in omega-3 fatty acids
Omega-3 fatty acid deficits in Borderline
Personality Disorder
EPA (20:5n3)
DHA, 22:6n3
% of total fatty acids
5
0.8
0.6
0.4
0.2
0.0
4
3
2
1
rl i
ne
r li
ne
de
de
or
or
-B
on
N
-B
on
N
B
or
or
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de
r li
er
li
ne
ne
0
B
% of total fatty acids
1.0
Is Omega-3 Supplementation Helpful?
• Clinical study results are mixed
• Probably does benefit some subgroups of
patients (probably the ones who have essential
fatty acid deficiencies)
• Dose and ratio of EPA:DHA is still uncertain
• Studies finding mental health benefit use EPA at
doses between 1000 to 2000 mg per day
• 81 adolescents & young adults with
subthreshold psychosis
• Half got 1200 mg/d of omega-3 fatty acids; the
other half got placebo for 12 weeks.
• 40 weeks later:
Percent with schizophrenia at 40 weeks
omega-3 treatment group: 5%
placebo group:
27%
Amminger, G.P., et al. (2010). Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders:
a randomized, placebo-controlled trial. Arch. Gen. Psychiatry 67, 146–154.
Diet studies
Jacka et al., 2010
• Derived from large-scale osteoporosis study in
southeast Australia
• Mental health and dietary data from 1,046
women
• Controlled for smoking, alcohol, socioeconomic
status, education, and activity level
Odds of Depression or Dysthymia
Jacka et al., 2010
Western Diet
Traditional Diet
Meat pies
Vegetables
Processed meats Fruit
Pizza
Beef
Chips
Lamb
Hamburgers
Fish
White bread
Whole grain foods
Sugar
Flavored milk drinks
Beer
Modern Diet
Fruits
Salads
Fish
Tofu
Beans
Nuts
Yogurt
Red wine
General Health Questionnaire – 12 item
Able to concentrate
Playing a useful part
Feel constantly under strain
Enjoy day-to-day activities
Feeling unhappy/depressed
Think of self as worthless
Loss of sleep over worry
Capable of making decisions
Can’t overcome difficulties
Able to face problems
Losing confidence
Feeling reasonably happy
Jacka et al., 2010
Caution: Correlation ≠ Causation
Prospective Studies
• Among 8,964 college graduates who were free
from depression at screening, those reporting
frequent consumption of fast foods or
commercial baked goods were 40% more likely
to develop major depression over a 6 year
followup period.
Sánchez-Villegas, A., et al. (2012). Fast-food and commercial baked goods consumption and the risk of
depression. Public Health Nutrition, 15(3), 424–432.
Prospective Studies
• 3,468 participants in the Whitehall II prospective
cohort  2 groups
• ‘Whole food’
(vegetables, fruits, fish)
• ‘Processed food’
(sweetened desserts, fried food, processed meats,
refined grains, high-fat dairy products)
•
•
•
5 year followup
High adherence to whole food diet  25% reduced
risk of depression
High consumption of processed foods  60%
increased risk of depression
Akbaraly, T. N. et al. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry
195, 408–413 (2009).
Interventional Study
• 95 forensic inpatients; mixed diagnoses (none
with psychosis);
• 23 week food intervention.
• Two groups:
• Salmon three times/week
• Meat three times/week
•
Hansen, A. L. et al. Reduced anxiety in forensic inpatients after a long-term
intervention with Atlantic salmon. Nutrients 6, 5405–5418 (2014).
Hansen et al., 2014
Mediterranean Diet
• Emphasizes whole foods (fruits, vegetables,
legumes, minimally-processed whole grains)
• Meat is primarily fish or poultry
• Added oil is olive
• Refined sugars are absent
• Moderate intake of wine with meals
• Dairy and red meats absent to minimally present
Mediterranean Diet
•
•
•
•
•
•
•
Meta-analysis of research publications
1.5 million research subjects
Adherence to Med Diet reduced:
Overall mortality (-9%)
Cardiovascular disease mortality (-9%)
Caner mortality (-6%)
Incidence of Alzheimer’s or Parkinson’s (-13%)
Sofi, F., Cesari, F., Abbate, R., Gensini, G. F. & Casini, A. Adherence to Mediterranean diet and health status: metaanalysis. BMJ 337, a1344 (2008).
Mediterranean Diet
• Increase telomere length (associated with
longevity)
• Improves insulin sensitivity
• Reduces inflammation
Inflammation
Inflammation
• Inflammation is strongly associated with
depression and psychosis.
• The body releases cytokines to stimulate
immune response.
• Cytokines cause ‘sickness behavior’
• Depression could be categorized into
‘inflammatory’ and ‘non-inflamed’ subtypes.
• Schizophrenia can definitely be classified
according to presence/absence of inflammation.
Obesity
• Moods can influence food choice.
• Some types of depression are associated with
increased food intake.
• However… obesity reduces likelihood of benefit
from antidepressant medications.
• Fat cells, especially those within the abdomen,
secrete inflammatory cytokines.
•
Hryhorczuk, C. et al. Metabolic disturbances connecting obesity and depression. Front Neurosci
7, 177 (2013).
Causes of Obesity
• Sugar: The Bitter Truth – Robert H. Lustig
• Junk food* rewired rat dopamine receptor levels,
setting the stage for addiction-like behaviors 1.
Johnson, P. M. & Kenny, P. J. Dopamine D2 receptors in addiction-like reward
dysfunction and compulsive eating in obese rats. Nat. Neurosci. 13, 635–641
(2010).
• Dopamine mediates pleasure, novelty, motivation
* Supplemental bacon, sausage, cheesecake, pound cake, frosting, and chocolate
Gluten
• Celiac disease involves antibodies formed
against wheat protein.
• Two case reports of schizophrenia-like
psychosis in otherwise normal individuals who –
years later – developed clinical signs of celiac
disease
Dohan, F.C., et al. (1969). Relapsed schizophrenics: more rapid improvement on a
milk- and cereal-free diet. Br J Psychiatry 115, 595–596.
Gluten antibodies over-represented in
schizophrenia
Schizophrenia
n = 1,401
Control group
n = 900
Tissue transglutaminase
antibodies
5.4%
0.8%
Anti-gliadin antibodies
23.1%
3.1%
Cascella, N. G. et al. Prevalence of celiac disease and gluten sensitivity in the United States clinical
antipsychotic trials of intervention effectiveness study population. Schizophr Bull 37, 94–100 (2011).