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Diet and Mental Health Erik Messamore, MD, PhD.

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1 Diet and Mental Health Erik Messamore, MD, PhD

2 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

3 Outline of Topics Current Diagnosed Illnesses (depression, schizophrenia, bipolar, etc) probably have multiple causes. Understand the various types of fats, fatty acids Review relationship of fatty acids to mental illness Correlations between diet and mental illness Obesity as a cause of inflammation/depression Gluten and schizophrenia

4 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

5 Proof of Heterogeneity: drug responses
Schizophrenia is at least 4 different diseases, based on medication response to first-line antipsychotic medication Rapid response Delayed response Non-response (but does respond to clozapine) Non-response (and non-responding to clozapine)

6 Proof of Heterogeneity: drug responses
Possibly at least 7 types of depression based on medication response SSRI fully responsive SSRI partially responsive SSRI non-responsive SSRI adverse responsive “atypical depression” responds to MAO inhibtor “atypical depression” MAO-I non-responsive Lithium responsive

7 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

8 Proof of Heterogeniety: genetics
Eight types of schizophrenia are suggested – based on a combination of symptom expression pattern and genetic variations.

9 Fats

10 46% of total calories in the sailors diets came from saturated fats
Sundby P & Nyhus P (1963) Major and minor psychiatric disorders in males in Oslo. An epidemiological study. Acta Psychiatrica Scandinavica. 39:

11 Christensen O & Christensen O (1988) Fat consumption and schizophrenia
Christensen O & Christensen O (1988) Fat consumption and schizophrenia. Acta Psychiatrica Scandinavica. 78:

12 Fats explained Fats and oils generally contain fatty acids
Fatty acids are long chains of carbon atoms Carbon atoms form 4 chemical bonds

13 Carbon can form double-bonds and keep its ‘4-bond rule’
Butane Methane Carbon Dioxide Butene

14 Fatty acids are long chains of carbon
Stearic acid, an 18-carbon-long fatty acid

15 “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

16 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

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18 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.

19 Fatty acids form triglycerides and phospholipids
A triglyceride A phospholipid

20 Triglycerides and Phospholipids form the cell membrane
Outer layer Inner layer

21 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)

22 Proteins exist within the cell membrane

23 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.

24 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.

25 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

26 Omega-3 fatty acid deficits in Borderline Personality Disorder

27 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

28 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: % 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.

29 Diet studies

30

31 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

32 Odds of Depression or Dysthymia
Jacka et al., 2010

33 Western Diet Traditional Diet Modern Diet
Meat pies Vegetables Fruits Processed meats Fruit Salads Pizza Beef Fish Chips Lamb Tofu Hamburgers Fish Beans White bread Whole grain foods Nuts Sugar Yogurt Flavored milk drinks Red wine Beer

34 General Health Questionnaire – 12 item
Able to concentrate Loss of sleep over worry Playing a useful part Capable of making decisions Feel constantly under strain Can’t overcome difficulties Enjoy day-to-day activities Able to face problems Feeling unhappy/depressed Losing confidence Think of self as worthless Feeling reasonably happy

35 Jacka et al., 2010

36 Caution: Correlation ≠ Causation

37 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.

38 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).

39 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).

40 Hansen et al., 2014

41 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

42 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: meta-analysis. BMJ 337, a1344 (2008).

43 Mediterranean Diet Increase telomere length (associated with longevity) Improves insulin sensitivity Reduces inflammation

44 Inflammation

45 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.

46 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).

47 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

48 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.

49 Gluten antibodies over-represented in schizophrenia
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).


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