2Consider 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 brainDHA (an omega-6 fatty acid) comprises 35% of the fatty acid content of nerve terminals
3Outline of TopicsCurrent Diagnosed Illnesses (depression, schizophrenia, bipolar, etc) probably have multiple causes.Understand the various types of fats, fatty acidsReview relationship of fatty acids to mental illnessCorrelations between diet and mental illnessObesity as a cause of inflammation/depressionGluten and schizophrenia
4Heterogeneity 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
5Proof of Heterogeneity: drug responses Schizophrenia is at least 4 different diseases, based on medication response to first-line antipsychotic medicationRapid responseDelayed responseNon-response (but does respond to clozapine)Non-response (and non-responding to clozapine)
6Proof of Heterogeneity: drug responses Possibly at least 7 types of depression based on medication responseSSRI fully responsiveSSRI partially responsiveSSRI non-responsiveSSRI adverse responsive“atypical depression” responds to MAO inhibtor“atypical depression” MAO-I non-responsiveLithium responsive
7Proof of heterogenity: brain waves Quantitative electroencephalography reveals6 distinct abnormal patterns in patients withschizophreniaJohn ER et al. (2007) Electrophysiological subtypes of psychotic states. Acta Psychiatrica Scandinavica. 116:17-35
8Proof of Heterogeniety: genetics Eight types of schizophrenia are suggested – based on a combination of symptom expression pattern and genetic variations.
1046% 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:
11Christensen O & Christensen O (1988) Fat consumption and schizophrenia Christensen O & Christensen O (1988) Fat consumption and schizophrenia. Acta Psychiatrica Scandinavica. 78:
12Fats explained Fats and oils generally contain fatty acids Fatty acids are long chains of carbon atomsCarbon atoms form 4 chemical bonds
13Carbon can form double-bonds and keep its ‘4-bond rule’ ButaneMethaneCarbon DioxideButene
14Fatty 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 hydrogenStearic acid,18 carbons,fully saturatedOleic acid,18 carbons,Mono-unsaturated
16Trans fat Hydrogen atoms on the same side of the double-bond Hydrogen atoms on opposite sides of the double-bondAssociated with increased risk of heart diseaseMay increase behavioral effects of stimulants, possibly leading to addictionHigh levels in rodents are transgenerational
23All 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.
24Implications of Fatty Acid Derangements Changes in cell membrane fatty acid composition can profoundly impact the sensitivity of membrane proteinsThese include the receptors for serotonin, norepinephrine, dopamine, GABA, acetylcholine, and glutamateIf the optimal fatty acids are not available (from the diet, or from metabolism), the body will substitute with suboptimal fatty acids.
25Evidence 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
26Omega-3 fatty acid deficits in Borderline Personality Disorder
27Is Omega-3 Supplementation Helpful? Clinical study results are mixedProbably does benefit some subgroups of patients (probably the ones who have essential fatty acid deficiencies)Dose and ratio of EPA:DHA is still uncertainStudies finding mental health benefit use EPA at doses between 1000 to 2000 mg per day
2881 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 weeksomega-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.
31Jacka et al., 2010Derived from large-scale osteoporosis study in southeast AustraliaMental health and dietary data from 1,046 womenControlled for smoking, alcohol, socioeconomic status, education, and activity level
32Odds of Depression or Dysthymia Jacka et al., 2010
33Western Diet Traditional Diet Modern Diet Meat pies Vegetables FruitsProcessed meats Fruit SaladsPizza Beef FishChips Lamb TofuHamburgers Fish BeansWhite bread Whole grain foods NutsSugar YogurtFlavored milk drinks Red wineBeer
34General 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
37Prospective StudiesAmong 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.
38Prospective Studies3,468 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 followupHigh adherence to whole food diet 25% reduced risk of depressionHigh consumption of processed foods 60% increased risk of depressionAkbaraly, T. N. et al. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry 195, 408–413 (2009).
39Interventional Study95 forensic inpatients; mixed diagnoses (none with psychosis);23 week food intervention.Two groups:Salmon three times/weekMeat three times/weekHansen, A. L. et al. Reduced anxiety in forensic inpatients after a long-term intervention with Atlantic salmon. Nutrients 6, 5405–5418 (2014).
41Mediterranean DietEmphasizes whole foods (fruits, vegetables, legumes, minimally-processed whole grains)Meat is primarily fish or poultryAdded oil is oliveRefined sugars are absentModerate intake of wine with mealsDairy and red meats absent to minimally present
42Mediterranean Diet Meta-analysis of research publications 1.5 million research subjectsAdherence 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).
43Mediterranean DietIncrease telomere length (associated with longevity)Improves insulin sensitivityReduces inflammation
45InflammationInflammation 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.
46Obesity 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).
47Causes 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
48GlutenCeliac 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 diseaseDohan, F.C., et al. (1969). Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet. Br J Psychiatry 115, 595–596.
49Gluten antibodies over-represented in schizophrenia Control groupn = 900Tissue transglutaminase antibodies5.4%0.8%Anti-gliadin antibodies23.1%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).