Diet, Inflammation, & Depression

Amber Dukes, MScMPH Student, Psychology PhD candidateUniversity of New Mexicoadukes@unm.edu

Outline Intro

Depression Inflammation The gut

Foods Mismatches in modern diet Adaptive responses

The modern gut

Ultimate explanation

Conclusion

Depression

2nd leading cause of disability by 2020 (Murray & Lopez,

1996)

Cost: US $83 billion per year (Greenberg et al., 2003)

Increased risk of suicide, substance abuse

50% of children/adolescents 20 % of adults

10 % on antidepressants (Leahy, 2010)

Inflammation

Signals injury or infection Recognition of pathogens (Lipopolysaccharide – LPS) Release of cytokines (e.g. Dantzer, 2008)

Occurs with modern diseases (e.g. Raison et al., 2006)

Associated with depression (e.g. Raison et al.,,2006)

Increased immune disorders in depressed persons Depression in cytokine therapy (Dunn et al., 2005)

The Gut Residents

Gut flora/commensals (up to 100 trillion; Sekirov et al., 2011) Pseudocommensals Pathogens

Brain-gut-enteric microbiota axis (e.g. Raison et al., 2010)

Central nervous system, neuroendocrine & neuroimmune systems, sympathetic & parasympathetic autonomic nervous system, enteric nervous system, & intestinal microbiota

Gut & depression Increased leakage of LPS (Maes et al., 2008)

Mismatch Foods

Lectins

• Grains, legumes

• Leaky gut• Immune

activation

Processed Foods

• High carb + high fat

• Dense acellular carbs (Spreadbury, 2012)

• Lack of traditional preparation

Lack of Anti-Inflammatories

• Plant flavonoids

• Spices• Lack of

fermented foods

Adaptive Response to Foods

Fats•Fuel for Gram-negative bacteria•Anti-microbial free fatty acids

Sugars•Glucose protects bacteria •Pre-biotic oligosaccharides

Alcock et al., 2012 Nutrient signalling: Evolutionary origins of the immune-modulating effect s of dietary fats. The Quarterly Review of Biology, 87, 187-223

Adaptive Response to Foods

Fat

Effect on bacteria

Pro-microbial

Increase inflammation

Anti-microbial

Decrease inflammation

Inflammatory

• Trans Fats• Long-Chain

Saturated Fats

Anti-Inflammatory• Short/Medium

Chain saturated• Unsaturated Fats

•PUFA (& MUFA)• Omega-3

Alcock et al., 2012 Nutrient signalling: Evolutionary origins of the immune-modulating effect s of dietary fats. The Quarterly Review of Biology, 87, 187-223

The Modern Gut

Inflammation

Depression

Food proteinsAuto-immuneEnvironmental

Irritants

Fewer “Old Friends”

Reduced immune training

Overactive immune response

Raison et al., (2010). Inflammation, sanitation, and consternation. Arch Gen Psychiatry, 67

Proximate Explanation

• Inflammationo IL-1, -2, -6, TNF-α, CRP, and sickness behavioro Also in depression

• Evidenceo Elevated in chronic illness (Capuron et al ., 2002)

o Depression in cytokine treatment (Raison et al., 2006; Dunn et al., 2005)

o Higher IL-1β (170%) in depressed persons (Thomas et al., 2005)

o Depression and LPS (Dantzer, 2006; Moreau et al., 2008)

Ultimate Explanation: Why?

Sickness Behavior

•Fatigue•Lethargy •Loss of interest•Social withdrawal•Hyperalgesia•Anxiety•Difficulty concentrating•Hypersomnia•Loss of appetite•Malaise

Depression•Fatigue•Lethargy•Loss of interest•Social withdrawal•Hyperalgesia•Anxiety•Difficulty concentrating•Change in sleep patterns•Overeating or loss of appetite•HopelessnessReprioritization & conservation of energy

Sickness healing

Depression reevaluate and seek new solutions, get help through social support

Implications & Future Directions

Some may be sick, not depressed Heal the gut to heal the mind

Traditional diets better for mental health OTC anti-inflammatory drugs not the answer

Intervention studies needed Diet and changes in depression/inflammation Diet and changes in gut flora

Further Reading

Alcock et al., (2012) Nutrient signaling: Evolutionary origins of the immune-modulating effect s of dietary fats. The Quarterly Review of Biology, 87, 187-223

Raison et al., (2010). Inflammation, sanitation, and consternation. Arch Gen Psychiatry, 67

ReferencesAlcock, J., Franklin, M., & Kuzawa, C. (2012). Nutrient signaling: Evolutionary origins of the immune-modulating effects of dietary fat. The Quarterly Review of Biology,

87(3), 187–223. Banwell JG, Howard R, Kabir I & Costerton JW (1988) Bacterial overgrowth by indigenous micromicrobiota in the phytohemaggluti- nin-fed rat. Canadian Journal of

Microbiology 34, 1009–1013.Capuron, L., Gumnick, J.F., Musselman, D. L., Lawson, D. H., Reemsnyder, A., Nemeroff, C. et al. (2002). Neurobehavioral effects of interferon-alpha in cancer patients:

phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology, 26, 643–52. doi:10.1016/S0893-133X(01)00407-9Chrispeels, M., & Raikhel, N. (1991). Lectins, lectin genes, and their role in plant defense. The Plant Cell, 3, 1–9. Cordain, L., Eaton, S.B., Sebastian, A., Mann, N., Lindeberg, S., et al. (2005). Origins and evolution of the Western diet: Health implications for the 21st century. The

American Journal of Clinical Nutrition, 81, 341-54.Cordain, L., Toohey, L., Smith, M.J., & Hickey, M.S. (2000). Modulation of immune function by dietary lectins in rheumatoid arthritis. British Journal of Nutrition, 83,

207–217.Dantzer, R. (2006). Cytokine, sickness behavior, and depression. Neurologic Clinics, 24(3), 441–60. doi:10.1016/j.ncl.2006.03.003Desbois, A., & Smith, V. (2010). Antibacterial free fatty acids: Activities, mechanisms of action and biotechnological potential. Applied Microbiology and Biotechnology,

44(1334). Du, H., van der A, D.L., van Bakel, M.M.E., van der Kallen, C J.H., Blaak, E.E., et al. (2008). Glycemic index and glycemic load in relation to food and nutrient intake and

metabolic risk factors in a Dutch population. The American Journal of Clinical Nutrition, 87, 655-61. Dunn, A.J., Swiergiel, A. H., & de Beaurepaire, R. (2005). Cytokines as mediators of depression: What can we learn from animal studies? Neuroscience and Biobehavioral

Reviews, 29, 891–909. doi:10.1016/j.neubiorev.2005.03.023Esposito, K., Nappo, F., Giugliano, F., Giugliano, G., Marfella, R., & Giugliano, D. (2003). Effect of dietary antioxidants on postprandial endothelial dysfunction induced

by a high-fat meal in healthy subjects. The American journal of clinical nutrition, 77(1), 139-143.Ghanim, H., Abuaysheh, S., Sia, C. L., Korzeniewski, K., Chaudhuri, A., Fernandez-Real, J. M., & Dandona, P. (2009). Increase in Plasma Endotoxin Concentrations and

the Expression of Toll-Like Receptors and Suppressor of Cytokine Signaling-3 in Mononuclear Cells After a High-Fat, High-Carbohydrate Meal Implications for insulin resistance. Diabetes Care, 32(12), 2281-2287.

Gibson, P. R., Newnham, E., Barrett, J. S., Shepherd, S. J., & Muir, J. G. (2007). Review article: fructose malabsorption and the bigger picture. Alimentary pharmacology & therapeutics, 25(4), 349–63. doi:10.1111/j.1365-2036.2006.03186.x

Goepfert, J. M., & Hicks, R. (1969). Effect of volatile fatty acids on Salmonella typhimurium. Journal of Bacteriology, 97(2), 956–958.Goldstein, I. J., & Hayes, C. E. (1978). The lectins: carbohydrate-binding proteins of plants and animals. Advances in carbohydrate chemistry and biochemistry, 35, 127-

340.Greenberg, P. E., Kessler, R. C., Birnbaum, H. G., Leong, S. A., Lowe, S. W., Berglund, P. A., & Corey-Lisle, P. K. (2003). The economic burden of depression in the

United States: how did it change between 1990 and 2000?.Journal of Clinical Psychiatry, 64(12), 1465-1475Hart, B. (1988). Biological basis of the behavior of sick animals. Neuroscience & Biobehavioral Reviews, 12, 123–137. Hughes RE and Wilson HK (1977) Flavonoids: Some physiological and nutritional consideration. Prog Med Chem 14:285–301. Jönsson, T., Olsson, S., Ahrén, B., Bøg-Hansen, T.C., Dole, A., & Lindeberg, S. (2005). Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause

leptin resistance? BMC Endocrine Disorders, 5, 10. doi:10.1186/1472-6823-5-10Keller, M.C. & Nesse, R.M. (2005). Is low mood an adaptation? Evidence for subtypes with symptoms that match precipitants. Journal of Affective Disorders, 86, 27-35.Kiecolt-Glaser, J.K., Belury, M.A., Porter, K., Beversdorf, M.D., Lemeshow, S., & Glaser, R. (2007). Depressive symptoms, n-6:n-3 fatty acids, and inflammation in older

adults. Psychosomatic Medicine, 69, 217-224.

Maes, M., Kubera, M., & Leunis, J.C. (2008). The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro endocrinology letters, 29(1), 117–24.

McDade, T. W., Borja, J. B., Adair, L. S., & Kuzawa, C. (2012). Depressive symptoms are not associated with inflammation in younger and older adults in the Philippines. Evolution, Medicine, and Public Health, 2013(1), 18–23. doi:10.1093/emph/eos004

Miller, G. E., & Wrosch, C. (2007). You’ve gotta know when to fold  'em. Psychological Science, 18(9), 773–777. Moreau, M., André, C., O’Connor, J. C., Dumich, S. a, Woods, J. a, Kelley, K. W., Dantzer, R., et al. (2008). Inoculation of Bacillus Calmette-Guerin to mice induces an

acute episode of sickness behavior followed by chronic depressive-like behavior. Brain, behavior, and immunity, 22(7), 1087–95. doi:10.1016/j.bbi.2008.04.001Mozaffarian, D., Aro, a, & Willett, W. C. (2009). Health effects of trans-fatty acids: experimental and observational evidence. European journal of clinical nutrition, 63

Suppl 2(S2), S5–21. doi:10.1038/sj.ejcn.1602973Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and

Projected to 2020.  Geneva, Switzerland;World Health OrganizationNappo, F., Esposito, K., Cioffi, M., Giugliano, G., Molinari, A. M., Paolisso, G et al. (2002). Postprandial endothelial activation in healthy subjects and in type 2 diabetic

patients: role of fat and carbohydrate meals. Journal of the American College of Cardiology, 39(7), 1145-1150.Netea, M.G., Brown, G.D., Kullberg, B.J., & Gow, N.A.R. (2008). An integrated model of the recognition of Candida albicans by the innate immune system. Nature

Reviews. Microbiology, 6(1), 67–78. doi:10.1038/nrmicro1815Oldstone, M. B. (1987). Molecular mimicry and autoimmune disease. Cell, 50(6), 819.Raison, C.L., Capuron, L., & Miller, A.H. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. TRENDS in Immunology, 27, 24-31. Raison,

C. L., Lowry, C. A., & Rook, G. A. W. (2013). Inflammation, sanitation, and consternation. Archives of General Psychiatry, 67(12), 1211–1224.Rook, G. A., Raison, C. L., & Lowry, C. A. (2012). Can we vaccinate against depression? Drug discovery today, 17(9-10), 451–8. doi:10.1016/j.drudis.2012.03.018Sekirov, I., Russell, S. L., Antunes, L. C. M., & Finlay, B. B. (2010). Gut Microbiota in Health and Disease. Physiological Reviews, 859 –904.

doi:10.1152/physrev.00045.2009Sherman, P.W., & Hash, G.A. (2001). Why vegetable recipes are not very spicy. Evolution and Human Behavior, 22, 147–163. Sicherer, S. H., & Sampson, H. A. (2009). Food Allergy : Recent Advances in Pathophysiology and Treatment. Annual Review of Medicine. Spreadbury, I. (2012).

Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota , and may be the primary dietary cause of leptin resistance and obesity. Diabetes, Metabolic Syndrome, and Obesity: Targets and Therapy, 5, 175–189.

Sudo, N., Sawamura, S. A., Tanaka, K., Aiba, Y., Kubo, C., & Koga, Y. (1997). The requirement of intestinal bacterial microbiota for the development of an IgE production system fully susceptible to oral tolerance induction. The Journal of Immunology, 159(4), 1739-1745.

Thomas, A. J., Davis, S., Morris, C., Jackson, E., Harrison, R., & O’Brien, J. T. (2005). Increase in interleukin-1ß in late-life depression. American Journal of …, 162, 175–177. Retrieved from http://ajp.psychiatryonline.org/article.aspx?volume=162&page=175

Watzl, B., Kulling, S.E., Möseneder, J., Barth, S.W., & Bub, A. (2005) A 4-week intervention with high intake of carotenoid-rich vegetables and fruit reduces plasma C-reactive protein in healthy, nonsmoking men. American Journal of Clinical Nutrition, 82, 1052