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Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

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Abstract

The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).

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References

  • Akhondzadeh, S., Jafari, S., Raisi, F., Nasehi, A. A., Ghoreishi, A., Salehi, B., et al. (2009). Clinical trial of adjunctive celecoxib treatment in patients with major depression: A double blind and placebo controlled trial. Depress Anxiety, 26(7), 607–611.

    PubMed  CAS  Google Scholar 

  • Anand, A., Li, Y., Wang, Y., Wu, J., Gao, S., Bukhari, L., et al. (2005). Activity and connectivity of brain mood regulating circuit in depression: A functional magnetic resonance study. Biological Psychiatry, 57(10), 1079–1088.

    PubMed  Google Scholar 

  • Arnone, D., Cavanagh, J., Gerber, D., Lawrie, S. M., Ebmeier, K. P., & McIntosh, A. M. (2009). Magnetic resonance imaging studies in bipolar disorder and schizophrenia: Meta-analysis. British Journal of Psychiatry, 195(3), 194–201.

    PubMed  Google Scholar 

  • Asnis, G. M., & De La, G. R. (2005). Interferon-induced depression: Strategies in treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29(5), 808–818.

    PubMed  CAS  Google Scholar 

  • Baptista, T., Teneud, L., Contreras, Q., Alastre, T., Burguera, J. L., de Burguera, M., et al. (1995). Lithium and body weight gain. Pharmacopsychiatry, 28(2), 35–44.

    PubMed  CAS  Google Scholar 

  • Berg, A. H., Combs, T. P., & Scherer, P. E. (2002). ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism. Trends in Endocrinology and Metabolism, 13(2), 84–89.

    PubMed  CAS  Google Scholar 

  • Berridge, K. C., Ho, C. Y., Richard, J. M., Difeliceantonio, A. G. (2010). The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders. Brain Research.

  • Beydoun, M. A., Wang, Y. (2009). Pathways linking socioeconomic status to obesity through depression and lifestyle factors among young US adults. Journal of Affection Disorders.

  • Bina, K. G., & Cincotta, A. H. (2000). Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice. Neuroendocrinology, 71(1), 68–78.

    PubMed  CAS  Google Scholar 

  • Boghossian, S., Lemmon, K., Park, M., & York, D. A. (2009). High-fat diets induce a rapid loss of the insulin anorectic response in the amygdala. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 297(5), R1302–R1311.

    PubMed  CAS  Google Scholar 

  • Bokarewa, M., Nagaev, I., Dahlberg, L., Smith, U., & Tarkowski, A. (2005). Resistin, an adipokine with potent proinflammatory properties. Journal of Immunology, 174(9), 5789–5795.

    CAS  Google Scholar 

  • Bora, E., Yucel, M., & Pantelis, C. (2009). Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. Journal of Affective Disorders, 113(1–2), 1–20.

    PubMed  Google Scholar 

  • Bornstein, S. R., Schuppenies, A., Wong, M. L., & Licinio, J. (2006). Approaching the shared biology of obesity and depression: The stress axis as the locus of gene-environment interactions. Molecular Psychiatry, 11(10), 892–902.

    PubMed  CAS  Google Scholar 

  • Boufidou, F., Nikolaou, C., Alevizos, B., Liappas, I. A., & Christodoulou, G. N. (2004). Cytokine production in bipolar affective disorder patients under lithium treatment. Journal of Affective Disorders, 82(2), 309–313.

    PubMed  CAS  Google Scholar 

  • Brands, A. M., Van den Berg, E., Manschot, S. M., Biessels, G. J., Kappelle, L. J., de Haan, E. H., et al. (2007). A detailed profile of cognitive dysfunction and its relation to psychological distress in patients with type 2 diabetes mellitus. Journal of International Neuropsychological Society, 13(2), 288–297.

    Google Scholar 

  • Brauch, R. A., dnan El-Masri, M., Parker, J. C., Jr., & El-Mallakh, R. S. (2006). Glial cell number and neuron/glial cell ratios in postmortem brains of bipolar individuals. Journal of Affective Disorders, 91(1), 87–90.

    PubMed  Google Scholar 

  • Breunis, M. N., Kupka, R. W., Nolen, W. A., Suppes, T., Denicoff, K. D., Leverich, G. S., et al. (2003). High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder. Biological Psychiatry, 53(2), 157–165.

    PubMed  CAS  Google Scholar 

  • Brietzke, E., & Kapczinski, F. (2008). TNF-alpha as a molecular target in bipolar disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(6), 1355–1361.

    PubMed  CAS  Google Scholar 

  • Brindley, D. N., & Rolland, Y. (1989). Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clinical Science (Lond), 77(5), 453–461.

    CAS  Google Scholar 

  • Brook, J. S., Zhang, C., Saar, N. S., & Brook, D. W. (2009). Psychosocial predictors, higher body mass index, and aspects of neurocognitive dysfunction. Perceptual and Motor Skills, 108(1), 181–195.

    PubMed  Google Scholar 

  • Bruce, D. G., Harrington, N., Davis, W. A., & Davis, T. M. (2001). Dementia and its associations in type 2 diabetes mellitus: The Fremantle Diabetes Study. Diabetes Research and Clinical Practice, 53(3), 165–172.

    PubMed  CAS  Google Scholar 

  • Bruce-Keller, A. J., Keller, J. N., & Morrison, C. D. (2009). Obesity and vulnerability of the CNS. Biochimica et Biophysica Acta, 1792(5), 395–400.

    PubMed  CAS  Google Scholar 

  • Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D. (2008). Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biological Psychiatry, 63(11), 1022–1029.

    PubMed  CAS  Google Scholar 

  • Campfield, L. A., Smith, F. J., & Burn, P. (1996). The OB protein (leptin) pathway—A link between adipose tissue mass and central neural networks. Hormone and Metabolic Research, 28(12), 619–632.

    PubMed  CAS  Google Scholar 

  • Capasso, A., Putrella, C., & Milano, W. (2009). Recent clinical aspects of eating disorders. Reviews on Recent Clinical Trials, 4(1), 63–69.

    PubMed  Google Scholar 

  • Capuron, L., & Miller, A. H. (2004). Cytokines and psychopathology: Lessons from interferon-alpha. Biological Psychiatry, 56(11), 819–824.

    PubMed  CAS  Google Scholar 

  • Carlson, P. J., Singh, J. B., Zarate, C. A., Jr., Drevets, W. C., & Manji, H. K. (2006). Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets. NeuroRx, 3(1), 22–41.

    PubMed  CAS  Google Scholar 

  • Carney, C. P., & Jones, L. E. (2006). Medical comorbidity in women and men with bipolar disorders: A population-based controlled study. Psychosomatic Medicine, 68(5), 684–691.

    PubMed  Google Scholar 

  • Carroll, M. E. (1984). Food deprivation produces persistent increases in self-administration behavior during cocaine extinction. NIDA Research Monograph, 55, 125–131.

    PubMed  CAS  Google Scholar 

  • Carson, M. J., & Sutcliffe, J. G. (1999). Balancing function vs. self defense: The CNS as an active regulator of immune responses. Journal of Neuroscience Research, 55(1), 1–8.

    PubMed  CAS  Google Scholar 

  • Cassidy, F., Ritchie, J. C., & Carroll, B. J. (1998). Plasma dexamethasone concentration and cortisol response during manic episodes. Biological Psychiatry, 43(10), 747–754.

    PubMed  CAS  Google Scholar 

  • Chana, G., Landau, S., Beasley, C., Everall, I. P., & Cotter, D. (2003). Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: Evidence for decreased neuronal somal size and increased neuronal density. Biological Psychiatry, 53(12), 1086–1098.

    PubMed  Google Scholar 

  • Channual, J., Wu, J. J., & Dann, F. J. (2009). Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Therapy, 22(1), 61–73.

    Google Scholar 

  • Chen, Y., Jiang, Y., & Mao, Y. (2009). Association between obesity and depression in Canadians. Journal of Womens Health (Larchmt), 18(10), 1687–1692.

    Google Scholar 

  • Cone, R. D. (2000). The corticotropin-releasing hormone system and feeding behavior—A complex web begins to unravel. Endocrinology, 141(8), 2713–2714.

    PubMed  CAS  Google Scholar 

  • Connor, T. J., Starr, N., O’Sullivan, J. B., & Harkin, A. (2008). Induction of indolamine 2, 3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: A role for IFN-gamma? Neuroscience Letters, 441(1), 29–34.

    PubMed  CAS  Google Scholar 

  • Coste, S. C., Murray, S. E., & Stenzel-Poore, M. P. (2001). Animal models of CRH excess and CRH receptor deficiency display altered adaptations to stress. Peptides, 22(5), 733–741.

    PubMed  CAS  Google Scholar 

  • Cotter, D., Mackay, D., Landau, S., Kerwin, R., & Everall, I. (2001). Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Archives of General Psychiatry, 58(6), 545–553.

    PubMed  CAS  Google Scholar 

  • Coyle, J. T., & Schwarcz, R. (2000). Mind glue: Implications of glial cell biology for psychiatry. Archives of General Psychiatry, 57(1), 90–93.

    PubMed  CAS  Google Scholar 

  • Craft, S., & Watson, G. S. (2004). Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurology, 3(3), 169–178.

    PubMed  CAS  Google Scholar 

  • Cunha, N. V., de Abreu, S. B., Panis, C., Grassiolli, S., Guarnier, F. A., Cecchini, R., et al. (2010). Cox-2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium glutamate-induced obese rats. Life Science, 87(11–12), 375–381.

    CAS  Google Scholar 

  • Czerski, P. M., Rybakowski, F., Kapelski, P., Rybakowski, J. K., Dmitrzak-Weglarz, M., Leszczynska-Rodziewicz, A., et al. (2008). Association of tumor necrosis factor -308G/A promoter polymorphism with schizophrenia and bipolar affective disorder in a Polish population. Neuropsychobiology, 57(1–2), 88–94.

    PubMed  CAS  Google Scholar 

  • Danaei, G., Ding, E. L., Mozaffarian, D., Taylor, B., Rehm, J., Murray, C. J., et al. (2009). The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Medicine, 6(4), e1000058.

    PubMed  Google Scholar 

  • Dantzer, R. (2004). Cytokine-induced sickness behaviour: A neuroimmune response to activation of innate immunity. European Journal of Pharmacology, 500(1–3), 399–411.

    PubMed  CAS  Google Scholar 

  • Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 46–56.

    PubMed  CAS  Google Scholar 

  • Davids, S., Lauffer, H., Thoms, K., Jagdhuhn, M., Hirschfeld, H., Domin, M., et al. (2010). Increased dorsolateral prefrontal cortex activation in obese children during observation of food stimuli. International Journal of Obesity (Lond), 34(1), 94–104.

    CAS  Google Scholar 

  • Desbriere, R., Vuaroqueaux, V., Achard, V., Boullu-Ciocca, S., Labuhn, M., Dutour, A., et al. (2006). 11beta-hydroxysteroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients. Obesity (Silver Spring), 14(5), 794–798.

    CAS  Google Scholar 

  • Diehl, D. J., & Gershon, S. (1992). The role of dopamine in mood disorders. Comprehensive Psychiatry, 33(2), 115–120.

    PubMed  CAS  Google Scholar 

  • Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., et al. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446–457.

    PubMed  CAS  Google Scholar 

  • Drevets, W. C. (2000). Neuroimaging studies of mood disorders. Biological Psychiatry, 48(8), 813–829.

    PubMed  CAS  Google Scholar 

  • Drevets, W. C. (2003). Neuroimaging abnormalities in the amygdala in mood disorders. Annals of the New York Academy of Sciences, 985, 420–444.

    PubMed  Google Scholar 

  • Drevets, W. C. (2007). Orbitofrontal cortex function and structure in depression. Annals of the New York Academy of Sciences, 1121, 499–527.

    PubMed  Google Scholar 

  • Drevets, W. C., Price, J. L., & Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Structures and Functions, 213(1–2), 93–118.

    Google Scholar 

  • Elmslie, J. L., Porter, R. J., Joyce, P. R., Hunt, P. J., Shand, B. I., & Scott, R. S. (2009). Comparison of insulin resistance, metabolic syndrome and adiponectin in overweight bipolar patients taking sodium valproate and controls. Australian and New Zealand Journal of Psychiatry, 43(1), 53–60.

    PubMed  Google Scholar 

  • Evans, D. L., & Charney, D. S. (2003). Mood disorders and medical illness: A major public health problem. Biological Psychiatry, 54(3), 177–180.

    PubMed  Google Scholar 

  • Farooqi, I. S., Bullmore, E., Keogh, J., Gillard, J., O’Rahilly, S., & Fletcher, P. C. (2007). Leptin regulates striatal regions and human eating behavior. Science, 317(5843), 1355.

    PubMed  CAS  Google Scholar 

  • Fasshauer, M., Kralisch, S., Klier, M., Lossner, U., Bluher, M., Klein, J., et al. (2003). Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3–L1 adipocytes. Biochemical and Biophysical Research Communications, 301(4), 1045–1050.

    PubMed  CAS  Google Scholar 

  • Fenn, H. H., Bauer, M. S., Alshuler, L., Evans, D. R., Williford, W. O., Kilbourne, A. M., et al. (2005). Medical comorbidity and health-related quality of life in bipolar disorder across the adult age span. Journal of Affective Disorders, 86(1), 47–60.

    PubMed  Google Scholar 

  • Fergenbaum, J. H., Bruce, S., Lou, W., Hanley, A. J., Greenwood, C., & Young, T. K. (2009). Obesity and lowered cognitive performance in a Canadian First Nations population. Obesity (Silver Spring), 17(10), 1957–1963.

    Google Scholar 

  • Floresco, S. B., St Onge, J. R., Ghods-Sharifi, S., & Winstanley, C. A. (2008). Cortico-limbic-striatal circuits subserving different forms of cost-benefit decision making. Cognitive Affect Behaviors in Neuroscience, 8(4), 375–389.

    Google Scholar 

  • Forti, P., Pisacane, N., Rietti, E., Lucicesare, A., Olivelli, V., Mariani, E., et al. (2010). Metabolic syndrome and risk of dementia in older adults. Journal of the American Geriatrics Society, 58(3), 487–492.

    PubMed  Google Scholar 

  • Friedman, J. M., & Halaas, J. L. (1998). Leptin and the regulation of body weight in mammals. Nature, 395(6704), 763–770.

    PubMed  CAS  Google Scholar 

  • Fu, C. H., Williams, S. C., Cleare, A. J., Brammer, M. J., Walsh, N. D., Kim, J., et al. (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment: A prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry, 61(9), 877–889.

    PubMed  Google Scholar 

  • Gispen, W. H., & Biessels, G. J. (2000). Cognition and synaptic plasticity in diabetes mellitus. Trends in Neurosciences, 23(11), 542–549.

    PubMed  CAS  Google Scholar 

  • Grundy, S. M., Cleeman, J. I., Daniels, S. R., Donato, K. A., Eckel, R. H., Franklin, B. A., et al. (2005). Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 112(17), 2735–2752.

    PubMed  Google Scholar 

  • Gustafson, D., Lissner, L., Bengtsson, C., Bjorkelund, C., & Skoog, I. (2004). A 24-year follow-up of body mass index and cerebral atrophy. Neurology, 63(10), 1876–1881.

    PubMed  CAS  Google Scholar 

  • Haack, M., Hinze-Selch, D., Fenzel, T., Kraus, T., Kuhn, M., Schuld, A., et al. (1999). Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: Effects of confounding factors and diagnosis. Journal of Psychiatric Research, 33(5), 407–418.

    PubMed  CAS  Google Scholar 

  • Haltia, L. T., Viljanen, A., Parkkola, R., Kemppainen, N., Rinne, J. O., Nuutila, P., et al. (2007). Brain white matter expansion in human obesity and the recovering effect of dieting. Journal of Clinical Endocrinology and Metabolism, 92(8), 3278–3284.

    PubMed  CAS  Google Scholar 

  • Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., & Critchley, H. D. (2009). Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biological Psychiatry, 66(5), 407–414.

    PubMed  Google Scholar 

  • Hervey, G. R. (1969). Regulation of energy balance. Nature, 222(5194), 629–631.

    PubMed  CAS  Google Scholar 

  • Hietala, J., West, C., Syvalahti, E., Nagren, K., Lehikoinen, P., Sonninen, P., et al. (1994). Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology (Berl), 116(3), 285–290.

    CAS  Google Scholar 

  • Himmerich, H., & Sheldrick, A. J. (2010). TNF-alpha and ghrelin: Opposite effects on immune system, metabolism and mental health. Protein and Peptide Letters, 17(2), 186–196.

    PubMed  CAS  Google Scholar 

  • Ho, A. J., Stein, J. L., Hua, X., Lee, S., Hibar, D. P., Leow, A. D., et al. (2010). A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. Proceedings of National Academics in Science USA, 107(18), 8404–8409.

    CAS  Google Scholar 

  • Hotamisligil, G. S. (2003). Inflammatory pathways and insulin action. International Journal of Obesity Related Metabolism Disorders, 27(Suppl 3), S53–S55.

    CAS  Google Scholar 

  • Hotamisligil, G. S., Murray, D. L., Choy, L. N., & Spiegelman, B. M. (1994). Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proceedings of National Academics in Science USA, 91(11), 4854–4858.

    CAS  Google Scholar 

  • Hsieh, P. S., Jin, J. S., Chiang, C. F., Chan, P. C., Chen, C. H., & Shih, K. C. (2009). COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity (Silver Spring), 17(6), 1150–1157.

    CAS  Google Scholar 

  • Hsieh, P. S., Lu, K. C., Chiang, C. F., & Chen, C. H. (2010). Suppressive effect of COX2 inhibitor on the progression of adipose inflammation in high-fat-induced obese rats. European Journal of Clinical Investigation, 40(2), 164–171.

    PubMed  CAS  Google Scholar 

  • Hughes, T. F., & Ganguli, M. (2009). Modifiable midlife risk factors for late-life cognitive impairment and dementia. Current Psychiatry Reviews, 5(2), 73–92.

    PubMed  Google Scholar 

  • Jacob, A., Rajan, D., Pathickal, B., Balouch, I., Hartman, A., Wu, R., et al. (2010). The inhibitory effect of ghrelin on sepsis-induced inflammation is mediated by the MAPK phosphatase-1. International Journal of Molecular Medicine, 25(1), 159–164.

    PubMed  CAS  Google Scholar 

  • Jagust, W., Harvey, D., Mungas, D., & Haan, M. (2005). Central obesity and the aging brain. Archives of Neurology, 62(10), 1545–1548.

    PubMed  Google Scholar 

  • Jensen, G. L. (2008). Drug-induced hyperphagia: What can we learn from psychiatric medications? JPEN Journal of Parenter Enteral Nutrition, 32(5), 578–581.

    Google Scholar 

  • Kahn, R., Buse, J., Ferrannini, E., & Stern, M. (2005). The metabolic syndrome: Time for a critical appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 28(9), 2289–2304.

    PubMed  Google Scholar 

  • Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: A pathology of motivation and choice. American Journal of Psychiatry, 162(8), 1403–1413.

    PubMed  Google Scholar 

  • Kapczinski, F., Vieta, E., Andreazza, A. C., Frey, B. N., Gomes, F. A., Tramontina, J., et al. (2008). Allostatic load in bipolar disorder: Implications for pathophysiology and treatment. Neuroscience and Biobehavioral Reviews, 32(4), 675–692.

    PubMed  Google Scholar 

  • Karalis, K. P., Giannogonas, P., Kodela, E., Koutmani, Y., Zoumakis, M., & Teli, T. (2009). Mechanisms of obesity and related pathology: Linking immune responses to metabolic stress. FEBS Journal, 276(20), 5747–5754.

    PubMed  CAS  Google Scholar 

  • Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., et al. (2003). The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA, 289(23), 3095–3105.

    PubMed  Google Scholar 

  • Kiefer, F., Jahn, H., Jaschinski, M., Holzbach, R., Wolf, K., Naber, D., et al. (2001). Leptin: A modulator of alcohol craving? Biological Psychiatry, 49(9), 782–787.

    PubMed  CAS  Google Scholar 

  • Kilbourne, A. M., Cornelius, J. R., Han, X., Pincus, H. A., Shad, M., Salloum, I., et al. (2004). Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disorders, 6(5), 368–373.

    PubMed  Google Scholar 

  • Kim, Y. K., Jung, H. G., Myint, A. M., Kim, H., & Park, S. H. (2007). Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. Journal of Affective Disorders, 104(1–3), 91–95.

    PubMed  CAS  Google Scholar 

  • Kim, S. J., Lee, H. J., Koo, H. G., Kim, J. W., Song, J. Y., Kim, M. K., et al. (2004a). Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder. Psychiatric Genetics, 14(3), 165–167.

    PubMed  CAS  Google Scholar 

  • Kim, Y. K., Myint, A. M., Lee, B. H., Han, C. S., Lee, S. W., Leonard, B. E., et al. (2004b). T-helper types 1, 2, and 3 cytokine interactions in symptomatic manic patients. Psychiatry Research, 129(3), 267–272.

    PubMed  CAS  Google Scholar 

  • Knijff, E. M., Breunis, M. N., Kupka, R. W., de Wit, H. J., Ruwhof, C., Akkerhuis, G. W., et al. (2007). An imbalance in the production of IL-1beta and IL-6 by monocytes of bipolar patients: Restoration by lithium treatment. Bipolar Disorders, 9(7), 743–753.

    PubMed  CAS  Google Scholar 

  • Knijff, E. M., Breunis, M. N., van Geest, M. C., Kupka, R. W., Ruwhof, C., de Wit, H. J., et al. (2006). A relative resistance of T cells to dexamethasone in bipolar disorder. Bipolar Disorders, 8(6), 740–750.

    PubMed  CAS  Google Scholar 

  • Konarski, J. Z., McIntyre, R. S., Kennedy, S. H., Rafi-Tari, S., Soczynska, J. K., Ketter, T.A. (2006). Volumetric neuroimaging in mood disorders: Bipolar disorder versus major depressive disorder. Bipolar Disorders (in press).

  • Konarski, J. Z., McIntyre, R. S., Kennedy, S. H., Rafi-Tari, S., Soczynska, J. K., & Ketter, T. A. (2008). Volumetric neuroimaging investigations in mood disorders: Bipolar disorder versus major depressive disorder. Bipolar Disorders, 10(1), 1–37.

    PubMed  Google Scholar 

  • Kral, J. G., Paez, W., & Wolfe, B. M. (2009). Vagal nerve function in obesity: Therapeutic implications. World Journal of Surgery, 33(10), 1995–2006.

    PubMed  Google Scholar 

  • Kraus, T., Reulbach, U., Bayerlein, K., Mugele, B., Hillemacher, T., Sperling, W., et al. (2004). Leptin is associated with craving in females with alcoholism. Addiction Biology, 9(3–4), 213–219.

    PubMed  CAS  Google Scholar 

  • Krebs, M., Leopold, K., Hinzpeter, A., & Schaefer, M. (2006). Neuroprotective agents in schizophrenia and affective disorders. Expert Opinion on Pharmacotherapy, 7(7), 837–848.

    PubMed  CAS  Google Scholar 

  • Kreutzberg, G. W. (1996). Microglia: A sensor for pathological events in the CNS. Trends in Neurosciences, 19(8), 312–318.

    PubMed  CAS  Google Scholar 

  • Kupka, R. W., Breunis, M. N., Knijff, E., Ruwhof, C., Nolen, W. A., & Drexhage, H. A. (2002). Immune activation, steroid resistancy and bipolar disorder. Bipolar Disorders, 4(Suppl 1), 73–74.

    PubMed  Google Scholar 

  • La, C. A., & Matarese, G. (2004). The weight of leptin in immunity. Nature Reviews Immunology, 4(5), 371–379.

    Google Scholar 

  • LaBar, K. S., Gitelman, D. R., Parrish, T. B., Kim, Y. H., Nobre, A. C., & Mesulam, M. M. (2001). Hunger selectively modulates corticolimbic activation to food stimuli in humans. Behavioral Neuroscience, 115(2), 493–500.

    PubMed  CAS  Google Scholar 

  • Larson, S. J., & Dunn, A. J. (2001). Behavioral effects of cytokines. Brain Behavior Immunology, 15(4), 371–387.

    CAS  Google Scholar 

  • Lee, A. L., Ogle, W. O., & Sapolsky, R. M. (2002). Stress and depression: Possible links to neuron death in the hippocampus. Bipolar Disorders, 4(2), 117–128.

    PubMed  CAS  Google Scholar 

  • Leverich, G. S., Altshuler, L. L., Frye, M. A., Suppes, T., Keck, P. E., Jr., McElroy, S. L., et al. (2003). Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. Journal of Clinical Psychiatry, 64(5), 506–515.

    PubMed  Google Scholar 

  • Levine, J., Barak, Y., Chengappa, K. N., Rapoport, A., Rebey, M., & Barak, V. (1999). Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology, 40(4), 171–176.

    PubMed  CAS  Google Scholar 

  • Licinio, J., Kling, M. A., & Hauser, P. (1998). Cytokines and brain function: Relevance to interferon-alpha-induced mood and cognitive changes. Seminars in Oncology, 25(1 Suppl 1), 30–38.

    PubMed  CAS  Google Scholar 

  • Liu, H. C., Yang, Y. Y., Chou, Y. M., Chen, K. P., Shen, W. W., & Leu, S. J. (2004). Immunologic variables in acute mania of bipolar disorder. Journal of Neuroimmunology, 150(1–2), 116–122.

    PubMed  CAS  Google Scholar 

  • Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., & Lechler, R. I. (1998). Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature, 394(6696), 897–901.

    PubMed  CAS  Google Scholar 

  • Lorenzetti, V., Allen, N. B., Fornito, A., Yucel, M. (2009). Structural brain abnormalities in major depressive disorder: A selective review of recent MRI studies. Journal of Affective Disorders.

  • Luchsinger, J. A., Tang, M. X., Shea, S., & Mayeux, R. (2004). Hyperinsulinemia and risk of Alzheimer disease. Neurology, 63(7), 1187–1192.

    PubMed  Google Scholar 

  • Macdonald, N. J., Delderfield, S. M., Zhang, W., & Taglialatela, G. (2003). Tumour necrosis factor-alpha- vs. growth factor deprivation-promoted cell death: Distinct converging pathways. Aging Cell, 2(5), 245–256.

    PubMed  CAS  Google Scholar 

  • MacQueen, G. M., Campbell, S., McEwen, B. S., Macdonald, K., Amano, S., Joffe, R. T., et al. (2003). Course of illness, hippocampal function, and hippocampal volume in major depression. Proceedings of National Academics in Science USA, 100(3), 1387–1392.

    CAS  Google Scholar 

  • Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., et al. (2002). Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Medicine, 8(7), 731–737.

    PubMed  CAS  Google Scholar 

  • Maes, M., Bosmans, E., Calabrese, J., Smith, R., & Meltzer, H. Y. (1995). Interleukin-2 and interleukin-6 in schizophrenia and mania: Effects of neuroleptics and mood stabilizers. Journal of Psychiatric Research, 29(2), 141–152.

    PubMed  CAS  Google Scholar 

  • Malik, S., McGlone, F., Bedrossian, D., & Dagher, A. (2008). Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metabolism, 7(5), 400–409.

    PubMed  CAS  Google Scholar 

  • Mandel, M. A., & Mahmoud, A. A. (1978). Impairment of cell-mediated immunity in mutation diabetic mice (db/db). Journal of Immunology, 120(4), 1375–1377.

    CAS  Google Scholar 

  • Manji, H. K., & Lenox, R. H. (2000). Signaling: Cellular insights into the pathophysiology of bipolar disorder. Biological Psychiatry, 48(6), 518–530.

    PubMed  CAS  Google Scholar 

  • Manji, H. K., Quiroz, J. A., Payne, J. L., Singh, J., Lopes, B. P., Viegas, J. S., et al. (2003). The underlying neurobiology of bipolar disorder. World Psychiatry, 2(3), 136–146.

    PubMed  Google Scholar 

  • Marques-Deak, A. H., Neto, F. L., Dominguez, W. V., Solis, A. C., Kurcgant, D., Sato, F., et al. (2007). Cytokine profiles in women with different subtypes of major depressive disorder. Journal of Psychiatric Research, 41(1–2), 152–159.

    PubMed  CAS  Google Scholar 

  • Martinez-Aran, A., Vieta, E., Colom, F., Reinares, M., Benabarre, A., Gasto, C., et al. (2000). Cognitive dysfunctions in bipolar disorder: Evidence of neuropsychological disturbances. Psychotherapy and Psychosomatics, 69(1), 2–18.

    PubMed  CAS  Google Scholar 

  • Matsumoto, S., Ogawa, H., Soda, S., Hirayama, S., Amarasena, N., Aizawa, Y., et al. (2009). Effect of antimicrobial periodontal treatment and maintenance on serum adiponectin in type 2 diabetes mellitus. Journal of Clinical Periodontology, 36(2), 142–148.

    PubMed  Google Scholar 

  • Mattsson, C., Reynolds, R. M., Simonyte, K., Olsson, T., & Walker, B. R. (2009). Combined receptor antagonist stimulation of the hypothalamic-pituitary-adrenal axis test identifies impaired negative feedback sensitivity to cortisol in obese men. Journal of Clinical Endocrinology and Metabolism, 94(4), 1347–1352.

    PubMed  CAS  Google Scholar 

  • Mayberg, H. S. (2003). Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin, 65, 193–207.

    PubMed  Google Scholar 

  • Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., et al. (2005). Deep brain stimulation for treatment-resistant depression. Neuron, 45(5), 651–660.

    PubMed  CAS  Google Scholar 

  • McElroy, S. L., Kotwal, R., Malhotra, S., Nelson, E. B., Keck, P. E., Nemeroff, C. B. (2004). Are mood disorders and obesity related? A review for the mental health professional. Journal of Clinical Psychiatry, 65(5), 634–651, quiz.

    Google Scholar 

  • McEwen, B. S. (1999). Stress and hippocampal plasticity. Annual Review of Neuroscience, 22, 105–122.

    PubMed  CAS  Google Scholar 

  • McEwen, B. S. (2003). Mood disorders and allostatic load. Biological Psychiatry, 54(3), 200–207.

    PubMed  Google Scholar 

  • McIntyre, R. S. (2002). Psychotropic drugs and adverse events in the treatment of bipolar disorders revisited. Journal of Clinical Psychiatry, 63(Suppl 3), 15–20.

    PubMed  CAS  Google Scholar 

  • McIntyre, R. S., Kenna, H. A., Nguyen, H. T., Law, C. W., Sultan, F., Woldeyohannes, H. O., Alsuwaidan, M. T., Soczynska, J. K., Adams, A. K., Cheng, J. S., Lourenco, M., Kennedy, S. H., Rasgon, N. L. (2010). Brain volume abnormalities and neurocognitive deficits in diabetes mellitus: Points of pathophysiological commonality with mood disorders? Advances in Therapy.

  • McIntyre, R. S., Konarski, J. Z., Soczynska, J. K., Wilkins, K., Panjwani, G., Bouffard, B., et al. (2006a). Medical comorbidity in bipolar disorder: Implications for functional outcomes and health service utilization. Psychiatric Services, 57(8), 1140–1144.

    PubMed  Google Scholar 

  • McIntyre, R. S., Konarski, J. Z., Wilkins, K., Soczynska, J. K., & Kennedy, S. H. (2006b). Obesity in bipolar disorder and major depressive disorder: Results from a national community health survey on mental health and well-being. Canadian Journal of Psychiatry, 51, 274–280.

    Google Scholar 

  • McIntyre, R. S., McCann, S. M., & Kennedy, S. H. (2001). Antipsychotic metabolic effects: Weight gain, diabetes mellitus, and lipid abnormalities. Canadian Journal of Psychiatry, 46(3), 273–281.

    CAS  Google Scholar 

  • McIntyre, R. S., McElroy, S., Konarski, J. Z., Soczynska, J. K., Bottas, A., Castel, S., Wilkins, K., Kennedy, S. H. (2007). Substance use disorders and overweight/obesity in bipolar I disorder: Preliminary evidence for competing addictions. Journal of Clinical Psychiatry (in press).

  • McIntyre, R. S., Soczynska, J. K., Woldeyohannes, H. O., Lewis, G. F., Leiter, L. A., MacQueen, G. M., et al. (2007b). Thiazolidinediones: Novel treatments for cognitive deficits in mood disorders? Expert Opinion on Pharmacotherapy, 8(11), 1615–1628.

    PubMed  CAS  Google Scholar 

  • McMahon, M., Gerich, J., & Rizza, R. (1988). Effects of glucocorticoids on carbohydrate metabolism. Diabetes/Metabolism Reviews, 4(1), 17–30.

    PubMed  CAS  Google Scholar 

  • McNally, L., Bhagwagar, Z., & Hannestad, J. (2008). Inflammation, glutamate, and glia in depression: A literature review. CNS Spectrums, 13(6), 501–510.

    PubMed  Google Scholar 

  • Meira-Lima, I. V., Pereira, A. C., Mota, G. F., Floriano, M., Araujo, F., Mansur, A. J., et al. (2003). Analysis of a polymorphism in the promoter region of the tumor necrosis factor alpha gene in schizophrenia and bipolar disorder: Further support for an association with schizophrenia. Molecular Psychiatry, 8(8), 718–720.

    PubMed  CAS  Google Scholar 

  • Miller, A. H. (2009). Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: Psychoneuroimmunology at the translational interface. Brain Behavior Immunlogy, 23(2), 149–158.

    CAS  Google Scholar 

  • Miller, A. H., Maletic, V., & Raison, C. L. (2009a). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65(9), 732–741.

    PubMed  CAS  Google Scholar 

  • Miller, A. H., Maletic, V., Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry.

  • Molina-Hernandez, M., Tellez-Alcantara, N. P., Perez-Garcia, J., Olivera-Lopez, J. I., & Jaramillo-Jaimes, M. T. (2008a). Antidepressant-like actions of minocycline combined with several glutamate antagonists. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(2), 380–386.

    PubMed  CAS  Google Scholar 

  • Molina-Hernandez, M., Tellez-Alcantara, N. P., Perez-Garcia, J., Olivera-Lopez, J. I., & Jaramillo-Jaimes, M. T. (2008b). Desipramine or glutamate antagonists synergized the antidepressant-like actions of intra-nucleus accumbens infusions of minocycline in male Wistar rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(7), 1660–1666.

    PubMed  CAS  Google Scholar 

  • Musselman, D. L., Betan, E., Larsen, H., & Phillips, L. S. (2003). Relationship of depression to diabetes types 1 and 2: Epidemiology, biology, and treatment. Biological Psychiatry, 54(3), 317–329.

    PubMed  Google Scholar 

  • Nakashima, K., Akiyoshi, J., Hatano, K., Hanada, H., Tanaka, Y., Tsuru, J., et al. (2008). Ghrelin gene polymorphism is associated with depression, but not panic disorder. Psychiatric Genetics, 18(5), 257.

    PubMed  Google Scholar 

  • Narita, K., Murata, T., Takahashi, T., Kosaka, H., Omata, N., & Wada, Y. (2006). Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 30(6), 1159–1162.

    PubMed  CAS  Google Scholar 

  • Nery, F. G., Monkul, E. S., Hatch, J. P., Fonseca, M., Zunta-Soares, G. B., Frey, B. N., et al. (2008). Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: A double-blind, randomized, placebo-controlled study. Human Psychopharmacology, 23(2), 87–94.

    PubMed  CAS  Google Scholar 

  • Nieto-Vazquez, I., Fernandez-Veledo, S., Kramer, D. K., Vila-Bedmar, R., Garcia-Guerra, L., & Lorenzo, M. (2008). Insulin resistance associated to obesity: The link TNF-alpha. Archives of Physiology and Biochemistry, 114(3), 183–194.

    PubMed  CAS  Google Scholar 

  • Nutrition Classics (1983). The anatomical record, vol. 78, 1940: Hypothalamic lesions and adiposity in the rat. Nutritional Reviews, 41(4), 124–127.

    Google Scholar 

  • O’Brien, S. M., Scully, P., Scott, L. V., & Dinan, T. G. (2006). Cytokine profiles in bipolar affective disorder: Focus on acutely ill patients. Journal of Affective Disorders, 90(2–3), 263–267.

    PubMed  Google Scholar 

  • Ogden, C. L., Carroll, M. D., Curtin, L. R., McDowell, M. A., Tabak, C. J., & Flegal, K. M. (2006). Prevalence of overweight and obesity in the United States, 1999–2004. JAMA, 295(13), 1549–1555.

    PubMed  CAS  Google Scholar 

  • Ohshima, K., Shargill, N. S., Chan, T. M., & Bray, G. A. (1984). Adrenalectomy reverses insulin resistance in muscle from obese (ob/ob) mice. American Journal of Physiology, 246(2 Pt 1), E193–E197.

    PubMed  CAS  Google Scholar 

  • Ongur, D., Drevets, W. C., & Price, J. L. (1998). Glial reduction in the subgenual prefrontal cortex in mood disorders. Proceedings of National Academics in Science USA, 95(22), 13290–13295.

    CAS  Google Scholar 

  • Ortiz-Dominguez, A., Hernandez, M. E., Berlanga, C., Gutierrez-Mora, D., Moreno, J., Heinze, G., et al. (2007). Immune variations in bipolar disorder: Phasic differences. Bipolar Disorders, 9(6), 596–602.

    PubMed  CAS  Google Scholar 

  • Ouchi, N., Kihara, S., Arita, Y., Maeda, K., Kuriyama, H., Okamoto, Y., et al. (1999). Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation, 100(25), 2473–2476.

    PubMed  CAS  Google Scholar 

  • Padmos, R. C., Hillegers, M. H., Knijff, E. M., Vonk, R., Bouvy, A., Staal, F. J., et al. (2008). A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Archives of General Psychiatry, 65(4), 395–407.

    PubMed  CAS  Google Scholar 

  • Pae, C. U., Lee, K. U., Han, H., Serretti, A., & Jun, T. Y. (2004). Tumor necrosis factor alpha gene-G308A polymorphism associated with bipolar I disorder in the Korean population. Psychiatry Research, 125(1), 65–68.

    PubMed  CAS  Google Scholar 

  • Pannacciulli, N., Del, P. A., Chen, K., Le, D. S., Reiman, E. M., & Tataranni, P. A. (2006). Brain abnormalities in human obesity: A voxel-based morphometric study. Neuroimage, 31(4), 1419–1425.

    PubMed  Google Scholar 

  • Papiol, S., Rosa, A., Gutierrez, B., Martin, B., Salgado, P., Catalan, R., et al. (2004). Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder. Journal of Medical Genetics, 41(3), 219–223.

    PubMed  CAS  Google Scholar 

  • Pasco, J. A., Jacka, F. N., Williams, L. J., Henry, M. J., Nicholson, G. C., Kotowicz, M. A., et al. (2008). Leptin in depressed women: Cross-sectional and longitudinal data from an epidemiologic study. Journal of Affective Disorders, 107(1–3), 221–225.

    PubMed  CAS  Google Scholar 

  • Patten, S. B., Wang, J. L., Williams, J. V., Currie, S., Beck, C. A., Maxwell, C. J., et al. (2006). Descriptive epidemiology of major depression in Canada. Canadian Journal of Psychiatry, 51(2), 84–90.

    Google Scholar 

  • Pinar, M., Gulsun, M., Tasci, I., Erdil, A., Bolu, E., Acikel, C., et al. (2008). Maprotiline induced weight gain in depressive disorder: Changes in circulating ghrelin and adiponectin levels and insulin sensitivity. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(1), 135–139.

    PubMed  CAS  Google Scholar 

  • Pine, D. S., Cohen, P., Brook, J., & Coplan, J. D. (1997). Psychiatric symptoms in adolescence as predictors of obesity in early adulthood: A longitudinal study. American Journal of Public Health, 87(8), 1303–1310.

    PubMed  CAS  Google Scholar 

  • Piser, T. M. (2010). Linking the cytokine and neurocircuitry hypotheses of depression: A translational framework for discovery and development of novel anti-depressants. Brain Behav Immun, 24(4), 515–524.

    PubMed  CAS  Google Scholar 

  • Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology, 27(1), 24–31.

    PubMed  CAS  Google Scholar 

  • Raji, C. A., Ho, A. J., Parikshak, N. N., Becker, J. T., Lopez, O. L., Kuller, L. H., et al. (2010). Brain structure and obesity. Human Brain Mapping, 31(3), 353–364.

    PubMed  Google Scholar 

  • Rajkowska, G. (2002). Cell pathology in bipolar disorder. Bipolar Disord, 4(2), 105–116.

    PubMed  Google Scholar 

  • Rajkowska, G., Halaris, A., & Selemon, L. D. (2001). Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biological Psychiatry, 49(9), 741–752.

    PubMed  CAS  Google Scholar 

  • Rajkowska, G., & Miguel-Hidalgo, J. J. (2007). Gliogenesis and glial pathology in depression. CNS & Neurological Disorders Drug Targets, 6(3), 219–233.

    CAS  Google Scholar 

  • Rajkowska, G., Miguel-Hidalgo, J. J., Wei, J., Dilley, G., Pittman, S. D., Meltzer, H. Y., et al. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry, 45(9), 1085–1098.

    PubMed  CAS  Google Scholar 

  • Rapaport, M. H., Guylai, L., & Whybrow, P. (1999). Immune parameters in rapid cycling bipolar patients before and after lithium treatment. Journal of Psychiatric Research, 33(4), 335–340.

    PubMed  CAS  Google Scholar 

  • Raven, P. W., & Taylor, N. F. (1998). 11Beta-HSD and 17beta-HSD as biological markers of depression: Sex differences and correlation with symptom severity. Endocrine Research, 24(3–4), 659–662.

    PubMed  CAS  Google Scholar 

  • Reichenberg, A., Gorman, J. M., & Dieterich, D. T. (2005). Interferon-induced depression and cognitive impairment in hepatitis C virus patients: A 72 week prospective study. AIDS, 19(Suppl 3), S174–S178.

    PubMed  CAS  Google Scholar 

  • Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., et al. (2001). Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry, 58(5), 445–452.

    PubMed  CAS  Google Scholar 

  • Roberts, R. E., Deleger, S., Strawbridge, W. J., & Kaplan, G. A. (2003). Prospective association between obesity and depression: Evidence from the Alameda County Study. International Journal of Obesity Related Metabolism Disorders, 27(4), 514–521.

    CAS  Google Scholar 

  • Rolls, E. T., Critchley, H. D., Browning, A. S., Hernadi, I., & Lenard, L. (1999). Responses to the sensory properties of fat of neurons in the primate orbitofrontal cortex. Journal of Neuroscience, 19(4), 1532–1540.

    PubMed  CAS  Google Scholar 

  • Rolls, E. T., Verhagen, J. V., & Kadohisa, M. (2003). Representations of the texture of food in the primate orbitofrontal cortex: Neurons responding to viscosity, grittiness, and capsaicin. Journal of Neurophysiology, 90(6), 3711–3724.

    PubMed  Google Scholar 

  • Rush, A. J., Giles, D. E., Schlesser, M. A., Orsulak, P. J., Parker, C. R., Jr., Weissenburger, J. E., et al. (1996). The dexamethasone suppression test in patients with mood disorders. Journal of Clinical Psychiatry, 57(10), 470–484.

    PubMed  CAS  Google Scholar 

  • Sanchez-Lasheras, C., Konner, A. C., & Bruning, J. C. (2010). Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators. Frontiers in Neuroendocrinology, 31(1), 4–15.

    PubMed  CAS  Google Scholar 

  • Santesso, D. L., Dillon, D. G., Birk, J. L., Holmes, A. J., Goetz, E., Bogdan, R., et al. (2008). Individual differences in reinforcement learning: Behavioral, electrophysiological, and neuroimaging correlates. Neuroimage, 42(2), 807–816.

    PubMed  Google Scholar 

  • Schiepers, O. J., Wichers, M. C., & Maes, M. (2005). Cytokines and major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29(2), 201–217.

    PubMed  CAS  Google Scholar 

  • Schwartz, T. L., Nihalani, N., Jindal, S., Virk, S., & Jones, N. (2004). Psychiatric medication-induced obesity: a review. Obesity Reviews, 5(2), 115–121.

    PubMed  CAS  Google Scholar 

  • Schwartz, M. W., Woods, S. C., Porte, D., Jr., Seeley, R. J., & Baskin, D. G. (2000). Central nervous system control of food intake. Nature, 404(6778), 661–671.

    PubMed  CAS  Google Scholar 

  • Seminowicz, D. A., Mayberg, H. S., McIntosh, A. R., Goldapple, K., Kennedy, S., Segal, Z., et al. (2004). Limbic-frontal circuitry in major depression: A path modeling metanalysis. Neuroimage, 22(1), 409–418.

    PubMed  CAS  Google Scholar 

  • Shin, A. C., Zheng, H., & Berthoud, H. R. (2009). An expanded view of energy homeostasis: Neural integration of metabolic, cognitive, and emotional drives to eat. Physiology & Behavior, 97(5), 572–580.

    CAS  Google Scholar 

  • Silswal, N., Singh, A. K., Aruna, B., Mukhopadhyay, S., Ghosh, S., & Ehtesham, N. Z. (2005). Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochemical and Biophysical Research Communications, 334(4), 1092–1101.

    PubMed  CAS  Google Scholar 

  • Simon, G. E., Von Korff, M., Saunders, K., Miglioretti, D. L., Crane, P. K., van Belle, G., et al. (2006). Association between obesity and psychiatric disorders in the US adult population. Archives of General Psychiatry, 63(7), 824–830.

    PubMed  Google Scholar 

  • Soczynska, J. K., Kennedy, S. H., Goldstein, B. I., Lachowski, A., Woldeyohannes, H. O., & McIntyre, R. S. (2009). The effect of tumor necrosis factor antagonists on mood and mental health-associated quality of life: Novel hypothesis-driven treatments for bipolar depression? Neurotoxicology, 30(4), 497–521.

    PubMed  CAS  Google Scholar 

  • Soory, M. (2008). A role for non-antimicrobial actions of tetracyclines in combating oxidative stress in periodontal and metabolic diseases: A literature review. The Open Dentistry Journal, 2, 5–12.

    PubMed  CAS  Google Scholar 

  • Spiliotaki, M., Salpeas, V., Malitas, P., Alevizos, V., & Moutsatsou, P. (2006). Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients. Psychoneuroendocrinology, 31(6), 748–760.

    PubMed  CAS  Google Scholar 

  • Steppan, C. M., Bailey, S. T., Bhat, S., Brown, E. J., Banerjee, R. R., Wright, C. M., et al. (2001). The hormone resistin links obesity to diabetes. Nature, 409(6818), 307–312.

    PubMed  CAS  Google Scholar 

  • Stockmeier, C. A., Mahajan, G. J., Konick, L. C., Overholser, J. C., Jurjus, G. J., Meltzer, H. Y., et al. (2004). Cellular changes in the postmortem hippocampus in major depression. Biological Psychiatry, 56(9), 640–650.

    PubMed  Google Scholar 

  • Stoeckel, L. E., Kim, J., Weller, R. E., Cox, J. E., Cook, E. W., I. I. I., & Horwitz, B. (2009). Effective connectivity of a reward network in obese women. Brain Research Bulletin, 79(6), 388–395.

    PubMed  Google Scholar 

  • Stolte, E. H., Nabuurs, S. B., Bury, N. R., Sturm, A., Flik, G., Savelkoul, H. F., Lidy Verburg-van Kemenade, B. M. (2008). Stress and innate immunity in carp: Corticosteroid receptors and pro-inflammatory cytokines. Molecular Immunology.

  • Stubner, S., Schon, T., Padberg, F., Teipel, S. J., Schwarz, M. J., Haslinger, A., et al. (1999). Interleukin-6 and the soluble IL-6 receptor are decreased in cerebrospinal fluid of geriatric patients with major depression: No alteration of soluble gp130. Neuroscience Letters, 259(3), 145–148.

    PubMed  CAS  Google Scholar 

  • Su, K. P., Leu, S. J., Yang, Y. Y., Shen, W. W., Chou, Y. M., & Tsai, S. Y. (2002). Reduced production of interferon-gamma but not interleukin-10 in bipolar mania and subsequent remission. Journal of Affective Disorders, 71(1–3), 205–209.

    PubMed  CAS  Google Scholar 

  • Swann, A. C., Stokes, P. E., Casper, R., Secunda, S. K., Bowden, C. L., Berman, N., et al. (1992). Hypothalamic-pituitary-adrenocortical function in mixed and pure mania. Acta Psychiatrica Scandinavica, 85(4), 270–274.

    PubMed  CAS  Google Scholar 

  • Takahashi, N., Waelput, W., & Guisez, Y. (1999). Leptin is an endogenous protective protein against the toxicity exerted by tumor necrosis factor. Journal of Experimental Medicine, 189(1), 207–212.

    PubMed  CAS  Google Scholar 

  • Taki, Y., Kinomura, S., Sato, K., Inoue, K., Goto, R., Okada, K., et al. (2008). Relationship between body mass index and gray matter volume in 1, 428 healthy individuals. Obesity (Silver Spring), 16(1), 119–124.

    Google Scholar 

  • Talmi, D., Dayan, P., Kiebel, S. J., Frith, C. D., & Dolan, R. J. (2009). How humans integrate the prospects of pain and reward during choice. Journal of Neuroscience, 29(46), 14617–14626.

    PubMed  CAS  Google Scholar 

  • Tataranni, P. A., & DelParigi, A. (2003). Functional neuroimaging: A new generation of human brain studies in obesity research. Obesity Reviews, 4(4), 229–238.

    PubMed  CAS  Google Scholar 

  • Taylor, V., & Macqueen, G. (2006). Associations between bipolar disorder and metabolic syndrome: A review. Journal of Clinical Psychiatry, 67(7), 1034–1041.

    PubMed  Google Scholar 

  • Thaler, J. P., Choi, S. J., Schwartz, M. W., Wisse, B. E. (2009). Hypothalamic inflammation and energy homeostasis: Resolving the paradox. Frontiers in Neuroendocrinology.

  • Thiele, T. E., Navarro, M., Sparta, D. R., Fee, J. R., Knapp, D. J., & Cubero, I. (2003). Alcoholism and obesity: Overlapping neuropeptide pathways? Neuropeptides, 37(6), 321–337.

    PubMed  CAS  Google Scholar 

  • Thompson, J. M., Gallagher, P., Hughes, J. H., Watson, S., Gray, J. M., Ferrier, I. N., et al. (2005). Neurocognitive impairment in euthymic patients with bipolar affective disorder. British Journal of Psychiatry, 186, 32–40.

    PubMed  Google Scholar 

  • Tiehuis, A. M., van der G. Y., Visseren, F. L., Vincken, K. L., Biessels, G. J., Appelman, A. P., Kappelle, L. J., Mali, W. P. (2008). Diabetes increases atrophy and vascular lesions on brain MRI in patients with symptomatic arterial disease. Stroke, 39(5), 1600–1603.

  • Tilg, H., & Moschen, A. R. (2006). Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nature Reviews Immunology, 6(10), 772–783.

    PubMed  CAS  Google Scholar 

  • Tomasi, D., Wang, G. J., Wang, R., Backus, W., Geliebter, A., Telang, F., et al. (2009). Association of body mass and brain activation during gastric distention: Implications for obesity. PLoS One, 4(8), e6847.

    PubMed  Google Scholar 

  • Tsai, S. Y., Chen, K. P., Yang, Y. Y., Chen, C. C., Lee, J. C., Singh, V. K., et al. (1999). Activation of indices of cell-mediated immunity in bipolar mania. Biological Psychiatry, 45(8), 989–994.

    PubMed  CAS  Google Scholar 

  • Tsai, S. Y., Yang, Y. Y., Kuo, C. J., Chen, C. C., & Leu, S. J. (2001). Effects of symptomatic severity on elevation of plasma soluble interleukin-2 receptor in bipolar mania. Journal of Affective Disorders, 64(2–3), 185–193.

    PubMed  CAS  Google Scholar 

  • Vasiliadis, H. M., Lesage, A., Adair, C., Wang, P. S., & Kessler, R. C. (2007). Do Canada and the United States differ in prevalence of depression and utilization of services? Psychiatric Services, 58(1), 63–71.

    PubMed  Google Scholar 

  • Venters, H. D., Dantzer, R., & Kelley, K. W. (2000). A new concept in neurodegeneration: TNFalpha is a silencer of survival signals. Trends in Neurosciences, 23(4), 175–180.

    PubMed  CAS  Google Scholar 

  • Vezzani, A., Ravizza, T., Balosso, S., & Aronica, E. (2008). Glia as a source of cytokines: Implications for neuronal excitability and survival. Epilepsia, 49(Suppl 2), 24–32.

    PubMed  CAS  Google Scholar 

  • Volkow, N. D., Fowler, J. S., Wang, G. J., Hitzemann, R., Logan, J., Schlyer, D. J., et al. (1993). Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse, 14(2), 169–177.

    PubMed  CAS  Google Scholar 

  • Volkow, N., & Li, T. K. (2005). The neuroscience of addiction. Nature Neuroscience, 8(11), 1429–1430.

    PubMed  CAS  Google Scholar 

  • Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Goldstein, R. Z., Alia-Klein, N., et al. (2009). Inverse association between BMI and prefrontal metabolic activity in healthy adults. Obesity (Silver Spring), 17(1), 60–65.

    Google Scholar 

  • Volkow, N. D., & Wise, R. A. (2005). How can drug addiction help us understand obesity? Nature Neuroscience, 8(5), 555–560.

    PubMed  CAS  Google Scholar 

  • Walker, B. R. (2007). Extra-adrenal regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1: Physiological regulator and pharmacological target for energy partitioning. Proceedings of the Nutrition Society, 66(1), 1–8.

    PubMed  CAS  Google Scholar 

  • Walther, K., Birdsill, A. C., Glisky, E. L., Ryan, L. (2009). Structural brain differences and cognitive functioning related to body mass index in older females. Human Brain Mapping.

  • Wang, G. J., Volkow, N. D., Fowler, J. S., Logan, J., Abumrad, N. N., Hitzemann, R. J., et al. (1997). Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal. Neuropsychopharmacology, 16(2), 174–182.

    PubMed  CAS  Google Scholar 

  • Wang, G. J., Volkow, N. D., Logan, J., Pappas, N. R., Wong, C. T., Zhu, W., et al. (2001). Brain dopamine and obesity. Lancet, 357(9253), 354–357.

    PubMed  CAS  Google Scholar 

  • Ward, M. A., Carlsson, C. M., Trivedi, M. A., Sager, M. A., & Johnson, S. C. (2005). The effect of body mass index on global brain volume in middle-aged adults: A cross sectional study. BMC Neurol, 5, 23.

    PubMed  Google Scholar 

  • Watson, S., Gallagher, P., Ritchie, J. C., Ferrier, I. N., & Young, A. H. (2004). Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder. British Journal of Psychiatry, 184, 496–502.

    PubMed  Google Scholar 

  • Weber-Hamann, B., Kratzsch, J., Kopf, D., Lederbogen, F., Gilles, M., Heuser, I., et al. (2007). Resistin and adiponectin in major depression: The association with free cortisol and effects of antidepressant treatment. Journal of Psychiatric Research, 41(3–4), 344–350.

    PubMed  Google Scholar 

  • Whitmer, R. A., Gunderson, E. P., Barrett-Connor, E., Quesenberry, C. P., Jr. & Yaffe, K. (2005). Obesity in middle age and future risk of dementia: A 27 year longitudinal population based study. BMJ, 330(7504):1360.

    Google Scholar 

  • Whitmer, R. A., Gustafson, D. R., Barrett-Connor, E., Haan, M. N., Gunderson, E. P., & Yaffe, K. (2008). Central obesity and increased risk of dementia more than three decades later. Neurology, 71(14), 1057–1064.

    PubMed  CAS  Google Scholar 

  • Wilson, C. J., Finch, C. E., & Cohen, H. J. (2002). Cytokines and cognition—The case for a head-to-toe inflammatory paradigm. Journal of the American Geriatrics Society, 50(12), 2041–2056.

    PubMed  Google Scholar 

  • Wolf, A. M., Wolf, D., Rumpold, H., Enrich, B., & Tilg, H. (2004). Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochemical and Biophysical Research Communications, 323(2), 630–635.

    PubMed  CAS  Google Scholar 

  • Wood, G. E., Young, L. T., Reagan, L. P., Chen, B., & McEwen, B. S. (2004). Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment. Proceedings of National Academics in Science USA, 101(11), 3973–3978.

    CAS  Google Scholar 

  • Yokota, T., Oritani, K., Takahashi, I., Ishikawa, J., Matsuyama, A., Ouchi, N., et al. (2000). Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 96(5), 1723–1732.

    PubMed  CAS  Google Scholar 

  • Zakrzewska, K. E., Cusin, I., Sainsbury, A., Rohner-Jeanrenaud, F., & Jeanrenaud, B. (1997). Glucocorticoids as counterregulatory hormones of leptin: Toward an understanding of leptin resistance. Diabetes, 46(4), 717–719.

    PubMed  CAS  Google Scholar 

  • Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., et al. (2001). The relationship of depression and stressors to immunological assays: A meta-analytic review. Brain, Behavior, and Immunity, 15(3), 199–226.

    PubMed  CAS  Google Scholar 

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Disclosures

The author has received research funding or honoraria in the past three years from AstraZeneca, Biovail, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Pfizer, St. Jude Medical and Servier.

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Authors and Affiliations

  1. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada

    Joanna K. Soczynska, Sidney H. Kennedy, Hanna O. Woldeyohannes, Samantha S. Liauw, Mohammad Alsuwaidan, Christina Y. Yim & Roger S. McIntyre

  2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Joanna K. Soczynska, Sidney H. Kennedy & Roger S. McIntyre

  3. McGill University, Montreal, QC, Canada

    Samantha S. Liauw

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Sidney H. Kennedy, Mohammad Alsuwaidan & Roger S. McIntyre

  5. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Christina Y. Yim & Roger S. McIntyre

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  1. Joanna K. Soczynska
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Correspondence to Hanna O. Woldeyohannes.

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Soczynska, J.K., Kennedy, S.H., Woldeyohannes, H.O. et al. Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus. Neuromol Med 13, 93–116 (2011). https://doi.org/10.1007/s12017-010-8140-8

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