Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015, 159(2):208-214 | DOI: 10.5507/bp.2014.060

The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review

Jana Kucerovaa,b, Zuzana Babinskaa,b, Katerina Horskac, Hana Kotolovac
a Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic
b Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno
c Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, Veterinary and Pharmaceutical University Brno

Background: There is a growing interest in metabolic alterations in patients with psychiatric disorders due to their increased risk for metabolic syndrome (MetS) development. Inflammation is known to underlie the pathophysiology of schizophrenia and depression as well as MetS. Vulnerability factors for schizophrenia/depression and MetS hence appear to be shared.

Methods and Results: Based on a Web of Science search, this review examines current evidence for MetS pathophysiology involving dysregulation of adipose tissue signaling - adipokines and pro-inflammatory cytokine, both also known to be aberrant in schizophrenia/depression. Further, gender differences in the incidence and course of schizophrenia/depression were reported. The disturbances linked to the MetS are also described. Therefore, this review further maps the gender differences in the psychiatric-metabolic comorbidities.

Conclusion: There is evidence supporting a pathological predisposition to MetS in both schizophrenia and depression in both humans and animal models. This predisposition is dramatically enhanced by antipsychotic medication. Further, there are gender differences from clinical findings suggesting women with schizophrenia/depression are more vulnerable to MetS development. This has not yet been assessed in animal studies. We suggest further validation of existing schizophrenia and depression animal models for the assessment of metabolic disturbances to provide tools for developing new antipsychotics and antidepressants with "metabolically inert" profile or improving the metabolic status in schizophrenic/depressed patients.

Keywords: metabolic syndrome, schizophrenia, depression, sex/gender differences, adipokines, leptin, adiponectin, resistin, AFABP

Received: August 13, 2014; Accepted: November 12, 2014; Prepublished online: December 5, 2014; Published: June 28, 2015  Show citation

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Kucerova, J., Babinska, Z., Horska, K., & Kotolova, H. (2015). The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review. Biomedical papers, 159(2), 208-214. doi: 10.5507/bp.2014.060
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    References

    1. Day C. Metabolic syndrome, or What you will: definitions and epidemiology. Diab Vasc Dis Res 2007;4(1):32-8. Go to original source... Go to PubMed...
    2. McCullough AJ. Epidemiology of the metabolic syndrome in the USA. J Dig Dis 2011;12(5):333-40. Go to original source... Go to PubMed...
    3. Lasic D, Bevanda M, Bosnjak N, Uglesic B, Glavina T, Franic T. Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder. Psychiatr Danub 2014;26(3):214-9. Go to PubMed...
    4. Curtis LH, Hammill BG, Bethel MA, Anstrom KJ, Gottdiener JS, Schulman KA. Costs of the metabolic syndrome in elderly individuals: findings from the Cardiovascular Health Study. Diabetes Care 2007;30(10):2553-8. Go to PubMed...
    5. Scholze J, Alegria E, Ferri C, Langham S, Stevens W, Jeffries D, Uhl-Hochgraeber K. Epidemiological and economic burden of metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model. BMC Public Health 2010;10(529. Go to original source... Go to PubMed...
    6. Misra A, Khurana L. The metabolic syndrome in South Asians: epidemiology, determinants, and prevention. Metab Syndr Relat Disord 2009;7(6):497-514. Go to original source... Go to PubMed...
    7. De Ferranti SD, Osganian SK. Epidemiology of paediatric metabolic syndrome and type 2 diabetes mellitus. Diab Vasc Dis Res 2007;4(4):285-96. Go to original source... Go to PubMed...
    8. Papanastasiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review. Ther Adv Psychopharmacol 2013;3(1):33-51. Go to original source... Go to PubMed...
    9. Pan A, Keum N, Okereke OI, Sun Q, Kivimaki M, Rubin RR, Hu FB. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care 2012;35(5):1171-80. Go to original source... Go to PubMed...
    10. Fuente-Martin E, Garcia-Caceres C, Morselli E, Clegg DJ, Chowen JA, Finan B, Brinton RD, Tschop MH. Estrogen, astrocytes and the neuroendocrine control of metabolism. Rev Endocr Metab Disord 2013;14(4):331-8. Go to original source... Go to PubMed...
    11. Mabry RM, Reeves MM, Eakin EG, Owen N. Gender differences in prevalence of the metabolic syndrome in Gulf Cooperation Council Countries: a systematic review. Diabet Med 2010;27(5):593-7. Go to original source... Go to PubMed...
    12. Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol 2006;95(3):136-47. Go to original source... Go to PubMed...
    13. Tanner RM, Brown TM, Muntner P. Epidemiology of obesity, the metabolic syndrome, and chronic kidney disease. Curr Hypertens Rep 2012;14(2):152-9. Go to original source... Go to PubMed...
    14. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC, Jr. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120(16):1640-5. Go to original source... Go to PubMed...
    15. Macchia A, Levantesi G, Borrelli G, Franzosi MG, Maggioni AP, Marfisi R, Scarano M, Tavazzi L, Tognoni G, Valagussa F, Marchioli R. A clinically practicable diagnostic score for metabolic syndrome improves its predictivity of diabetes mellitus: the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI)-Prevenzione scoring. Am Heart J 2006;151(3):754 e7-754 e17. Go to original source... Go to PubMed...
    16. Na KS, Jung HY, Kim YK. The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2014;48(277-86. Go to original source...
    17. Ahima RS. Revisiting leptin's role in obesity and weight loss. J Clin Invest 2008;118(7):2380-3. Go to original source... Go to PubMed...
    18. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83(7):1263-71. Go to original source... Go to PubMed...
    19. Baskin DG, Figlewicz Lattemann D, Seeley RJ, Woods SC, Porte D, Jr., Schwartz MW. Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res 1999;848(1-2):114-23. Go to original source... Go to PubMed...
    20. Koleva DI, Orbetzova MM, Atanassova PK. Adipose tissue hormones and appetite and body weight regulators in insulin resistance. Folia Med (Plovdiv) 2013;55(1):25-32. Go to original source... Go to PubMed...
    21. Kotolova H, Horska K, Kucerova J, Adipose Tissue Endocrine Regulations in Metabolic Syndrome and Appetite, in Appetite: Regulation, Use of Stimulants and Cultural and Biological Influences, J. Bienertova-Vasku, Editor 2014, Nova Science Publishers, Inc.: New York. p. 97-122
    22. Kong AP, Chan NN, Chan JC. The role of adipocytokines and neurohormonal dysregulation in metabolic syndrome. Curr Diabetes Rev 2006;2(4):397-407. Go to original source... Go to PubMed...
    23. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 2010;316(2):129-39. Go to original source... Go to PubMed...
    24. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001;409(6818):307-12. Go to original source... Go to PubMed...
    25. Nagaev I, Bokarewa M, Tarkowski A, Smith U. Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes. PLoS One 2006;(1):e31. Go to original source... Go to PubMed...
    26. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005;174(9):5789-95. Go to original source... Go to PubMed...
    27. Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR. Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun 2003;309(2):286-90. Go to original source... Go to PubMed...
    28. Rabe K, Lehrke M, Parhofer KG, Broedl UC. Adipokines and insulin resistance. Mol Med 2008;14(11-12):741-51. Go to original source... Go to PubMed...
    29. Karpisek M, Stejskal D, Kotolova H, Kollar P, Janoutova G, Ochmanova R, Cizek L, Horakova D, Yahia RB, Lichnovska R, Janout V. Treatment with atorvastatin reduces serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia. Eur J Clin Invest 2007;37(8):637-42. Go to original source... Go to PubMed...
    30. Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, Yeung DC, Janus ED, Sham PC, Lam KS. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 2007;115(12):1537-43. Go to original source... Go to PubMed...
    31. Alemany M. Relationship between energy dense diets and white adipose tissue inflammation in metabolic syndrome. Nutr Res 2013;33(1):1-11. Go to original source... Go to PubMed...
    32. Tracy RP. Inflammation, the metabolic syndrome and cardiovascular risk. Int J Clin Pract Suppl 2003;134):10-7.
    33. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112(12):1821-30. Go to original source... Go to PubMed...
    34. Santos MJ, Fonseca JE. Metabolic syndrome, inflammation and atherosclerosis - the role of adipokines in health and in systemic inflammatory rheumatic diseases. Acta Reumatol Port 2009;34(4):590-8. Go to PubMed...
    35. Charriere G, Cousin B, Arnaud E, Andre M, Bacou F, Penicaud L, Casteilla L. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 2003;278(11):9850-5. Go to original source... Go to PubMed...
    36. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002;5(5):551-9. Go to original source... Go to PubMed...
    37. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259(5091):87-91. Go to original source... Go to PubMed...
    38. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365(9468):1415-28. Go to original source... Go to PubMed...
    39. Drexhage RC, Knijff EM, Padmos RC, Heul-Nieuwenhuijzen L, Beumer W, Versnel MA, Drexhage HA. The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Rev Neurother 2010;10(1):59-76. Go to original source... Go to PubMed...
    40. Meyer U, Nyffeler M, Yee BK, Knuesel I, Feldon J. Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice. Brain Behav Immun 2008;22(4):469-86. Go to original source... Go to PubMed...
    41. Lodge DJ. The MAM rodent model of schizophrenia. Curr Protoc Neurosci 2013;Chapter 9(Unit9):43. Go to original source... Go to PubMed...
    42. Dinieri JA, Hurd YL. Rat models of prenatal and adolescent cannabis exposure. Methods Mol Biol 2012;829:231-42. Go to original source... Go to PubMed...
    43. Leonard BE, Schwarz M, Myint AM. The metabolic syndrome in schizophrenia: is inflammation a contributing cause? J Psychopharmacol 2012;26(5 Suppl):33-41. Go to original source... Go to PubMed...
    44. Halaris A. Inflammation, heart disease, and depression. Curr Psychiatry Rep 2013;15(10):400. Go to original source... Go to PubMed...
    45. Leonard B, Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 2012;36(2):764-85. Go to original source... Go to PubMed...
    46. Park S, Joo YH, McIntyre RS, Kim B. Metabolic Syndrome and Elevated C-Reactive Protein Levels in Elderly Patients With Newly Diagnosed Depression. Psychosomatics 2013; Go to original source...
    47. Patel A. Review: the role of inflammation in depression. Psychiatr Danub 2013;25 Suppl 2(S216-23.
    48. Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M. In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35(3):744-59. Go to original source... Go to PubMed...
    49. Song C, Leonard BE. The olfactory bulbectomised rat as a model of depression. Neurosci. Biobehav. Rev. 2005;29(4-5):627-47. Go to original source... Go to PubMed...
    50. Wu X, Huang Z, Wu R, Zhong Z, Wei Q, Wang H, Diao F, Wang J, Zheng L, Zhao J, Zhang J. The comparison of glycometabolism parameters and lipid profiles between drug-naive, first-episode schizophrenia patients and healthy controls. Schizophr Res 2013;150(1):157-62. Go to original source... Go to PubMed...
    51. Jin H, Meyer JM, Mudaliar S, Jeste DV. Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin. Schizophr Res 2008;100(1-3):70-85. Go to original source... Go to PubMed...
    52. Bajaj S, Varma A, Srivastava A, Verma AK. Association of metabolic syndrome with schizophrenia. Indian J Endocrinol Metab 2013;17(5):890-5. Go to original source... Go to PubMed...
    53. Centorrino F, Masters GA, Talamo A, Baldessarini RJ, Ongur D. Metabolic syndrome in psychiatrically hospitalized patients treated with antipsychotics and other psychotropics. Hum Psychopharmacol 2012;27(5):521-6. Go to original source... Go to PubMed...
    54. Ko YK, Soh MA, Kang SH, Lee JI. The prevalence of metabolic syndrome in schizophrenic patients using antipsychotics. Clin Psychopharmacol Neurosci 2013;11(2):80-8. Go to original source... Go to PubMed...
    55. Vancampfort D, Vansteelandt K, Correll CU, Mitchell AJ, De Herdt A, Sienaert P, Probst M, De Hert M. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry 2013;170(3):265-74. Go to original source... Go to PubMed...
    56. Beumer W, Drexhage RC, de Wit H, Versnel MA, Drexhage HA, Cohen D. Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 2012;37(12):1901-11. Go to original source... Go to PubMed...
    57. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 2006;51(6):801-10. Go to original source... Go to PubMed...
    58. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, Lopez-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rossler A, Grobbee DE. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008;371(9618):1085-97. Go to original source... Go to PubMed...
    59. Davey KJ, O'Mahony SM, Schellekens H, O'Sullivan O, Bienenstock J, Cotter PD, Dinan TG, Cryan JF. Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl) 2012;221(1):155-69. Go to original source... Go to PubMed...
    60. von Wilmsdorff M, Sprick U, Bouvier ML, Schulz D, Schmitt A, Gaebel W. Sex-dependent behavioral effects and morphological changes in the hippocampus after prenatal invasive interventions in rats: implications for animal models of schizophrenia. Clinics (Sao Paulo) 2010;65(2):209-19. Go to original source... Go to PubMed...
    61. Dunbar JA, Reddy P, Davis-Lameloise N, Philpot B, Laatikainen T, Kilkkinen A, Bunker SJ, Best JD, Vartiainen E, Kai Lo S, Janus ED. Depression: an important comorbidity with metabolic syndrome in a general population. Diabetes Care 2008;31(12):2368-73. Go to original source... Go to PubMed...
    62. Butnoriene J, Bunevicius A, Norkus A, Bunevicius R. Depression but not anxiety is associated with metabolic syndrome in primary care based community sample. Psychoneuroendocrinology 2014;40(269-76. Go to original source... Go to PubMed...
    63. Kahl KG, Greggersen W, Schweiger U, Cordes J, Balijepalli C, Losch C, Moebus S. Prevalence of the metabolic syndrome in unipolar major depression. Eur Arch Psychiatry Clin Neurosci 2012;262(4):313-20. Go to original source... Go to PubMed...
    64. Goldbacher EM, Bromberger J, Matthews KA. Lifetime history of major depression predicts the development of the metabolic syndrome in middle-aged women. Psychosom Med 2009;71(3):266-72. Go to original source... Go to PubMed...
    65. Lin KP, Liang TL, Liao IC, Tsay SL. Associations Among Depression, Obesity, and Metabolic Syndrome in Young Adult Females. Biol Res Nurs 2013; Go to original source...
    66. Fagiolini A, Chengappa KN, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs 2008;22(8):655-69. Go to original source... Go to PubMed...
    67. Skilton MR, Moulin P, Terra JL, Bonnet F. Associations between anxiety, depression, and the metabolic syndrome. Biol Psychiatry 2007;62(11):1251-7. Go to original source... Go to PubMed...
    68. Foley DL, Morley KI, Madden PA, Heath AC, Whitfield JB, Martin NG. Major depression and the metabolic syndrome. Twin Res Hum Genet 2010;13(4):347-58. Go to original source... Go to PubMed...
    69. Vargas HO, Nunes SO, Barbosa DS, Vargas MM, Cestari A, Dodd S, Venugopal K, Maes M, Berk M. Castelli risk indexes 1 and 2 are higher in major depression but other characteristics of the metabolic syndrome are not specific to mood disorders. Life Sci 2014; Go to original source...
    70. Kemp DE, Ismail-Beigi F, Calabrese JR. Antidepressant response associated with pioglitazone: support for an overlapping pathophysiology between major depression and metabolic syndrome. Am J Psychiatry 2009;166(5):619. Go to original source... Go to PubMed...
    71. Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW. Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 2013;18(6):692-9. Go to original source... Go to PubMed...
    72. Lu XY. The leptin hypothesis of depression: a potential link between mood disorders and obesity? Curr Opin Pharmacol 2007;7(6):648-52. Go to original source... Go to PubMed...
    73. Lutter M, Elmquist J. Depression and metabolism: linking changes in leptin and ghrelin to mood. F1000 Biol Rep 2009;1(63.
    74. Yamada N, Katsuura G, Ochi Y, Ebihara K, Kusakabe T, Hosoda K, Nakao K. Impaired CNS leptin action is implicated in depression associated with obesity. Endocrinology 2011;152(7):2634-43. Go to original source... Go to PubMed...
    75. Diniz BS, Teixeira AL, Campos AC, Miranda AS, Rocha NP, Talib LL, Gattaz WF, Forlenza OV. Reduced serum levels of adiponectin in elderly patients with major depression. J Psychiatr Res 2012;46(8):1081-5. Go to original source... Go to PubMed...
    76. Leo R, Di Lorenzo G, Tesauro M, Cola C, Fortuna E, Zanasi M, Troisi A, Siracusano A, Lauro R, Romeo F. Decreased plasma adiponectin concentration in major depression. Neurosci Lett 2006;407(3):211-3. Go to original source... Go to PubMed...
    77. Wilhelm CJ, Choi D, Huckans M, Manthe L, Loftis JM. Adipocytokine signaling is altered in Flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression. Pharmacol Biochem Behav 2013;103(3):643-51. Go to original source... Go to PubMed...
    78. Jeong HG, Min BJ, Lim S, Kim TH, Lee JJ, Park JH, Lee SB, Han JW, Choi SH, Park YJ, Jang HC, Kim KW. Plasma adiponectin elevation in elderly individuals with subsyndromal depression. Psychoneuroendocrinology 2012;37(7):948-55. Go to original source... Go to PubMed...
    79. Narita K, Murata T, Takahashi T, Kosaka H, Omata N, Wada Y. Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy. Prog Neuropsychopharmacol Biol Psychiatry 2006;30(6):1159-62. Go to original source... Go to PubMed...
    80. Weber-Hamann B, Kratzsch J, Kopf D, Lederbogen F, Gilles M, Heuser I, Deuschle M. Resistin and adiponectin in major depression: the association with free cortisol and effects of antidepressant treatment. J Psychiatr Res 2007;41(3-4):344-50. Go to original source... Go to PubMed...
    81. Castle D, Sham P, Murray R. Differences in distribution of ages of onset in males and females with schizophrenia. Schizophr Res 1998;33(3):179-83. Go to original source... Go to PubMed...
    82. Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int Rev Psychiatry 2010;22(5):417-28. Go to original source... Go to PubMed...
    83. Leung A, Chue P. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl 2000;401:3-38. Go to original source... Go to PubMed...
    84. Mann S, Chintoh A, Giacca A, Fletcher P, Nobrega J, Hahn M, Remington G. Chronic olanzapine administration in rats: effect of route of administration on weight, food intake and body composition. Pharmacol Biochem Behav 2013;103(4):717-22. Go to original source... Go to PubMed...
    85. van der Zwaal EM, Janhunen SK, la Fleur SE, Adan RA. Modelling olanzapine-induced weight gain in rats. Int J Neuropsychopharmacol 2014;17(1):169-86. Go to original source... Go to PubMed...
    86. Marijnissen RM, Smits JE, Schoevers RA, van den Brink RH, Holewijn S, Franke B, de Graaf J, Oude Voshaar RC. Association between metabolic syndrome and depressive symptom profiles--sex-specific? J Affect Disord 2013;151(3):1138-42. Go to original source... Go to PubMed...
    87. Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortmann SP. Depression and the metabolic syndrome in young adults: findings from the Third National Health and Nutrition Examination Survey. Psychosom Med 2004;66(3):316-22. Go to PubMed...
    88. Toker S, Shirom A, Melamed S. Depression and the metabolic syndrome: gender-dependent associations. Depress Anxiety 2008;25(8):661-9. Go to original source... Go to PubMed...
    89. Vancampfort D, Correll CU, Wampers M, Sienaert P, Mitchell AJ, De Herdt A, Probst M, Scheewe TW, De Hert M. Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables. Psychol Med 2013;1-12. Go to original source...
    90. Esel E, Ozsoy S, Tutus A, Sofuoglu S, Kartalci S, Bayram F, Kokbudak Z, Kula M. Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005;29(4):565-70. Go to original source... Go to PubMed...
    91. Beumer W, Drexhage RC, de Wit H, Versnel MA, Drexhage HA, Cohen D. Increased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome. Psychoneuroendocrinology 2011;37(12):1901-11. Go to original source... Go to PubMed...
    92. Lindenmayer JP, Khan A, Kaushik S, Thanju A, Praveen R, Hoffman L, Cherath L, Valdez G, Wance D. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr Res 2012;142(1-3):171-6. Go to original source... Go to PubMed...
    93. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27(2):596-601. Go to PubMed...
    94. Lee IT, Fu CP, Lee WJ, Liang KW, Lin SY, Wan CJ, Sheu WH. Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study. Diabetol Metab Syndr 2014;6(1):18. Go to original source... Go to PubMed...
    95. Schultz SK. Late-life depression research: lessons learned from the metabolic syndrome. Am J Psychiatry 2012;169(11):1133-6. Go to original source... Go to PubMed...
    96. Loprinzi PD, Cardinal BJ. Interrelationships among physical activity, depression, homocysteine, and metabolic syndrome with special considerations by sex. Prev Med 2012;54(6):388-92. Go to original source... Go to PubMed...
    97. Venkatasubramanian G, Debnath M. The TRIPS (Toll-like receptors in immuno-inflammatory pathogenesis) Hypothesis: a novel postulate to understand schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013;44(301-11. Go to original source... Go to PubMed...
    98. Kinney DK, Hintz K, Shearer EM, Barch DH, Riffin C, Whitley K, Butler R. A unifying hypothesis of schizophrenia: abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction. Med Hypotheses 2010;74(3):555-63. Go to original source... Go to PubMed...
    99. Kucerova J, Tabiova K, Drago F, Micale V. Therapeutic potential of cannabinoids in schizophrenia. Recent Pat CNS Drug Discov 2014;9(1):13-25. Go to original source... Go to PubMed...
    100. Micale V, Kucerova J, Sulcova A. Leading compounds for the validation of animal models of psychopathology. Cell Tissue Res. 2013; Go to original source...
    101. Micale V, Di Marzo V, Sulcova A, Wotjak CT, Drago F. Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacol. Ther. 2013;138(1):18-37. Go to original source... Go to PubMed...
    102. Gelfand EV, Cannon CP. Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs 2006;15(3):307-15. Go to original source... Go to PubMed...
    103. Moreira FA, Crippa JA. The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr 2009;31(2):145-53. Go to original source... Go to PubMed...
    104. Soyka M. Rimonabant and depression. Pharmacopsychiatry 2008;41(5):204-5. Go to original source... Go to PubMed...
    105. Kakafika AI, Mikhailidis DP, Karagiannis A, Athyros VG. The role of endocannabinoid system blockade in the treatment of the metabolic syndrome. J Clin Pharmacol 2007;47(5):642-52. Go to original source... Go to PubMed...
    106. Perkins JM, Davis SN. Endocannabinoid system overactivity and the metabolic syndrome: prospects for treatment. Curr Diab Rep 2008;8(1):12-9. Go to original source... Go to PubMed...
    107. Vemuri VK, Janero DR, Makriyannis A. Pharmacotherapeutic targeting of the endocannabinoid signaling system: drugs for obesity and the metabolic syndrome. Physiol Behav 2008;93(4-5):671-86. Go to original source... Go to PubMed...
    108. de Luis DA, Gonzalez Sagrado M, Aller R, Izaola O, Conde R. Relation of G1359A polymorphism of the cannabinoid receptor (CB1) gene with metabolic syndrome by ATP III classification. Diabetes Metab Res Rev 2011;27(5):506-11. Go to original source... Go to PubMed...
    109. Merroun I, Sanchez-Gonzalez C, Martinez R, Lopez-Chaves C, Porres JM, Aranda P, Llopis J, Galisteo M, Zarzuelo A, Errami M, Lopez-Jurado M. Novel effects of the cannabinoid inverse agonist AM 251 on parameters related to metabolic syndrome in obese Zucker rats. Metabolism 2013;62(11):1641-50. Go to original source... Go to PubMed...
    110. Slavic S, Lauer D, Sommerfeld M, Kemnitz UR, Grzesiak A, Trappiel M, Thone-Reineke C, Baulmann J, Paulis L, Kappert K, Kintscher U, Unger T, Kaschina E. Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome. J Mol Med (Berl) 2013;91(7):811-23. Go to original source... Go to PubMed...

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