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Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders

Nousen E.K.a · Franco J.G.a · Sullivan E.L.a, b

Author affiliations

aDivision of Diabetes, Obesity, and Metabolism, Oregon National Primate Research Center, Beaverton, Oreg., and bDepartment of Biology, University of Portland, Portland, Oreg., USA

Corresponding Author

Elinor L. Sullivan

University of Portland

5000 N. Willamette Blvd.

Portland, OR 97203 (USA)

E-Mail sullivae@up.edu

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Neuroendocrinology 2013;98:254-266

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Abstract

The increased prevalence and high comorbidity of metabolic syndrome (MetS) and mental health disorders (MHDs) have prompted investigation into the potential contributing mechanisms. There is a bidirectional association between MetS and MHDs including schizophrenia, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders. Medication side effects and social repercussions are contributing environmental factors, but there are a number of shared underlying neurological and physiological mechanisms that explain the high comorbidity between these two disorders. Inflammation is a state shared by both disorders, and it contributes to disruptions of neuroregulatory systems (including the serotonergic, dopaminergic, and neuropeptide Y systems) as well as dysregulation of the hypothalamic-pituitary-adrenal axis. MetS in pregnant women also exposes the developing fetal brain to inflammatory factors that predispose the offspring to MetS and psychopathologies. Due to the shared nature of these conditions, treatment should address aspects of both mental health and metabolic disorders. Additionally, interventions that can interrupt the transfer of increased risk of the disorders to the next generation need to be developed.

© 2013 S. Karger AG, Basel


References

  1. Alberti KG, et al: The metabolic syndrome - a new worldwide definition. Lancet 2005;366:1059-1062.
  2. Huang PL: A comprehensive definition for metabolic syndrome. Dis Model Mech 2009;2:231-237.
  3. Weiss R: Childhood metabolic syndrome: must we define it to deal with it? Diabetes Care 2011;34(suppl 2):S171-S176.
  4. Cook S, et al: Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003;157:821-827.
  5. Obesity trends among US adults between. 1985 and 2010. Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
  6. Flegal KM, et al: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012;307:491-497.
  7. Duncan GE, Li SM, Zhou XH: Prevalence and trends of a metabolic syndrome phenotype among US adolescents, 1999-2000. Diabetes Care 2004;27:2438-2443.
  8. Ogden CL, et al: Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295:1549-1555.
  9. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
  10. Boyle JP, et al: Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr 2010;8:29.
  11. Sullivan EL, Grove KL: Metabolic imprinting in obesity. Forum Nutr 2010;63:186-194.
  12. Kessler RC, et al: Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-627.
  13. Boyle CA, et al: Trends in the prevalence of developmental disabilities in US children, 1997-2008. Pediatrics 2011;127:1034-1042.
  14. Sullivan EL, Smith MS, Grove KL: Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology 2011;93:1-8.
  15. Sullivan EL, Nousen EK, Chamlou KA: Maternal high-fat diet consumption during the perinatal period programs offspring behavior. Physiol Behav 2012;pii.
  16. Carpiniello B, et al: Mental disorders in patients with metabolic syndrome. The key role of central obesity. Eat Weight Disord 2012;17:e259-e266.
  17. Newcomer JW: Metabolic syndrome and mental illness. Am J Manag Care 2007;13(suppl):S170-S177.
    External Resources
  18. Stanley SH, Laugharne JD: Obesity, cardiovascular disease and type 2 diabetes in people with a mental illness: a need for primary health care. Aust J Prim Health 2012;18:258-264.
  19. Grover S, et al: Comparative study of prevalence of metabolic syndrome in bipolar disorder and schizophrenia from North India. Nord J Psychiatry 2013, E-pub ahead of print.
  20. Ahmed AT, Blair TR, McIntyre RS: Surgical treatment of morbid obesity among patients with bipolar disorder: a research agenda. Adv Ther 2011;28:389-400.
  21. Mansur RB, et al: Selfish brain and neuroprogression in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2013;43:66-71.
  22. Allison DB, et al: Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156:1686-1696.
    External Resources
  23. Almandil NB, et al: Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatr Drugs 2013;15:139-150.
  24. Allison DB, et al: Obesity among those with mental disorders: a National Institute of Mental Health meeting report. Am J Prev Med 2009;36:341-350.
  25. Bensenor IM, et al: Cardiovascular risk factors in patients with first-episode psychosis in Sao Paulo, Brazil. Gen Hosp Psychiatry 2012;34:268-275.
  26. Rofey DL, et al: A longitudinal study of childhood depression and anxiety in relation to weight gain. Child Psychiatry Hum Dev 2009;40:517-526.
  27. Halfon N, Larson K, Slusser W: Associations between obesity and comorbid mental health, developmental, and physical health conditions in a nationally representative sample of US children aged 10 to 17. Acad Pediatr 2013;13:6-13.
  28. Maddi SR, et al: Psychosocial correlates of psychopathology in a national sample of the morbidly obese. Obes Surg 1997;7:397-404.
  29. Scott KM, et al: Obesity and mental disorders in the general population: results from the world mental health surveys. Int J Obes (Lond) 2008;32:192-200.
  30. Zhao G, et al: Waist circumference, abdominal obesity, and depression among overweight and obese US adults: National Health and Nutrition Examination Survey 2005-2006. BMC Psychiatry 2011;11:130.
  31. Petry NM, et al: Overweight and obesity are associated with psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med 2008;70:288-297.
  32. Zhong W, et al: Obesity and depression symptoms in the Beaver Dam Offspring Study population. Depress Anxiety 2010;27:846-851.
  33. Nichols GA, Brown JB: Unadjusted and adjusted prevalence of diagnosed depression in type 2 diabetes. Diabetes Care 2003;26:744-749.
  34. Bajaj S, et al: Association of depression and its relation with complications in newly diagnosed type 2 diabetes. Indian J Endocrinol Metab 2012;16:759-763.
  35. Mezuk B, et al: Is ignorance bliss? Depression, antidepressants, and the diagnosis of prediabetes and type 2 diabetes. Health Psychol 2013;32:254-263.
  36. Pouwer F, et al: Rates and risks for co-morbid depression in patients with type 2 diabetes mellitus: results from a community-based study. Diabetologia 2003;46:892-898.
  37. Peyrot M, Rubin RR: Levels and risks of depression and anxiety symptomatology among diabetic adults. Diabetes Care 1997;20:585-590.
  38. Fowler-Brown AG, Ngo LH, Wee CC: The relationship between symptoms of depression and body weight in younger adults. Obesity (Silver Spring) 2012;20:1922-1928.
  39. Waring ME, Lapane KL: Overweight in children and adolescents in relation to attention-deficit/hyperactivity disorder: results from a national sample. Pediatrics 2008;122:e1-e6.
  40. Pagoto SL, et al: Association between adult attention-deficit/hyperactivity disorder and obesity in the US population. Obesity (Silver Spring) 2009;17:539-544.
  41. Erhart M, et al: Examining the relationship between attention-deficit/hyperactivity disorder and overweight in children and adolescents. Eur Child Adolesc Psychiatry 2012;21:39-49.
  42. Chen AY, et al: Prevalence of obesity among children with chronic conditions. Obesity (Silver Spring) 2010;18:210-213.
  43. Alfonsson S, Parling T, Ghaderi A: Screening of adult ADHD among patients presenting for bariatric surgery. Obes Surg 2012;22:918-926.
  44. Rimmer JH, et al: Obesity and obesity-related secondary conditions in adolescents with intellectual/developmental disabilities. J Intellect Disabil Res 2010;54:787-794.
  45. Hyman SL, et al: Nutrient intake from food in children with autism. Pediatrics 2012;130 (suppl 2):S145-S153.
  46. De Zwaan M: Binge eating disorder and obesity. Int J Obes Relat Metab Disord 2001;25 (suppl 1):S51-S55.
    External Resources
  47. Cleator J, et al: Night eating syndrome: implications for severe obesity. Nutr Diabetes 2012;2:e44.
  48. Milano W, et al: Night eating syndrome: an overview. J Pharm Pharmacol 2012;64:2-10.
  49. Vander Wal JS: Night eating syndrome: a critical review of the literature. Clin Psychol Rev 2012;32:49-59.
  50. Grilo CM, et al: Night eating in obese treatment-seeking Hispanic patients with and without binge eating disorder. Int J Eat Disord 2012;45:787-791.
  51. Docet MF, et al: Attention-deficit hyperactivity disorder increases the risk of having abnormal eating behaviours in obese adults. Eat Weight Disord 2012;17:e132-e136.
    External Resources
  52. Al-Ayadhi LY: Pro-inflammatory cytokines in autistic children in central Saudi Arabia. Neurosciences (Riyadh) 2005;10:155-158.
    External Resources
  53. Lopez-Pantoja JL, et al: Personality profiles between obese and control subjects assessed with five standardized personality scales. Actas Esp Psiquiatr 2012;40:266-274.
    External Resources
  54. Zhao G, et al: Depression and anxiety among US adults: associations with body mass index. Int J Obes (Lond) 2009;33:257-266.
  55. Czegledi E, Urban R: Risk factors and alteration of depression among participants of an inpatient weight loss program (in Hungarian). Psychiatr Hung 2012;27:361-378.
    External Resources
  56. McLaren L, et al: The relationship between body mass index and mental health. A population-based study of the effects of the definition of mental health. Soc Psychiatry Psychiatr Epidemiol 2008;43:63-71.
  57. Pickering RP, et al: Temporal relationships between overweight and obesity and DSM-IV substance use, mood, and anxiety disorders: results from a prospective study, the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2011;72:1494-1502.
  58. Carpenter KM, et al: Relationships between obesity and DSM-IV major depressive disorder, suicide ideation, and suicide attempts: results from a general population study. Am J Public Health 2000;90:251-257.
  59. Heo M, et al: Depressive mood and obesity in US adults: comparison and moderation by sex, age, and race. Int J Obes (Lond) 2006;30:513-519.
  60. Onyike CU, et al: Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2003;158:1139-1147.
  61. Stunkard AJ, Faith MS, Allison KC: Depression and obesity. Biol Psychiatry 2003;54:330-337.
  62. Papageorgiou GM, et al: Pre- and postoperative psychological characteristics in morbidly obese patients. Obes Surg 2002;12:534-539.
  63. Fleming JP, Levy LD, Levitan RD: Symptoms of attention-deficit hyperactivity disorder in severely obese women. Eat Weight Disord 2005;10:e10-e13.
    External Resources
  64. Kasen S, et al: Obesity and psychopathology in women: a three decade prospective study. Int J Obes (Lond) 2008;32:558-566.
  65. Black DW, Goldstein RB, Mason EE: Prevalence of mental disorder in 88 morbidly obese bariatric clinic patients. Am J Psychiatry 1992;149:227-234.
    External Resources
  66. Pan A, et al: Bidirectional association between depression and type 2 diabetes mellitus in women. Arch Intern Med 2010;170:1884-1891.
  67. Roberts RE, et al: Prospective association between obesity and depression: evidence from the Alameda County Study. Int J Obes Relat Metab Disord 2003;27:514-521.
  68. Luppino FS, et al: Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 2010;67:220-229.
  69. Simon GE, et al: Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry 2006;63:824-830.
  70. Koponen H, et al: Metabolic syndrome predisposes to depressive symptoms: a population-based 7-year follow-up study. J Clin Psychiatry 2008;69:178-182.
    External Resources
  71. Aarts S, et al: Diabetes mellitus type II as a risk factor for depression: a lower than expected risk in a general practice setting. Eur J Epidemiol 2009;24:641-648.
  72. O'Connor PJ, et al: Does diabetes double the risk of depression? Ann Fam Med 2009;7:328-335.
  73. Mezuk B, et al: Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008;31:2383-2390.
  74. Bisschop MI, et al: The longitudinal relation between chronic diseases and depression in older persons in the community: the Longitudinal Aging Study Amsterdam. J Clin Epidemiol 2004;57:187-194.
  75. Nouwen A, et al: Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 2010;53:2480-2486.
  76. Kivimaki M, et al: Antidepressant use before and after the diagnosis of type 2 diabetes: a longitudinal modeling study. Diabetes Care 2010;33:1471-1476.
  77. Knol MJ, et al: Antidepressant use before and after initiation of diabetes mellitus treatment. Diabetologia 2009;52:425-432.
  78. Tyler CV, et al: Chronic disease risks in young adults with autism spectrum disorder: forewarned is forearmed. Am J Intellect Dev Disabil 2011;116:371-380.
  79. Cortese S, et al: Obesity in men with childhood ADHD: a 33-year controlled, prospective, follow-up study. Pediatrics 2013;131:e1731-1738.
  80. Valtonen MK, et al: Low-grade inflammation and depressive symptoms as predictors of abdominal obesity. Scand J Public Health 2012;40:674-680.
  81. Hasnain M, Vieweg WV, Hollett B: Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 2012;124:154-167.
  82. Deuschle M: Effects of antidepressants on glucose metabolism and diabetes mellitus type 2 in adults. Curr Opin Psychiatry 2013;26:60-65.
  83. Appelhans BM, et al: Depression severity, diet quality, and physical activity in women with obesity and depression. J Acad Nutr Diet 2012;112:693-698.
  84. Gibson EL: The psychobiology of comfort eating: implications for neuropharmacological interventions. Behav Pharmacol 2012;23:442-460.
  85. Champaneri S, et al: Biological basis of depression in adults with diabetes. Curr Diab Rep 2010;10:396-405.
  86. Kinzl JF, Maier C, Bosch A: Morbidly obese patients: psychopathology and eating disorders - Results of a preoperative evaluation (in German). Neuropsychiatr 2012;26:159-165.
  87. Karlsson J, et al: Psychosocial functioning in the obese before and after weight reduction: construct validity and responsiveness of the obesity-related problems scale. Int J Obes Relat Metab Disord 2003;27:617-630.
  88. Maddi SR, et al: Reduction in psychopathology following bariatric surgery for morbid obesity. Obes Surg 2001;11:680-685.
  89. Sysko R, et al: Psychological outcomes and predictors of initial weight loss outcomes among severely obese adolescents receiving laparoscopic adjustable gastric banding. J Clin Psychiatry 2012;73:1351-1357.
  90. Dixon JB, Dixon ME, O'Brien PE: Depression in association with severe obesity: changes with weight loss. Arch Intern Med 2003;163:2058-2065.
  91. Peterhansel C, et al: Risk of completed suicide after bariatric surgery: a systematic review. Obes Rev 2013;14:369-382.
  92. Klinitzke G, et al: Obesity and suicide risk in adults - a systematic review. J Affect Disord 2013;145:277-284.
  93. Krakowiak P, et al: Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012;129:e1121-e1128.
  94. Leonard H, et al: Maternal health in pregnancy and intellectual disability in the offspring: a population-based study. Ann Epidemiol 2006;16:448-454.
  95. Hamlyn J, Duhig M, McGrath J, Scott J: Modifiable risk factors for schizophrenia and autism - shared risk factors impacting on brain development. Neurobiol Dis 2013;53:3-9.
  96. Rodriguez A: Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J Child Psychol Psychiatry 2010;51:134-143.
  97. Robinson M, et al: Pre-pregnancy maternal overweight and obesity increase the risk for affective disorders in offspring. J Dev Orig Health Dis 2013;4:42-48.
    External Resources
  98. Buss C, et al: Impaired executive function mediates the association between maternal pre-pregnancy body mass index and child ADHD symptoms. PLoS One 2012;7:e37758.
  99. Rodriguez A, et al: Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond) 2008;32:550-557.
  100. Ray GT, Croen LA, Habel LA: Mothers of children diagnosed with attention-deficit/hyperactivity disorder: health conditions and medical care utilization in periods before and after birth of the child. Med Care 2009;47:105-114.
  101. Tozuka Y, et al: Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring. Neurochem Int 2010;57:235-247.
  102. Raygada M, Cho E, Hilakivi-Clarke L: High maternal intake of polyunsaturated fatty acids during pregnancy in mice alters offsprings' aggressive behavior, immobility in the swim test, locomotor activity and brain protein kinase C activity. J Nutr 1998;128:2505-2511.
    External Resources
  103. Peleg-Raibstein D, Luca E, Wolfrum C: Maternal high-fat diet in mice programs emotional behavior in adulthood. Behav Brain Res 2012;233:398-404.
  104. Bilbo SD, Tsang V: Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J 2010;24:2104-2115.
  105. Sullivan EL, et al: Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in non-human primate offspring. J Neurosci 2010;30:3826-3830.
  106. Gong Y, et al: Female early adult depression results in detrimental impacts on the behavioral performance and brain development in offspring. CNS Neurosci Ther 2012;18:461-470.
  107. Deng T, et al: Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation. Cell Metab 2013;17:411-422.
  108. Bauer S, Kerr BJ, Patterson PH: The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 2007;8:221-232.
  109. Monje ML, Toda H, Palmer TD: Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003;302:1760-1765.
  110. Lagace DC, Noonan MA, Eisch AJ: Hippocampal neurogenesis: a matter of survival. Am J Psychiatry 2007;164:205.
  111. Watanabe Y, Someya T, Nawa H: Cytokine hypothesis of schizophrenia pathogenesis: evidence from human studies and animal models. Psychiatry Clin Neurosci 2010;64:217-230.
  112. Sasayama D, et al: Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder. J Psychiatr Res 2013;47:401-406.
  113. McKernan DP, et al: Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype. Transl Psychiatry 2011;1:e36.
  114. Kubistova A, Horacek J, Novak T: Increased interleukin-6 and tumor necrosis factor-α in first episode schizophrenia patients versus healthy controls. Psychiatr Danub 2012;24(suppl 1):S153-S156.
    External Resources
  115. Fillman SG, et al: Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 2013;18:206-214.
  116. Nawa H, Yamada K: Experimental schizophrenia models in rodents established with inflammatory agents and cytokines. Methods Mol Biol 2012;829:445-451.
  117. Tohmi M, et al: Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin. Neurosci Res 2004;50:67-75.
  118. Alesci S, et al: Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications. J Clin Endocrinol Metab 2005;90:2522-2530.
  119. Danner M, et al: Association between depression and elevated C-reactive protein. Psychosom Med 2003;65:347-356.
  120. Vogelzangs N, et al: Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry 2012;2:e79.
  121. Penninx BW, et al: Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study. Biol Psychiatry 2003;54:566-572.
  122. Bremmer MA, et al: Inflammatory markers in late-life depression: results from a population-based study. J Affect Disord 2008;106:249-255.
  123. Dentino AN, et al: Association of interleukin-6 and other biologic variables with depression in older people living in the community. J Am Geriatr Soc 1999;47:6-11.
    External Resources
  124. Donev R, Thome J: Inflammation: good or bad for ADHD? Atten Defic Hyperact Disord 2010;2:257-266.
  125. Fredriksson A, Archer T: Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD. Neurotox Res 2004;6:435-456.
  126. Wei H, et al: IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflamm 2011;8:52.
  127. El-Ansary A, Al-Ayadhi L: Neuroinflammation in autism spectrum disorders. J Neuroinflammation 2012;9:265.
  128. Wei H, et al: Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta 2012;1822:831-842.
  129. Hall FS, et al: Reduced behavioral effects of cocaine in heterozygous brain-derived neurotrophic factor knockout mice. Neuropsychopharmacology 2003;28:1485-1490.
  130. Byerly MS, et al: Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro. Am J Physiol Regul Integr Comp Physiol 2009;296:R1180-R1189.
  131. Unger TJ, et al: Selective deletion of BDNF in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 2007;27:14265-14274.
  132. Li W, et al: Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population. Am J Med Genet B Neuropsychiatr Genet 2013;162B:538-545.
  133. Watanabe Y, Nunokawa A, Someya T: Association of the BDNF C270T polymorphism with schizophrenia: updated meta-analysis. Psychiatry Clin Neurosci 2013;67:123-125.
  134. Favalli G, et al: The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 2012;46:1-11.
  135. Sun MM, et al: BDNF Val66Met polymorphism and anxiety/depression symptoms in schizophrenia in a Chinese Han population. Psychiatr Genet 2013;23:124-129.
  136. Ernst C, et al: Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity. Arch Gen Psychiatry 2012;69:1238-1246.
  137. Hallden S, et al: Smoking and obesity associated BDNF gene variance predicts total and cardiovascular mortality in smokers. Heart 2013;99:949-953.
  138. Hotta K, et al: Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. J Hum Genet 2009;54:727-731.
  139. Beckers S, et al: Association of the BDNF Val66Met variation with obesity in women. Mol Genet Metab 2008;95:110-112.
  140. Gray J, et al: Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor gene. Diabetes 2006;55:3366-3371.
  141. Coppola V, Tessarollo L: Control of hyperphagia prevents obesity in BDNF heterozygous mice. Neuroreport 2004;15:2665-2668.
  142. Sha H, et al: Disruption of a novel regulatory locus results in decreased BDNF expression, obesity, and type 2 diabetes in mice. Physiol Genomics 2007;31:252-263.
  143. Faludi G, et al: Pharmaco- and therapygenetic aspects in the treatment of anxiety disorders beyond the serotonergic system: a brief review. Neuropsychopharmacol Hung 2012;14:221-229.
    External Resources
  144. Spindelegger C, et al: Influence of escitalopram treatment on 5-HT1A receptor binding in limbic regions in patients with anxiety disorders. Mol Psychiatry 2009;14:1040-1050.
  145. Sullivan GM, et al: Low cerebrospinal fluid transthyretin levels in depression: correlations with suicidal ideation and low serotonin function. Biol Psychiatry 2006;60:500-506.
  146. Kiyohara C, Yoshimasu K: Molecular epidemiology of major depressive disorder. Environ Health Prev Med 2009;14:71-87.
  147. Oades RD, et al: The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder: findings from a family-based association test analysis. Behav Brain Funct 2008;4:48.
  148. Chugani DC, et al: Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 1999;45:287-295.
  149. Challier JC, et al: Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008;29:274-281.
  150. Andrews N, et al: 5-HT1A receptors in the median raphe nucleus and dorsal hippocampus may mediate anxiolytic and anxiogenic behaviours respectively. Eur J Pharmacol 1994;264:259-264.
  151. Ghosh MN, Parvathy S: The effect of cyproheptadine on water and food intake and on body weight in the fasted adult and weanling rats. Br J Pharmacol 1973;48:328P-329P.
    External Resources
  152. Blundell JE, Leshem MB: Central action of anorexic agents: effects of amphetamine and fenfluramine in rats with lateral hypothalamic lesions. Eur J Pharmacol 1974;28:81-88.
  153. Geyer MA, et al: Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. Brain Res 1976;106:257-269.
  154. Saller CF, Stricker EM: Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Science 1976;192:385-387.
  155. Blundell JE, Leshem MB: The effect of 5-hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine. J Pharm Pharmacol 1975;27:31-37.
  156. Grinker JA, et al: Effects of D-amphetamine and fenfluramine on feeding patterns and activity of obese and lean Zucker rats. Pharmacol Biochem Behav 1980;12:265-275.
  157. Foltin RW, Moran TH: Food intake in baboons: effects of a long-acting cholecystokinin analog. Appetite 1989;12:145-152.
  158. Rogers PJ, Blundell JE: Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects. Psychopharmacology (Berl) 1979;66:159-165.
  159. McGuirk J, et al: Differential effects of D-fenfluramine, L-fenfluramine and D-amphetamine on the microstructure of human eating behaviour. Behav Pharmacol 1991;2:113-119.
    External Resources
  160. Hoffman BJ, Mezey E: Distribution of serotonin 5-HT1C receptor mRNA in adult rat brain. FEBS Lett 1989;247:453-462.
  161. Wright DE, et al: Comparative localization of serotonin 1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol 1995;351:357-373.
  162. Pasqualetti M, et al: Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain. Neuroscience 1999;92:601-611.
  163. Pazos A, Palacios JM: Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 1985;346:205-230.
  164. Kennett GA, Curzon G: Evidence that hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU-24969 only requires 5-HT1B receptors. Psychopharmacology (Berl) 1988;96:93-100.
  165. Halford JC, Blundell JE: The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the behavioural satiety sequence. Physiol Behav 1996;60:933-939.
  166. Lee MD, Simansky KJ: CP-94,253: a selective serotonin 1B agonist that promotes satiety. Psychopharmacology (Berl) 1997;131:264-270.
  167. Tecott LH, et al: Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 1995;374:542-546.
  168. Nonogaki K, et al: Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 1998;4:1152-1156.
  169. Mangge H, et al: Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome. Obesity (Silver Spring) 2013.
  170. Dean B: Neurochemistry of schizophrenia: the contribution of neuroimaging postmortem pathology and neurochemistry in schizophrenia. Curr Top Med Chem 2012;12:2375-2392.
  171. Wu H, et al: SPECT imaging of dopamine transporters with 99mTc-TRODAT-1 in major depression and Parkinson's disease. J Neuropsychiatry Clin Neurosci 2011;23:63-67.
  172. Felicio AC, et al: Higher dopamine transporter density in Parkinson's disease patients with depression. Psychopharmacology (Berl) 2010;211:27-31.
  173. Cervenka S, et al: Changes in dopamine D2-receptor binding are associated to symptom reduction after psychotherapy in social anxiety disorder. Transl Psychiatry 2012;2:e120.
  174. Spencer TJ, et al: Functional genomics of attention-deficit/hyperactivity disorder (ADHD) risk alleles on dopamine transporter binding in ADHD and healthy control subjects. Biol Psychiatry 2013;74:84-89.
  175. Nakamura K, et al: Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 2010;67:59-68.
  176. Sun X, Yue J, Zheng C: Study of dopamine transporter imaging on the brain of children with autism (in Chinese). Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2008;25:327-330.
    External Resources
  177. Pattarachotanant N, et al: Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population. Genet Mol Res 2010;9:565-572.
  178. Van der Wee NJ, et al: Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-β-(4-iodophenyl)tropane SPECT. J Nucl Med 2008;49:757-763.
  179. Oh KS, et al: Dopamine transporter genotype influences the attention deficit in Korean boys with ADHD. Yonsei Med J 2003;44:787-792.
    External Resources
  180. El-Tarras AE, et al: Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique. Mol Biol Rep 2012;39:11081-11086.
  181. Gadow KD, et al: Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder. J Child Psychol Psychiatry 2008;49:1331-1338.
  182. Staal WG, de Krom M, de Jonge MV: Brief report: the dopamine-3 receptor gene is associated with specific repetitive behavior in autism spectrum disorder. J Autism Dev Disord 2012;42:885-888.
  183. Wu J, et al: Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol 2012;45:605-620.
  184. Hori H, Kunugi H: The efficacy of pramipexole, a dopamine receptor agonist, as an adjunctive treatment in treatment-resistant depression: an open-label trial. ScientificWorldJournal 2012;2012:372474.
  185. Wang GJ, et al: Imaging of brain dopamine pathways: implications for understanding obesity. J Addict Med 2009;3:8-18.
  186. Narayanan NS, Guarnieri DJ, DiLeone RJ: Metabolic hormones, dopamine circuits, and feeding. Front Neuroendocrinol 2010;31:104-112.
  187. Baldo BA, Kelley AE: Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl) 2007;191:439-459.
  188. Wang GJ, et al: Brain dopamine and obesity. Lancet 2001;357:354-357.
  189. Volkow ND, et al: Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage 2008;42:1537-1543.
  190. Bailer UF, et al: Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa. Int J Eat Disord 2012;45:263-271.
  191. Zhou QY, Palmiter RD: Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 1995;83:1197-1209.
  192. Morrison CD, Berthoud HR: Neurobiology of nutrition and obesity. Nutr Rev 2007;65:517-534.
  193. Raghanti MA, et al: Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates. Am J Primatol 2013;75:415-424.
  194. Kuromitsu J, et al: Reduced neuropeptide Y mRNA levels in the frontal cortex of people with schizophrenia and bipolar disorder. Brain Res Gene Expr Patterns 2001;1:17-21.
  195. Caberlotto L, Hurd YL: Reduced neuropeptide Y mRNA expression in the prefrontal cortex of subjects with bipolar disorder. Neuroreport 1999;10:1747-1750.
  196. Morales-Medina JC, Dumont Y, Quirion R: A possible role of neuropeptide Y in depression and stress. Brain Res 2010;1314:194-205.l
  197. Oades RD, Daniels R, Rascher W: Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder. Psychiatry Res 1998;80:177-186.
  198. Kask A, Rago L, Harro J: NPY Y1 receptors in the dorsal periaqueductal gray matter regulate anxiety in the social interaction test. Neuroreport 1998;9:2713-2716.
  199. Sajdyk TJ, Shekhar A, Gehlert DR: Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides 2004;38:225-234.
  200. Heilig M, et al: Centrally administered neuropeptide Y produces anxiolytic-like effects in animal anxiety models. Psychopharmacology (Berl) 1989;98:524-529.
  201. Bjorntorp P: Endocrine abnormalities of obesity. Metabolism 1995:44(suppl 3):21-23.
  202. Adam TC, Epel ES: Stress, eating and the reward system. Physiol Behav 2007;91:449-458.
  203. Prasad A, Prasad C: Short-term consumption of a diet rich in fat decreases anxiety response in adult male rats. Physiol Behav 1996;60:1039-1042.
  204. Raadsheer FC, et al: Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994;60:436-444.
  205. Arborelius L, et al: The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 1999;160:1-12.
  206. Nemeroff CB, et al: Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984;226:1342-1344.
  207. Nemeroff CB, et al: Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988;45:577-579.
  208. Stenzel-Poore MP, et al: Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. Endocrinology 1992;130:3378-3386.
  209. Coste SC, Murray SE, Stenzel-Poore MP: Animal models of CRH excess and CRH receptor deficiency display altered adaptations to stress. Peptides 2001;22:733-741.
  210. Muller MB, et al: Hypothalamic-pituitary-adrenocortical system and mood disorders: highlights from mutant mice. Neuroendocrinology 2004;79:1-12.
  211. Bornstein SR, et al: Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions. Mol Psychiatry 2006;11:892-902.
  212. Soares-Miranda L, et al: Metabolic syndrome, physical activity and cardiac autonomic function. Diabetes Metab Res Rev 2012;28:363-369.
  213. Soares-Miranda L, et al: Trans-fatty acid consumption and heart rate variability in two separate cohorts of older and younger adults. Circ Arrhythm Electrophysiol 2012;5:728-738.
  214. Assoumou HG, et al: Metabolic syndrome and short-term and long-term heart rate variability in elderly free of clinical cardiovascular disease: the PROOF study. Rejuvenation Res 2010;13:653-663.
  215. Lee K, et al: Heart rate variability and metabolic syndrome in hospitalized patients with schizophrenia. J Korean Acad Nurs 2011;41:788-794.
  216. Koskinen T, et al: Metabolic syndrome and short-term heart rate variability in young adults. The cardiovascular risk in young Finns study. Diabet Med 2009;26:354-361.
  217. Min KB, et al: The impact of the components of metabolic syndrome on heart rate variability: using the NCEP-ATP III and IDF definitions. Pacing Clin Electrophysiol 2008;31:584-591.
  218. Nemeroff C, Goldschmidt-Clermont P: Heartache and heartbreak - the link between depression and cardiovascular disease. Nat Rev Cardiol 2012;9:526-539.
  219. Thayer JF, Yamamoto SS, Brosschot JF: The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol 2010;141:122-131.
  220. Valiengo L, et al: The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases. Depress Anxiety 2013;30:646-653.
  221. Kemp AH, et al: Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol Psychiatry 2010;67:1067-1074.
  222. Ieda M, et al: Evaluation of autonomic nervous system by salivary α-amylase level and heart rate variability in patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 2013, E-pub ahead of print.
  223. Tonhajzerova I, et al: Changes in the cardiac autonomic regulation in children with attention-deficit hyperactivity disorder. Indian J Med Res 2009;130:44-50.
    External Resources
  224. Kemp AH, Quintana DS: The relationship between mental and physical health: insights from the study of heart rate variability. Int J Psychophysiol 2013;89:288-296.
  225. Licht CM, et al: Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability. Biol Psychiatry 2010;68:861-868.
  226. Brunoni AR, et al: Transcranial direct current stimulation in unipolar vs. bipolar depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:96-101.
  227. Sampaio LA, et al: A systematic review of non-invasive brain stimulation therapies and cardiovascular risk: implications for the treatment of major depressive disorder. Front Psychiatry 2012;3:87.
  228. Vucetic Z, et al: Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 2010;151:4756-4764.
  229. Basu S, et al: Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring) 2011;19:476-482.
  230. Roberts KA, et al: Placental structure and inflammation in pregnancies associated with obesity. Placenta 2011;32:247-254.
  231. Radaelli T, et al: Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 2003;52:2951-2958.
  232. Wallace JM, et al: Serial measurement of uterine blood flow from mid to late gestation in growth restricted pregnancies induced by overnourishing adolescent sheep dams. Placenta 2008;29:718-724.
  233. Frias AE, et al: Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology 2011;152:2456-2464.
  234. Madan I, et al: The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation. J Perinat Med 2010;38:275-279.
  235. Toker S, et al: The association between burnout, depression, anxiety, and inflammation biomarkers: C-reactive protein and fibrinogen in men and women. J Occup Health Psychol 2005;10:344-362.
  236. Das UN: Is obesity an inflammatory condition? Nutrition 2001;17:953-966.
  237. Buehler MR: A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder. Med Hypotheses 2011;76:863-870.
  238. Ellman LM, et al: Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8. Schizophr Res 2010;121:46-54.
  239. Smith SE, et al: Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 2007;27:10695-10702.
  240. Goines PE, et al: Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Mol Autism 2011;2:13.
  241. Ashwood P, et al: Altered T-cell responses in children with autism. Brain Behav Immun 2011;25:840-849.
  242. Ashwood P, et al: Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 2011;232:196-199.
  243. Oken E, Gillman MW: Fetal origins of obesity. Obes Res 2003;11:496-506.
  244. Simerly RB: Hypothalamic substrates of metabolic imprinting. Physiol Behav 2008;94:79-89.
  245. Jones AP, et al: Maternal hormonal manipulations in rats cause obesity and increase medial hypothalamic norepinephrine release in male offspring. Brain Res Dev Brain Res 1995;88:127-131.
  246. Jones AP, Dayries M: Maternal hormone manipulations and the development of obesity in rats. Physiol Behav 1990;47:1107-1110.
  247. Plagemann A, et al: Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organization. Exp Clin Endocrinol 1992;99:91-95.

Article / Publication Details

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Abstract of At the Cutting Edge

Received: April 08, 2013
Accepted: September 10, 2013
Published online: September 21, 2013
Issue release date: March 2014

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ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

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