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Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions

Molecular Psychiatry volume 11, pages 892–902 (2006)Cite this article

Abstract

Obesity and depression are serious public health problems and also constitute cardiovascular disease risk factors. Research organizations have called for efforts to explore the interrelationship between obesity and depression. A useful starting point is the fact that in both disorders there is dysregulation of stress systems. We review molecular and clinical evidence indicating that the mediators of the stress response are a key locus for gene–environment interactions in the shared biology of depression and obesity. Scientific milestones include translational paradigms such as mice knockouts, imaging and pharmacogenomic approaches that can identify new therapeutic strategies for those burdened by these two afflictions of contemporary civilization. Perspectives for the future are promising. Our ability to dissect the underpinnings of common and complex diseases with shared substrates will be greatly enhanced by the Genes and Environment Initiative, the emerging Large Scale Studies of Genes and Environment in Common Disease, and the UK Biobank Project.

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References

  1. Collins FS . The case for a US prospective cohort study of genes and environment. Nature 2004; 429: 475–477.

    Article  CAS  PubMed  Google Scholar 

  2. Klerman GL . Harvard Guide to Modern Psychiatry. Belknap/Havard University Press: Cambrigde, 1978.

    Google Scholar 

  3. McElroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE, Nemeroff CB . Are mood disorders and obesity related? A review for the mental health professional. J Clin Psychiatry 2004; 65: 634–651, quiz.

    Article  PubMed  Google Scholar 

  4. Hebert S, Beland R, onne-Fournelle O, Crete M, Lupien SJ . Physiological stress response to video-game playing: the contribution of built-in music. Life Sci 2005; 76: 2371–2380.

    Article  CAS  PubMed  Google Scholar 

  5. Korenblum W, Barthel A, Licinio J, Wong ML, Wolf OT, Kirschbaum C et al. Elevated cortisol levels and increased rates of diabetes and mood symptoms in Soviet Union-born Jewish immigrants to Germany. Mol Psychiatry 2005; 10: 974–975.

    Article  CAS  PubMed  Google Scholar 

  6. http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-009.html, 28–9–2001. Ref Type: Internet Communication.

  7. Sonino N, Fava GA . Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs 2001; 15: 361–373.

    Article  CAS  PubMed  Google Scholar 

  8. McMahon M, Gerich J, Rizza R . Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 1988; 4: 17–30.

    Article  CAS  PubMed  Google Scholar 

  9. Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R et al. Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 1989; 84: 1663–1670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Campfield LA, Smith FJ, Burn P . The OB protein (leptin) pathway – a link between adipose tissue mass and central neural networks. Horm Metab Res 1996; 28: 619–632.

    Article  CAS  PubMed  Google Scholar 

  11. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250–252.

    Article  CAS  PubMed  Google Scholar 

  12. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632–635.

    Article  CAS  PubMed  Google Scholar 

  13. Ohshima K, Shargill NS, Chan TM, Bray GA . Adrenalectomy reverses insulin resistance in muscle from obese (ob/ob) mice. Am J Physiol 1984; 246 (2 Part 1): E193–E197.

    CAS  PubMed  Google Scholar 

  14. Bray GA, York DA . Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev 1979; 59: 719–809.

    Article  CAS  PubMed  Google Scholar 

  15. Bjorntorp P . Endocrine abnormalities of obesity. Metabolism 1995; 44 (9 Suppl 3): 21–23.

    Article  CAS  PubMed  Google Scholar 

  16. Yanovski SZ, Yanovski JA . Obesity. N Engl J Med 2002; 346: 591–602.

    Article  CAS  PubMed  Google Scholar 

  17. Dallman MF, la Fleur SE, Pecoraro NC, Gomez F, Houshyar H, Akana SF . Minireview: glucocorticoids – food intake, abdominal obesity, and wealthy nations in 2004. Endocrinology 2004; 145: 2633–2638.

    Article  CAS  PubMed  Google Scholar 

  18. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB . The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 1999; 160: 1–12.

    Article  CAS  PubMed  Google Scholar 

  19. Plotsky PM, Owens MJ, Nemeroff CB . Psychoneuroendocrinology of depression. Hypothalamic–pituitary–adrenal axis. Psychiatr Clin North Am 1998; 21: 293–307.

    Article  CAS  PubMed  Google Scholar 

  20. Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH et al. Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications. N Engl J Med 1986; 314: 1329–1335.

    Article  CAS  PubMed  Google Scholar 

  21. Kathol RG, Jaeckle RS, Lopez JF, Meller WH . Consistent reduction of ACTH responses to stimulation with CRH, vasopressin and hypoglycaemia in patients with major depression. Br J Psychiatry 1989; 155: 468–478.

    Article  CAS  PubMed  Google Scholar 

  22. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB . Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry 2001; 158: 575–581.

    Article  CAS  PubMed  Google Scholar 

  23. Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab 2005; 90: 2851–2854.

    Article  CAS  PubMed  Google Scholar 

  24. Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M . Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988; 45: 577–579.

    Article  CAS  PubMed  Google Scholar 

  25. Holsboer-Trachsler E, Stohler R, Hatzinger M . Repeated administration of the combined dexamethasone-human corticotropin releasing hormone stimulation test during treatment of depression. Psychiatry Res 1991; 38: 163–171.

    Article  CAS  PubMed  Google Scholar 

  26. Holsboer F, Lauer CJ, Schreiber W, Krieg JC . Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology 1995; 62: 340–347.

    Article  CAS  PubMed  Google Scholar 

  27. Modell S, Lauer CJ, Schreiber W, Huber J, Krieg JC, Holsboer F . Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology 1998; 18: 253–262.

    Article  CAS  PubMed  Google Scholar 

  28. Austin MC, Janosky JE, Murphy HA . Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry 2003; 8: 324–332.

    Article  CAS  PubMed  Google Scholar 

  29. Nemeroff CB, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226: 1342–1344.

    Article  CAS  PubMed  Google Scholar 

  30. Raadsheer FC, Hoogendijk WJ, Stam FC, Tilders FJ, Swaab DF . Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994; 60: 436–444.

    Article  CAS  PubMed  Google Scholar 

  31. Amsterdam JD, Maislin G, Winokur A, Berwish N, Kling M, Gold P . The oCRH stimulation test before and after clinical recovery from depression. J Affect Disord 1988; 14: 213–222.

    Article  CAS  PubMed  Google Scholar 

  32. Nemeroff CB, Bissette G, Akil H, Fink M . Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Corticotrophin-releasing factor, beta-endorphin and somatostatin. Br J Psychiatry 1991; 158: 59–63.

    Article  CAS  PubMed  Google Scholar 

  33. Gillespie CF, Nemeroff CB . Hypercortisolemia and depression. Psychosom Med 2005; 67 (Suppl 1): S26–S28.

    Article  PubMed  Google Scholar 

  34. Brady LS, Whitfield Jr HJ, Fox RJ, Gold PW, Herkenham M . Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. J Clin Invest 1991; 87: 831–837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Reul JM, Stec I, Soder M, Holsboer F . Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic–pituitary–adrenocortical system. Endocrinology 1993; 133: 312–320.

    Article  CAS  PubMed  Google Scholar 

  36. Michelson D, Galliven E, Hill L, Demitrack M, Chrousos G, Gold P . Chronic imipramine is associated with diminished hypothalamic–pituitary–adrenal axis responsivity in healthy humans. J Clin Endocrinol Metab 1997; 82: 2601–2606.

    Article  CAS  PubMed  Google Scholar 

  37. Licinio J, O'Kirwan F, Irizarry K, Merriman B, Thakur S, Jepson R et al. Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans. Mol Psychiatry 2004; 9: 1075–1082.

    Article  CAS  PubMed  Google Scholar 

  38. Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004; 36: 1319–1325.

    Article  CAS  PubMed  Google Scholar 

  39. Stenzel-Poore MP, Cameron VA, Vaughan J, Sawchenko PE, Vale W . Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. Endocrinology 1992; 130: 3378–3386.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

  41. Muller MB, Uhr M, Holsboer F, Keck ME . Hypothalamic–pituitary–adrenocortical system and mood disorders: highlights from mutant mice. Neuroendocrinology 2004; 79: 1–12.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. Cone RD . The corticotropin-releasing hormone system and feeding behavior--a complex web begins to unravel. Endocrinology 2000; 141: 2713–2714.

    Article  CAS  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 2000; 24: 410–414.

    Article  CAS  PubMed  Google Scholar 

  46. Holsboer F . The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477–501.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

  48. Zemel MB, Shi H . Pro-opiomelanocortin (POMC) deficiency and peripheral melanocortins in obesity. Nutr Rev 2000; 58: 177–180.

    Article  CAS  PubMed  Google Scholar 

  49. Stenzel-Poore MP, Duncan JE, Rittenberg MB, Bakke AC, Heinrichs SC . CRH overproduction in transgenic mice: behavioral and immune system modulation. Ann NY Acad Sci 1996; 780: 36–48.

    Article  CAS  PubMed  Google Scholar 

  50. Bornstein SR, Tajima T, Eisenhofer G, Haidan A, Aguilera G . Adrenomedullary function is severely impaired in 21-hydroxylase-deficient mice. FASEB J 1999; 13: 1185–1194.

    Article  CAS  PubMed  Google Scholar 

  51. Bland ML, Jamieson CA, Akana SF, Bornstein SR, Eisenhofer G, Dallman MF et al. Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response. Proc Natl Acad Sci USA 2000; 97: 14488–14493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Merke DP, Bornstein SR . Congenital adrenal hyperplasia. Lancet 2005; 365: 2125–2136.

    Article  PubMed  Google Scholar 

  53. Bjorntorp P . Do stress reactions cause abdominal obesity and comorbidities? Obes Rev 2001; 2: 73–86.

    Article  CAS  PubMed  Google Scholar 

  54. Seckl JR . 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 2004; 4: 597–602.

    Article  CAS  PubMed  Google Scholar 

  55. Paterson JM, Seckl JR, Mullins JJ . Genetic manipulation of 11beta-hydroxysteroid dehydrogenases in mice. Am J Physiol Regul Integr Comp Physiol 2005; 289: R642–R652.

    Article  CAS  PubMed  Google Scholar 

  56. Holmes MC, Yau JL, Kotelevtsev Y, Mullins JJ, Seckl JR . 11 Beta-hydroxysteroid dehydrogenases in the brain: two enzymes two roles. Ann NY Acad Sci 2003; 1007: 357–366.

    Article  CAS  PubMed  Google Scholar 

  57. Masuzaki H, Flier JS . Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) – a promising drug target for the treatment of metabolic syndrome. Curr Drug Targets Immune Endocr Metabol Disord 2003; 3: 255–262.

    Article  CAS  PubMed  Google Scholar 

  58. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166–2170.

    Article  CAS  PubMed  Google Scholar 

  59. Tomlinson JW . 11Beta-hydroxysteroid dehydrogenase type 1 in human disease: a novel therapeutic target. Minerva Endocrinol 2005; 30: 37–46.

    CAS  PubMed  Google Scholar 

  60. Rajan V, Edwards CR, Seckl JR . 11 beta-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. J Neurosci 1996; 16: 65–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kershaw EE, Morton NM, Dhillon H, Ramage L, Seckl JR, Flier JS . Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. Diabetes 2005; 54: 1023–1031.

    Article  CAS  PubMed  Google Scholar 

  62. Masuzaki H, Flier JS . Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) – a promising drug target for the treatment of metabolic syndrome. Curr Drug Targets Immune Endocr Metabol Disord 2003; 3: 255–262.

    Article  CAS  PubMed  Google Scholar 

  63. Seckl JR . 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 2004; 4: 597–602.

    Article  CAS  PubMed  Google Scholar 

  64. Wintermantel TM, Berger S, Greiner EF, Schutz G . Genetic dissection of corticosteroid receptor function in mice. Horm Metab Res 2004; 36: 387–391.

    Article  CAS  PubMed  Google Scholar 

  65. Opherk C, Tronche F, Kellendonk C, Kohlmuller D, Schulze A, Schmid W et al. Inactivation of the glucocorticoid receptor in hepatocytes leads to fasting hypoglycemia and ameliorates hyperglycemia in streptozotocin-induced diabetes mellitus. Mol Endocrinol 2004; 18: 1346–1353.

    Article  CAS  PubMed  Google Scholar 

  66. Liu Y, Nakagawa Y, Wang Y, Sakurai R, Tripathi PV, Lutfy K et al. Increased glucocorticoid receptor and 11{beta}-hydroxysteroid dehydrogenase type 1 expression in hepatocytes may contribute to the phenotype of type 2 diabetes in db/db mice. Diabetes 2005; 54: 32–40.

    Article  CAS  PubMed  Google Scholar 

  67. Davani B, Portwood N, Bryzgalova G, Reimer MK, Heiden T, Ostenson CG et al. Aged transgenic mice with increased glucocorticoid sensitivity in pancreatic beta-cells develop diabetes. Diabetes 2004; 53 (Suppl 1): S51–S59.

    Article  CAS  PubMed  Google Scholar 

  68. van Rossum EF, Koper JW, Huizenga NA, Uitterlinden AG, Janssen JA, Brinkmann AO et al. A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. Diabetes 2002; 51: 3128–3134.

    Article  CAS  PubMed  Google Scholar 

  69. Roussel R, Reis AF, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G . The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2003; 59: 237–241.

    Article  CAS  Google Scholar 

  70. Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W et al. Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 2005; 25: 6243–6250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pariante CM . Glucocorticoid receptor function in vitro in patients with major depression. Stress 2004; 7: 209–219.

    Article  CAS  PubMed  Google Scholar 

  72. Dinan TG, Scott LV . Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin. J Anat 2005; 207: 259–264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pariante CM . Glucocorticoid receptor function in vitro in patients with major depression. Stress 2004; 7: 209–219.

    Article  CAS  PubMed  Google Scholar 

  74. Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab 2005; 90: 2851–2854.

    Article  CAS  PubMed  Google Scholar 

  75. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA 2004; 101: 4531–4536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Licinio J . Longitudinally sampled human plasma leptin and cortisol concentrations are inversely correlated. J Clin Endocrinol Metab 1998; 83: 1042.

    Article  CAS  PubMed  Google Scholar 

  77. Bornstein SR, Uhlmann K, Haidan A, Ehrhart-Bornstein M, Scherbaum WA . Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly. Diabetes 1997; 46: 1235–1238.

    Article  CAS  PubMed  Google Scholar 

  78. Allard JS, Tizabi Y, Shaffery JP, Trouth CO, Manaye K . Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression. Neuropeptides 2004; 38: 311–315.

    Article  CAS  PubMed  Google Scholar 

  79. Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM et al. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry 2003; 54: 96–104.

    Article  CAS  PubMed  Google Scholar 

  80. Li Y, van den Pol AN . Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons. J Neurosci 2005; 25: 173–183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Haj-Dahmane S, Shen RY . The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci 2005; 25: 896–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Path G, Bornstein SR, Gurniak M, Chrousos GP, Scherbaum WA, Hauner H . Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function. J Clin Endocrinol Metab 2001; 86: 2281–2288.

    CAS  PubMed  Google Scholar 

  83. Alesci S, Martinez PE, Kelkar S, Ilias I, Ronsaville DS, Listwak SJ 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.

    Article  CAS  PubMed  Google Scholar 

  84. Caberlotto L, Rimondini R, Hansson A, Eriksson S, Heilig M . Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift? Neuropsychopharmacology 2004; 29: 15–22.

    Article  CAS  PubMed  Google Scholar 

  85. Manzanares J, Corchero J, Fuentes JA . Opioid and cannabinoid receptor-mediated regulation of the increase in adrenocorticotropin hormone and corticosterone plasma concentrations induced by central administration of delta(9)-tetrahydrocannabinol in rats. Brain Res 1999; 839: 173–179.

    Article  CAS  PubMed  Google Scholar 

  86. Nikisch G, Mathe AA, Czernik A, Thiele J, Bohner J, Eap CB et al. Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response. Psychopharmacology (Berl) 2005; 181: 751–760.

    Article  CAS  Google Scholar 

  87. Basta-Kaim A, Budziszewska B, Jaworska-Feil L, Tetich M, Kubera M, Leskiewicz M et al. Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene promoter activity operates through a PI3-K/AKT mediated pathway. Neuropharmacology 2005; 49: 156–164.

    Article  CAS  PubMed  Google Scholar 

  88. Inder WJ, Prickett TC, Mulder RT, Donald RA, Joyce PR . Reduction in basal afternoon plasma ACTH during early treatment of depression with fluoxetine. Psychopharmacology (Berl) 2001; 156: 73–78.

    Article  CAS  Google Scholar 

  89. Frost P, Bornstein S, Ehrhart-Bornstein M, O'Kirwan F, Hutson C, Heber D et al. The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St John's Wort), reduces HPA-axis function in the rat. Horm Metab Res 2003; 35: 602–606.

    Article  CAS  PubMed  Google Scholar 

  90. Moncek F, Duncko R, Jezova D . Repeated citalopram treatment but not stress exposure attenuates hypothalamic–pituitary–adrenocortical axis response to acute citalopram injection. Life Sci 2003; 72: 1353–1365.

    Article  CAS  PubMed  Google Scholar 

  91. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA 2004; 101: 4531–4536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H et al. Chronic stress and obesity: a new view of ‘comfort food’. Proc Natl Acad Sci USA 2003; 100: 11696–11701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bondy B . Pharmacogenomics in depression and antidepressants. Dialogues Clin Neurosci 2005; 7: 223–230.

    PubMed  PubMed Central  Google Scholar 

  94. Clement K, Boutin P, Froguel P . Genetics of obesity. Am J Pharmacogenom 2002; 2: 177–187.

    Article  CAS  Google Scholar 

  95. Adan RA, Vink T . Drug target discovery by pharmacogenetics: mutations in the melanocortin system and eating disorders. Eur Neuropsychopharmacol 2001; 11: 483–490.

    Article  CAS  PubMed  Google Scholar 

  96. Yoshida K, Takahashi H, Higuchi H, Kamata M, Ito K, Sato K et al. Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms. Am J Psychiatry 2004; 161: 1575–1580.

    Article  PubMed  Google Scholar 

  97. Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9: 442–473.

    Article  CAS  PubMed  Google Scholar 

  98. Wild J . Software shakes up schizophrenia diagnosis. Nature 2005; 438: 407.

    Article  CAS  PubMed  Google Scholar 

  99. Gottfried JA, O'Doherty J, Dolan RJ . Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science 2003; 301: 1104–1107.

    Article  CAS  PubMed  Google Scholar 

  100. Welberg LA, Seckl JR, Holmes MC . Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: possible implications for behaviour. Neuroscience 2001; 104: 71–79.

    Article  CAS  PubMed  Google Scholar 

  101. Merke DP, Giedd JN, Keil MF, Mehlinger SL, Wiggs EA, Holzer S et al. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab 2005; 90: 2531–2536.

    Article  CAS  PubMed  Google Scholar 

  102. Merke DP, Fields JD, Keil MF, Vaituzis AC, Chrousos GP, Giedd JN . Children with classic congenital adrenal hyperplasia have decreased amygdala volume: potential prenatal and postnatal hormonal effects. J Clin Endocrinol Metab 2003; 88: 1760–1765.

    Article  CAS  PubMed  Google Scholar 

  103. Ward MA, Carlsson CM, Trivedi MA, Sager MA, Johnson SC . The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study. BMC Neurol 2005; 5: 23.

    Article  PubMed  PubMed Central  Google Scholar 

  104. King BM, Cook JT, Rossiter KN, Rollins BL . Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport. Am J Physiol Regul Integr Comp Physiol 2003; 284: R965–R982.

    Article  CAS  PubMed  Google Scholar 

  105. Holsen LM, Zarcone JR, Thompson TI, Brooks WM, Anderson MF, Ahluwalia JS et al. Neural mechanisms underlying food motivation in children and adolescents. Neuroimage 2005; 27: 669–676.

    Article  PubMed  Google Scholar 

  106. Clark CP, Brown GG, Archibald SL, Fennema-Notestine C, Braun DR, Thomas LS et al. Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression? Psychiatry Res 2006; 146: 43–51.

    Article  PubMed  Google Scholar 

  107. Yoshida-Hiroi M, Bradbury MJ, Eisenhofer G, Hiroi N, Vale WW, Novotny GE et al. Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice. Mol Psychiatry 2002; 7: 967–974.

    Article  CAS  PubMed  Google Scholar 

  108. Willenberg HS, Bornstein SR, Dumser T, Ehrhart-Bornstein M, Barocka A, Chrousos GP et al. Morphological changes in adrenals from victims of suicide in relation to altered apoptosis. Endocr Res 1998; 24: 963–967.

    Article  CAS  PubMed  Google Scholar 

  109. Seres J, Bornstein SR, Seres P, Willenberg HS, Schulte KM, Scherbaum WA et al. Corticotropin-releasing hormone system in human adipose tissue. J Clin Endocrinol Metab 2004; 89: 965–970.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

M-LW and JL have been supported by NIH grants GM61394, RR000865, HL04526, RR16996, CA16042, RR017365, MH062777, HG002500, DK063240, and DK58851, and by an award from the Dana Foundation. This work was supported by grants from the Kröner-Fresenius Foundation and Deutsche Forschungsgemeinschaft (DFG-EH 161/4-1).

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  1. Department of Medicine, University of Dresden, Carl Gustav Carus, Dresden, Germany

    S R Bornstein & A Schuppenies

  2. Center for Pharmacogenomics and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA

    M-L Wong & J Licinio

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  1. S R Bornstein
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  2. A Schuppenies
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  3. M-L Wong
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  4. J Licinio
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Correspondence to S R Bornstein or J Licinio.

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Bornstein, S., Schuppenies, A., Wong, ML. et al. Approaching the shared biology of obesity and depression: the stress axis as the locus of gene–environment interactions. Mol Psychiatry 11, 892–902 (2006). https://doi.org/10.1038/sj.mp.4001873

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  • DOI: https://doi.org/10.1038/sj.mp.4001873

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