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New Paradigm for Treating Recurrent Depression: From Symptom Control to Managing Enduring Vulnerabilities

Published online by Cambridge University Press:  07 November 2014

Abstract

Optimal management of depression remains a long-term challenge. Long-term maintenance treatment with antidepressants has been shown to be effective for preventing or delaying recurrence for many patients with a history of previous multiple episodes. However, aside from a history of multiple recurrences, it remains difficult to identify patients who are most likely to experience recurrence and when. Thus we do not really know who might particularly benefit from maintenance therapy and what type may be efficacious. In patients with depression, research has shown there are structural and functional alterations in the brain, particularly in patients with recurrent or chronic depression. These changes have been generally viewed to be consequences of the disease, which are seen to worsen with a longer duration of untreated illness and with a greater number of depressive episodes. However, these neurobiological characteristics may also represent risk factors or vulnerabilities that predispose some patients to chronic or recurrent depression. Additional research has demonstrated that antidepressant treatment may reduce or modulate these functional and structural changes, suggesting that long-term treatment may, in fact, benefit patients not only by controlling symptoms but also by managing these underlying vulnerabilities. A new treatment paradigm, which focuses on identifying patients with risk factors and managing the disease process rather than suppression of symptoms, is needed for recurrent depression.

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Supplement
Copyright
Copyright © Cambridge University Press 2006

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References

REFERENCES

1.Mueller, TI, Leon, AC, Keller, MB, et al.Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. Am J Psychiatry. 1999;156:10001006.CrossRefGoogle ScholarPubMed
2.Solomon, DA, Keller, MB, Leon, AC, et al.Multiple recurrences of major depressive disorder. Am J Psychiatry. 2000;157:229233.CrossRefGoogle ScholarPubMed
3.Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA. 1996;93:39083913.CrossRefGoogle ScholarPubMed
4.Sheline, YI, Sanghavi, M, Mintun, MA, Gado, MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19:50345043.CrossRefGoogle Scholar
5.Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS. Hippocampal volume reduction in major depression. Am J Psychiatry. 2000;157:115118.CrossRefGoogle ScholarPubMed
6.Mervaala, E, Fohr, J, Kononen, Met al.Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000;30:117125.CrossRefGoogle ScholarPubMed
7.Steffens, DC, Byrum, CE, McQuoid, DRet al.Hippocampal volume in geriatrie depression. Biol Psychiatry. 2000;48:301309.CrossRefGoogle Scholar
8.Nemeroff, CB, Owens, MJ. Pharmacologie differences among the SSRIs: focus on monoamine transporters and the HPA axis. CNS Spectr. 2004;9:2331.CrossRefGoogle Scholar
9.Pezawas, L, Meyer-Lindenberg, A, Drabant, EM, et al.5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci. 2005;8:828834.CrossRefGoogle ScholarPubMed
10.Heim, C, Newport, DJ, Heit, S, et al.Pituitary-adrenal and autonomie responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000;284:592597.CrossRefGoogle Scholar
11.Arborelius, L, Owens, MJ, Plotsky, PM, Nemeroff, CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160:112.CrossRefGoogle ScholarPubMed
12.Plotsky, PM, Owens, MJ, Nemeroff, CB. Neuropeptide Alteration in Mood Disorders. Psychopharmacology-the 4th Generation of Progress 2000; Available at: http://www.acnp.org/g4/GN401000097/Default.htm. Accessed on September 20, 2006.Google Scholar
13.Plotsky, PM, Thrivikraman, KV, Nemeroff, CB, Caldji, C, Sharma, S, Meaney, MJ. Long-term consequences of neonatal rearing on central corticotropin-releasing factor Systems in adult maie rat offspring. Neuropsychopharmacology. 2005;30:21922204.CrossRefGoogle Scholar
14.Ladd, CO, Thrivikraman, KV, Huot, RL, Plotsky, PM. Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates. Psychoneuroendocrinology. 2005;30:520533.CrossRefGoogle ScholarPubMed
15.Levine, S, Johnson, DF, Gonzalez, CA. Behavioral and hormonal responses to separation in infant rhesus monkeysand mothers. Behav Neurosci. 1985;99:399410.CrossRefGoogle Scholar
16.Levine, S, Wiener, SG, Coe, CL. Temporal and social factors influencing behavioral and hormonal responses to separation in mother and infant squirrel monkeys. Psychoneuroendocrinology. 1993;18:297306.CrossRefGoogle ScholarPubMed
17.Kraemer, GW, Ebert, MH, Schmidt, DE, McKinney, WT. Strangers in a strange land: a psychobiological study of infant monkeys before and after separation from real or inanimate mothers. Child Dev. 1991;62:548566.CrossRefGoogle ScholarPubMed
18.Suomi, SJ. Early stress and adult emotional reactivity in rhesus monkeys. Ciba Found Symp. 1991;156:171183.Google ScholarPubMed
19.Nemeroff, CB. Neurobiological consequences of childhood trauma. J Clin Psychiatry. 2004;65(Suppl 1):1828.Google ScholarPubMed
20.Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatrie disorders. Arch Gen Psychiatry. 2000;57:925935.CrossRefGoogle Scholar
21.Sapolsky, RM. Depression, antidepressants, and the shrinking hippocampus. Proc Natl Acad Sci U S A. 2001;98:1232012322.CrossRefGoogle ScholarPubMed
22.Czeh, B, Michaelis, T, Watanabe, T, et al.Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA. 2001;98:1279612801.CrossRefGoogle ScholarPubMed
23.Smith, MA, Makino, S, Kvetnansky, R, Post, RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995;15:17681777.CrossRefGoogle ScholarPubMed
24.Videbech, P, Ravnkilde, B. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry. 2004;161:19571966.CrossRefGoogle ScholarPubMed
25.Keller, J, Flores, B, Gomez, RG, et al.Cortisol circadian rhythm alterations in psychotic major depression. Biol Psychiatry. 2006;60:275281.CrossRefGoogle ScholarPubMed
26.Sheline, YI, Gado, MH, Kraemer, HC. Untreated depression and hippocampal volume loss. Am J Psychiatry. 2003;160:15161518.CrossRefGoogle ScholarPubMed
27.Neumeister, A, Wood, S, Bonne, O, et al.Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects. Biol Psychiatry. 2005;57:935937.CrossRefGoogle ScholarPubMed
28.Frodl, T, Meisenzahl, EM, Zetzsche, T, et al.Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry. 2002;159:11121118.CrossRefGoogle ScholarPubMed
29.Lyons, DM, Yang, C, Sawyer-Glover, AM, Moseley, ME, Schatzberg, AF. Early life stress and inherited variation in monkey hippocampal volumes. Arch Gen Psychiatry. 2001;58:11451151.CrossRefGoogle ScholarPubMed
30.Sullivan, EV, Pfefferbaum, A, Swan, GE, Carmelli, D. Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment. Hippocampus. 2001;11:754762.CrossRefGoogle ScholarPubMed
31.Gilbertson, MW, Shenton, ME, Ciszewski, A, et al.Smaller hippocampal volume predicts pathologie vulnerability to psychological trauma. Nat Neurosci. 2002;5:12421247.CrossRefGoogle Scholar
32.Pitman, RK, Gilbertson, MW, Gurvits, TV, et al.Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure. Ann N Y Acad Sci. 2006;1071:242254.CrossRefGoogle Scholar
33.Lyons, DM, Parker, KH, Zeitzer, JM, Buckmaster, CL, Schatzberg, AF. Hippocampal volume variation and stress-related psychopathology. Presented at: Society for Neuroscience Annual Meeting; November 12-16, 2005; Washington, DC.Google Scholar
34.Willis-Owen, SA, Turri, MG, Munafo, MR, et al.The serotonin transporter length polymorphism, neuroticism, and depression: a comprehensive assessment of association. Biol Psychiatry. 2005;58:451456.CrossRefGoogle ScholarPubMed
35.Caspi, A, Sugden, K, Moffitt, TE, et al.Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386389.CrossRefGoogle ScholarPubMed
36.Merikangas, KR. What does a short form of the serotonin transporter really signify for major depression. Biol Psychiatry. 2006;59:25.Google Scholar
37.Hariri, AR, Drabant, EM, Munoz, KE, et al.A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry. 2005;62:146152.CrossRefGoogle ScholarPubMed
38.Hamann, S. Blue genes: wiring the brain for depression. Nat Neurosci. 2005;8:701703.CrossRefGoogle ScholarPubMed
39.Binder, EB, Salyakina, D, Lichtner, P, et al.Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 2004;36:13191325.CrossRefGoogle ScholarPubMed
40.van Rossum, EF, Binder, EB, Majer, M, et al.Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry. 2006;59:681688.CrossRefGoogle ScholarPubMed
41.Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001;50:651658.CrossRefGoogle ScholarPubMed
42.Drevets, WC, Bogers, W, Raichle, ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol. 2002;12:527544.CrossRefGoogle ScholarPubMed
43.Pariante, CM, Thomas, SA, Lovestone, S, Makoff, A, Kerwin, RW. Do antidepressants regulate how cortisol affects the brain? Psychoneuroendocrinology. 2004;29:423447.CrossRefGoogle ScholarPubMed
44.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;133:312320.CrossRefGoogle ScholarPubMed
45.Nikisch, G, Mathe, AA, Czernik, A, 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;181:751760.CrossRefGoogle ScholarPubMed
46.Duman, RS, Monteggia, LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:11161127.CrossRefGoogle ScholarPubMed
47.Shimizu, E, Hashimoto, K, Okamura, N, et al.Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry. 2003;54:70–5.CrossRefGoogle ScholarPubMed
48.Chen, B, Dowlatshahi, D, MacQueen, GM, Wang, JF, Young, LT. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001;50:260–5.CrossRefGoogle ScholarPubMed
49.Santarelli, L, Saxe, M, Gross, C, et al.Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805809.CrossRefGoogle ScholarPubMed
50.Vermetten, E, Vythilingam, M, Southwick, SM, Charney, DS, Bremner, JD. Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry. 2003;54:693702.CrossRefGoogle ScholarPubMed