1. World Health Organization. WHO global report: Preventing chronic diseases: A vital investment. Geneva: World Health Organization. 2005 Available: http://www.who.int/chp/chronic_disease_report/en/. Accessed 8 January 2009.
2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine. 2007;3:e442. doi: 10.1371/journal.pmed.0030442.
3. Malhi GS, Moore J, McGuffin P. The genetics of major depressive disorder. Curr Psychiatry Rep. 2000;2:165–169.[PubMed]
4. Binder EB, Holsboer F. Pharmacogenomics and antidepressant drugs. Ann Med. 2006;38:82–94.[PubMed]
5. Bosker FJ, Westerink BH, Cremers TI, Gerrits M, van der Hart MG, et al. Future antidepressants: what is in the pipeline and what is missing? CNS Drugs. 2004;18:705–732.[PubMed]
6. Greden JF. Unmet need: what justifies the search for a new antidepressant? J Clin Psychiatry. 2002;63(Suppl 2):3–7.
7. Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, et al. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron. 2007;55:712–725.[PubMed]
8. Holsboer F. How can we realize the promise of personalized antidepressant medicines? Nat Rev Neurosci. 2008;9:638–646.[PubMed]
9. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:1116–1127.[PubMed]
10. Lesch KP. Gene-environment interaction and the genetics of depression. J Psychiatry Neurosci. 2004;29:174–184.[PMC free article][PubMed]
11. Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, et al. Preclinical models: status of basic research in depression. Biol Psychiatry. 2002;52:503–528.[PubMed]
12. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, (4th ed.), Text Revised (DSM-IV-TR) Washington, DC: American Psychiatric Association; 2000.
13. Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008;455:894–902.[PMC free article][PubMed]
14. Parker G. Beyond major depression. Psychol Med. 2006;35:467–474.
15. Antonijevic IA. Depressive disorders—is it time to endorse different pathophysiologies? Psychoneuroendocrinology. 2006;31:1–15.[PubMed]
16. Rush AJ. The varied clinical presentations of major depressive disorder. J Clin Psychiatry. 2007;68(Suppl 8):4–10.
17. Hyman SE. Can neuroscience be integrated into the DSM-V? Nat Rev Neurosci. 2007;8:725–732.[PubMed]
18. Åsberg M, Nygren A, Leopardi R, Rylander G, Peterson U, et al. Novel biochemical markers of psychosocial stress in women. PLoS ONE. 2009;3:e?.
19. Schüle C, Baghai TC, Eser D, Häfner S, Born C, et al. The combined dexamethasone/CRH test (DEX/CRH test) and prediction of acute treatment response in major depression. PLoS ONE. 2009;3:e.
20. Warner-Schmidt JL, Duman RS. VEGF as a potential target for therapeutic intervention in depression. Curr Opin Pharmacol. 2008;8:14–19.[PMC free article][PubMed]
21. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56.[PMC free article][PubMed]
22. Czéh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A. 2001;98:12796–12801.[PMC free article][PubMed]
23. Sapolsky RM. Depression, antidepressants, and the shrinking hippocampus. Proc Natl Acad Sci U S A. 2001;98:12320–12322.[PMC free article][PubMed]
24. Sullivan P, de Geus E, Willeen G, James MR, Smit JH, et al. Genomwide Association for Major Depressive Disorder: possible role for the presynaptic protein piccolo. Mol Psych. 2009 In press.
25. Baune BT, Hohoff C, Berger K, Neumann A, Mortensen LS, et al. Association of the COMT val158met variant with antidepressant treatment response in Major Depression. Neuropsychopharmacology. 2008;33:924–932.[PubMed]
26. Gizatullin R, Zaboli G, Jönsson EG, Asberg M, Leopardi R. Haplotype analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression. Biol Psychiatry. 2006;59:295–300.[PubMed]
27. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386–389.[PubMed]
28. Urani A, Chourbaji S, Gass P. Mutant mouse models of depression: candidate genes and current mouse lines. Neurosci Biobehav Rev. 2005;29:805–828.[PubMed]
29. Touma C, Fenzl T, Ruschel J, Palme R, Holsboer F, et al. Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression. PLoS ONE. 2009;3:e.
30. Schweizer MC, Henniger MSH, Sillaber I. Chronic Mild Stress (CMS) in Mice: of Anhedonia, ‘Anomalous Anxiolysis’ and Activity. PLoS ONE. 2009;3:e.
31. McEwen BS. Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology. 2000;22:108–124.[PubMed]
32. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87:873–904.[PubMed]
33. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000;21:55–89.[PubMed]
34. de Kloet ER, Joëls M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6:463–475.[PubMed]
35. Anisman H, Merali Z, Hayley S. Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol. 2008;85:1–74.[PubMed]
36. Moreau M, André C, O'Connor JC, Dumich SA, Woods JA, et al. Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior. Brain Behav Immun. 2008;22:1087–1095.[PMC free article][PubMed]
37. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U S A. 2003;100:1920–1925.[PMC free article][PubMed]
38. Bartolomucci A. Social stress, immune functions and disease in rodents. Front Neuroendocrinol. 2007;28:28–49.[PubMed]
39. van der Laan S, de Kloet ER, Meijer OC. Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene. PLoS ONE. 2009;4(1):e4327.[PMC free article][PubMed]
40. Charney DS, Manji HK. Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention. Sci STKE. 2004;205:re5.
41. Cryan JF, Mombereau C. In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry. 2004;9:326–357.[PubMed]
42. Bartolomucci A, Cabassi A, Covoni P, Ceresini G, Cero C, et al. Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress. PLoS ONE. 2009;4(1):e4331.[PMC free article][PubMed]
43. Cooper B, Fuchs E, Flügge G. Expression of the axonal membrane glycoprotein M6a is regulated by chronic stress. PLoS ONE. 2009;4(1):e4659.[PMC free article][PubMed]
44. Ilin Y, Richter-Levin G. Enriched environment experience overcomes learning deficits and depressive-like behavior induced by juvenile (early life) stress. PLoS ONE. 2009;4(1):e4329.[PMC free article][PubMed]
45. Hunter RG, Bellani R, Bloss E, Costa A, McCarthy K, et al. Regulation of Kainate Receptor Subunit mRNA by Stress and Corticosteroids in the Rat Hippocampus. PLoS ONE. 2009;4(1):e4328.[PMC free article][PubMed]
46. Oomen CA, Girardi CEN, Cahyadi R, Verbeek EC, Krugers H, et al. Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS ONE. 2009;4(1):e3675.[PMC free article][PubMed]
47. Holsboer F, Ising M. Central CRH system in depression and anxiety—evidence from clinical studies with CRH1 receptor antagonists. Eur J Pharmacol. 2008;583:350–357.[PubMed]
48. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006;7:137–151.[PubMed]
49. Miczek KA, Yap JJ, Covington HE III. Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake. Pharmacol Ther. 2008;120:102–128.[PMC free article][PubMed]
50. Willner P, Mitchell PJ. The validity of animal models of predisposition to depression. Behav Pharmacol. 2002;13:169–188.[PubMed]
51. Koolhaas JM, Meerlo P, De Boer SF, Strubbe JH, Bolhus B. Social stress in rats: an animal model of depression? Acta Neuropsychiatrica. 1995;7:27–29.[PubMed]
52. Koolhaas JM, Meerlo P, De Boer SF, Strubbe JH, Bohus B. The temporal dynamics of the stress response. Neurosci Biobehav Rev. 1997;21:775–782.[PubMed]
53. Collins A, Hill LE, Chandramohan Y, Whitcomb D, Droste SK, et al. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus. PLoS ONE. 2009;4(1):e4330.[PMC free article][PubMed]
54. Anisman H, Matheson K. Stress, depression, and anhedonia: caveats concerning animal models. Neurosci Biobehav Rev. 2005;29:525–546.[PubMed]
55. McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, et al. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet. 2006;78:804–814.[PMC free article][PubMed]
56. Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, et al. Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry. 2007;164:1181–1188.[PubMed]
57. Laifenfeld D, Karry R, Klein E, Ben-Shachar D. Alterations in cell adhesion molecule L1 and functionally related genes in major depression: a postmortem study. Biol Psychiatry. 2005;57:716–725.[PubMed]
58. Alfonso J, Frick LR, Silberman DM, Palumbo ML, Genaro AM, et al. Regulation of hippocampal gene expression is conserved in two species subjected to different stressors and antidepressant treatments. Biol Psychiatry. 2006;59:244–251.[PubMed]
59. Alfonso J, Pollevick GD, Van Der Hart MG, Flügge G, Fuchs E, et al. Identification of genes regulated by chronic psychosocial stress and antidepressant treatment in the hippocampus. Eur J Neurosci. 2004;19:659–666.[PubMed]
60. Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci. 2007;8:355–367.[PubMed]
61. Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci. 2007;10:1110–1115.[PubMed]
62. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301:805–809.[PubMed]
63. Surget A, Saxe M, Leman S, Ibarguen-Vargas Y, Chalon S, et al. Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol Psychiatry. 2008;64:293–301.[PubMed]
64. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron. 2008;59:399–412.[PMC free article][PubMed]
65. Reif A, Fritzen S, Finger M, Strobel A, Lauer M, et al. Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry. 2006;11:514–522.[PubMed]
66. Kornstein SG. Gender differences in depression: implication for treatment. J Clin Psychiatry. 1997;58:12–18.
67. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology. 1997;134:319–29.
68. Stunkard AJ, Faith MS, Allison KC. Depression and obesity. Biol Psychiatry. 2003;54:330–337.[PubMed]
69. Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62:321–326.[PubMed]
70. van Praag HM. Can stress cause depression? Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:891–907.[PubMed]
71. Rydmark I, Wahlberg K, Ghatan PH, Modell S, Nygren A, et al. Neuroendocrine, cognitive and structural imaging characteristics of women on longterm sickleave with job stress-induced depression. Biol Psychiatry. 2006;60:867–873.[PubMed]
72. Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999;156:837–841.[PubMed]
73. Vaez M, Rylander G, Nygren A, Asberg M, Alexanderson K. Sickness absence and disability pension in a cohort of employees initially on long-term sick leave due to psychiatric disorders in Sweden. Soc Psychiatry Psychiatr Epidemiol. 2007;42:381–388.[PubMed]
74. Tennant C. Work-related stress and depressive disorders. J Psychosom Res. 2001;51:697–704.[PubMed]
Depression is the common cold of mental disorders — most people will be affected by depression in their lives either directly or indirectly, through a friend or family member. Confusion about depression is commonplace, e.g., with regard to what depression exactly is and what makes it different from just feeling down.
There is also confusion surrounding the many types of depression that people experience — unipolar depression, biological depression, manic depression, seasonal affective disorder, dysthymia, etc. There have been so many terms used to describe this set of feelings we’ve all felt at one time or another in our lives, it may be difficult to understand the difference between just being blue and having clinical depression.
Depression is characterized by a number of common symptoms. These include a persistent sad, anxious, or “empty” mood, and feelings of hopelessness or pessimism that lasts nearly every day, for weeks on end. A person who is depressed also often has feelings of guilt, worthlessness, and helplessness. They no longer take interest or pleasure in hobbies and activities that were once enjoyed; this may include things like going out with friends or even sex. Insomnia, early-morning awakening, and oversleeping are all common.
Appetite and/or weight loss or overeating and weight gain may be symptoms of depression in some people. Many others experience decreased energy, fatigue, and a constant feeling of being “slowed down.” Thoughts of death or suicide are not uncommon in those suffering from severe depression. Restlessness and irritability among those who have depression is common. A person who is depressed also has difficulty concentrating, remembering, and trouble making decisions. And sometimes, persistent physical symptoms that do not respond to traditional treatments — such as headaches, digestive disorders, and chronic pain — may be signs of a depressive illness.
Do I Have Just The Blues… Or Something More?
Feeling down or feeling like you’ve got the blues is pretty common in today’s fast-paced society. People are more stressed than ever, working longer hours than ever, for less pay than ever. It is therefore natural to not feel 100% some days. That’s completely normal.
Depression can be a gradual withdrawal from your active life.
What differentiates occasionally feeling down for a few days from depression is the severity of the symptoms listed above, and how long you’ve had the symptoms. Typically, for most depressive disorders, you need to have felt some of those symptoms for longer than two weeks. They also need to cause you a fair amount of distress in your life, and interfere with your ability to carry on your normal daily routine.
Depression is a severe disorder, and one that can often go undetected in some people’s lives because it can creep up on you. Depression doesn’t need to strike all at once; it can be a gradual and nearly unnoticeable withdrawal from your active life and enjoyment of living. Or it can be caused by a clear event, such as the breakup of a long-term relationship, a divorce, family problems, etc. Finding and understanding the causes of depression isn’t nearly as important as getting appropriate and effective treatment for it.
Grief after the death or loss of a loved one is common and not considered depression in the usual sense. Teenagers going through the usual mood swings common to that age usually don’t experience clinical depression either. Depression usually strikes adults, and twice as many women as men. It is theorized that men express their depressive feelings in more external ways that often don’t get diagnosed as depression. For example, men may spend more time or energy focused on an activity to the exclusion of all other activities, or may have difficulty controlling outbursts of rage or anger. These types of reactions can be symptoms of depression.