What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated?

European Archives of Psychiatry and Clinical Neuroscience

Volumn 257, Issue 5, 2007, Pages 250-260

  Czéh, Boldizsár ^a   Lucassen, Paul J ^b  

^a GERMAN PRIMATE CENTER   (Germany)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

Depression; Glia; Hippocampus; Mood disorder; Neuroplasticity

Indexed keywords

ANTIDEPRESSANT AGENT; CORTICOSTERONE; DEXAMETHASONE; GLUCOCORTICOID; HYDROCORTISONE; PREDNISONE;

APOPTOSIS; BRAIN DEATH; BRAIN TISSUE; CAUSE OF DEATH; CELL COUNT; CELL DEATH; CELL STRUCTURE; CEREBROSPINAL FLUID ANALYSIS; CHRONIC STRESS; DENTATE NUCLEUS; DEPRESSION; GLIA CELL; HIPPOCAMPUS; HISTOPATHOLOGY; HORMONE BLOOD LEVEL; HUMAN; MORPHOMETRICS; NERVE FIBER; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; REVIEW; STEREOMETRY; SYNAPSE;

APOPTOSIS; CELL PROLIFERATION; DEPRESSIVE DISORDER; HIPPOCAMPUS; HUMANS; NEUROGLIA; NEURONS; STRESS, PSYCHOLOGICAL;

EID: 34447120290     PISSN: 09401334     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00406-007-0728-0     Document Type: Review

References (113)

1. Alonso G (2000) Prolonged corticosterone treatment of adult rats inhibits the proliferation of oligodendrocyte progenitors present throughout white and gray matter regions of the brain. Glia 31:219-231
2. Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrie P (2004) Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry 9:278-286
3. Boekhoorn K, Joels M, Lucassen PJ (2006) Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis 24:1-14
4. Bowley MP, Drevets WC, Ongur D, Price JL (2002) Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 52:404-412
5. Bremner JD, (2002) Structural changes in the brain in depression and relationship to symptom recurrence. CNS Spectr 7:129-130, 135-139
6. Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161:598-607
7. Cameron HA, McKay RD (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435:406-417
8. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386-389
9. Castren E (2005) Is mood chemistry? Nat Rev Neurosci 6:241-246
10. Castren E, Voikar V, Rantamaki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7:18-21
11. Cobb JA, Mahajan G, Lawrence TJ, Miguel-Hidalgo JJ, Dieter L, Herbst N, Matzinger M, Overholser JC, Jurjus GJ, Rajkowska G, Stockmeier CA (2006) Stereological estimation of cell number, cell size, and hippocampal volume in major depressive disorder (MDD). Neuroscience Meeting Planner. Society for Neuroscience, Atlanta, GA, 2006. Online
12. Cotter DR, Pariante CM, Everall IP (2001) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585-595
13. Coyle JT, Schwarcz R (2000). Mind glue: implications of glial cell biology for psychiatry. Arch Gen Psychiatry 57:90-93
14. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98:12796-12801
15. Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, Toschi N, Fuchs E, Keck ME (2002) Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 52:1057-1065
16. Czeh B, Simon M, Schmelting B, Hiemke C, Fuchs E (2006) Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology 31:1616-1626
17. Damadzic R, Bigelow LB, Krimer LS, Goldenson DA, Saunders RC, Kleinman JE, Herman MM (2001) A quantitative immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia, bipolar disorder and major depression: absence of significant astrocytosis. Brain Res Bull 55:611-618
18. Dayer AG, Ford AA, Cleaver KM, Yassaee M, Cameron HA (2003) Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 460:563-572
19. Del Bigio MR (1999) Proliferative status of cells in adult human dentate gyrus. Microsc Res Tech 45:353-358
20. Diamond DM, Campbell A, Park CR, Vouimba RM (2004) Preclinical research on stress, memory, and the brain in the development of pharmacotherapy for depression. Eur Neuropsychopharmacol 14(Suppl 5):S491-S495
21. Dranovsky A, Hen R (2006) Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry 59:1136-1143
22. Drevets WC (2000) Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res 126:413-431
23. Driessen M, Herrmann J, Stahl K, Zwaan M, Meier S, Hill A, Osterheider M, Petersen D (2000) Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 57:1115-1122
24. Duman RS (2004) Depression: a case of neuronal life and death? Biol Psychiatry 56:140-145
25. D'Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4:183-194
26. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage H (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313-1317
27. Fields RD, Stevens-Graham B (2002) New insights into neuron-glia communication. Science 298:556-562
28. Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492-2498
29. Gould E, Tanapat P, McEwen BS, Flügge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95:3168-3171
30. Geuze E, Vermetten E, Bremner JD (2005) MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry 10:160-184
31. Hajszan T, MacLusky NJ, Leranth C (2005) Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 21:1299-1303
32. Hamidi M, Drevets WC, Price JL (2004) Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 55:563-569
33. Harlan J, Chen Y, Gubbins E, Mueller R, Roch JM, Walter K, Lake M, Olsen T, Metzger P, Dorwin S, Ladror U, Egan DA, Severin J, Johnson RW, Holzman TF, Voelp K, Davenport C, Beck A, Potter J, Gopalakrishnan M, Hahn A, Spear BB, Halbert DN, Sullivan JP, Abkevich V, Neff CD, Skolnick MH, Shattuck D, Katz DA (2006) Variants in Apaf-1 segregating with major depression promote apoptosome function. Mol Psychiatry 11:76-85
34. Harrison PJ (2002) The neuropathology of primary mood disorder. Brain 125:1428-1449
35. Haydon PG (2001) GLIA: listening and talking to the synapse. Nat Rev Neurosci 2:185-193
36. Heine VM, Maslam S, Joels M, Lucassen PJ (2004) Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging 25:361-375
37. Heine VM, Maslam S, Zareno J, Joels M, Lucassen PJ (2004) Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. Eur J Neurosci 19:131-144
38. Heine VM, Zareno J, Maslam S, Joels M, Lucassen PJ (2005). Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression. Eur J Neurosci 21(5):1304-1314
39. Heckers S (2001) Neuroimaging studies of the hippocampus in schizophrenia. Hippocampus 11:520-528
40. Henn FA, Vollmayr B (2004) Neurogenesis and depression: etiology or epiphenomenon? Biol Psychiatry 56:146-150
41. Hu Z, Yuri K, Ozawa H, Lu H, Kawata M (1997) The in vivo time course for elimination of adrenalectomy-induced apoptotic profiles from the granule cell layer of the rat hippocampus. J Neurosci 17:3981-3989
42. Jacobs BL, Praag H, Gage FH (2000) Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry 5:262-269
43. Jayatissa MN, Bisgaard C, Tingstrom A, Papp M, Wiborg O (2006) Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology 31:2395-2404
44. Joels M, Karst H, Alfarez D, Heine VM, Qin Y, van Riel E, Verkuyl M, Lucassen PJ, Krugers HJ (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 7:221-231
45. Joelving FC, Billeskov R, Christensen JR, West M, Pakkenberg B (2006) Hippocampal neuron and glial cell numbers in Parkinson's disease-a stereological study. Hippocampus 16:826-833
46. Keilhoff G, Becker A, Grecksch G, Bernstein HG, Wolf G (2006) Cell proliferation is influenced by bulbectomy and normalized by imipramine treatment in a region-specific manner. Neuropsychopharmacology 31:1165-1176
47. Kempermann G, Gast D, Gage FH (2002) Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52:135-143
48. Kempermann G, Kronenberg G (2003) Depressed new neurons-adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry 54:499-503
49. Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837-841
50. Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96:5768-5773
51. Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027-2033
52. Lee HJ, Kim JW, Yim SV, Kim MJ, Kim SA, Kim YJ, Kim CJ, Chung JH (2001) Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats. Mol Psychiatry 6:610, 725-728
53. Leverenz JB, Wilkinson CW, Wamble M, Corbin S, Grabber JE, Raskind MA, Peskind ER (1999) Effect of chronic high-dose exogenous cortisol on hippocampal neuronal number in aged nonhuman primates. J Neurosci 19:2356-2361
54. Lucassen PJ, Chung WC, Vermeulen JP, Van Lookeren Campagne M, Van Dierendonck JH, Swaab DF (1995) Microwave-enhanced in situ end-labeling of fragmented DNA: parametric studies in relation to postmortem delay and fixation of rat and human brain. J Histochem Cytochem 43:1163-1171
55. Lucassen PJ, Fuchs E, Czeh B (2004) Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 55:789-796
56. Lucassen PJ, Negoescu A, Labat-Moleur F, van Lookeren Campagne M (2000) Microwave enhanced in situ end labelling of apoptotic cells in tissue sections; pitfalls and possibilities. In: Shi SR, Gu J, Taylor CR (eds) Antigen retrieval techniques (biotechniques series). Eaton Publishing, Natick, MA, USA, pp 71-91
57. Lucassen PJ De Kloet ER (2001) Glucocorticoids and the aging brain; cause or consequence? In: Hof P, Charles Mobbs C (eds) Functional neurobiology of aging. Academic Press, Elsevier, pp 883-905
58. Lucassen PJ, Muller MB, Holsboer F, Bauer J, Holtrop A, Wouda J, Hoogendijk WJ, De Kloet ER, Swaab DF (2001a) Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure. Am J Pathol 158:453-468
59. Lucassen PJ, Vollmann-Honsdorf GK, Gleisberg M, Czeh B, De Kloet ER, Fuchs E (2001b) Chronic psychosocial stress differentially affects apoptosis in hippocampal subregions and cortex of the adult tree shrew. Eur J Neurosci 14:161-166
60. Lupien SJ, de Leon M, de Santi S, Convit A, Tarshish C, Nair NP, Thakur M, McEwen BS, Hauger RL, Meaney MJ (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1:69-73
61. MacQueen GM, Campbell S, McEwen BS, Macdonald K, Amano S, Joffe RT, Nahmias C, Young LT (2003) Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 100:1387-1392
62. Magariños AM, McEwen BS, Flügge G, Fuchs E (1996) Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 16:3534-3540
63. Magariños AM, Verdugo JM, McEwen BS (1997) Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci USA 94:14002-14008
64. Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562-1571
65. Malberg JE, Schechter LE (2005) Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs. Curr Pharm Des 11:145-155
66. Manji HK, Drevets WC, Charney DS (2001) The cellular neurobiology of depression. Nat Med 7:541-547
67. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, A Gray N, Zarate CA Jr, Charney DS (2003) Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 53:707-742
68. Mayer JL, Klumpers L, Maslam S, de Kloet ER, Joels M, Lucassen PJ (2006) Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis. J Neuroendocrinol 18:629-631
69. McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172-189
70. Mirescu C, Gould E (2006) Stress and adult neurogenesis. Hippocampus 16:233-238
71. Muller MB, Lucassen PJ, Yassouridis A, Hoogendijk WJ, Holsboer F, Swaab DF (2001) Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus. Eur J Neurosci 14:1603-1612
72. Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523-530
73. Neumeister A, Wood S, Bonne O, Nugent AC, Luckenbaugh DA, Young T, Bain EE, Charney DS, Drevets WC (2005) Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects. Biol Psychiatry 57:935-937
74. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13-25
75. Norrholm SD, Ouimet CC (2001) Altered dendritic spine density in animal models of depression and in response to antidepressant treatment. Synapse 42:151-163
76. Oberheim NA, Wang X, Goldman S, Nedergaard M (2006) Astrocytic complexity distinguishes the human brain. Trends Neurosci 29:547-553
77. O'Brien J, Thomas A, Ballard C, Brown A, Ferrier N, Jaros E, Perry R (2001) Cognitive impairment in depression is not associated with neuropathologic evidence of increased vascular or Alzheimer-type pathology. Biol Psychiatry 49:130-136
78. Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879-886
79. Rajkowska G (2002) Cell pathology in mood disorders. Semin Clin Neuropsychiatry 7:281-292
80. Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch KP (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11:514-522
81. Rosoklija G, Toomayan G, Ellis SP, Keilp J, Mann JJ, Latov N, Hays AP, Dwork AJ (2000) Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry 57:349-356
82. Roy M, Sapolsky RM (2003) The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis. Neuroendocrinology 77:24-31
83. Sandi C, Davies HA, Cordero MI, Rodriguez JJ, Popov VI, Stewart MG (2003) Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus following water maze training. Eur J Neurosci 17:2447-2456
84. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805-809
85. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57:925-935
86. Sapolsky RM, Krey LC, McEwen BS (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5:1222-1227
87. Sapolsky RM, Uno H, Rebert CS, Finch CE (1990) Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 10:2897-2902
88. Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA 103:17501-17506
89. Shapiro EM, Gonzalez-Perez O, Manuel Garcia-Verdugo J, Alvarez-Buylla A, Koretsky AP (2006) Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain. Neuroimage 32:1150-1157
90. Simon M, Czeh B, Fuchs E (2005) Age-dependent susceptibility of adult hippocampal cell proliferation to chronic psychosocial stress. Brain Res 1049:244-248
91. Sheline YI (2000) 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry 48:791-800
92. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93:3908-3913
93. Sheline YI, Sanghavi M, Mintun MA, Gado MH (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19:5034-5043
94. Sheline YI, Gado MH, Kraemer HC (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160:1516-1518
95. Smith ME (2005) Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies. Hippocampus 15:798-807
96. Sousa N, Almeida OF (2002) Corticosteroids: sculptors of the hippocampal formation. Rev Neurosci 13:59-84
97. Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM (2000) Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience 97:253-266
98. Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, Schteingart DE (1999) Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease. Biol Psychiatry 46:1595-1602
99. Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, Uylings HB, Friedman L, Rajkowska G (2004) Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry 56:640-650
100. Sykova E, Chvatal A (2000) Glial cells and volume transmission in the CNS. Neurochem Int 36:397-409
101. Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141-194
102. Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705-1711
103. van der Hart MG, Czeh B, de Biurrun G, Michaelis T, Watanabe T, Natt O, Frahm J, Fuchs E (2002) Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume. Mol Psychiatry 7:933-941
104. van der Beek EM, Wiegant VM, Schouten WG, van Eerdenburg FJ, Loijens LW, van der Plas C, Benning MA, de Vries H, de Kloet ER, Lucassen PJ (2004) Neuronal number, volume, and apoptosis of the left dentate gyrus of chronically stressed pigs correlate negatively with basal saliva cortisol levels. Hippocampus 14:688-700
105. Vermetten E, Schmahl C, Lindner S, Loewenstein RJ, Bremner JD (2006) Hippocampal and amygdalar volumes in dissociative identity disorder. Am J Psychiatry 163:630-636
106. Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161:1957-1966
107. Vollmann-Honsdorf GK, Flugge G, Fuchs E (1997) Chronic psychosocial stress does not affect the number of pyramidal neurons in tree shrew hippocampus. Neurosci Lett 233:121-124
108. Vollmayr B, Simonis C, Weber S, Gass P, Henn F (2003) Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biol Psychiatry 54:1035-1040
109. Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16:239-249
110. Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS (1992) Tianeptine attenuates stress-induced morphological changes in the hippocampus. Eur J Pharmacol 222:157-162
111. Wennstrom M, Hellsten J, Ekstrand J, Lindgren H, Tingstrom A (2006) Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biol Psychiatry 59:178-186
112. West MJ, Gundersen HJ (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296:1-22
113. Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225-231