Signaling pathways underlying the pathophysiology and treatment of depression: Novel mechanisms for rapid-acting agents

Trends in Neurosciences

Volumn 35, Issue 1, 2012, Pages 47-56

  Duman, Ronald S ^a   Voleti, Bhavya ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHETAMINE; ANTIDEPRESSANT AGENT; BRAIN DERIVED NEUROTROPHIC FACTOR; FIBROBLAST GROWTH FACTOR 2; FRIZZLED PROTEIN; GLUTAMIC ACID; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; KETAMINE; LITHIUM; METHIONINE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE PHOSPHATASE 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NERVE GROWTH FACTOR; NEUROTROPHIC FACTOR; NEUROTROPHIN 3; NEUROTROPHIN 4; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAS PROTEIN; RECOMBINANT BRAIN DERIVED NEUROTROPHIC FACTOR; SEROTONIN UPTAKE INHIBITOR; SOMATOMEDIN C; UNINDEXED DRUG; VALINE; VALPROIC ACID; VASCULOTROPIN; WNT PROTEIN;

AMINO ACID SUBSTITUTION; ANTIDEPRESSANT ACTIVITY; BRAIN REGION; DEPRESSION; DRUG EFFICACY; DRUG INHIBITION; DRUG SAFETY; EMOTION; GENE EXPRESSION; HIPPOCAMPUS; HUMAN; IMMUNOHISTOCHEMISTRY; LOCOMOTION; MOOD; MOOD DISORDER; NERVE CELL NETWORK; NERVE CELL PLASTICITY; NEUROTRANSMISSION; NONHUMAN; PATHOPHYSIOLOGY; PREFRONTAL CORTEX; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; STRESS; SYNAPTOGENESIS; TREATMENT INDICATION; TREATMENT RESPONSE;

AFFECT; ANTIDEPRESSIVE AGENTS; BRAIN; DEPRESSIVE DISORDER; EMOTIONS; FRIZZLED RECEPTORS; HUMANS; MOOD DISORDERS; NERVE GROWTH FACTORS; RECEPTORS, N-METHYL-D-ASPARTATE; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 84855297758     PISSN: 01662236     EISSN: 1878108X     Source Type: Journal    
DOI: 10.1016/j.tins.2011.11.004     Document Type: Review

References (119)

1. Kessler R., et al. The epidemiology of major depressive disorder: results for the National Comorbidity Survey Replication (NCS-R). JAMA 2003, 289:3095-3105.
2. Lopez A., Murray C.C. The global burden of disease, 1990-2020. Nat. Med. 1998, 4:1241-1243.
3. Pincus H., Pettit A.R. The societal costs of chronic major depression. J. Clin. Psychiatry 2001, 62:5-9.
4. Krishnan V., Nestler E.J. The molecular neurobiology of depression. Nature 2008, 455:894-902.
5. Trivedi M., et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am. J. Psychiatry 2006, 163:28-40.
6. Duman R., et al. A molecular and cellular theory of depression. Arch. Gen. Psychiatry 1997, 54:597-606.
7. Berman R., et al. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 2000, 47:351-354.
8. Zarate C.J., et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry 2006, 63:856-864.
9. Li N., et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010, 329:959-964.
10. Mayberg H. Targeted electrode-based modulation of neural circuits for depression. J. Clin. Invest. 2009, 119:717-725.
11. Savitz J., Drevets W.C. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci. Biobehav. Rev. 2009, 33:699-771.
12. Macqueen G., et al. Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol. Psychiatry 2008, 64:880-883.
13. Sheline Y., et al. Untreated depression and hippocampal volume loss. Am. J. Psychiatry 2003, 160:1516-1518.
14. Rajkowska G., et al. GABAengic neurons immunoreactive for calcium binding proteins are reduced in the prefrontal cortex in major depression. Neuropsychopharmacology 2007, 32:471-482.
15. Banasr M., et al. Chronic stress decreases cell proliferation in adult cerebral cortex of rat: reversal by antidepressant treatment. Biol. Psychiatry 2007, 62:496-504.
16. Duman R., Monteggia L.M. A neurotrophic model for stress-related mood disorders. Biol. Psychiatry 2006, 59:1116-1127.
17. McEwen B. Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. Eur. J. Pharmacol. 2008, 583:174-185.
18. Shansky R., Morrison J.H. Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res. 2009, 1293:108-113.
19. Roozendaal B., et al. Stress, memory and the amygdala. Nat. Rev. Neurosci. 2009, 10:423-433.
20. Sotres-Bayon F., Quirk G.J. Prefrontal control of fear: more than just extinction. Curr. Opin. Neurobiol. 2010, 20:231-235.
21. Berton O., et al. Essential role of BDNF in the misolimbic dopamine pathway in social defeat stress. Science 2006, 311:868-878.
22. Covington H., et al. Antidepressant actions of histone deacetylase inhibitors. J. Neurosci. 2009, 29:11451-11460.
23. Krishnan V., et al. AKT signaling within the ventral tegmental area regulates cellular and behavioral responses to stressful stimuli. Biol. Psychiatry 2008, 64:691-700.
24. Krishnan V., Nestler E.J. Linking molecules to mood: new insight into the biology of depression. Am. J. Psychiatry 2010, 167:1305-1320.
25. Lindsay R.M., et al. Neurotrophic factors: from molecule to man. Trends Neurosci. 1994, 17:182-190.
26. Arancio O., Chao M.V. Neurotrophins, synaptic plasticity and dementia. Curr. Opin. Neurobiol. 2007, 17:325-330.
27. Greenberg M., et al. New insights in the biology of BDNF synthesis and release: implications in CNS function. J. Neurosci. 2009, 29:12764-12767.
28. Lu Y., et al. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?. Neurobiol. Learn. Mem. 2008, 89:312-323.
29. Martinovich K., Lu B. Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 2008, 33:73-83.
30. Minichiello L. TrkB signalling pathways in LTP and learning. Nat. Rev. Neurosci. 2009, 10:850-860.
31. Akil H., et al. The fibroblast growth factor family and mood disorders. Novartis Found. Symp. 2008, 289:94-96.
32. Duman C., et al. Peripheral IGF-1 produces antidepressant-like behavior and is required for the effect of exercise. Behav. Brain Res. 2009, 198:366-371.
33. Schmidt H., et al. Functional markers of depression: diagnosis, treatment and pathophysiology. Neuropsychopharmacology 2011, 36:2375-2394.
34. Warner-Schmidt J., Duman R.S. VEGF is an essential mediator of neurogenic and behavioral actions of antidepressants. PNAS 2007, 104:4647-4652.
35. Castren E., Rantamaki T. The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev. Neurobiol. 2010, 70:289-297.
36. Schmidt H., Duman R.S. The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav. Pharmacol. 2007, 18:391-418.
37. Autry A., et al. Gender-specific impact of brain-derived neurotrophic factor signaling on stress-induced depression-like behavior. Biol. Psychiatry 2009, 66:84-90.
38. Monteggia L., et al. Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol. Psychiatry 2007, 61:187-197.
39. Taliaz D., et al. Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol. Psychiatry 2010, 15:80-92.
40. Hoshaw B., et al. Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Res. 2005, 1037:204-208.
41. Schmidt H., Duman R.S. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology 2010, 35:2378-2391.
42. Duman C., et al. Blockade of ERK produces a pro-depressive effect and blocks the behavioral actions of antidepressants. Biol. Psychiatry 2007, 61:661-670.
43. Casey B., et al. Brain-derived neurotrophic factor as a model system for examining gene by environment interactions across development. Neuroscience 2009, 164:108-120.
44. Egan M., et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003, 112:257-269.
45. Chiaruttini C., et al. Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation. PNAS 2009, 106:16481-16486.
46. Frodl T., et al. Reduced hhippocampal vollume correlates with executive dysfunctioning in major depression. J. Psychiatry Neurosci. 2006, 31:316-323.
47. Hajek T., et al. Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: meta-analysis. World J. Biol. Psychiatry 2011, 1-10.
48. Tsai S.-J., et al. Effects of BDNF polymorphisms on antidepressant action. Psychiatry Investig. 2010, 7:236-242.
49. Matsuo K., et al. Neuronal correlates of brain-derived neurotrophic factor Val66Met polymorphism and morphometric abnormalities in bipolar disorder. Neuropsychopharmacology 2009, 34:1904-1913.
50. Soliman F., et al. A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science 2010, 327:863-866.
51. Clasen P., et al. 5-HTTLPR and BDNF Val66Met polymorphisms moderate effects of stress on rumination. Genes Brain Behav. 2011, 10:740-746. (epub).
52. Gatt J., et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol. Psychiatry 2009, 14:681-695.
53. Chen H., et al. Hippocampal cell proliferation regulation by repeated stress and antidepressants. Neuroreport 2006, 17:863-867.
54. Chen Z.-Y., et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006, 314:140-143.
55. Spencer J., et al. BDNF variant Val66Met interacts with estrous cycle in the control of hippocampal function. PNAS 2010, 107:4395-4400.
56. Liu R., et al. Brain-derived neurotrophic factor val66met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol. Psychiatry 2011, 10.1016/j.biopsych.2011.09.030.
57. Li N., et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic defi{ligature}cits caused by chronic stress. Exposure. Biol. Psychiatry 2011, 69:754-761.
58. Magariños A., et al. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons. Hippocampus 2010, 21:253-264.
59. Bath K., et al. Variant brain-derived neurotrophic factor (Val66Met) alters adult olfactory bulb neurogenesis and spontaneous olfactory discrimination. J. Neurosci. 2008, 28:2383-2393.
60. Sairanen M., et al. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J. Neurosci. 2005, 25:1089-1094.
61. Li Y., et al. TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 2008, 59:399-412.
62. Einat H., et al. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J. Neurosci. 2003, 23:7311-7316.
63. Galeotti N., Ghelardini C. Regionally selective activation and differential regulation of ERK, JNK and p38 MAP kinase signalling pathway by protein kinase C in mood modulation. Int. J. Neuropsychopharmacol. 2011, 20:1-13.
64. First M., et al. The effects of fluoxetine treatment in a chronic mild stress rat model on depression-related behavior, brain neurotrophins and ERK expression. J. Mol. Neurosci. 2011, 45:246-255.
65. Qi X., et al. A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior. Behav. Brain Res. 2008, 199:203-209.
66. Dwivedi Y., et al. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J. Neurochem. 2001, 77:916-928.
67. Dwivedi Y., et al. ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf. Mol. Psychiatry 2006, 11:86-98.
68. Yuan P., et al. Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia. J. Affect. Disord. 2010, 124:164-169.
69. Duric V., et al. Negative regulator of MAP kinase is increased in depression and is necessary and sufficient for depressive behavior. Nat. Med. 2010, 16:1328-1332.
70. Hsiung S., et al. Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J. Neurochem. 2003, 87:182-194.
71. Karege N., et al. Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims. Biol. Psychiatry 2007, 61:240-245.
72. Dwivedi Y., et al. Modulation in activation and expression of phosphatase and tensin homolog on chromosome ten, Akt1, and 3-phosphoinositide-dependent kinase 1: further evidence demonstrating altered phosphoinositide 3-kinase signaling in postmortem brain of suicide subjects. Biol. Psychiatry 2010, 67:1017-1025.
73. De Sarno P., et al. Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 2002, 43:1158-1164.
74. Klein P., Melton D.A. A molecular mechanism for the effect of lithium on development. PNAS 1996, 93:8455-8459.
75. Beaulieu J., et al. Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency. PNAS 2008, 105:1333-1338.
76. Li X., Jope R.S. Is glycogen synthase kinase-3 a central modulator in mood regulation?. Neuropsychopharmacology 2010, 35:2143-2154.
77. Henderson B. Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover. Nat. Cell Biol. 2000, 2:653-660.
78. Carlezon W., et al. The many faces of CREB. Trends Neurosci. 2005, 28:436-445.
79. Phiel C., et al. GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 2003, 423:435-439.
80. Beurel E., Jope R.S. Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3. J. Neuroinflamm. 2009, 11:6-9.
81. Martin M., et al. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat. Immunol. 2005, 6:777-784.
82. Miller A., et al. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 2009, 65:732-741.
83. Mao Y., et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell 2009, 136:1017-1031.
84. Inkster B., et al. Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder. Arch. Gen. Psychiatry 2009, 66:721-728.
85. Saus E., et al. A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression. Genes Brain Behav. 2010, 9:799-807.
86. Beaulieu J., et al. Lithium antagonizes dopamine- dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. PNAS 2004, 101:5099-5104.
87. Gould T., et al. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int. J. Neuropsychopharmacol. 2004, 7:387-390.
88. Rosa A., et al. Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice. Biol. Psychiatry 2008, 32:1549-1556.
89. Der-Avakian A., Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci. 2012, (in press). 10.1016/j.tins.2011.11.005.
90. Beurel E., et al. Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Mol. Psychiatry 2011, 16:1068-1070.
91. Jourdi H., et al. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J. Neurosci. 2009, 29:8688-8697.
92. Wang H., et al. Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-β-signaling pathways regulates the innate inflammatory response. J. Immunol. 2011, 186:5217-5226.
93. Phiel C., Klein P.S. Molecular targets of lithium action. Annu. Rev. Pharmacol. Toxicol. 2001, 41:789-813.
94. Aubry J., et al. Early effects of mood stabilizers on the Akt/GSK-3beta signaling pathway and on cell survival and proliferation. Psychopharmacology 2009, 205:419-429.
95. Lamarre M., Desrosieurs R.R. Up-regulation of protein l-isoaspartyl methyltransferase expression by lithium is mediated by glycogen synthase kinase-3 inactivation and beta-catenin stabilization. Neuropharmacology 2008, 55:669-676.
96. Hu L., et al. The role of Wnt signaling and its interaction with diverse mechanisms of cellular apoptosis in the pathophysiology of bipolar disorder. Prog. Neuropsychopharmcol. Biol. Psychiatry 2011, 35:11-17.
97. Budnik V., Salinas P.C. Wnt signaling during synaptic development and plasticity. Curr. Opin. Neurobiol. 2011, 21:151-159.
98. Inestrosa N., Arenas E. Emerging roles of Wnts in the adult nervous system. Nat. Rev. Neurosci. 2010, 11:77-86.
99. Lie D., et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature 2005, 437:1370-1375.
100. Tissir F., Gofnet A.M. Expression of planar cell polarity genes during development of mouse CNS. Eur. J. Neurosci. 2006, 23:597-607.
101. Okamoto H., et al. Wnt2 expression and signaling is increased by different classes of antidepressants. Biol. Psychiatry 2010, 68:521-527.
102. Pinnock S., et al. The roles of BDNF, pCREB and Wnt3a in the latent period preceding activation of progenitor cell mitosis in the adult dentate gyrus by fluoxetine. PLoS ONE 2011, 5:e13652.
103. Voleti B., et al. Analysis of target genes regulated by chronic electroconvulsive therapy reveals role for Fzd6 in depression. Biol. Psychiatry 2011, 10.1016/j.biopsych.2011.08.004.
104. Wilkinson M., et al. A novel role of the WNT-dishevelled-GSK3β signaling cascade in the mouse nucleus accumbens in a social defeat model of depression. J. Neurosci. 2011, 31:9084-9092.
105. Diazgranados N., et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch. Gen. Psych. 2010, 67:793-802.
106. Larkin G., Beautrais A.L. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int. J. Neuropsychopharmacol. 2011, 14:1127-1131.
107. Price R., et al. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol. Psychiatry 2009, 66:522-526.
108. Hoeffer C., Klann E. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci. 2010, 33:67-75.
109. Zarate C., et al. Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol. Psychiatry 2006, 59:1006-1020.
110. Koike H., et al. Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists. Neuropharmacology 2011, 61:1419-1423.
111. Kelleher R., Bear M.F. The autistic neuron: troubled translation?. Cell 2008, 135:401-406.
112. Bove J., et al. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat. Rev. Neurosci. 2011, 12:437-452.
113. Moghaddam B., et al. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J. Neurosci. 1997, 17:2912-2917.
114. Homayoun H., Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J. Neurosci. 2007, 27:11496-11500.
115. Maeng S., et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol. Psychiatry 2008, 63:349-352.
116. Autry A., et al. NMDA receptor blockade at rest triggers rapid behavioural anatidepressant responses. Nature 2011, 475:91-95.
117. Behrens M., et al. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 2007, 318:1645-1647.
118. Preskorn S., et al. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-asparate antagonist, CP-101, 606, in patients with treatment-refractory major depressive dosorder. J. Clin. Psychopharmacol. 2008, 28:631-637.
119. Dwyer J., et al. mTOR activation is required for the antidepressant effects of mGluR2/3 blockade. Int. J. Neuropsychopharmacol. 2011, 10.1017/S1461145711001702.