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Novel Insights into Depression and Antidepressants: A Synergy Between Synaptogenesis and Neurogenesis?

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Book cover Neurogenesis and Neural Plasticity

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 15))

Abstract

Major depressive disorder has been associated with manifold pathophysiological changes. These include metabolic abnormalities in discreet brain areas; modifications in the level of stress hormones, neurotransmitters, and neurotrophic factors; impaired spinogenesis and synaptogenesis in crucial brain areas, such as the prefrontal cortex and the hippocampus; and impaired neurogenesis in the hippocampus. Antidepressant therapy facilitates remission by reversing most of these disturbances, indicating that these dysfunctions may participate causally in depressive symptomatology. However, few attempts have been made to integrate these different pathophysiologies into one model. The present chapter endeavors (1) to review the extant literature in the field, with particular focus on the role of neurogenesis and synaptogenesis in depression; (2) and to suggest a possible interplay between these two processes, as well as, describe the ways by which improving both neurogenesis and synaptogenesis may enable effective recovery by acting on a larger neuronal network.

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References

  • Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20(8):2896–2903

    Google Scholar 

  • Airan RD, Meltzer LA, Roy M, Gong Y, Chen H, Deisseroth K (2007) High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science 317:819–823

    PubMed  CAS  Google Scholar 

  • Alfarez DN, Wiegert O, Joëls M, Krugers HJ (2002) Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation. Neuroscience 115(4):1119–1126

    PubMed  CAS  Google Scholar 

  • Alfarez DN, Joëls M, Krugers HJ (2003) Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro. Eur J Neurosci 17(9):1928–1934

    PubMed  Google Scholar 

  • Alonso R, Griebel G, Pavone G, Stemmelin J, Le FG, 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

    PubMed  CAS  Google Scholar 

  • Altman J, Das GD (1965) Post-natal origin of microneurones in the rat brain. Nature 207(5000):953–956

    PubMed  CAS  Google Scholar 

  • Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686

    PubMed  CAS  Google Scholar 

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. APA, Washington

    Google Scholar 

  • Amsterdam JD, Marinelli DL, Arger P, Winokur A (1987) Assessment of adrenal gland volume by computed tomography in depressed patients and healthy volunteers: a pilot study. Psychiatr Res 21:189–197

    CAS  Google Scholar 

  • An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F, Torre ER, Jones KR, Feng Y, Lu B, Xu B (2008) Distinct role of long 3’ UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134(1):175–187

    PubMed  CAS  Google Scholar 

  • Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258

    PubMed  CAS  Google Scholar 

  • Autry AE, Adachi M, Nosyreva N, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475(7354):91–95

    PubMed  CAS  Google Scholar 

  • Avitsur R, Stark JL, Sheridan JF (2001) Social stress induces glucocorticoid resistance in subordinate animals. Horm Behav 39:247–257

    PubMed  CAS  Google Scholar 

  • Bachis A, Cruz MI, Nosheny RL, Mocchetti I (2008) Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex. Neurosci Lett 442:104–108

    PubMed  CAS  Google Scholar 

  • Bagley J, Moghaddam B (1997) Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam. Neuroscience 77(1):65–73

    PubMed  CAS  Google Scholar 

  • Bambico FR, Gobbi G (2008) The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert Opin Ther Targets 12:1347–1366

    PubMed  CAS  Google Scholar 

  • Bambico FR, Duranti A, Tontini A, Tarzia G, Gobbi G (2009) Endocannabinoids in the treatment of mood disorders: evidence from animal models. Curr Pharm Des 15:1623–1646

    PubMed  CAS  Google Scholar 

  • Bambico FR, Nguyen NT, Katz N, Gobbi G (2010) Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiol Dis 37(3):641–655

    PubMed  CAS  Google Scholar 

  • Banasr M, Hery M, Printemps R, Daszuta A (2004) Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29:450–460

    PubMed  CAS  Google Scholar 

  • Banasr M, Soumier A, Hery M, Mocaer E, Daszuta A (2006) Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 59:1087–1096

    PubMed  CAS  Google Scholar 

  • Bannerman DM, Rawlins JN, McHugh SB, Deacon RM, Yee BK, Bast T, Zhang WN, Pothuizen HH, Feldon J (2004) Regional dissociations within the hippocampus–memory and anxiety. Neurosci Biobehav Rev 28(3):273–283

    PubMed  CAS  Google Scholar 

  • Beck AT (1967) Depression: causes and treatment. University of Pennsylvania Press, Philadelphia

    Google Scholar 

  • Belzung C, de Villemeur Billette (2010) The design of new antidepressants: can formal models help? A first attempt using a model of the hippocampal control over the HPA-axis based on a review from the literature. Behav Pharmacol 21:677–689

    CAS  Google Scholar 

  • Belzung C, Lemoine M (2011) Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biology of Mood & Anxiety Disorders 1:9

    Google Scholar 

  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 15 47(4):351-354

    Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    PubMed  CAS  Google Scholar 

  • Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway insocial defeat stress. Science 311:864–868

    PubMed  CAS  Google Scholar 

  • Bessa JM, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, Almeida OF, Sousa N (2009) The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry 14:764–773

    PubMed  CAS  Google Scholar 

  • Bhagwagar Z, Hinz R, Taylor M, Fancy S, Cowen P, Grasby P (2006) Increased 5-HT2A receptor binding in euthymic, medication-free patients recovered from depression: A positron emission study with [11C]MDL 100,907. Am J Psychiatry 163:1580–1587

    PubMed  Google Scholar 

  • Bhatt DH, Zhang S, Gan WB (2009) Dendritic spine dynamics. Annu Rev Physiol 71:261–282

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Bjarkam CR, Sorensen JC, Geneser FA (2003) Distribution and morphology of serotonin-immunoreactive axons in the hippocampal region of the New Zealand white rabbit. I. area dentata and hippocampus. Hippocampus 13:21–37

    PubMed  Google Scholar 

  • Blier P (2001) Pharmacology of rapid-onset antidepressant treatment strategies. J Clin Psychiatry 62(Suppl 15):12–17

    PubMed  CAS  Google Scholar 

  • Blier P, de Montigny C (1999) Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology 21(2 Suppl):91S–98S

    PubMed  CAS  Google Scholar 

  • Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John MJ et al (2009) Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34:2376–2389

    PubMed  CAS  Google Scholar 

  • Bolton MM, Eroglu C (2009) Look who is weaving the neural web: glial control of synapse formation. Curr Opin Neurobiol 19(5):491–497

    PubMed  Google Scholar 

  • Bondolfi L, Ermini F, Long JM, Ingram DK, Jucker M (2004) Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging 25:333–340

    PubMed  CAS  Google Scholar 

  • Bresler T, Ramati Y, Zamorano PL, Zhai R, Garner CC, Ziv NE (2001) Mol Cell Neurosci 18:149–167

    PubMed  CAS  Google Scholar 

  • Bresler T, Shapira M, Boeckers T, Dresbach T, Futter M, Garner CC, Rosenblum K, Gundelfinger ED, Ziv NE (2004) J Neurosci 24:1507–1520

    PubMed  CAS  Google Scholar 

  • Brezun JM, Daszuta A (1999) Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 89:999–1002

    PubMed  CAS  Google Scholar 

  • Brezun JM, Daszuta A (2000) Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons. Eur J Neurosci 12:391–396

    PubMed  CAS  Google Scholar 

  • Brown GW, Harris T (1978) Social origins of depression. Tavistock, London

    Google Scholar 

  • Brown SM, Henning S, Wellman CL (2005) Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex. Cereb Cortex 15:1714–1722

    PubMed  Google Scholar 

  • Bush TG, Savidge TC, Freeman TC, Cox HJ, Campbell EA, Mucke L, Johnson MH, Sofroniew MV (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93:189–201

    PubMed  CAS  Google Scholar 

  • Calabrese F, Molteni R, Maj PF, Cattaneo A, Gennarelli M, Racagni G, Riva MA (2007) Chronic duloxetine treatment induces specific changes in the expression of BDNF transcripts and in the subcellular localization of the neurotrophin protein. Neuropsychopharmacology 32(11):2351–2359

    PubMed  CAS  Google Scholar 

  • Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61:203–209

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Castren E (2005) Is mood chemistry? Nat Rev Neurosci 6(3):241–246

    Google Scholar 

  • Castrén E, Rantamäki T (2010a) The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 70:289–297

    PubMed  Google Scholar 

  • Castrén E, Rantamäki T (2010b) Role of brain-derived neurotrophic factor in the aetiology of depression: implications for pharmacological treatment. CNS Drugs 24(1):1–7

    PubMed  Google Scholar 

  • Castrén E, Võikar V, Rantamäki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7(1):18–21

    PubMed  Google Scholar 

  • Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK (2000) Enhancement of hippocampal neurogenesis by lithium. J Neurochem 75:1729–1734

    PubMed  CAS  Google Scholar 

  • Chen F, Madsen TM, Wegener G, Nyengaard JR (2010) Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression. Hippocampus 20(12):1376–1384

    PubMed  CAS  Google Scholar 

  • Chiaruttini C, Vicario A, Li Z, Baj G, Braiuca P, Wu Y et al (2009) Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation. Proc Natl Acad Sci USA 106:16481–16486

    PubMed  CAS  Google Scholar 

  • Christoffel DJ, Golden SA, Russo SJ (2011a) Structural and synaptic plasticity in stress-related disorders. Rev Neurosci 22(5):535–549

    PubMed  Google Scholar 

  • Christoffel DJ, Golden SA, Dumitriu D, Robison AJ, Janssen WG, Ahn HF, Krishnan V, Reyes CM, Han MH, Ables JL, Eisch AJ, Dietz DM, Ferguson D, Neve RL, Greengard P, Kim Y, Morrison JH, Russo SJ (2011b) IκB kinase regulates social defeat stress-induced synaptic and behavioral plasticity. J Neurosci 31(1):314–321

    PubMed  CAS  Google Scholar 

  • Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213

    PubMed  CAS  Google Scholar 

  • Coppell AL, Pei Q, Zetterström TS (2003) Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacol 44(7):903–910

    CAS  Google Scholar 

  • Cowen DS, Takase LF, Fornal CA, Jacobs BL (2008) Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine. Brain Res 1228:14–19

    PubMed  CAS  Google Scholar 

  • Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M et al (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

    PubMed  CAS  Google Scholar 

  • Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB et al (2002) Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 52:1057–1065

    PubMed  CAS  Google Scholar 

  • David DJ, Klemenhagen KC, Holick KA, Saxe MD, Mendez I, Santarelli L et al (2007) Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphen yl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. J Pharmacol Exp Ther 321:237–248

    PubMed  CAS  Google Scholar 

  • David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, Drew M, Craig DA, Guiard BP, Guilloux JP, Artymyshyn RP, Gardier AM, Gerald C, Antonijevic IA, Leonardo ED, Hen R (2009) Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety / depression. Neuron 62:479–493

    PubMed  CAS  Google Scholar 

  • de Kloet ER, Vreugdenhil E, Oitzl MS, Joëls M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269–301

    PubMed  Google Scholar 

  • de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    PubMed  Google Scholar 

  • de Kloet ER, Fitzsimons CP, Datson NA, Meijer OC, Vreugdenhil E (2009) Glucocorticoid signaling and stress-related limbic susceptibility pathway: about receptors, transcription machinery and microRNA. Brain Res 1293:129–141

    PubMed  Google Scholar 

  • Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR (1990) Serotonin function and the mechanism of antidepressant action: Reversal of antidepressant induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47:411–418

    PubMed  CAS  Google Scholar 

  • Delgado PL, Miller HM, Salomon RM, Licinio J, Gelenberg AJ, Charney DS (1993) Monoamines and the mechanism of antidepressant action: Effects of catecholamine depletion on mood in patients treated with antidepressants. Psychopharmacol Bull 29:389–396

    PubMed  CAS  Google Scholar 

  • Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, Moreno FA, Heninger GR, Charney DS (1999) Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry 46:212–220

    PubMed  CAS  Google Scholar 

  • Deltheil T, Guiard BP, Cerdan J, David DJ, Tanaka KF, Repérant C, Guilloux JP, Coudoré F, Hen R, Gardier AM (2008) Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice. Neuropharmacology 55:1006–1014

    PubMed  CAS  Google Scholar 

  • Deppmann CD, Mihalas S, Sharma N, Lonze BE, Niebur E, Ginty DD (2008) A model for neuronal competition during development. Science 320(5874):369–373

    PubMed  CAS  Google Scholar 

  • Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, Burger C, Auberson YP, Sovago J, Stockmeier CA, Buck A, Hasler G (2011) Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study. Am J Psychiatry 168(7):727–734

    PubMed  Google Scholar 

  • Dias BG, Banerjee SB, Duman RS, Vaidya VA (2003) Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacology 45:553–563

    PubMed  CAS  Google Scholar 

  • Dickens M, Romero LM, Cyr NE, Dunn IC, Meddle SL (2009) Chronic stress alters glucocorticoid receptor and mineralocorticoid receptor mRNA expression in the European starling (Sturnus vulgaris) brain. J Neuroendocrinol 21:832–840

    PubMed  CAS  Google Scholar 

  • Disner SG, Beevers CG, Haigh EA, Beck AT (2011) Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci 12:467–477

    PubMed  CAS  Google Scholar 

  • Dorovini-Zis K, Zis AP (1987) Increased adrenal weight in victims of violent suicide. Am J Psychiatry 144:1214–1215

    PubMed  CAS  Google Scholar 

  • Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387

    PubMed  CAS  Google Scholar 

  • Drevets WC, Bogers W, Raichle ME (2002) Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacology 12(6):527–544

    CAS  Google Scholar 

  • Drevets WC, Thase ME, Moses-Kolko EL, Price J, Frank E, Kupfer DJ, Mathis C (2007) Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nucl Med Biol 34:865–877

    PubMed  CAS  Google Scholar 

  • Drevets WC, Savitz J, Trimble M (2008) The subgenual anterior cingulate cortex in mood disorders. CNS Spectr 13:663–681

    PubMed  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    PubMed  CAS  Google Scholar 

  • Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35(1):47–56

    PubMed  CAS  Google Scholar 

  • Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54(7):597–606

    PubMed  CAS  Google Scholar 

  • Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L, Duman RS (2012) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol 17:1–14

    Google Scholar 

  • Duman CH, Schlesinger L, Terwilliger R, Russell DS, Newton SS, Duman RS (2009) Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behav Brain Res 198(2):366–371

    Google Scholar 

  • Eastwood SL, Harrison PJ (2000) Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5(4):425–432

    PubMed  CAS  Google Scholar 

  • Eastwood SL, Harrison PJ (2001) Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. a review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull 55(5):569–578

    PubMed  CAS  Google Scholar 

  • Eisch AJ, Bolanos CA, de Wit J, Simonak RD, Pudiak CM, Barrot M et al (2003) Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry 54:994–1005

    PubMed  CAS  Google Scholar 

  • Elfving B, Wegener G (2012) Electroconvulsive Seizures Stimulate the VEGF Pathway via mTORC1. Synapse 66:340–345

    PubMed  CAS  Google Scholar 

  • Elias GM, Funke L, Stein V, Grant SG, Bredt DS, Nicoll RA (2006) Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins. Neuron 52(2):307–320

    PubMed  CAS  Google Scholar 

  • Elizalde N, Pastor PM, Garcia-García AL, Serres F, Venzala E, Huarte J, Ramírez MJ, Del Rio J, Sharp T, Tordera RM (2010) Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1. J Neurochem 114(5):1302–1314

    PubMed  CAS  Google Scholar 

  • Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci USA 103:8233–8238

    PubMed  CAS  Google Scholar 

  • Epstein J, Pan H, Kocsis JH, Yang Y, Butler T, Chusid J, Hochberg H, Murrough J, Strohmayer E, Stern E, Silbersweig DA (2006) Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am J Psychiatry 163:1784–1790

    PubMed  Google Scholar 

  • Eroglu C, Barres BA (2010) Regulation of synaptic connectivity by glia. Nature 468(7321):223–231

    PubMed  CAS  Google Scholar 

  • Fabel K, Kempermann G (2008) Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromol Med 10:59–66

    CAS  Google Scholar 

  • Fanselow M, Dongv HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19

    PubMed  CAS  Google Scholar 

  • Farmer AE, McGuffin P (2003) Humiliation, loss and other types of life events and difficulties: a comparison of depressed subjects, healthy controls and their siblings. Psychol Med 33:1169–1175

    PubMed  Google Scholar 

  • Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J (2001) Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. NeuroReport 12(15):3257–3262

    PubMed  CAS  Google Scholar 

  • Feyissa AM, Woolverton WL, Miguel-Hidalgo JJ, Wang Z, Kyle PB, Hasler G, Stockmeier CA, Iyo AH, Karolewicz B (2010) Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 34(2):279–283

    PubMed  CAS  Google Scholar 

  • Fiore M, Korf J, Antonelli A, Talamini L, Aloe L (2002) Long-lasting effects of prenatal MAM treatment on water maze performance in rats: associations with altered brain development and neurotrophin levels. Neurotoxicol Teratol 24(2):179–191

    PubMed  CAS  Google Scholar 

  • Fricker AD, Rios C, Devi LA, Gomes I (2005) Serotonin receptor activation leads to neurite outgrowth and neuronal survival. Brain Res Mol Brain Res 138(2):228–235

    PubMed  CAS  Google Scholar 

  • Friedel E, Schlagenhauf F, Sterzer P, Park SQ, Bermpohl F, Ströhle A, Stoy M, Puls I, Hägele C, Wrase J, Büchel C, Heinz A (2009) 5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls. Psychopharmacology (Berl) 205(2):261–271

    Google Scholar 

  • Friedman HV, Bresler T, Garner CC, Ziv NE (2000) Neuron 27:57–69

    PubMed  CAS  Google Scholar 

  • Furey ML, Drevets WC (2006) Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 63(10):1121–1129

    PubMed  CAS  Google Scholar 

  • Fuss J, Ben Abdallah NM, Hensley FW, Weber KJ, Hellweg R, Gass P (2010) Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice. PLoS One 5(9):e12769

    PubMed  Google Scholar 

  • Gage FH, Thompson RG (1980) Differential distribution of norepinephrine and serotonin along the dorsal-ventral axis of the hippocampal formation. Brain Res Bull 5:771–773

    PubMed  CAS  Google Scholar 

  • Garner CC, Zhai RG, Gundelfinger ED, Ziv NE (2002) Trends Neurosci 25:243–251

    PubMed  CAS  Google Scholar 

  • Ge S, Yang CH, Hsu KS, Ming GL, Song H (2007) A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54:559–566

    PubMed  CAS  Google Scholar 

  • Givalois L, Marmigère F, Rage F, Ixart G, Arancibia S, Tapia-Arancibia L (2001) Immobilization stress rapidly and differentially modulates BDNF and TrkB mRNA expression in the pituitary gland of adult male rats. Neuroendocrinology 74(3):148–159

    Google Scholar 

  • Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8:481–488

    PubMed  CAS  Google Scholar 

  • Gould E, Daniels DC, Cameron HA, McEwen BS (1992) Expression of adrenal steroid receptors by newly born cells and pyknotic cells in the dentate gyrus of the postnatal rat. Mol Cell Neurosci 3:44–48

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Gould E, Tanapat P, McEwen BS, Flugge 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

    PubMed  CAS  Google Scholar 

  • Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA et al (2003) The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry 64:1465–1475

    PubMed  Google Scholar 

  • Greer PL, Greenberg ME (2008) From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 59(6):846–860

    PubMed  CAS  Google Scholar 

  • Grutzendler J, Kasthuri N, Gan WB (2002) Long-term dendritic spine stability in the adult cortex. Nature 420(6917):812–816

    PubMed  CAS  Google Scholar 

  • 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(5):1299–1303

    Google Scholar 

  • Hamilton JP, Furman DJ, Chang C, Thomason ME, Dennis E, Gotlib IH (2011) Default-mode and task-positive network activity in major depressive disorder: implications for adaptive and maladaptive rumination. Biol Psychiatry 70:327–333

    PubMed  Google Scholar 

  • Hanson ND, Owens MJ, Nemeroff CB (2011) Depression, antidepressants, and neurogenesis: a critical reappraisal. Neuropsychopharmacology 36:2589–2602

    PubMed  Google Scholar 

  • Hao Y, Creson T, Zhang L, Li P, Du F, Yuan P et al (2004) Mood stabilizer valproate promotes erk pathway-dependent cortical neuronal growth and neurogenesis. J Neurosci 24:6590–6599

    PubMed  CAS  Google Scholar 

  • Hardingham GE, Chawla S, Johnson CM, Bading H (1997) Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature 385(6613):260–265

    Google Scholar 

  • Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nature 11(10):682–696

    CAS  Google Scholar 

  • Harkness KL, Monroe SM (2006) Severe melancholic depression is more vulnerable than non-melancholic depression to minor precipitating life events. J Affect Disord 91:257–263

    PubMed  Google Scholar 

  • He J, Crews FT (2007) Neurogenesis decreases during brain maturation from adolescence to adulthood. Pharmacol Biochem Behav 86(2):327–333

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, Klein S, Grüsser SM, Flor H, Schumann G, Mann K, Büchel C (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8(1):20–21

    Google Scholar 

  • Herman JP, Mueller NK (2006) Role of the ventral subiculum in stress integration. Behav Brain Res 174:215–224

    PubMed  CAS  Google Scholar 

  • Herman JP, Adams D, Prewitt C (1995) Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology 61:180–190

    PubMed  CAS  Google Scholar 

  • Hill MN, Hillard CJ, McEwen BS (2011) Alterations in corticolimbic dendritic morphology and emotional behavior in cannabinoid CB1 receptor-deficient mice parallel the effects of chronic stress. Cereb Cortex 21(9):2056–2064

    PubMed  Google Scholar 

  • Hobin JA, Ji J, Maren S (2006) Ventral hippocampal muscimol disrupts context-specific fear memory retrieval after extinction in rats. Hippocampus 16:174–182

    PubMed  CAS  Google Scholar 

  • Hoeffer CA, Klann E (2010) mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 33(2):67–75

    PubMed  CAS  Google Scholar 

  • Holick KA, Lee DC, Hen R, Dulawa SC (2008) Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor. Neuropsychopharmacology 33:406–417

    PubMed  CAS  Google Scholar 

  • Holsboer F, Ising M (2010) Stress hormone regulation: biological role and translation into therapy. Annu Rev Psychol 61:81–109

    PubMed  Google Scholar 

  • Homayoun H, Moghaddam B (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27(43):11496–11500

    PubMed  CAS  Google Scholar 

  • Honer WG, Falkai P, Bayer TA, Xie J, Hu L, Li HY, Arango V, Mann JJ, Dwork AJ, Trimble WS (2002) Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. Cereb Cortex 12(4):349–356

    PubMed  Google Scholar 

  • Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJ, Papanicolaou GJ, Fava M, Trivedi MH, Wisniewski SR, Laje G, Paddock S, McMahon FJ, Manji H, Lipsky RH (2007) Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Arch Gen Psychiatry 64:783–792

    PubMed  CAS  Google Scholar 

  • Huttenlocher PR (1990) Morphometric study of human cerebral cortex development. Neuropsychologia 28(6):517–527

    PubMed  CAS  Google Scholar 

  • Ibarguen-Vargas Y, Surget A, Vourc’h P, Leman S, Andres C, Gardier A, Belzung C (2009) Deficit in BDNF level does not increase vulnerability to stress but dampens antidepressant-like effects in the unpredictable chronic mild stress. Behav Brain Res 202:245–251

    PubMed  CAS  Google Scholar 

  • Jayatissa MN, Henningsen K, Nikolajsen G, West MJ, Wiborg O (2010) A reduced number of hippocampal granule cells does not associate with an anhedonia-like phenotype in a rat chronic mild stress model of depression. Stress 13:95–105

    PubMed  Google Scholar 

  • Jernigan CS, Goswami DB, Austin MC, Iyo AH, Chandran A, Stockmeier CA, Karolewicz B (2011) The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 35(7):1774–1779

    PubMed  CAS  Google Scholar 

  • Jiang W, Zhang Y, Xiao L, Van CJ, Ji SP, Bai G et al (2005) Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest 115:3104–3116

    PubMed  CAS  Google Scholar 

  • Joëls 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(4):221–231

    PubMed  Google Scholar 

  • Johnston-Wilson NL, Sims NL, Hofmann2 J-P, Anderson L, Shore AD, Torrey EF, Yolken RH, The Stanley Neuropathology Consortium (2000) Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Molecular Psychiatry 5:142–149

    Google Scholar 

  • Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R (2005) Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 136:29–37

    PubMed  CAS  Google Scholar 

  • Karpova NN, Lindholm J, Pruunsild P, Timmusk T, Castrén E (2009) Long-lasting behavioural and molecular alterations induced by early postnatal fluoxetine exposure are restored by chronic fluoxetine treatment in adult mice. Eur Neuropsychopharmacol 19(2):97–108

    PubMed  CAS  Google Scholar 

  • Karst H, Joëls M (2003) Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus neurons. J Neurophysiol 89(1):625–633

    PubMed  Google Scholar 

  • Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274(5290):1133–1138

    PubMed  CAS  Google Scholar 

  • Keedwell PA, Andrew C, Williams SC, Brammer MJ, Phillips ML (2005) The neural correlates of anhedonia in major depressive disorder. Biol Psychiatry 58(11):843–853

    PubMed  Google Scholar 

  • Kempermann G (2002) Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci 22(3):635–638

    PubMed  CAS  Google Scholar 

  • Kempermann G, Gage FH (2000) Neurogenesis in the adult hippocampus. Novartis Found Symp 231:220–235

    PubMed  CAS  Google Scholar 

  • Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452

    PubMed  CAS  Google Scholar 

  • Kendler KS, Gardner CO, Prescott CA (2002) Toward a comprehensive developmental model for major depression in women. Am J Psychiatry 159:1133–1145

    PubMed  Google Scholar 

  • Kendler KS, Gardner CO, Prescott CA (2006) Toward a comprehensive developmental model for major depression in men. Am J Psychiatry 163:115–124

    PubMed  Google Scholar 

  • Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR et al (2003) The epidemiology of major depressive disorder: results from the national comorbidity survey replication (NCS-R). JAMA 289:3095–3105

    PubMed  Google Scholar 

  • Kitraki E, Karandrea D, Kittas C (1999) Long-lasting effects of stress on glucocorticoid receptor gene expression in the rat brain. Neuroendocrinology 69:331–338

    PubMed  CAS  Google Scholar 

  • Kitraki E, Kremmyda O, Youlatos D, Alexis M, Kittas C (2004) Spatial performance and corticosteroid receptor status in the 21-day restraint stress paradigm. Ann NY Acad Sci 1018:323–327

    PubMed  CAS  Google Scholar 

  • Kjelstrup KG, Tuvnes FA, Steffenach HA, Murison R, Moser EI, Moser MB (2002) Reduced fear expression after lesions of the ventral hippocampus. Proc Natl Acad Sci USA 99:10825–10830

    PubMed  CAS  Google Scholar 

  • Klann E, Dever TE (2004) Biochemical mechanisms for translational regulation in synaptic plasticity. Nat Rev Neurosci 5(12):931–942

    PubMed  CAS  Google Scholar 

  • Knöchel C, Oertel-Knöchel V, O’Dwyer L, Prvulovic D, Alves G, Kollmann B, Hampel H (2012) Cognitive and behavioural effects of physical exercise in psychiatric patients. Prog Neurobiol 96:46–68

    PubMed  Google Scholar 

  • Koehl M, Abrous DN (2011) A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci 33:1101–1114

    PubMed  Google Scholar 

  • Kononen J, Soinila S, Persson H, Honkaniemi J, Hökfelt T, Pelto-Huikko M (1994) Neurotrophins and their receptors in the rat pituitary gland: regulation of BDNF and trkB mRNA levels by adrenal hormones. Brain Res Mol Brain Res 27(2):347–354

    PubMed  CAS  Google Scholar 

  • Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105:751–756

    PubMed  CAS  Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902

    PubMed  CAS  Google Scholar 

  • Krishnan V, Nestler EJ (2010) Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 167(11):1305–1320

    PubMed  Google Scholar 

  • Krishnan KRR, Doraiswamy PM, Lurie SN, Figiel GS, Husain MM, Boyko OB et al (1991) Pituitary size in depression. J Clin Endocrinol Metab 72:256–259

    PubMed  CAS  Google Scholar 

  • Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M, Kempermann G (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kulkarni VA, Jha S, Vaidya VA (2002) Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus. Eur J Neurosci 16:2008–2012

    PubMed  Google Scholar 

  • Kumamaru E, Numakawa T, Adachi N, Kunugi H (2011) Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB. FEBS Lett 585(20):3224–3228

    PubMed  CAS  Google Scholar 

  • Lauterbach EC (2011) Dextromethorphan as a potential rapid-acting antidepressant. Med Hypotheses 76(5):717–719

    PubMed  CAS  Google Scholar 

  • Leuner B, Kozorovitskiy Y, Gross CG, Gould E (2007) Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci USA 104:17169–17173

    PubMed  CAS  Google Scholar 

  • Leyton M, Ghadirian AM, Young SN, Palmour RM, Blier P, Helmers KF, Benkelfat C (2000) Depressive relapse following acute tryptophan depletion in patients with major depressive disorder. J Psychopharmacol 14:284–287

    PubMed  CAS  Google Scholar 

  • Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

    PubMed  CAS  Google Scholar 

  • Li N, Liu R-J, Dwyer JM, Banasr M, Lee B, Son H, Li X-Y, Aghajanian G, Duman RS (2011a) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69:754–761

    PubMed  CAS  Google Scholar 

  • Li B, Piriz J, Mirrione M, Chung C, Proulx CD, Schulz D, Henn F, Malinow R (2011b) Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470(7335):535–539

    PubMed  CAS  Google Scholar 

  • Liston C, Gan WB (2011) Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci USA 108(38):16074–16079

    PubMed  CAS  Google Scholar 

  • Liu RJ, Lee FS, Li XY, Bambico FR, Duman RS, Aghajanian GK (2011) Brain-derived neurotrophic factor val66met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol Psychiatry 71(11):996–1005

    Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117(3):697–706

    PubMed  CAS  Google Scholar 

  • Lowy MT, Wittenberg L, Yamamoto BK (1995) Effect of acute stress on hippocampal glutamate levels and spectrin proteolysis in young and aged rats. J Neurochem 65(1):268–274

    PubMed  CAS  Google Scholar 

  • Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S et al (2007) Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55:712–725

    PubMed  CAS  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    PubMed  CAS  Google Scholar 

  • Lyons DM, Buckmaster PS, Lee AG, Wu C, Mitra R, Duffey LM et al (2010) Stress coping stimulates hippocampal neurogenesis in adult monkeys. Proc Natl Acad Sci USA 107:14823–14827

    PubMed  CAS  Google Scholar 

  • Macmaster FP, Russell A, Mirza Y, Keshavan MS, Taormina SP, Bhandari R, Boyd C, Lynch M, Rose M, Ivey J, Moore GJ, Rosenberg DR (2006) Pituatary volume in treatment-naive pediatric major depressive disorder. Biol Psychiatry 60(8):862–866

    Google Scholar 

  • MacMaster FP, Kusumakar V (2004) MRI study of the pituitary gland in adolescent depression. J Psychiatr Res 38:231–236

    PubMed  Google Scholar 

  • Magariños AM, Verdugo JM, McEwen BS (1997) Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci USA 94(25):14002–14008

    PubMed  Google Scholar 

  • Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571

    PubMed  CAS  Google Scholar 

  • Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110

    PubMed  CAS  Google Scholar 

  • Manev R, Uz T, Manev H (2001) Fluoxetine increases the content of neurotrophic protein S100beta in the rat hippocampus. Eur J Pharmacol 420:R1–R2

    PubMed  CAS  Google Scholar 

  • Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, Gray NA, 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

    PubMed  CAS  Google Scholar 

  • Maroun M, Richter-Levin G (2003) Exposure to acute stress blocks the induction of long-term potentiation of the amygdala-prefrontal cortex pathway in vivo. J Neurosci 23(11):4406–4409

    PubMed  CAS  Google Scholar 

  • Martinowich K, Manji H, Lu B (2007) New insights into BDNF function in depression and anxiety. Nat Neurosci 10(9):1089–1093

    PubMed  CAS  Google Scholar 

  • Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45(5):651–660

    PubMed  CAS  Google Scholar 

  • McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122

    PubMed  CAS  Google Scholar 

  • McEwen BS (2001) Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci 933:265–277

    PubMed  CAS  Google Scholar 

  • McEwen BS, Magarinos AM, Reagan LP (2002) Structural plasticity and tianeptine: cellular and molecular targets. Eur Psychiatry 17(Suppl 3):318–330

    PubMed  Google Scholar 

  • Meltzer CC, Price JC, Mathis CA, Butters MA, Ziolko SK, Moses-Kolko E et al (2004) Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacol 29:2258–2265

    CAS  Google Scholar 

  • Meltzer LA, Yabaluri R, Deisseroth K (2005) A role for circuit homeostasis in adult neurogenesis. Trends Neurosci 28(12):653–660

    PubMed  CAS  Google Scholar 

  • Meshi D, Drew MR, Saxe M, Ansorge MS, David D, Santarelli L et al (2006) Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci 9:729–731

    PubMed  CAS  Google Scholar 

  • Messaoudi E, Ying SW, Kanhema T, Croll SD, Bramham CR (2002) Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo. J Neurosci 22(17):7453–7461

    PubMed  CAS  Google Scholar 

  • Miczek KA, Nikulina EM, Shimamoto A, Covington HE 3rd (2011) Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats. J Neurosci 31(27):9848–9857

    PubMed  CAS  Google Scholar 

  • Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS (1996) Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Arch Gen Psychiatry 53:117–128

    PubMed  CAS  Google Scholar 

  • Mineur YS, Belzung C, Crusio WE (2007) Functional implications of decreases in neurogenesis following chronic mild stress in mice. Neuroscience 150:251–259

    PubMed  CAS  Google Scholar 

  • Mirescu C, Gould E (2006) Stress and adult neurogenesis. Hippocampus 16:233–238

    PubMed  CAS  Google Scholar 

  • Mitra R, Jadhav S, McEwen BS, Vyas A, Chattarji S (2005) Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proc Natl Acad Sci USA 102:9371–9376

    PubMed  CAS  Google Scholar 

  • Mizoguchi K, Ishige A, Aburada M, Tabira T (2003) Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus. Neuroscience 119:887–897

    PubMed  CAS  Google Scholar 

  • Moghaddam B, Adams B, Verma A, Daly D (1997) Activation of glutama- tergic 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 17:2921–2927

    PubMed  CAS  Google Scholar 

  • Molteni R, Calabrese F, Bedogni F, Tongiorgi E, Fumagalli F, Racagni G, Riva MA (2006) Chronic treatment with fluoxetine up-regulates cellular BDNF mRNA expression in rat dopaminergic regions. Int J Neuropsychopharmacol 9(3):307–317

    PubMed  CAS  Google Scholar 

  • Monroe SM, Simons AD (1991) Diathesis-stress theories in the context of life-stress research: Implications for the depressive disorders. Psychol Bull 110:406–425

    PubMed  CAS  Google Scholar 

  • Montaron MF, Piazza PV, Aurousseau C, Urani A, Le MM, Abrous DN (2003) Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity. Eur J Neurosci 18:3105–3111

    PubMed  CAS  Google Scholar 

  • Monteggia LM, Barrot M, Powell CM, Berton O, Galanis V, Gemelli T et al (2004) Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci USA 101:10827–10832

    PubMed  CAS  Google Scholar 

  • Müller HK, Wegener G, Popoli M, Elfving B (2011) Differential expression of synaptic proteins after chronic restraint stress in rat prefrontal cortex and hippocampus. Brain Res 1385:26–37

    PubMed  Google Scholar 

  • Musazzi L, Milanese M, Farisello P, Zappettini S, Tardito D, Barbiero VS, Bonifacino T, Mallei A, Baldelli P, Racagni G, Raiteri M, Benfenati F, Bonanno G, Popoli M (2010) Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants. PLoS One 5(1):e8566

    PubMed  Google Scholar 

  • Nakagawa S, Kim JE, Lee R, Chen J, Fujioka T, Malberg J et al (2002) Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. J Neurosci 22:9868–9876

    PubMed  CAS  Google Scholar 

  • Nestler EJ, Gould E, Manji H, Buncan M, Duman RS, Greshenfed HK, Hen R, Koester S, Lederhendler I, Meaney M, RObbin T, WInsky L, Zalcman S (2002) Preclinical models: status of basic research in depression. Biol Psychiatry 52(6):503–528

    Google Scholar 

  • Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59(12):1151–1159

    PubMed  CAS  Google Scholar 

  • Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13(10):1161–1169

    PubMed  CAS  Google Scholar 

  • Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and TrkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539–7547

    PubMed  CAS  Google Scholar 

  • Nibuya M, Nestler EJ, Duman RS (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 16:2365–2372

    PubMed  CAS  Google Scholar 

  • Noonan MA, Bulin SE, Fuller DC, Eisch AJ (2010) Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction. J Neurosci 30:304–315

    PubMed  CAS  Google Scholar 

  • O’Leary OF, Wu X, Castren E (2009) Chronic fluoxetine treatment increases expression of synaptic proteins in the O’Leary et al. hippocampus of the ovariectomized rat: role of BDNF signaling. Psychoneuroendocrinology 34:367–381

    Google Scholar 

  • Oomen CA, Mayer JL, de Kloet ER, Joels M, Lucassen PJ (2007) Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress. Eur J Neurosci 26:3395–3401

    PubMed  Google Scholar 

  • Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494

    PubMed  CAS  Google Scholar 

  • Papadia S, Stevenson P, Hardingham NR, Bading H, Hardingham GE (2005) Nuclear Ca2 + and the cAMP response element-binding protein family mediate a late phase of activity-dependent neuroprotection. J Neurosci 25(17):4279–4287

    PubMed  CAS  Google Scholar 

  • Parihar VK, Hattiangady B, Kuruba R, Shuai B, Shetty AK (2011) Predictable chronic mild stress improves mood, hippocampal neurogenesis and memory. Mol Psychiatry 16:171–183

    PubMed  CAS  Google Scholar 

  • Parsey RV, Hastings RS, Oquendo MA, Huang YY, Simpson N, Arcement J et al (2006a) Lower serotonin transporter binding potential in the human brain during major depressive episodes. Am J Psychiatry 163:52–58

    PubMed  Google Scholar 

  • Parsey RV, Kent JM, Oquendo MA, Richards MC, Pratap M, Cooper TB et al (2006b) Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography. Biol Psychiatry 59:821–828

    PubMed  CAS  Google Scholar 

  • Pentkowski NS, Blanchard DC, Lever C, Litvin Y, Blanchard RJ (2006) Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats. Eur J Neurosci 23:2185–2196

    PubMed  Google Scholar 

  • Perera TD, Dwork AJ, Keegan KA, Thirumangalakudi L, Lipira CM, Joyce N, Lange C, Higley JD, Rosoklija G, Hen R, Sackeim HA, Coplan JD (2011) Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates. PLoS One 6:e17600

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Pinheiro M, Pinto L, Bessa J, Morais M, Monteiro S, Sousa NN (2011) Long-lasting mood and cognitive recovery from depression is neurogenesis-dependent. Soc Neurosci Abstr 683.19/GG10

    Google Scholar 

  • Pittenger C, Duman RS (2008) Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33:88–109

    PubMed  CAS  Google Scholar 

  • Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, Dougherty DD, Iosifescu DV, Rauch SL, Fava M (2009b) Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry 166:702–710

    PubMed  Google Scholar 

  • Ponti G, Peretto P, Bonfanti L (2006) A subpial, transitory germinal zone forms chains of neuronal precursors in the rabbit cerebellum. Dev BIol 294(1):168–180

    Google Scholar 

  • Popoli M, Yan Z, McEwen BS, Sanacora G (2011) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13(1):22–37

    PubMed  Google Scholar 

  • Price JL, Drevets WC (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology 35:192–216

    PubMed  Google Scholar 

  • Price JL, Drevets WC (2012) Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn Sci 16:61–71

    PubMed  Google Scholar 

  • Prybylowski K, Chang K, Sans N, Kan L, Vicini S, Wenthold RJ (2005) The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron 47(6):845–857

    PubMed  CAS  Google Scholar 

  • Radley JJ, Jacobs BL (2002) 5-HT1A receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res 955:264–267

    PubMed  CAS  Google Scholar 

  • Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125(1):1–6

    PubMed  CAS  Google Scholar 

  • Radley JJ, Rocher AB, Miller M, Janssen WG, Liston C, Hof PR et al (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16:313–320

    PubMed  Google Scholar 

  • Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6(3):219–233

    PubMed  CAS  Google Scholar 

  • Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA (1999) Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 45(9):1085–1098

    PubMed  CAS  Google Scholar 

  • Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG (2010) Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. Psychol Med 40:557–567

    PubMed  CAS  Google Scholar 

  • Rao MS, Hattiangady B, Shetty AK (2006) The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus. Aging Cell 5:545–558

    PubMed  CAS  Google Scholar 

  • Rapp S, Baader M, Hu M, Jennen-Steinmetz C, Henn FA, Thome J (2004) Differential regulation of synaptic vesicle proteins by antidepressant drugs. Pharmacogenomics J 4(2):110–113

    PubMed  CAS  Google Scholar 

  • Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A et al (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11:514–522

    PubMed  CAS  Google Scholar 

  • Reinés A, Cereseto M, Ferrero A, Sifonios L, Podestá MF, Wikinski S (2008) Maintenance treatment with fluoxetine is necessary to sustain normal levels of synaptic markers in an experimental model of depression: correlation with behavioral response. Neuropsychopharmacology 33(8):1896–1908

    PubMed  Google Scholar 

  • Revest JM, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza PV, Abrous DN (2009) Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry 14:959–967

    PubMed  Google Scholar 

  • Revesz D, Tjernstrom M, Ben-Menachem E, Thorlin T (2008) Effects of vagus nerve stimulation on rat hippocampal progenitor proliferation. Exp Neurol 214:259–265

    PubMed  Google Scholar 

  • Reznikov LR, Grillo CA, Piroli GG, Pasumarthi RK, Reagan LP, Fadel J (2007) Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressan treatment. Eur J Neurosci 25(10):3109–3114

    PubMed  Google Scholar 

  • Rizk P, Salazar J, Raisman-Vozari R, Marien M, Ruberg M, Colpaert F et al (2006) The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacology 31:1146–1157

    PubMed  CAS  Google Scholar 

  • Roche KW, Standley S, McCallum J, Dune Ly C, Ehlers MD, Wenthold RJ (2001) Molecular determinants of NMDA receptor internalization. Nat Neurosci 4(8):794–802

    PubMed  CAS  Google Scholar 

  • Rosenkranz JA, Venheim ER, Padival M (2010) Chronic stress causes amygdala hyperexcitability in rodents. Biol Psychiatry 67:1128–1136

    PubMed  Google Scholar 

  • 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(4):349–356

    PubMed  CAS  Google Scholar 

  • Rubin RT, Phillips JJ, Sadow TF, McCracken JT (1995) Adrenal gland volume in major depression. increase during the depressive episode and decrease with successful treatment. Arch Gen Psychiatry 52:213–218

    PubMed  CAS  Google Scholar 

  • Rubin RT, Phillips JJ, McCracken JT, Sadow TF (1996) Adrenal gland volume in major depression: relationship to basal and stimulated pituitary–adrenal cortical axis function. Biol Psychiatry 40:89–97

    PubMed  CAS  Google Scholar 

  • Rubino T, Vigano’ D, Realini N, Guidali C, Braida D, Capurro V, Castiglioni C, Cherubino F, Romualdi P, Candeletti S, Sala M, Parolaro D (2008) Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology 33(11):2760–27671

    PubMed  CAS  Google Scholar 

  • Russo-Neustadt A, Beard RC, Cotman CW (1999) Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 21(5):679–682

    PubMed  CAS  Google Scholar 

  • Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, Agerman K et al (2003) Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 23:349–357

    PubMed  CAS  Google Scholar 

  • Sahay A, Scobie KN, Hill AS, O’Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472:466–470

    PubMed  CAS  Google Scholar 

  • Sairanen M, O’Leary OF, Knuuttila JE, Castrén E (2007) Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience 144(1):368–374

    PubMed  CAS  Google Scholar 

  • Sakata K, Jin L, Jha S (2010) Lack of promoter IV-driven BDNF transcription results in depression-like behavior. Genes Brain Behav 9(7):712–721

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Sapolsky RM, Krey LC, McEwen BS (1984a) Stress down-regulates corticosteronereceptors in a site specific manner in the brain. Endocrinology 114:287–292

    PubMed  CAS  Google Scholar 

  • Sapolsky RM, Krey LC, McEwen BS (1984b) Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA 81:6174–6177

    PubMed  CAS  Google Scholar 

  • Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J et al (2000) Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 57:174–180

    PubMed  CAS  Google Scholar 

  • Sawada K, Young CE, Barr AM, Longworth K, Takahashi S, Arango V, Mann JJ, Dwork AJ, Falkai P, Phillips AG, Honer WG (2002) Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness. Mol Psychiatry 7(5):484–492

    PubMed  CAS  Google Scholar 

  • Schloesser RJ, Manji HK, Martinowich K (2009) Suppression of adult neurogenesis leads to an increased hypothalamo-pituitary-adrenal axis response. NeuroReport 20:553–557

    PubMed  CAS  Google Scholar 

  • Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M (2010) Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. Mol Psychiatry 15:1152–1163

    PubMed  CAS  Google Scholar 

  • Schmidt HD, Duman RS (2010) Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology 35:2378–2391

    PubMed  CAS  Google Scholar 

  • Segal M, Richter-Levin G, Maggio N (2010) Stress-induced dynamic routing of hippocampal connectivity: a hypothes. Hippocampus 20(12):1332–1338

    PubMed  Google Scholar 

  • Shansky RM, Morrison JH (2009) Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res 13(1293):108–113

    Google Scholar 

  • Shansky RM, Hamo C, Hof PR, McEwen BS, Morrison JH (2009) Stress-induced dendritic remodeling in the prefrontal cortex is circuit specific. Cereb Cortex 19(10):2479–2484

    PubMed  Google Scholar 

  • Shapira M, Zhai RG, Dresbach T, Bresler T, Torres VI, Gundelfinger ED, Ziv NE, Garner CC (2003) Unitary assembly of presynaptic active zones from Piccolo-Bassoon transport vesicles. Neuron 38:237–252

    PubMed  CAS  Google Scholar 

  • Sheline YI, Gado MH, Kraemer HC (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160(8):1516–1518

    PubMed  Google Scholar 

  • Sheline YI, Barch DM, Price JL, Rundle MM, Vaishnavi SN, Snyder AZ, Mintun MA, Wang S, Coalson RS, Raichle ME (2009) The default mode network and self-referential processes in depression. Proc Natl Acad Sci USA 106:1942–1947

    PubMed  CAS  Google Scholar 

  • Shirayama Y, Chen AC, Nakagaway S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261

    PubMed  CAS  Google Scholar 

  • Shors TJ, Mathew J, Sisti HM, Edgecomb C, Beckoff S, Dalla C (2007) Neurogenesis and helplessness are mediated by controllability in males but not in females. Biol Psychiatry 62:487–495

    PubMed  Google Scholar 

  • Silva R, Mesquita AR, Bessa J, Sousa JC, Sotiropoulos I, Leao P et al (2008) Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogensynthase-kinase-3beta. Neuroscience 152:656–669

    PubMed  CAS  Google Scholar 

  • Singer BH, Jutkiewicz EM, Fuller CL, Lichtenwalner RJ, Zhang H, Velander AJ, Li X, Gnegy ME, Burant CF, Parent JM (2009) Conditional ablation and recovery of forebrain neurogenesis in the mouse. J Comp Neurol 514:567–582

    PubMed  CAS  Google Scholar 

  • Slavich GM, O’Donovan A, Epel ES, Kemeny ME (2010) Black sheep get the blues: a psychobiological model of social rejection and depression. Neurosci Biobehav Rev 35:39–45

    PubMed  Google Scholar 

  • Slavich GM, Monroe SM, Gotlib IH (2011) Early parental loss and depression history: associations with recent life stress in major depressive disorder. J Psychiatr Res 45:1146–1152

    PubMed  Google Scholar 

  • Slipczuk L, Bekinschtein P, Katche C, Cammarota M, Izquierdo I, Medina JH (2009) BDNF activates mTOR to regulate GluR1 expression required for memory formation. PLoS One 4(6):e6007

    PubMed  Google Scholar 

  • Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15(3 Pt 1):1768–1777

    Google Scholar 

  • Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476:458–461

    PubMed  CAS  Google Scholar 

  • Stein E, McCrank E, Schaeffer B, Goyer R (1993) Adrenal gland weight and suicide. Can J Psychiatry 38:563–566

    PubMed  CAS  Google Scholar 

  • Sterlemann V, Ganea K, Liebl C, Harbich D, Alam S, Holsboer F et al (2008) Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: implications for stress-related disorders. Horm Behav 53:386–394

    PubMed  CAS  Google Scholar 

  • Surget A, Saxe M, Leman S, Ibarguen-Vargas Y, Chalon S, Griebel G, Hen R, Belzung C (2008) Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol Psychiatry 64:293–301

    PubMed  CAS  Google Scholar 

  • Surget A, Tanti A, Leonardo ED, Laugeray A, Rainer Q, Touma C, Palme R, Griebel G, Ibarguen-Vargas Y, Hen R, Belzung C (2011) Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry 16:1177–1188

    PubMed  CAS  Google Scholar 

  • Sutton MA, Wall NR, Aakalu GN, Schuman EM (2004) Regulation of dendritic protein synthesis by miniature synaptic events. Science 304(5679):1979–1983

    PubMed  CAS  Google Scholar 

  • Sutton MA, Taylor AM, Ito HT, Pham A, Schuman EM (2007) Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis. Neuron 55(4):648–661

    PubMed  CAS  Google Scholar 

  • Szigethy E, Conwell Y, Forbes NT, Cox C, Caine ED (1994) Adrenal weight and morphology in victims of completed suicide. Biol Psychiatry 36:374–380

    PubMed  CAS  Google Scholar 

  • Taliaz D, Stall N, Dar DE, Zangen A (2009) Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 15:80–92

    PubMed  Google Scholar 

  • Tanis KQ, Duman RS (2007) Intracellular signaling pathways pave roads to recovery for mood disorders. Ann Med 39:531–544

    PubMed  CAS  Google Scholar 

  • Tanis KQ, Newton SS, Duman RS (2007) Targeting neurotrophic/growth factor expression and signaling for antidepressant drug development. CNS Neurol Disord Drug Targets 6:151–160

    PubMed  CAS  Google Scholar 

  • Tata DA, Marciano VA, Anderson BJ (2006) Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3. J Comp Neurol 498:363–374

    PubMed  CAS  Google Scholar 

  • Thompson Ray M, Weickert CS, Wyatt E, Webster MJ (2011) Decreased BDNF, trkB-TK + and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci 36(3):195–203

    PubMed  Google Scholar 

  • Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH et al (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11:901–907

    PubMed  CAS  Google Scholar 

  • Treadway MT, Grant MM, Ding Z, Hollon SD, Gore JC, Shelton RC (2009) Early adverse events, HPA activity and rostral anterior cingulate volume in MDD. PLoS One 24:e6598

    Google Scholar 

  • Tronel S, Belnoue L, Grosjean N, Revest JM, Piazza PV, Koehl M, Abrous DN (2012) Adult-born neurons are necessary for extended contextual discrimination. Hippocampus 22:292–298

    PubMed  Google Scholar 

  • Tsutsumi A, Kayaba K, Theorell T, Siegrist J (2001) Association between job stress and depression among Japanese employees threatened by job loss in a comparison between two complementary job-stress models. Scan J Work Environ Health 27:146–153

    CAS  Google Scholar 

  • Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci 10:397–409

    PubMed  CAS  Google Scholar 

  • van Bokhoven P, Oomen CA, Hoogendijk WJ, Smit AB, Lucassen PJ, Spijker S (2011) Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment. Eur J Neurosci 33:1833–1840

    PubMed  Google Scholar 

  • Van Praag PH, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270

    PubMed  Google Scholar 

  • van Strien NM, Cappaert NL, Witter MP (2009) The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci 10:272–282

    PubMed  Google Scholar 

  • Vaynmana SS, Yinga Z, Yina D, Gomez-Pinilla F (2006) Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Res 1070(1):124–130

    Google Scholar 

  • Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455:178–182

    PubMed  CAS  Google Scholar 

  • Victor TA, Furey ML, Fromm SJ, Ohman A, Drevets WC (2010) Relationship of emotional processing to masked faces in the amgydala to mood state and treatment in major depressive disorder. Arch Gen Psychiatry 67:1128–1138

    PubMed  Google Scholar 

  • Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161:1957–1966

    PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Vyas A, Bernalb S, Chattarji S (2003) Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res 965:290–294

    PubMed  CAS  Google Scholar 

  • Vyas A, Pillai AG, Chattarji S (2004) Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 128:667–673

    Google Scholar 

  • Vyas A, Jadhav S, Chattarji S (2006) Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala. Neuroscience 143:387–393

    PubMed  CAS  Google Scholar 

  • Wacker J, Dillon DG, Pizzagalli DA (2009) The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques. Neuroimage 46(1):327–337

    PubMed  Google Scholar 

  • Wang JW, David DJ, Monckton JE, Battaglia F, Hen R (2008) Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 28:1374–1384

    PubMed  CAS  Google Scholar 

  • Washbourne P, Bennett JE, McAllister AK (2002) Nat Neurosci 5:751–759

    PubMed  CAS  Google Scholar 

  • Wei L, Meaney MJ, Duman RS, Kaffman A (2011) Affiliative behavior requires juvenile, but not adult neurogenesis. J Neurosci 31:14335–14345

    PubMed  CAS  Google Scholar 

  • WHO (2008) The global burden of disease: 2004 update. WHO, Geneva

    Google Scholar 

  • Wilson MA, Molliver ME (1991) The organization of serotonergic projections to cerebral cortex in primates: retrograde transport studies. Neuroscience 44:555–570

    PubMed  CAS  Google Scholar 

  • Wong EY, Herbert J (2004) The corticoid environment: a determining factor for neural progenitors’ survival in the adult hippocampus. Eur J Neurosci 20:2491–2498

    PubMed  Google Scholar 

  • Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8(8):1069–1077

    Google Scholar 

  • Yanpallewar SU, Fernandes K, Marathe SV, Vadodaria KC, Jhaveri D, Rommelfanger K, Ladiwala U, Jha S, Muthig V, Hein L, Bartlett P, Weinshenker D, Vaidya VA (2010) Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. J Neurosci 30:1096–1109

    PubMed  CAS  Google Scholar 

  • Yin Y, Edelman GM, Vanderklish PW (2002) The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proc Natl Acad Sci USA 99(4):2368–2373

    PubMed  CAS  Google Scholar 

  • Yoshimizu T, Chaki S (2004) Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039. Biochem Biophys Res Commun 315:493–496

    PubMed  CAS  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864

    PubMed  CAS  Google Scholar 

  • Zarate C Jr, Machado-Vieira R, Henter I, Ibrahim L, Diazgranados N, Salvadore G (2010) Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry 18(5):293–303

    PubMed  Google Scholar 

  • Zarate Jr. CA, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA (2012) Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71(11):939–946

    Google Scholar 

  • Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3–11

    PubMed  CAS  Google Scholar 

  • Zhu XH, Yan HC, Zhang J, Qu HD, Qiu XS, Chen L, Li SJ, Cao X, Bean JC, Chen LH, Qin XH, Liu JH, Bai XC, Mei L, Gao TM (2010) Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J Neurosci 30:12653–12663

    PubMed  CAS  Google Scholar 

  • Zink M, Rapp S, Gebicke-Haerter PJ, Henn FA, Thome J (2005) Antidepressants differentially affect expression of complexin I and II RNA in rat hippocampus. Psychopharmacology 181(3):560–565

    PubMed  CAS  Google Scholar 

  • Zink M, Vollmayr B, Gebicke-Haerter PJ, Henn FA, Thome J (2007) Reduced expression of complexins I and II in rats bred for learned helplessness. Brain Res 1144:202–208

    PubMed  CAS  Google Scholar 

  • Ziv NE, Garner CC (2001) Principles of glutamatergic synapse formation: seeing the forest for the trees. Curr Opin Neurobiol 11(5):536–543

    PubMed  CAS  Google Scholar 

  • Ziv NE, Garner CC (2004) Cellular and molecular mechanisms of presynaptic assembly. Nat Rev Neurosci 5(5):385–399

    PubMed  CAS  Google Scholar 

  • Zuo DY, Zhang YH, Cao Y, Wu CF, Tanaka M, Wu YL (2006) Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior. Life Sci 78(19):2172–2178

    PubMed  CAS  Google Scholar 

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Bambico, F.R., Belzung, C. (2012). Novel Insights into Depression and Antidepressants: A Synergy Between Synaptogenesis and Neurogenesis?. In: Belzung, C., Wigmore, P. (eds) Neurogenesis and Neural Plasticity. Current Topics in Behavioral Neurosciences, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2012_234

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