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Neuroprotective Agents in Mood Disorders: Pathophysiological and Therapeutic Implications

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Brain Protection in Schizophrenia, Mood and Cognitive Disorders

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Abstract

Drug development for mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) has undergone an important paradigm shift in the last decade due to our expanding knowledge of the pathophysiology and treatment of these illnesses. While previous research focused exclusively on abnormalities of the monoaminergic neurotransmitter systems, more recent preclinical and clinical studies have emphasized the role of impaired neuroplasticity and cellular resilience in mood disorders.

Also informing our thinking for drug development are the neurotrophic/neuroprotective properties associated with several agents currently used as treatments for mood disorders—including antidepressants, mood stabilizers, atypical antipsychotics, and a number of experimental agents currently under investigation. Many of these agents share some potent neurotrophic and neuroprotective properties, exert significant effects on signaling pathways that regulate cellular plasticity, and are believed to act directly on some of the core pathophysiological mechanisms underlying these devastating illnesses.

In this chapter, we discuss how drugs that modulate signaling pathways involved in regulating cell survival and cell death target some of the core pathophysiological mechanisms of BPD and MDD, with a particular emphasis on brain imaging and neuropathological abnormalities in mood disorders. Cellular and molecular mechanisms of action of agents with neurotrophic and neuroplastic properties are also discussed, with a special focus on the mood stabilizers lithium and valproate.

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Abbreviations

ACC:

Anterior cingulate cortex

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid peptide precursor protein

Bcl-2:

B-cell lymphoma 2

BDNF:

Brain Derived Neurotrophic Factor

BPD:

Bipolar disorder

Cho:

Choline-containing compounds

CNS:

central nervous system

Cr:

phosphocreatine and creatine

CREB:

Cyclic adenine monophospate response element-binding protein

DLPFC:

Dorsolateral prefrontal cortex

ECT:

Electroconvulsive therapy

ERK:

Extracellular Signal-Regulated Kinase

GABA:

Gamma-aminobutyric acid

GDNF:

Glial cell line-derived neurotrophic factor

GM:

Gray matter

GSK-3:

Glycogen synthase kinase-3

1H MRS:

Proton magnetic resonance spectroscopy

HPA:

hypothalamic-pituitary-adrenal

MAPK:

Mitogen-activated protein kinases

MDD:

Major depressive disorder

mI:

myo-inositol

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NAA:

N-acetyl aspartate

NGF:

Nerve Growth Factor

NMDA:

N-methyl-D-aspartate

OFC:

Orbitofrontal cortex

PFC:

Prefrontal cortex

PI-3-K:

Phosphatidylinositol-3-kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

SGPFC:

Subgenual prefrontal cortex

SNP:

Single nucleotide polymorphism

SSRIs:

Selective serotonin reuptake inhibitors

VEGF:

Vascular Endothelial Growth Factor

References

  1. Manji HK, Moore GJ, Rajkowska G, Chen G. Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry 2000 Nov; 5(6):578–593

    Article  PubMed  CAS  Google Scholar 

  2. Costa C, Martella G, Picconi B, et al. Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia. Stroke 2006 May; 37(5):1319–1326

    Article  PubMed  CAS  Google Scholar 

  3. Manji HK, Moore GJ, Chen G. Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilizers. Br J Psychiatry Suppl 2001 Jun; 41:s107–s119

    Article  PubMed  CAS  Google Scholar 

  4. Gould TD, Manji HK. Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 2005 Jul; 30(7):1223–1237

    PubMed  CAS  Google Scholar 

  5. Gurvich N, Klein PS. Lithium and valproic acid: parallels and contrasts in diverse signaling contexts. Pharmacol Ther 2002 Oct; 96(1):45–66

    Article  PubMed  CAS  Google Scholar 

  6. Li X, Bijur GN, Jope RS. Glycogen synthase kinase-3beta, mood stabilizers, and neuroprotection. Bipolar Disord 2002 Apr; 4(2):137–144

    Article  PubMed  CAS  Google Scholar 

  7. Bernier PJ, Parent A. The anti-apoptosis bcl-2 proto-oncogene is preferentially expressed in limbic structures of the primate brain. Neuroscience 1998 Feb; 82(3):635–640

    Article  PubMed  CAS  Google Scholar 

  8. Bonfanti L, Strettoi E, Chierzi S, et al. Protection of retinal ganglion cells from natural and axotomy-induced cell death in neonatal transgenic mice overexpressing bcl-2. J Neurosci 1996 Jul 1; 16(13):4186–4194

    PubMed  CAS  Google Scholar 

  9. Chen G, Zeng WZ, Yuan PX, et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 1999 Feb; 72(2):879–882

    Article  PubMed  CAS  Google Scholar 

  10. Manji HK, Bebchuk JM, Moore GJ, Glitz D, Hasanat KA, Chen G. Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: therapeutic implications. J Clin Psychiatry 1999; 60(Suppl 2):27–39; discussion 40–21, 113–116

    Google Scholar 

  11. Rajkowska G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000 Oct 15; 48(8):766–777

    Article  PubMed  CAS  Google Scholar 

  12. Lu R, Song L, Jope RS. Lithium attenuates p53 levels in human neuroblastoma SH-SY5Y cells. Neuroreport 1999 Apr 6; 10(5):1123–1125

    Article  PubMed  CAS  Google Scholar 

  13. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998 Aug 28; 281(5381):1322–1326

    Article  PubMed  CAS  Google Scholar 

  14. Bruckheimer EM, Cho SH, Sarkiss M, Herrmann J, McDonnell TJ. The Bcl-2 gene family and apoptosis. Adv Biochem Eng Biotechnol 1998; 62:75–105

    PubMed  CAS  Google Scholar 

  15. Merry DE, Korsmeyer SJ. Bcl-2 gene family in the nervous system. Annu Rev Neurosci 1997; 20:245–267

    Article  PubMed  CAS  Google Scholar 

  16. Sadoul R. Bcl-2 family members in the development and degenerative pathologies of the nervous system. Cell Death Differ 1998 Oct; 5(10):805–815

    Article  PubMed  CAS  Google Scholar 

  17. Li H, Yuan J. Deciphering the pathways of life and death. Curr Opin Cell Biol 1999 Apr; 11(2):261–266

    Article  PubMed  CAS  Google Scholar 

  18. Chen DF, Schneider GE, Martinou JC, Tonegawa S. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997 Jan 30; 385(6615):434–439

    Article  PubMed  CAS  Google Scholar 

  19. Lawrence MS, Ho DY, Sun GH, Steinberg GK, Sapolsky RM. Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo. J Neurosci 1996 Jan 15; 16(2):486–496

    PubMed  CAS  Google Scholar 

  20. Raghupathi R, Fernandez SC, Murai H, et al. BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice. J Cereb Blood Flow Metab 1998 Nov; 18(11):1259–1269

    Article  PubMed  CAS  Google Scholar 

  21. Yang L, Matthews RT, Schulz JB, et al. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride neurotoxicity is attenuated in mice overexpressing Bcl-2. J Neurosci 1998 Oct 15; 18(20):8145–8152

    PubMed  CAS  Google Scholar 

  22. Kostic V, Jackson-Lewis V, de Bilbao F, Dubois-Dauphin M, Przedborski S. Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 1997 Jul 25; 277(5325):559–562

    Article  PubMed  CAS  Google Scholar 

  23. Yuan PX, Baum AE, Zhou R, et al. Bcl-2 Polymorphisms Associated with Mood Disorders and Antidepressant-Responsiveness Regulate Bcl-2 Gene Expression and Cellular Resilience in Human Lymphoblastoid Cell Lines. Biol Psychiatry 2008; 63(7):63S

    Google Scholar 

  24. Salvadore G Nugent AC, Chen G, Akula N, Yuan P, Cannon DM, Zarate CA, Jr., McMahon FJ, Manji HK, Drevets WC. Bcl-2 polymorphism influences gray matter volume in the ventral striatum in healthy humans. Biol Psychiatry 2009; 66(8):804–807

    Google Scholar 

  25. Jope RS, Bijur GN. Mood stabilizers, glycogen synthase kinase-3beta and cell survival. Mol Psychiatry 2002; 7(Suppl 1):S35–S45

    Article  PubMed  CAS  Google Scholar 

  26. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J 2001 Oct 1; 359(Pt 1):1–16

    Article  PubMed  CAS  Google Scholar 

  27. Gould TD, Zarate CA, Manji HK. Glycogen synthase kinase-3: a target for novel bipolar disorder treatments. J Clin Psychiatry 2004 Jan; 65(1):10–21

    Article  PubMed  CAS  Google Scholar 

  28. Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA 1996 Aug 6; 93(16):8455–8459

    Article  PubMed  CAS  Google Scholar 

  29. Grimes CA, Jope RS. The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 2001 Nov; 65(4):391–426

    Article  PubMed  CAS  Google Scholar 

  30. Bachmann RF, Schloesser RJ, Gould TD, Manji HK. Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics. Mol Neurobiol 2005 Oct; 32(2):173–202

    Article  PubMed  CAS  Google Scholar 

  31. Hong M, Chen DC, Klein PS, Lee VM. Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem 1997 Oct 3; 272(40):25326–25332

    Article  PubMed  CAS  Google Scholar 

  32. Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 2003 May 22; 423(6938):435–439

    Article  PubMed  CAS  Google Scholar 

  33. Scherk H, Backens M, Schneider-Axmann T, et al. Cortical neurochemistry in euthymic patients with bipolar I disorder. World J Biol Psychiatry 2007 Sep; 13:1–10

    Article  Google Scholar 

  34. Trentani A, Kuipers SD, Ter Horst GJ, Den Boer JA. Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress-related cortical pathology? Eur J Neurosci 2002 May; 15(10):1681–1691

    Article  PubMed  CAS  Google Scholar 

  35. Einat H, Yuan P, Gould TD, et al. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 2003 Aug 13; 23(19):7311–7316

    PubMed  CAS  Google Scholar 

  36. Ozaki N, Chuang DM. Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain. J Neurochem 1997 Dec; 69(6):2336–2344

    Article  PubMed  CAS  Google Scholar 

  37. Tardito D, Tiraboschi E, Kasahara J, Racagni G, Popoli M. Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus. Int J Neuropsychopharmacol 2007; 10:491–496

    Article  PubMed  CAS  Google Scholar 

  38. Stewart RJ, Chen B, Dowlatshahi D, MacQueen GM, Young LT. Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium. Brain Res Bull 2001 Jul 15; 55(5):625–629

    Article  PubMed  CAS  Google Scholar 

  39. Young LT, Bezchlibnyk YB, Chen B, Wang JF, MacQueen GM. Amygdala cyclic adenosine monophosphate response element binding protein phosphorylation in patients with mood disorders: effects of diagnosis, suicide, and drug treatment. Biol Psychiatry 2004 Mar 15; 55(6):570–577

    Article  PubMed  CAS  Google Scholar 

  40. Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S. Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology (Berl) 2001 Oct; 158(1):100–106

    Article  CAS  Google Scholar 

  41. Frey BN, Andreazza AC, Rosa AR, et al. Lithium increases nerve growth factor levels in the rat hippocampus in an animal model of mania. Behav Pharmacol 2006 Jun; 17(4):311–318

    Article  PubMed  CAS  Google Scholar 

  42. Jacobsen JP, Mork A. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res 2004 Oct 22; 1024(1–2):183–192

    Article  PubMed  CAS  Google Scholar 

  43. Yasuda S, Liang MH, Marinova Z, Yahyavi A, Chuang DM. The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatry 2009 Jan; 14(1):51–59

    Article  PubMed  CAS  Google Scholar 

  44. McQuillin A, Rizig M, Gurling HM. A microarray gene expression study of the molecular pharmacology of lithium carbonate on mouse brain mRNA to understand the neurobiology of mood stabilization and treatment of bipolar affective disorder. Pharmacogenet Genomics 2007 Aug; 17(8):605–617

    Article  PubMed  CAS  Google Scholar 

  45. Hammonds MD, Shim SS, Feng P, Calabrese JR. Effects of subchronic lithium treatment on levels of BDNF, Bcl-2 and phospho-CREB in the rat hippocampus. Basic Clin Pharmacol Toxicol 2007 May; 100(5):356–359

    Article  PubMed  CAS  Google Scholar 

  46. Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002 Dec; 43(7):1173–1179

    Article  PubMed  CAS  Google Scholar 

  47. Angelucci F, Aloe L, Jimenez-Vasquez P, Mathe AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. The International Journal of Neuropsychopharmacology/Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 2003 Sep; 6(3):225–231

    Article  CAS  Google Scholar 

  48. Hellweg R, Lang UE, Nagel M, Baumgartner A. Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry 2002; 7(6):604–608

    Article  PubMed  CAS  Google Scholar 

  49. Walz JC, Frey BN, Andreazza AC, et al. Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels in an animal model of mania. J Psychiatr Res 2008 Apr; 42(5):416–421

    Article  PubMed  Google Scholar 

  50. Warner-Schmidt JL, Duman RS. VEGF as a potential target for therapeutic intervention in depression. Curr Opin Pharmacol 2008 Feb; 8(1):14–19

    Article  PubMed  CAS  Google Scholar 

  51. Silva R, Martins L, Longatto-Filho A, Almeida OF, Sousa N. Lithium prevents stress-induced reduction of vascular endothelium growth factor levels. Neurosci Lett 2007 Dec 11; 429(1):33–38

    Article  PubMed  CAS  Google Scholar 

  52. Zgouras D, Becker U, Loitsch S, Stein J. Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem Biophys Res Commun 2004 Apr 9; 316(3):693–697

    Article  PubMed  CAS  Google Scholar 

  53. Dong XF, Song Q, Li LZ, Zhao CL, Wang LQ. Histone deacetylase inhibitor valproic acid inhibits proliferation and induces apoptosis in KM3 cells via downregulating VEGF receptor. Neuro Endocrinol Lett 2007 Dec; 28(6):775–780

    PubMed  CAS  Google Scholar 

  54. Chuang DM, Priller J. Potential use of lithium in neurodegenerative disorders. In: Bauer M, Grof P, Muller-Oerlinghausen B (eds) Lithium in Neuropsychiatry The Comprehensive Guide. Abingdon, Oxon, United Kingdom Informa UK Ltd, 2006; pp. 381–398

    Google Scholar 

  55. Liang MH, Chuang DM. Regulation and function of glycogen synthase kinase-3 isoforms in neuronal survival. J Biol Chem 2007 Feb 9; 282(6):3904–3917

    Article  PubMed  CAS  Google Scholar 

  56. Ren M, Senatorov VV, Chen RW, Chuang DM. Postinsult treatment with lithium reduces brain damage and facilitates neurological recovery in a rat ischemia/reperfusion model. Proc Natl Acad Sci USA 2003 May 13; 100(10):6210–6215

    Article  PubMed  CAS  Google Scholar 

  57. Xu J, Culman J, Blume A, Brecht S, Gohlke P. Chronic treatment with a low dose of lithium protects the brain against ischemic injury by reducing apoptotic death. Stroke 2003 May; 34(5):1287–1292

    Article  PubMed  CAS  Google Scholar 

  58. Noble W, Planel E, Zehr C, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci USA 2005 May 10; 102(19):6990–6995

    Article  PubMed  CAS  Google Scholar 

  59. Rockenstein E, Torrance M, Adame A, et al. Neuroprotective effects of regulators of the glycogen synthase kinase-3beta signaling pathway in a transgenic model of Alzheimer’s disease are associated with reduced amyloid precursor protein phosphorylation. J Neurosci 2007 Feb 21; 27(8):1981–1991

    Article  PubMed  CAS  Google Scholar 

  60. De Ferrari GV, Chacon MA, Barria MI, et al. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. Mol Psychiatry 2003 Feb; 8(2):195–208

    Article  PubMed  CAS  Google Scholar 

  61. Schloesser RJ, Huang J, Klein PS, Manji HK. Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology 2008 Jan; 33(1):110–133

    Article  PubMed  CAS  Google Scholar 

  62. Chen G, Manji HK. The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers. Curr Opin Psychiatry 2006 May; 19(3):313–323

    Article  PubMed  Google Scholar 

  63. Yuan PX, Huang LD, Jiang YM, Gutkind JS, Manji HK, Chen G. The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem 2001 Aug 24; 276(34):31674–31683

    Article  PubMed  CAS  Google Scholar 

  64. Wang JF, Azzam JE, Young LT. Valproate inhibits oxidative damage to lipid and protein in primary cultured rat cerebrocortical cells. Neuroscience 2003; 116(2):485–489

    Article  PubMed  CAS  Google Scholar 

  65. Sinn DI, Kim SJ, Chu K, et al. Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol Dis 2007 May; 26(2):464–472

    Article  PubMed  CAS  Google Scholar 

  66. Hashimoto R, Hough C, Nakazawa T, Yamamoto T, Chuang DM. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem 2002 Feb; 80(4):589–597

    Article  PubMed  CAS  Google Scholar 

  67. Coyle JT, Manji HK. Getting balance: drugs for bipolar disorder share target. Nat Med 2002 Jun; 8(6):557–558

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  69. Thome J, Sakai N, Shin K, et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 2000 Jun 1; 20(11):4030–4036

    PubMed  CAS  Google Scholar 

  70. Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996 Apr 1; 16(7):2365–2372

    PubMed  CAS  Google Scholar 

  71. Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006 Jun 15; 59(12):1116–1127

    Article  PubMed  CAS  Google Scholar 

  72. Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003 Aug 8; 301(5634):805–809

    Article  PubMed  CAS  Google Scholar 

  73. Warner-Schmidt JL, Duman RS. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci USA 2007 Mar 13; 104(11):4647–4652

    Article  PubMed  CAS  Google Scholar 

  74. Peng CH, Chiou SH, Chen SJ, et al. Neuroprotection by Imipramine against lipopolysaccharide-induced apoptosis in hippocampus-derived neural stem cells mediated by activation of BDNF and the MAPK pathway. Eur Neuropsychopharmacol 2008 Feb; 18(2):128–140

    Article  PubMed  CAS  Google Scholar 

  75. Chiou SH, Chen SJ, Peng CH, et al. Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell. Biochem Biophys Res Commun 2006 May 5; 343(2):391–400

    Article  PubMed  CAS  Google Scholar 

  76. Lim CM, Kim SW, Park JY, Kim C, Yoon SH, Lee JK. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res 2008 Oct 14

    Google Scholar 

  77. Chen SJ, Kao CL, Chang YL, et al. Antidepressant administration modulates neural stem cell survival and serotoninergic differentiation through bcl-2. Curr Neurovasc Res 2007 Feb; 4(1):19–29

    Article  PubMed  CAS  Google Scholar 

  78. Mercier G, Lennon AM, Renouf B, et al. MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes. J Mol Neurosci 2004; 24(2):207–216

    Article  PubMed  CAS  Google Scholar 

  79. Chen X, Wen W, Malhi GS, Ivanovski B, Sachdev PS. Regional gray matter changes in bipolar disorder: a voxel-based morphometric study. Aust NZ J Psychiatry 2007 Apr; 41(4):327–336

    Article  Google Scholar 

  80. Nugent AC, Milham MP, Bain EE, et al. Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 2006 Apr 1; 30(2):485–497

    Article  PubMed  Google Scholar 

  81. Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 2009 May; 33(5):699–771

    Article  PubMed  Google Scholar 

  82. Sassi RB, Brambilla P, Hatch JP, et al. Reduced left anterior cingulate volumes in untreated bipolar patients. Biol Psychiatry 2004 Oct 1; 56(7):467–475

    Article  PubMed  Google Scholar 

  83. Atmaca M, Ozdemir H, Cetinkaya S, et al. Cingulate gyrus volumetry in drug free bipolar patients and patients treated with valproate or valproate and quetiapine. J Psychiatr Res 2007 Nov; 41(10):821–827

    Article  PubMed  Google Scholar 

  84. Lyoo IK, Kim MJ, Stoll AL, et al. Frontal lobe gray matter density decreases in bipolar I disorder. Biol Psychiatry 2004 Mar 15; 55(6):648–651

    Article  PubMed  Google Scholar 

  85. Chiu S, Widjaja F, Bates ME, et al. Anterior cingulate volume in pediatric bipolar disorder and autism. J Affect Disord 2008 Jan; 105(1–3):93–99

    Article  PubMed  Google Scholar 

  86. Wilke M, Kowatch RA, DelBello MP, Mills NP, Holland SK. Voxel-based morphometry in adolescents with bipolar disorder: first results. Psychiatry Res 2004 May 30; 131(1):57–69

    Article  PubMed  Google Scholar 

  87. Hajek T, Gunde E, Bernier D, et al. Subgenual cingulate volumes in affected and unaffected offspring of bipolar parents. J Affect Disord 2008 Jun; 108(3):263–269

    Article  PubMed  Google Scholar 

  88. Vasic N, Walter H, Hose A, Wolf RC. Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study. J Affect Disord 2008 Jul; 109(1–2):107–116

    Article  PubMed  Google Scholar 

  89. Drevets WC, Price JL, Simpson JR Jr., et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997 Apr 24; 386(6627):824–827

    Article  PubMed  CAS  Google Scholar 

  90. Hirayasu Y, Shenton ME, Salisbury DF, et al. Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiatry 1999 Jul; 156(7):1091–1093

    PubMed  CAS  Google Scholar 

  91. Sharma V, Menon R, Carr TJ, Densmore M, Mazmanian D, Williamson PC. An MRI study of subgenual prefrontal cortex in patients with familial and non-familial bipolar I disorder. J Affect Disord 2003 Nov; 77(2):167–171

    Article  PubMed  Google Scholar 

  92. Frodl T, Koutsouleris N, Bottlender R, et al. Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression. Mol Psychiatry 2008 Dec; 13(12):1093–1101

    Article  PubMed  CAS  Google Scholar 

  93. Adler CM, Levine AD, DelBello MP, Strakowski SM. Changes in gray matter volume in patients with bipolar disorder. Biol Psychiatry 2005 Jul 15; 58(2):151–157

    Article  PubMed  Google Scholar 

  94. Lavretsky H, Kurbanyan K, Ballmaier M, Mintz J, Toga A, Kumar A. Sex differences in brain structure in geriatric depression. Am J Geriatr Psychiatry 2004 Nov–Dec; 12(6):653–657

    PubMed  Google Scholar 

  95. Lai T, Payne ME, Byrum CE, Steffens DC, Krishnan KR. Reduction of orbital frontal cortex volume in geriatric depression. Biol Psychiatry 2000 Nov 15; 48(10):971–975

    Article  PubMed  CAS  Google Scholar 

  96. Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 2004 Nov; 161(11):1957–1966

    Article  PubMed  Google Scholar 

  97. Campbell S, Marriott M, Nahmias C, MacQueen GM. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 2004 Apr; 161(4):598–607

    Article  PubMed  Google Scholar 

  98. Strasser HC, Lilyestrom J, Ashby ER, et al. Hippocampal and ventricular volumes in psychotic and nonpsychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study. Biol Psychiatry 2005 Mar 15; 57(6):633–639

    Article  PubMed  Google Scholar 

  99. Blumberg HP, Kaufman J, Martin A, et al. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry 2003 Dec; 60(12):1201–1208

    Article  PubMed  Google Scholar 

  100. Brambilla P, Harenski K, Nicoletti M, et al. MRI investigation of temporal lobe structures in bipolar patients. J Psychiatr Res 2003 Jul–Aug; 37(4):287–295

    Article  PubMed  Google Scholar 

  101. Hauser P, Matochik J, Altshuler LL, et al. MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders. J Affect Disord 2000 Oct; 60(1):25–32

    Article  PubMed  CAS  Google Scholar 

  102. Altshuler LL, Bartzokis G, Grieder T, et al. An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry 2000 Jul 15; 48(2):147–162

    Article  PubMed  CAS  Google Scholar 

  103. McDonald C, Marshall N, Sham PC, et al. Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry 2006 Mar; 163(3):478–487

    Article  PubMed  Google Scholar 

  104. Swayze VW, 2nd, Andreasen NC, Alliger RJ, Yuh WT, Ehrhardt JC. Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study. Biol Psychiatry 1992 Feb 1; 31(3):221–240

    Article  PubMed  Google Scholar 

  105. Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005 Oct 20; 48(2):175–187

    Article  PubMed  CAS  Google Scholar 

  106. Lange C, Irle E. Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med 2004 Aug; 34(6):1059–1064

    Article  PubMed  CAS  Google Scholar 

  107. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Hippocampal volume reduction in major depression. Am J Psychiatry 2000 Jan; 157(1):115–118

    PubMed  CAS  Google Scholar 

  108. Frodl T, Schule C, Schmitt G, et al. Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 2007 Apr; 64(4):410–416

    Article  PubMed  CAS  Google Scholar 

  109. Inagaki M, Matsuoka Y, Sugahara Y, et al. Hippocampal volume and first major depressive episode after cancer diagnosis in breast cancer survivors. Am J Psychiatry 2004 Dec; 161(12):2263–2270

    Article  PubMed  Google Scholar 

  110. Hickie IB, Naismith SL, Ward PB, et al. Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. J Affect Disord 2007 Feb; 98(1–2):137–142

    Article  PubMed  CAS  Google Scholar 

  111. Tang Y, Wang F, Xie G, et al. Reduced ventral anterior cingulate and amygdala volumes in medication-naive females with major depressive disorder: A voxel-based morphometric magnetic resonance imaging study. Psychiatry Res 2007 Oct 15; 156(1):83–86

    Article  PubMed  Google Scholar 

  112. Strakowski SM, DelBello MP, Sax KW, et al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999 Mar; 56(3):254–260

    Article  PubMed  CAS  Google Scholar 

  113. Frangou S. The Maudsley Bipolar Disorder Project. Epilepsia 2005; 46(Suppl 4):19–25

    Article  PubMed  Google Scholar 

  114. DelBello MP, Zimmerman ME, Mills NP, Getz GE, Strakowski SM. Magnetic resonance imaging analysis of amygdala and other subcortical brain regions in adolescents with bipolar disorder. Bipolar Disord 2004 Feb; 6(1):43–52

    Article  PubMed  Google Scholar 

  115. Dickstein DP, Milham MP, Nugent AC, et al. Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry 2005 Jul; 62(7):734–741

    Article  PubMed  Google Scholar 

  116. Chang K, Karchemskiy A, Barnea-Goraly N, Garrett A, Simeonova DI, Reiss A. Reduced amygdalar gray matter volume in familial pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005 Jun; 44(6):565–573

    Article  PubMed  Google Scholar 

  117. Foland LC, Altshuler LL, Sugar CA, et al. Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. Neuroreport 2008 Jan 22; 19(2):221–224

    Article  PubMed  Google Scholar 

  118. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet 2000 Oct 7; 356(9237):1241–1242

    Article  PubMed  CAS  Google Scholar 

  119. Sassi RB, Nicoletti M, Brambilla P, et al. Increased gray matter volume in lithium-treated bipolar disorder patients. Neurosci Lett 2002 Aug 30; 329(2):243–245

    Article  PubMed  CAS  Google Scholar 

  120. Moore GJ, Cortese BM, Glitz DA, et al. A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients. J Clin Psychiatry 2009; 70(5):699–705

    Google Scholar 

  121. Blumberg HP, Krystal JH, Bansal R, et al. Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study. Biol Psychiatry 2006 Apr 1; 59(7):611–618

    Article  PubMed  CAS  Google Scholar 

  122. Bearden CE, Thompson PM, Dutton RA, et al. Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder. Neuropsychopharmacology 2008 May; 33(6):1229–1238

    Article  PubMed  CAS  Google Scholar 

  123. Brambilla P, Harenski K, Nicoletti MA, et al. Anatomical MRI study of basal ganglia in bipolar disorder patients. Psychiatry Res 2001 Apr 10; 106(2):65–80

    Article  PubMed  CAS  Google Scholar 

  124. Sassi RB, Nicoletti M, Brambilla P, et al. Decreased pituitary volume in patients with bipolar disorder. Biol Psychiatry 2001 Aug 15; 50(4):271–280

    Article  PubMed  CAS  Google Scholar 

  125. Caetano SC, Sassi R, Brambilla P, et al. MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals. Psychiatry Res 2001 Dec 30; 108(3):161–168

    Article  PubMed  CAS  Google Scholar 

  126. Brambilla P, Nicoletti MA, Sassi RB, et al. Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder. Biol Psychiatry 2003 Dec 1; 54(11):1294–1297

    Article  PubMed  Google Scholar 

  127. Yucel K, McKinnon MC, Taylor VH, et al. Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology (Berl) 2007 Dec; 195(3):357–367

    Article  CAS  Google Scholar 

  128. Yucel K, Taylor VH, McKinnon MC, et al. Bilateral hippocampal volume increase in patients with bipolar disorder and short-term lithium treatment. Neuropsychopharmacology 2008 Jan; 33(2):361–367

    Article  PubMed  CAS  Google Scholar 

  129. Atmaca M, Yildirim H, Ozdemir H, Ogur E, Tezcan E. Hippocampal 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine. Psychol Med 2007 Jan; 37(1):121–129

    Article  PubMed  Google Scholar 

  130. Hwang J, Lyoo IK, Dager SR, et al. Basal ganglia shape alterations in bipolar disorder. Am J Psychiatry 2006 Feb; 163(2):276–285

    Article  PubMed  Google Scholar 

  131. Regenold WT. Lithium and increased cortical gray matter-more tissue or more water? Biol Psychiatry 2008 Feb 1; 63(3):e17; author reply e19

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  133. Lavretsky H, Roybal DJ, Ballmaier M, Toga AW, Kumar A. Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression. J Clin Psychiatry 2005 Aug; 66(8):964–967

    Article  PubMed  Google Scholar 

  134. Vythilingam M, Vermetten E, Anderson GM, et al. Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 2004 Jul 15; 56(2):101–112

    Article  PubMed  CAS  Google Scholar 

  135. Bates TE, Strangward M, Keelan J, Davey GP, Munro PM, Clark JB. Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport 1996 May 31; 7(8):1397–1400

    Article  PubMed  CAS  Google Scholar 

  136. Clarke CE, Lowry M, Quarrell OW. No change in striatal glutamate in Huntington’s disease measured by proton magnetic resonance spectroscopy. Parkinsonism Relat Disord 1998 Oct; 4(3):123–127

    Article  PubMed  CAS  Google Scholar 

  137. Michael N, Erfurth A, Ohrmann P, et al. Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology (Berl) 2003 Jul; 168(3):344–346

    Article  CAS  Google Scholar 

  138. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000 Feb 15; 47(4):305–313

    Article  PubMed  CAS  Google Scholar 

  139. Coupland NJ, Ogilvie CJ, Hegadoren KM, Seres P, Hanstock CC, Allen PS. Decreased prefrontal Myo-inositol in major depressive disorder. Biol Psychiatry 2005 Jun 15; 57(12):1526–1534

    Article  PubMed  CAS  Google Scholar 

  140. Binesh N, Kumar A, Hwang S, Mintz J, Thomas MA. Neurochemistry of late-life major depression: a pilot two-dimensional MR spectroscopic study. J Magn Reson Imaging 2004 Dec; 20(6):1039–1045

    Article  PubMed  Google Scholar 

  141. Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy: a proton magnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 2000 Oct; 57(10):937–943

    Article  PubMed  CAS  Google Scholar 

  142. Hamakawa H, Kato T, Murashita J, Kato N. Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Eur Arch Psychiatry Clin Neurosci 1998; 248(1):53–58

    Article  PubMed  CAS  Google Scholar 

  143. Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA. Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry 2000 Mar 15; 47(6):475–481

    Article  PubMed  CAS  Google Scholar 

  144. Molina V, Sanchez J, Sanz J, et al. Dorsolateral prefrontal N-acetyl-aspartate concentration in male patients with chronic schizophrenia and with chronic bipolar disorder. Eur Psychiatry 2007 Nov; 22(8):505–512

    Article  PubMed  CAS  Google Scholar 

  145. Cecil KM, DelBello MP, Morey R, Strakowski SM. Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy. Bipolar Disord 2002 Dec; 4(6):357–365

    Article  PubMed  CAS  Google Scholar 

  146. Bertolino A, Frye M, Callicott JH, et al. Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry 2003 May 15; 53(10):906–913

    Article  PubMed  Google Scholar 

  147. Dager SR, Friedman SD, Parow A, et al. Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry 2004 May; 61(5):450–458

    Article  PubMed  CAS  Google Scholar 

  148. Frey BN, Stanley JA, Nery FG, et al. Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1H MRS study. Bipolar Disord 2007 Jun; 9(Suppl 1):119–127

    Article  PubMed  Google Scholar 

  149. Moore GJ, Bebchuk JM, Hasanat K, et al. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects? Biol Psychiatry 2000 Jul 1; 48(1):1–8

    Article  PubMed  CAS  Google Scholar 

  150. Brambilla P, Stanley JA, Nicoletti MA, et al. 1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients. J Affect Disord 2005 May; 86(1):61–67

    Article  PubMed  Google Scholar 

  151. Blasi G, Bertolino A, Brudaglio F, et al. Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study. Psychiatry Res 2004 Jul 30; 131(2):95–105

    Article  PubMed  CAS  Google Scholar 

  152. Deicken RF, Pegues MP, Anzalone S, Feiwell R, Soher B. Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder. Am J Psychiatry 2003 May; 160(5):873–882

    Article  PubMed  Google Scholar 

  153. Atmaca M, Yildirim H, Ozdemir H, Poyraz AK, Tezcan E, Ogur E. Hippocampal 1H MRS in first-episode bipolar I patients. Prog Neuropsychopharmacol Biol Psychiatry 2006 Sep 30; 30(7):1235–1239

    Article  PubMed  CAS  Google Scholar 

  154. Zarate CA Jr, Singh J, Manji HK. Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 2006 Jun 1; 59(11):1006–1020

    Article  PubMed  CAS  Google Scholar 

  155. Sanacora G, Mason GF, Rothman DL, et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry 1999 Nov; 56(11):1043–1047

    Article  PubMed  CAS  Google Scholar 

  156. Sanacora G, Gueorguieva R, Epperson CN, et al. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 2004 Jul; 61(7):705–713

    Article  PubMed  CAS  Google Scholar 

  157. Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2007 Feb; 64(2):193–200

    Article  PubMed  CAS  Google Scholar 

  158. Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Neurotrophic effects of electroconvulsive therapy: a proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 2003 Apr; 28(4):720–725

    Article  PubMed  CAS  Google Scholar 

  159. Bhagwagar Z, Wylezinska M, Jezzard P, et al. Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry 2007 Mar 15; 61(6):806–812

    Article  PubMed  CAS  Google Scholar 

  160. Frye MA, Watzl J, Banakar S, et al. Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in bipolar depression. Neuropsychopharmacology 2007 Dec; 32(12):2490–2499

    Article  PubMed  CAS  Google Scholar 

  161. Friedman SD, Dager SR, Parow A, et al. Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder. Biol Psychiatry 2004 Sep 1; 56(5):340–348

    Article  PubMed  CAS  Google Scholar 

  162. Brambilla P, Stanley JA, Sassi RB, et al. 1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration. Neuropsychopharmacology 2004 Oct; 29(10):1918–1924

    Article  PubMed  CAS  Google Scholar 

  163. Silverstone PH, Wu RH, O’Donnell T, Ulrich M, Asghar SJ, Hanstock CC. Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients. Int Clin Psychopharmacol 2003 Mar; 18(2):73–79

    Article  PubMed  Google Scholar 

  164. Block W, Traber F, von Widdern O, et al. Proton MR spectroscopy of the hippocampus at 3 T in patients with unipolar major depressive disorder: correlates and predictors of treatment response. Int J Neuropsychopharmacol 2008 Oct 10:1–8

    Google Scholar 

  165. Sanacora G, Mason GF, Rothman DL, Krystal JH. Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry 2002 Apr; 159(4):663–665

    Article  PubMed  Google Scholar 

  166. Sanacora G, Mason GF, Rothman DL, et al. Increased cortical GABA concentrations in depressed patients receiving ECT. Am J Psychiatry 2003 Mar; 160(3):577–579

    Article  PubMed  Google Scholar 

  167. Sanacora G, Fenton LR, Fasula MK, et al. Cortical gamma-aminobutyric acid concentrations in depressed patients receiving cognitive behavioral therapy. Biol Psychiatry 2006 Feb 1; 59(3):284–286

    Article  PubMed  CAS  Google Scholar 

  168. Pfleiderer B, Michael N, Erfurth A, et al. Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res 2003 Apr 1; 122(3):185–192

    Article  PubMed  CAS  Google Scholar 

  169. Manganas LN, Zhang X, Li Y, et al. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 2007 Nov 9; 318(5852):980–985

    Article  PubMed  CAS  Google Scholar 

  170. Bowley MP, Drevets WC, Ongur D, Price JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 2002 Sep 1; 52(5):404–412

    Article  PubMed  Google Scholar 

  171. Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex 2002 Apr; 12(4):386–394

    Article  PubMed  Google Scholar 

  172. Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998 Oct 27; 95(22):13290–13295

    Article  PubMed  CAS  Google Scholar 

  173. Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999 May 1; 45(9):1085–1098

    Article  PubMed  CAS  Google Scholar 

  174. Stockmeier CA, Rajkowska G. Cellular abnormalities in depression: evidence from postmortem brain tissue. Dialogues Clin Neurosci 2004; 6(2):185–197

    PubMed  Google Scholar 

  175. Tkachev D, Mimmack ML, Ryan MM, et al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 2003 Sep 6; 362(9386):798–805

    Article  PubMed  CAS  Google Scholar 

  176. Webster MJ, O’Grady J, Kleinman JE, Weickert CS. Glial fibrillary acidic protein mRNA levels in the cingulate cortex of individuals with depression, bipolar disorder and schizophrenia. Neuroscience 2005; 133(2):453–461

    Article  PubMed  CAS  Google Scholar 

  177. Rajkowska G. Cell pathology in bipolar disorder. Bipolar Disord 2002 Apr; 4(2):105–116

    Article  PubMed  Google Scholar 

  178. Benes FM, Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 2001 Jul; 25(1):1–27

    Article  PubMed  CAS  Google Scholar 

  179. Cotter D, Landau S, Beasley C, et al. The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia. Biol Psychiatry 2002 Mar 1; 51(5):377–386

    Article  PubMed  CAS  Google Scholar 

  180. Pantazopoulos H, Lange N, Baldessarini RJ, Berretta S. Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia. Biol Psychiatry 2007 Mar 1; 61(5):640–652

    Article  PubMed  CAS  Google Scholar 

  181. Knable MB, Barci BM, Webster MJ, Meador-Woodruff J, Torrey EF. Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Mol Psychiatry 2004 Jun; 9(6):609–620, 544

    Article  PubMed  CAS  Google Scholar 

  182. Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J. Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Neuroreport 2001 Oct 29; 12(15):3257–3262

    Article  PubMed  CAS  Google Scholar 

  183. Scarr E, Gray L, Keriakous D, Robinson PJ, Dean B. Increased levels of SNAP-25 and synaptophysin in the dorsolateral prefrontal cortex in bipolar I disorder. Bipolar Disord 2006 Apr; 8(2):133–143

    Article  PubMed  CAS  Google Scholar 

  184. Eastwood SL, Harrison PJ. 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 2001 Jul 15; 55(5):569–578

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  186. Rosoklija G, Toomayan G, Ellis SP, et al. Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry 2000 Apr; 57(4):349–356

    Article  PubMed  CAS  Google Scholar 

  187. Kugaya A, Sanacora G. Beyond monoamines: glutamatergic function in mood disorders. CNS Spectr 2005 Oct; 10(10):808–819

    PubMed  Google Scholar 

  188. Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000 Oct; 57(10):925–935

    Article  PubMed  CAS  Google Scholar 

  189. McEwen BS. The neurobiology of stress: from serendipity to clinical relevance. Brain Res 2000 Dec 15; 886(1–2):172–189

    Article  PubMed  CAS  Google Scholar 

  190. Varea E, Blasco-Ibanez JM, Gomez-Climent MA, et al. Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex. Neuropsychopharmacology 2007 Apr; 32(4):803–812

    Article  PubMed  CAS  Google Scholar 

  191. Varea E, Castillo-Gomez E, Gomez-Climent MA, et al. Chronic antidepressant treatment induces contrasting patterns of synaptophysin and PSA-NCAM expression in different regions of the adult rat telencephalon. Eur Neuropsychopharmacol 2007 Jul; 17(8):546–557

    Article  PubMed  CAS  Google Scholar 

  192. Hajszan T, MacLusky NJ, Leranth C. Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 2005 Mar; 21(5):1299–1303

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the support of the Intramural Research Program of the National Institute of Mental Health. Ioline Henter provided outstanding editorial assistance.

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Authors and Affiliations

  1. Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD, USA

    Giacomo Salvadore, Rodrigo Machado-Vieira & Husseini K. Manji

  2. Institute and Department of Psychiatry, University of Sao Paulo, LIM-27, MD, USA

    Rodrigo Machado-Vieira

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  1. Giacomo Salvadore
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  2. Rodrigo Machado-Vieira
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  3. Husseini K. Manji
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Correspondence to Giacomo Salvadore .

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  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

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Salvadore, G., Machado-Vieira, R., Manji, H.K. (2010). Neuroprotective Agents in Mood Disorders: Pathophysiological and Therapeutic Implications. In: Ritsner, M. (eds) Brain Protection in Schizophrenia, Mood and Cognitive Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8553-5_14

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