Advertisement

Neuroprotection in Bipolar Depression

  • Chris B. AikenEmail author
Chapter

Abstract

The past 10 years have seen a growth of therapeutic options for bipolar depression. Evidence for the clinical and neuroprotective effects of these treatments is reviewed in this chapter, including lamotrigine, pramipexole, modafinil, and atypical antipsychotics. Their neuroprotective profiles are compared to the better established effects of lithium and valproate, which include upregulation of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (bcl-2) and inhibition of glycogen synthase kinase-3β (GSK-3β) and glutamate transmission.

The neuroprotective profile of antidepressants will also be examined to better understand their controversial role in bipolar depression. Treatments with efficacy in multiple phases of bipolar illness exert neuroprotective effects in multiple brain regions, including the anterior cingulate cortex, striatum, and hippocampus. Antidepressants, in contrast, have a more focal neuroprotective effect through BDNF in the hippocampus.

Finally, this chapter will explore both the clinical and neuroprotective effects of adjunctive and complimentary treatments for bipolar depression, including psychotherapy, omega-3 fatty acids, N-acetylcysteine, diet and exercise. Lastly, the neuroplasticity model will be explored as a tool for engaging patients in their recovery and improving medication adherence.

Keywords

Neuroprotective agents Bipolar disorder Depression Brain-derived neurotrophic factor b-cell lymphoma 2 Glutamate Glycogen synthase kinase 3 Lithium Lamotrigine Pramipexole Modafinil Antipsychotic agents Quetiapine Olanzapine Olanzapine-fluoxetine combination Antidepressive agents Glutathione Acetylcysteine Omega-3 fatty acids Diet Exercise Psychotherapy Patient education 

Abbreviations

AMPA

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

COX-2

Cyclooxygenase 2

CREB

cAMP-response element binding protein

BDNF

Brain-derived neurotrophic factor

Bcl-2

B-cell lymphoma 2

DHA

docosahexaenoic acid

EPA

eicosapentaenoic acid

ERK1/2

Extracellular Signal-Regulated Kinases 1 and 2

FDA

Food and Drug Administration

GSK-3β

glycogen synthase kinase-3β

NAA

N-acetylaspartate

NMDA

N-methyl-D-aspartate

MPTP

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

References

  1. 1.
    Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, 2nd ed. Oxford University Press, New York; 2007Google Scholar
  2. 2.
    Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs 2003; 17:491–511PubMedCrossRefGoogle Scholar
  3. 3.
    Roshanaei-Moghaddam B, Katon W. Premature mortality from general medical illnesses among persons with bipolar disorder: a review. Psychiatr Serv 2009; 60:147–156PubMedCrossRefGoogle Scholar
  4. 4.
    Judd LL, Schettler PJ, Akiskal HS, et al. Long-term symptomatic status of bipolar I vs. bipolar II disorders. Int J Neuropsychopharmacol 2003; 6:127–137PubMedCrossRefGoogle Scholar
  5. 5.
    Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002; 59:530–537PubMedCrossRefGoogle Scholar
  6. 6.
    Valenstein M, McCarthy JF, Austin KL, et al. What happened to lithium? Antidepressant augmentation in clinical settings. Am J Psychiatry 2006; 163:1219–1225PubMedCrossRefGoogle Scholar
  7. 7.
    Ghaemi SN, Gilmer WS, Goldberg JF et al. Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry 2007; 68:1840–1844PubMedCrossRefGoogle Scholar
  8. 8.
    Davis LL, Bartolucci A, Petty F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord 2005; 85:259–266PubMedCrossRefGoogle Scholar
  9. 9.
    Gyulai L, Bowden CL, McElroy SL, et al. Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacology 2003; 28:1374–1313Google Scholar
  10. 10.
    Calabrese J, Bowden C, Sachs G, et al. A placebo-controlled, 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003; 64:1013–1024PubMedCrossRefGoogle Scholar
  11. 11.
    Bowden CL, Calabrese JR, Sachs G, et al. A placebo-controlled, 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60:392–400PubMedCrossRefGoogle Scholar
  12. 12.
    Calabrese JR, Huffman RF, White RL, et al. Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord 2008; 10:323–333PubMedCrossRefGoogle Scholar
  13. 13.
    van der Loos ML, Mulder PG, Hartong EG, et al. LamLit Study Group. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry 2009; 70:223–231PubMedCrossRefGoogle Scholar
  14. 14.
    Bechtold DA, Miller SJ, Dawson AC, et al. Axonal protection achieved in a model of multiple sclerosis using lamotrigine. J Neurol 2006; 253:1542–1551PubMedCrossRefGoogle Scholar
  15. 15.
    Prica C, Hascoet M, Bourin M. Antidepressant-like effect of lamotrigine is reversed by veratrine: a possible role of sodium channels in bipolar depression. Behav Brain Res 2008; 191:49–54PubMedCrossRefGoogle Scholar
  16. 16.
    Hashimoto R, Hough C, Nakazawa T, et al. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem 2002; 80:589–597PubMedCrossRefGoogle Scholar
  17. 17.
    Morland C, Boldingh KA, Iversen EG, et al. Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake. J Cereb Blood Flow Metab 2004; 24:1226–1234PubMedCrossRefGoogle Scholar
  18. 18.
    Machado-Vieira R, Manji HK, Zarate CA. The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology and Therapeutics of Mood Disorders. Neuroscientist. 2009 May 26 (Epub ahead of print)Google Scholar
  19. 19.
    Zarate CA Jr, Quiroz JA, Singh JB, et al. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry. 2005; 57:430–432PubMedCrossRefGoogle Scholar
  20. 20.
    Singh J, Zarate CA Jr, Krystal AD. Case report: Successful riluzole augmentation therapy in treatment-resistant bipolar depression following the development of rash with lamotrigine. Psychopharmacology (Berl) 2004; 173:227–228CrossRefGoogle Scholar
  21. 21.
    Tsai SJ. Sipatrigine could have therapeutic potential for major depression and bipolar depression through antagonism of the two-pore-domain K+ channel TREK-1. Med Hypotheses 2008; 70:548–550PubMedCrossRefGoogle Scholar
  22. 22.
    Chang YC, Rapoport SI, Rao JS. Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression levels in rat frontal cortex. Neurochem Res 2009; 34:536–541PubMedCrossRefGoogle Scholar
  23. 23.
    Di Daniel E, Mudge AW, Maycox PR. Comparative analysis of the effects of four mood stabilizers in SH-SY5Y cells and in primary neurons. Bipolar Disord 2005; 7:33–41PubMedCrossRefGoogle Scholar
  24. 24.
    Li X, Bijur GN, Jope RS. Glycogen synthase kinase-3β, mood stabilizers, and neuroprotection. Bipolar Disord 2002; 4:137–144PubMedCrossRefGoogle Scholar
  25. 25.
    Cui J, Shao L, Young LT, et al. Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate. Neuroscience 2007; 144:1447–1453PubMedCrossRefGoogle Scholar
  26. 26.
    Eren I, Naziroglu M, Demirdas A. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 2007; 32:1188–1195PubMedCrossRefGoogle Scholar
  27. 27.
    Anttila V, Rimpilainen J, Pokela M, et al. Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model. J Thorac Cardiovasc Surg 2000; 120:247–255PubMedCrossRefGoogle Scholar
  28. 28.
    Crumrine RC, Bergstrand K, Cooper AT, et al. Lamotrigine protects hippocampal CA1 neurons from ischemic damage after cardiac arrest. Stroke 1997; 28:2230–2236PubMedCrossRefGoogle Scholar
  29. 29.
    Lee YS, Yoon BW, Roh JK. Neuroprotective effects of lamotrigine enhanced by flunarizine in gerbil global ischemia. Neurosci Lett 1999; 265:215–217PubMedCrossRefGoogle Scholar
  30. 30.
    Calabresi P, Centonze D, Cupini LM, et al. Ionotropic glutamate receptors: still a target for neuroprotection in brain ischemia? Insights from in vitro studies. Neurobiol Dis 2003; 12:82–88PubMedCrossRefGoogle Scholar
  31. 31.
    Wiard RP, Dickerson MC, Beek O, et al. Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Stroke 1995; 26:466–472PubMedCrossRefGoogle Scholar
  32. 32.
    Papazisis G, Kallaras K, Kaiki-Astara A, et al. Neuroprotection by lamotrigine in a rat model of neonatal hypoxic-ischaemic encephalopathy. Int J Neuropsychopharmacol 2008; 11:321–329PubMedCrossRefGoogle Scholar
  33. 33.
    Casanovas A, Ribera J, Hukkanen M, et al. Prevention by lamotrigine, MK-801 and N omega-nitro-L-arginine methyl ester of motoneuron cell death after neonatal axotomy. Neuroscience 1996:71:313–325PubMedCrossRefGoogle Scholar
  34. 34.
    Park SH, Seo YH, Moon BH, et al. Lamotrigine prevents MK801-induced alterations in early growth response factor-1 mRNA levels and immunoreactivity in the rat brain. Eur J Pharmacol 2008; 589:58–65PubMedCrossRefGoogle Scholar
  35. 35.
    Connop BP, Boegman RJ, Beninger RJ, et al. Malonate-induced degeneration of basal forebrain cholinergic neurons: attenuation by lamotrigine, MK-801, and 7-nitroindazole. J Neurochem 1997; 68:1191–11919PubMedCrossRefGoogle Scholar
  36. 36.
    Lee WT, Shen YZ, Chang C. Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Neuroscience 2000; 95:89–95PubMedCrossRefGoogle Scholar
  37. 37.
    Lagrue E, Chalon S, Bodard S, et al, Lamotrigine is neuroprotective in the energy deficiency model of MPTP intoxicated mice. Pediatric Res 2007; 62:14–19CrossRefGoogle Scholar
  38. 38.
    Kim YJ, Ko HH, Han ES, et al. Lamotrigine inhibition of rotenone- or 1-methyl-4-phenylpyridinium-induced mitochondrial damage and cell death. Brain Res Bull 2007; 71:633–640PubMedCrossRefGoogle Scholar
  39. 39.
    Schulz JB, Matthews RT, Henshaw DR, et al. Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: implications for neurodegenerative diseases. Neuroscience 1996; 71:1043–1048PubMedCrossRefGoogle Scholar
  40. 40.
    Ng F, Berk M, Dean O, et al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 2008; 11:851–876PubMedCrossRefGoogle Scholar
  41. 41.
    Calabrese JR, Keck PE Jr, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162:1351–1360PubMedCrossRefGoogle Scholar
  42. 42.
    Thase ME, Macfadden W, Weisler RH, et al. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 2006; 26:600–609PubMedCrossRefGoogle Scholar
  43. 43.
    Vieta E, Calabrese JR, Goikolea JM, Raines, et al. Quetiapine monotherapy in the treatment of patients with bipolar I or II depression and a rapid-cycling disease course: a randomized, double-blind, placebo-controlled study. Bipolar Disord 2007; 9:413–425PubMedCrossRefGoogle Scholar
  44. 44.
    Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60:1079–1088PubMedCrossRefGoogle Scholar
  45. 45.
    Marcus RN, McQuade RD, Carson WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2008; 28:156–65PubMedCrossRefGoogle Scholar
  46. 46.
    Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007; 68:843–853PubMedCrossRefGoogle Scholar
  47. 47.
    Thase ME, Jonas A, Khan A, et al. Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol 2008; 28:13–20PubMedCrossRefGoogle Scholar
  48. 48.
    Keck PE Jr, Calabrese JR, McIntyre RS, McQuade RD, et al. Aripiprazole Study Group. Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo. J Clin Psychiatry 2007; 68:1480–1491PubMedCrossRefGoogle Scholar
  49. 49.
    Nierenberg AA, Ostacher MJ, Calabrese JR, et al. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry 2006; 163:210–216PubMedCrossRefGoogle Scholar
  50. 50.
    Shelton RC, Stahl SM. Risperidone and paroxetine given singly and in combination for bipolar depression. J Clin Psychiatry 2004; 65:1715–1719PubMedCrossRefGoogle Scholar
  51. 51.
    Fumagalli F, Molteni R, Bedogni F, et al. Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals treated with MK-801. Neuroreport 2004; 15:2109–2112PubMedCrossRefGoogle Scholar
  52. 52.
    Park, Sung Woo SW. Differential effects of ziprasidone and haloperidol on immobilization stress-induced mRNA BDNF expression in the hippocampus and neocortex of rats. J Psychiatr Res 2009; 43:274–281PubMedCrossRefGoogle Scholar
  53. 53.
    Xu H, Qing H, Lu W, et al. Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus. Neurosci Lett 2002; 321:65–68PubMedCrossRefGoogle Scholar
  54. 54.
    Bai O, Chlan-Fourney J, Bowen R, et al. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs. J Neurosci Res 2003; 71:127–131PubMedCrossRefGoogle Scholar
  55. 55.
    Hammonds MD, Shim SS. Effects of 4-week Treatment with Lithium and Olanzapine on Levels of Brain-derived Neurotrophic Factor, B-Cell CLL/Lymphoma 2 and Phosphorylated Cyclic Adenosine Monophosphate Response Element-binding Protein in the Sub-regions of the Hippocampus. Basic Clin Pharmacol Toxicol Basic Clin Pharmacol Toxicol 2009 Apr 17 (Epub ahead of print)Google Scholar
  56. 56.
    Balu DT, Hoshaw BA, Malberg JE, et al. Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments. Brain Res 2008; 1211:37–43PubMedCrossRefGoogle Scholar
  57. 57.
    Linden AM, Vaisanen J,Lakso M. Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents. J Mol Neurosci 2000; 14:27–37PubMedCrossRefGoogle Scholar
  58. 58.
    Valvassori SS, Stertz L, Andreazza AC, et al. Lack of effect of antipsychotics on BDNF and NGF levels in hippocampus of Wistar rats. Metab Brain Dis 2008; 23:213–219PubMedCrossRefGoogle Scholar
  59. 59.
    Brown RW, Perna MK, Maple AM, et al. Adulthood olanzapine treatment fails to alleviate decreases of ChAT and BDNF RNA expression in rats quinpirole-primed as neonates. Brain Res 2008; 1200:66–77PubMedCrossRefGoogle Scholar
  60. 60.
    Lipska BK, Khaing ZZ, Weickert CS, et al. BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs. Eur J Neurosci 2001; 14:135–144PubMedCrossRefGoogle Scholar
  61. 61.
    Angelucci F, Aloe L, Iannitelli A, et al. Effect of chronic olanzapine treatment on nerve growth factor and brain-derived neurotrophic factor in the rat brain. Eur Neuropsychopharmacol 2005; 15:311–317PubMedCrossRefGoogle Scholar
  62. 62.
    Angelucci F, Mathe AA, Aloe L. Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration. J Neurosci Res 2000; 60:783–794PubMedCrossRefGoogle Scholar
  63. 63.
    Pillai A, Dhandapani KM, Pillai, et al. Erythropoietin Prevents Haloperidol Treatment-Induced Neuronal Apoptosis through Regulation of BDNF. Neuropsychopharmacology 2008; 33:1942–1951PubMedCrossRefGoogle Scholar
  64. 64.
    Chlan-Fourney J, Ashe P, Nylen K, et al. Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration. Brain Res 2002; 954:11–20PubMedCrossRefGoogle Scholar
  65. 65.
    Pan W, Banks WA, Fasold M.B, et al. Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 1998; 37:1553–1561PubMedCrossRefGoogle Scholar
  66. 66.
    Karege F, Schwald M, Cisse M. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 2002; 328:261–264PubMedCrossRefGoogle Scholar
  67. 67.
    Iritani S, Niizato K, Nawa H, et al. Immunohistochemical study of brain-derived neurotrophic factor and its receptor, TrkB, in the hippocampal formation of schizophrenic brains. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27:801–807PubMedCrossRefGoogle Scholar
  68. 68.
    Takahashi M, Shirakawa O, Toyooka K, et al. Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Mol Psychiatry 2000; 5:293–300PubMedCrossRefGoogle Scholar
  69. 69.
    Weickert CS, Hyde TM, Lipska BK, et al. Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2003; 8:592–610PubMedCrossRefGoogle Scholar
  70. 70.
    Toyooka K, Asama K, Watanabe Y, et al. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 2002; 110:249–257PubMedCrossRefGoogle Scholar
  71. 71.
    Tan YL, Zhou DF, Zhang XY. Decreased plasma brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. Schizophr Res 2005; 74:263–270PubMedCrossRefGoogle Scholar
  72. 72.
    Grillo RW, Ottoni GL, Leke R, et al. Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatr Res 2007; 4:31–35CrossRefGoogle Scholar
  73. 73.
    Jockers-Scherubl MC, Danker-Hopfe H, Mahlberg R, Selig F, et al. Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic cannabis abuse and multiplesubstance abuse. Neurosci Lett 2004; 371:79–83PubMedCrossRefGoogle Scholar
  74. 74.
    Shimizu E, Hashimoto K, Watanabe H, et al. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls. Neurosci Lett 2003; 351:111–114PubMedCrossRefGoogle Scholar
  75. 75.
    Pirildar S, Gönül AS, Taneli F, et al. Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28:709–713PubMedCrossRefGoogle Scholar
  76. 76.
    Hori H, Yoshimura R, Yamada Y,et al. Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. Int Clin Psychopharmacol 2007; 22:21–27PubMedCrossRefGoogle Scholar
  77. 77.
    Lee BH, Kim YK. Increased plasma brain-derived neurotropic factor, not nerve growth factor-Beta, in schizophrenia patients with better response to risperidone treatment. Neuropsychobiology 2009; 59:51–58PubMedCrossRefGoogle Scholar
  78. 78.
    Yoshimura R, Nakano Y, Hori H, et al. Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders. Hum Psychopharmacol 2006; 21:433–438PubMedCrossRefGoogle Scholar
  79. 79.
    Atmaca M, Yildirim H, Ozdemir H, et al. 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine. Psychol Med 2007; 37:121–129PubMedCrossRefGoogle Scholar
  80. 80.
    DelBello MP, Cecil KM, Adler CM, et al. Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a proton magnetic resonance spectroscopy study. Neuropsychopharmacology 2006; 31:1264–1273PubMedGoogle Scholar
  81. 81.
    Bustillo JR, Wolff C, Gutierrez AM, et al. Treatment of rats with antipsychotic drugs: lack of an effect on brain N-acetyl aspartate levels. Schizophr Res 2004; 66:31–39PubMedCrossRefGoogle Scholar
  82. 82.
    Lindquist DM, Hawk RM, Karson CN, et al. Effects of antipsychotic drugs on metabolite ratios in rat brain in vivo. Magn Reson Med 2000; 43:355–358PubMedCrossRefGoogle Scholar
  83. 83.
    Harte MK, Bachus SB, Reynolds GP. Increased N-acetylaspartate in rat striatum following long-term administration of haloperidol. Schizophr Res 2005; 75:303–308PubMedCrossRefGoogle Scholar
  84. 84.
    Bertolino A, Callicott JH, Mattay VS, et al. The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia. Biol Psychiatry 2001; 49:39–46PubMedCrossRefGoogle Scholar
  85. 85.
    Alimohamad H, Sutton L, Mouyal J, et al. The effects of on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats. J Neuralchem 2005; 95:513–525CrossRefGoogle Scholar
  86. 86.
    Alimohamad H, Rajakumar N, Seah YH, et al. Antipsychotics alter the protein expression levels of beta-catenin and GSK-3β in the rat medial prefrontal cortex and striatum. Biol Psychiatry 2005:57:533–542PubMedCrossRefGoogle Scholar
  87. 87.
    Li X, Rosborough KM, Friedman AB, et al. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Intl J Neuropsychopharmacol 2007; 10:7–19CrossRefGoogle Scholar
  88. 88.
    Bai O, Zhang H, Li XM, et al. Antipsychotic drugs clozapine and olanzapine upregulate bcl-2 mRNA and protein in rat frontal cortex and hippocampus. Brain Res 2004; 1010:81–96PubMedCrossRefGoogle Scholar
  89. 89.
    Kim NR, Park SW, Lee JG, et al. Protective effects of olanzapine and haloperidol on serum withdrawal-induced apoptosis in SH-SY5Y cells. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:633–42PubMedCrossRefGoogle Scholar
  90. 90.
    Yang TT, Wang SJ. Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic mechanism, glutamate release in rat prefrontal cortex: possible relevance to neuroprotective interventions in schizophrenia. Synapse 2008; 62:804–818PubMedCrossRefGoogle Scholar
  91. 91.
    Qing H, Xu H, Wei Z, et.al. The ability of atypical antipsychotic drugs vs. haloperidol to protect PC12 cells against MPP+-induced apoptosis. Eur J Neurosci 2003; 17:1563–1570PubMedCrossRefGoogle Scholar
  92. 92.
    Wang HD, Dunnavant FD, Jarman T, et al. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 2004; 29:1230–1238PubMedCrossRefGoogle Scholar
  93. 93.
    Yulug B, Bakar M, Ozan E. The neuroprotective effect of olanzapine. J Neuropsychiatry Clin Neurosci 2008; 20:107–8Google Scholar
  94. 94.
    Wei Z, Mousseau DD, Richardson JS, et al. Atypical antipsychotics attenuate neurotoxicity of beta-amyloid (25–35) by modulating Bax and Bcl-X(l/s) expression and localization. J Neurosci Res 2003; 74:942–947PubMedCrossRefGoogle Scholar
  95. 95.
    He J, Yang Y, Xu H, Zhang X, et al. Olanzapine attenuates the okadaic acid-induced spatial memory impairment and hippocampal cell death in rats. Neuropsychopharmacology 2005; 30:1511–1520PubMedCrossRefGoogle Scholar
  96. 96.
    Wang C, McInnis J, Ross-Sanchez M, et al. Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 2001; 107:535–550PubMedCrossRefGoogle Scholar
  97. 97.
    He J, Xu H, Yang Y, et al. The effects of chronic administration of quetiapine on the phencyclidine-induced reference memory impairment and decrease of Bcl-XL/Bax ratio in the posterior cingulate cortex in rats. Behav Brain Res 2006; 168:236–242PubMedCrossRefGoogle Scholar
  98. 98.
    He J, Xu H, Yang Y, et al. Neuroprotective effects of olanzapine on methamphetamine-induced neurotoxicity are associated with an inhibition of hyperthermia and prevention of Bcl-2 decrease in rats. Brain Res 2004; 1018:186–192PubMedCrossRefGoogle Scholar
  99. 99.
    Cosi C, Waget A, Rollet K, et al. Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation. Brain Res 2005; 1043:32–41PubMedCrossRefGoogle Scholar
  100. 100.
    Bai O, Wei Z, Lu W, et al. Protective effects of atypical antipsychotic drugs on PC12 cells after serum withdrawal. J Neurosci Res 2002; 69:278–283PubMedCrossRefGoogle Scholar
  101. 101.
    Wei Z, Bai O, Richardson JS, et al. Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide. J Neurosci Res 2003; 73:364–368PubMedCrossRefGoogle Scholar
  102. 102.
    Jarskog LF, Gilmore JH, Glantz LA, et al. Caspase-3 activation in rat frontal cortex following treatment with typical and atypical antipsychotics. Neuropsychopharmacology 2007; 32:95–102PubMedCrossRefGoogle Scholar
  103. 103.
    Behl C, Rupprecht R, Skutella T, et al. Haloperidol-induced cell death: mechanism and protection with vitamin E in vitro. NeuroReport 1995; 7:360–364PubMedGoogle Scholar
  104. 104.
    Noh JS, Kang HJ, Kim EY, et al. Haloperidol induced neuronal apoptosis: role of p38 and c-Jun-NH (2)-terminal protein kinase. J Neurochem 2000; 75:2327–2334PubMedCrossRefGoogle Scholar
  105. 105.
    Gerlach M, Double K, Arzberger T, et al. Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm 2003; 110:1119–1127PubMedCrossRefGoogle Scholar
  106. 106.
    Zarate CA Jr, Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 2004; 56:54–60PubMedCrossRefGoogle Scholar
  107. 107.
    Muscat R, Papp M, Willner P. Antidepressant-like effects of dopamine agonists in an animal model of depression. Biol Psychiatry 1992; 31:937–946PubMedCrossRefGoogle Scholar
  108. 108.
    Willner P, Lappas S, Cheeta S, et al. Reversal of stress-induced anhedonia by the dopamine agonist, pramipexole. Psychopharmacology 1994; 115:454–462PubMedCrossRefGoogle Scholar
  109. 109.
    Maj J, Rogoz Z, Skuza G, et al. Antidepressant effects of pramipexole, a novel dopamine receptor agonist. J Neural Transm 1997; 104:525–533PubMedCrossRefGoogle Scholar
  110. 110.
    Szegedi A, Hilibert A, Wetzel H, et al. Pramipexole, a dopamine agonist, in major depression: Antidepressant effects and tolerability in an open-label study with multiple doses. Clin Neuropharmacol 1997; 20(suppl 1):S36–S45CrossRefGoogle Scholar
  111. 111.
    Sporn J, Ghaemi SN, Sambur MR, et al. Pramipexole augmentation in the treatment of unipolar and bipolar depression: A retrospective chart review. Ann Clin Psychiatry 2000; 12:137–140PubMedGoogle Scholar
  112. 112.
    Perugi G, Toni C, Ruffolo G, et al. Adjunctive dopamine agonists in treatment-resistant bipolar II depression: An open case series. Pharmacopsychiatry 2001; 34:137–141PubMedCrossRefGoogle Scholar
  113. 113.
    Lattanzi L, Dell’Osso L, Cassano P, et al. Pramipexole in treatment-resistant depression: A 16-week naturalistic study. Bipolar Disord 2002; 4:307–314PubMedCrossRefGoogle Scholar
  114. 114.
    Ostow M. Pramipexole for Depression. Am J Psychiatry 2002; 159:320–321PubMedCrossRefGoogle Scholar
  115. 115.
    Cassano P, Lattanzi L, Soldani F, et al. Pramipexole in treatment-resistant depression: an extended follow-up. Depress Anxiety 2004; 20:131–138PubMedCrossRefGoogle Scholar
  116. 116.
    Corrigan MH, Denahan AQ, Wright CE, et al. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000; 11:58–65PubMedCrossRefGoogle Scholar
  117. 117.
    Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004; 161:564–566PubMedCrossRefGoogle Scholar
  118. 118.
    Du F, Li R, Huang Y, et al. Dopamine D3 receptor-preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons. Eur J Neurosci 2005; 22:2422–2430PubMedCrossRefGoogle Scholar
  119. 119.
    Perugi G, Toni C, Ruffolo G, et al. Adjunctive dopamine agonists in treatment-resistant bipolar II depression: An open case series. Pharmacopsychiatry 2001; 34:137–141PubMedCrossRefGoogle Scholar
  120. 120.
    Cassano P, Lattanzi L, Fava M, et al. Ropinirole in treatment-resistant depression: a 16-week pilot study. Can J Psychiatry 2005; 50:357–360PubMedGoogle Scholar
  121. 121.
    Tanaka K, Miyazaki I, Fujita N, et al. Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist. Neurochem Res 2001; 26:31–36PubMedCrossRefGoogle Scholar
  122. 122.
    Le WD, Jankovic J, Xie W, et al. Antioxidant property of pramipexole independent of dopamine receptor activation in neuroprotection. J Neural Transm. 2000; 107:1165–1173PubMedCrossRefGoogle Scholar
  123. 123.
    Du F, Li R, Huang Y, et al. Dopamine D3 receptor-preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons. Eur J Neurosci 2005; 22:2422–2430PubMedCrossRefGoogle Scholar
  124. 124.
    Hall ED, Andrus PK, Oostveen JA, et al. Neuroprotective effects of the dopamine D2/D3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons. Brain Res 1996; 742:80–88PubMedCrossRefGoogle Scholar
  125. 125.
    Zou L, Jankovic J, Rowe DB, et al. Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity. Life Sci 1999; 64:1275–1285PubMedCrossRefGoogle Scholar
  126. 126.
    Pan T, Xie W, Jankovic J, et al. Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection. Neurosci Lett 2005; 377:106–109PubMedCrossRefGoogle Scholar
  127. 127.
    Nakayama H, Zhao J, Ei-Fakhrany A, et al. Neuroprotective effects of pramipexole against tunicamycin-induced cell death in PC12 cells. Clin Exp Pharmacol Physiol 2009 Jun 8 (Epub ahead of print)Google Scholar
  128. 128.
    Sethy VH, Wu H, Oostveen JA, et al. Neuroprotective effects of the dopamine agonists pramipexole and bromocriptine in 3-acetylpyridine-treated rats. Brain Res 1997; 754:181–186PubMedCrossRefGoogle Scholar
  129. 129.
    Dunlop BW, Crits-Christoph P, Evans DL, et al. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007; 27:614–619PubMedCrossRefGoogle Scholar
  130. 130.
    Fava M, Thase ME, DeBattista C, et al. Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness. Ann Clin Psychiatry 2007; 19:153–159PubMedCrossRefGoogle Scholar
  131. 131.
    DeBattista C, Doghramji K, Menza MA, et al. Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003; 64:1057–1064PubMedCrossRefGoogle Scholar
  132. 132.
    Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005; 66:85–93PubMedCrossRefGoogle Scholar
  133. 133.
    Vaishnavi S, Gadde K, Alamy S, et al. Modafinil for atypical depression: effects of open-label and double-blind discontinuation treatment. J Clin Psychopharmacol 2006; 26:373–378PubMedCrossRefGoogle Scholar
  134. 134.
    Frye MA, Grunze H, Suppes T, et al. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 2007; 164:1242–1249PubMedCrossRefGoogle Scholar
  135. 135.
    Fountoulakis KN, Siamouli M, Panagiotidis P, et al. Ultra short manic-like episodes after antidepressant augmentation with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:891–892PubMedCrossRefGoogle Scholar
  136. 136.
    Wolf J, Fiedler U, Anghelescu I, et al. Manic switch in a patient with treatment-resistant bipolar depression treated with modafinil. J Clin Psychiatry 2006; 67:1817PubMedCrossRefGoogle Scholar
  137. 137.
    Ranjan S, Chandra PS. Modafinil-induced irritability and aggression? A report of 2 bipolar patients. J Clin Psychopharmacol 2005; 25:628–629PubMedCrossRefGoogle Scholar
  138. 138.
    Dunlop BW, Crits-Christoph P, Evans DL, et al. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007; 27:614–619PubMedCrossRefGoogle Scholar
  139. 139.
    Antonelli T, Ferraro L, Hillion J, et al. Modafinil prevents glutamate cytotoxicity in cultured cortical neurons. Neuroreport 1998; 9:4209–4213PubMedCrossRefGoogle Scholar
  140. 140.
    Ueki A, Rosen L, Andbjer B, et al. Evidence for a preventive action of the vigilance-promoting drug modafinil against striatal ischemic injury induced by endothelin-1 in the rat. Exp Brain Res 1993; 96:89–99PubMedGoogle Scholar
  141. 141.
    Lallement G, Pierard C, Masqueliez C, et al. Neuroprotective effect of modafinil against soman-induced hippocampal lesions. Med Sci Res 1997; 25:437–440Google Scholar
  142. 142.
    Xiao YL, Fu JM, Dong Z, et al. Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Acta Pharmacol Sin 2004; 25:301–305PubMedGoogle Scholar
  143. 143.
    van Vliet SA, Blezer EL, Jongsma MJ, et al. Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model with immunohistochemistry, magnetic resonance imaging and spectroscopy. Brain Res 2008; 1189:219–228PubMedCrossRefGoogle Scholar
  144. 144.
    van Vliet SA, Vanwersch RA, Jongsma MJ, van et al. Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects. Behavioural Pharmacol 2006; 17:453–462CrossRefGoogle Scholar
  145. 145.
    Baldessarini RJ, Leahy L, Arcona S, et al. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv 2007; 58:85–91PubMedCrossRefGoogle Scholar
  146. 146.
    Schaffer A, Cairney J, Cheung AH, et al. Use of treatment services and pharmacotherapy for bipolar disorder in a general population-based mental health survey. J Clin Psychiatry 2006; 67:386–393PubMedCrossRefGoogle Scholar
  147. 147.
    Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr 2009; 14:197–206PubMedGoogle Scholar
  148. 148.
    Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med 2007; 147:593–602PubMedGoogle Scholar
  149. 149.
    Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2007; 68:843–853PubMedCrossRefGoogle Scholar
  150. 150.
    Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry 2007; 68:224–236PubMedCrossRefGoogle Scholar
  151. 151.
    Papakostas GI, Shelton RC, Smith J, et al. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry 2007; 68:826–831PubMedCrossRefGoogle Scholar
  152. 152.
    Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007; 356:1711–1722PubMedCrossRefGoogle Scholar
  153. 153.
    Nemeroff CB, Evans DL, Gyulai L, et al. Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry 2001; 158:906–912PubMedGoogle Scholar
  154. 154.
    Altshuler L, Suppes T, Black D et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry 2003; 160:1252–1262PubMedCrossRefGoogle Scholar
  155. 155.
    Ghaemi SN, Wingo AP, Filkowski MA, et al. Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks. Acta Psychiatr Scand 2008; 118:347–56PubMedCrossRefGoogle Scholar
  156. 156.
    Goldberg JF, Perlis RH, Ghaemi SN, et al. Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD. Am J Psychiatry 2007; 164:1348–1355PubMedCrossRefGoogle Scholar
  157. 157.
    Bond DJ, Noronha MM, Kauer-Sant’Anna M, et al. Antidepressant-associated mood elevations in bipolar II disorder compared with bipolar I disorder and major depressive disorder: a systematic review and meta-analysis. J Clin Psychiatry 2008; 69:1589–1601PubMedCrossRefGoogle Scholar
  158. 158.
    Truman CJ, Goldberg JF, Ghaemi SN, et al. Self-reported history of manic/hypomanic switch associated with antidepressant use: data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). J Clin Psychiatry 2007; 68:1472–1479PubMedCrossRefGoogle Scholar
  159. 159.
    Goldberg JF, Truman CJ. Antidepressant-induced mania: an overview of current controversies. Bipolar Disord 2003; 5:407–420PubMedCrossRefGoogle Scholar
  160. 160.
    Baumer FM, Howe M, Gallelli K, et al. A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene. Biol Psychiatry 2006; 60:1005–1012PubMedCrossRefGoogle Scholar
  161. 161.
    Cunha, AB, Cunha, BN, Andreazza AC, et al. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes, Neurosci Lett 2006; 398:215–219PubMedCrossRefGoogle Scholar
  162. 162.
    de Oliveira GS, Ceresér KM, Fernandes BS, et al. Decreased brain-derived neurotrophic factor in medicated and drug-free bipolar patients. J Psychiatr Res 2009 May 26 (Epub ahead of print)Google Scholar
  163. 163.
    Fernandes BS, Gama CS, et al. Serum brain-derived neurotrophic factor in bipolar and unipolar depression: A potential adjunctive tool for differential diagnosis. J Psychiatr Res 2009 Jun 6 (Epub ahead of print)Google Scholar
  164. 164.
    Fan J, Sklar P. Genetics of bipolar disorder: focus on BDNF Val66Met polymorphism. Novartis Found Symp 2008; 289:60–72PubMedCrossRefGoogle Scholar
  165. 165.
    Xu J, Liu Y, Wang P, et al. Positive association between the brain-derived neurotrophic factor (BDNF) gene and bipolar disorder in the Han Chinese population. Am J Med Genet B Neuropsychiatr Genet 2009 Mar 27 (Epub ahead of print)Google Scholar
  166. 166.
    Liu L, Foroud T, Xuei X, et al. Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder Psychiatr Genet 2008; 18:267–274PubMedCrossRefGoogle Scholar
  167. 167.
    Pandey GN, Rizavi HS, Dwivedi Y, Pavuluri MN. Brain-derived neurotrophic factor gene expression in pediatric bipolar disorder: effects of treatment and clinical response. J Am Acad Child Adolesc Psychiatry 2008; 47:1077–1085PubMedCrossRefGoogle Scholar
  168. 168.
    Vincze I, Perroud N, Buresi C, et al. Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene. Bipolar Disord 2008; 10:580–587PubMedCrossRefGoogle Scholar
  169. 169.
    Post RM. Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications. J Psychiatr Res 2007; 41:979–990PubMedCrossRefGoogle Scholar
  170. 170.
    Dmitrzak-Weglarz M, Rybakowski JK, Suwalska A, et al. Association studies of the BDNF and the NTRK2 gene polymorphisms with prophylactic lithium response in bipolar patients. Pharmacogenomics 2008; 9:1595–1603PubMedCrossRefGoogle Scholar
  171. 171.
    Machado-Vieira R, Dietrich MO, Leke R, et al. Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode. Biol Psychiatry 2007; 61:142–144PubMedCrossRefGoogle Scholar
  172. 172.
    Tramontina JF, Andreazza AC, Kauer-Sant’anna M, et al. Brain-derived neurotrophic factor serum levels before and after treatment for acute mania. Neurosci Lett 2009; 452:111–113PubMedCrossRefGoogle Scholar
  173. 173.
    Berk D, Copolov O, Dean K, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia: A double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008; 64:361–368PubMedCrossRefGoogle Scholar
  174. 174.
    Berk M, Copolov DL, Dean O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder – a double-blind randomized placebo-controlled trial. Biol Psychiatry 2008; 64:468–475PubMedCrossRefGoogle Scholar
  175. 175.
    Varma RR, Khuteta KP, Dandiya PC. The effect of some psychopharmacological agents on heat stress-induced changes in the glutathione levels of brain and blood in rats. Psychopharmacologia 1968; 12:170–175PubMedCrossRefGoogle Scholar
  176. 176.
    Schulz JB, Lindenau J, Seyfried J, et al. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 2000; 267:4904–4911PubMedCrossRefGoogle Scholar
  177. 177.
    Tchantchou F, Graves M, Ortiz D, et al. Dietary supplementation with 3-deaza adenosine, N-acetyl cysteine, and S-adenosyl methionine provide neuroprotection against multiple consequences of vitamin deficiency and oxidative challenge: relevance to age-related neurodegeneration. Neuromolecular Med 2004; 6:93–103PubMedCrossRefGoogle Scholar
  178. 178.
    Hart AM, Terenghi G, Kellerth JO, et al. Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury. Neuroscience 2004; 125:91–101PubMedCrossRefGoogle Scholar
  179. 179.
    Zhang CG, Welin D, Novikov L, et al. Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy. Br J Plast Surg 2005; 58:765–73PubMedCrossRefGoogle Scholar
  180. 180.
    West CA, Hart AM, Terenghi G, et al. Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury. Acta Neurochir Suppl 2007; 100:29–31PubMedCrossRefGoogle Scholar
  181. 181.
    Wang X, Svedin P, Nie C, et al. N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury. Ann Neurol 2007; 61:263–271PubMedCrossRefGoogle Scholar
  182. 182.
    Moschou M, Kosmidis EK, Kaloyianni M, et al. In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl-L-cysteine (NAC) on the rat sciatic nerve fibers. Toxicol In Vitro 2008; 22:267–274PubMedCrossRefGoogle Scholar
  183. 183.
    Shimizu E, Hashimoto K, Komatsu N et al. Roles of endogenous glutathione levels on 6-hydroxydopamine-induced apoptotic neuronal cell death in human neuroblastoma SK-N-SH cells. Neuropharmacology 2002; 43:434–443PubMedCrossRefGoogle Scholar
  184. 184.
    Fukami G, Hashimoto K, Koike K, et al. Effect of antioxidant N-acetyl-L-cysteine on behavioral changes and neurotoxicity in rats after administration of methamphetamine. Brain Res 2004; 1016:90–95PubMedCrossRefGoogle Scholar
  185. 185.
    Hashimoto K, Tsukada H, Nishiyama S, et al. Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine. Neuropsychopharmacology 2004; 29:2018–2023PubMedCrossRefGoogle Scholar
  186. 186.
    Muñoz AM, Rey P, Soto-Otero R, et al. Systemic administration of N-acetylcysteine protects dopaminergic neurons against 6-hydroxydopamine-induced degeneration. J Neurosci Res 2004; 76:551–562PubMedCrossRefGoogle Scholar
  187. 187.
    Paintlia MK, Paintlia AS, Barbosa E, et al. N-acetylcysteine prevents endotoxin-induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain. J Neurosci Res 2004; 78:347–361PubMedCrossRefGoogle Scholar
  188. 188.
    Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry 2006; 188:46–50PubMedCrossRefGoogle Scholar
  189. 189.
    Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56:407–412PubMedCrossRefGoogle Scholar
  190. 190.
    Keck PE Jr, Mintz J, McElroy SL, et al. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 2006; 60:1020–1022PubMedCrossRefGoogle Scholar
  191. 191.
    Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 2007; 68:1056–1061PubMedCrossRefGoogle Scholar
  192. 192.
    Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006; 296:1885–1899PubMedCrossRefGoogle Scholar
  193. 193.
    Bazan NG. Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer’s disease. J Lipid Res 2009; 50(Suppl):S400–S405PubMedCrossRefGoogle Scholar
  194. 194.
    Moreira JD, Knorr L, Thomazi AP, et al. Dietary omega-3 fatty acids attenuate cellular damage after a hippocampal ischemic insult in adult rats. J Nutr Biochem 2009 May 1 (Epub ahead of print)Google Scholar
  195. 195.
    Wang X, Zhao X, Mao ZY, et al. Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures. Neuroreport 2003; 14:2457–2461PubMedCrossRefGoogle Scholar
  196. 196.
    Ménard C, Patenaude C, Gagné AM, et al. AMPA receptor-mediated cell death is reduced by docosahexaenoic acid but not by eicosapentaenoic acid in area CA1 of hippocampal slice cultures. J Neurosci Res 2009; 87:876–886PubMedCrossRefGoogle Scholar
  197. 197.
    Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 2008; 155:751–759PubMedCrossRefGoogle Scholar
  198. 198.
    Wu A,Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 2004; 21:1457–1467PubMedCrossRefGoogle Scholar
  199. 199.
    Frangou S, Lewis M, Wollard J, Simmons A. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder. J Psychopharmacol 2007; 21:435–439PubMedCrossRefGoogle Scholar
  200. 200.
    Hirashima F, Parow AM, Stoll AL, et al. Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder. Am J Psychiatry 2004; 161:1922–1924PubMedCrossRefGoogle Scholar
  201. 201.
    Yavin E, Brand A, Green P. Docosahexaenoic acid abundance in the brain: a biodevice to combat oxidative stress. Nutr Neurosci 2002; 5:149–157PubMedCrossRefGoogle Scholar
  202. 202.
    Berry CB, Hayes D, Murphy A, et al. Differential modulation of the glutamate transporters GLT1, GLAST and EAAC1 by docosahexaenoic acid. Brain Res 2005; 1037:123–133PubMedCrossRefGoogle Scholar
  203. 203.
    Bousquet M, Saint-Pierre M, Julien C, et al. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease. FASEB J 2008; 22:1213–1225PubMedCrossRefGoogle Scholar
  204. 204.
    Calon F, Lim GP, Yang F. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron 2004; 43:633–645PubMedCrossRefGoogle Scholar
  205. 205.
    Calon F, Lim GP, Morihara T, et al. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer’s disease. Eur J Neurosci 2005; 22:617–626PubMedCrossRefGoogle Scholar
  206. 206.
    Belayev L, Khoutorova L, Atkins KD, et al. Robust docosahexaenoic acid-mediated neuroprotection in a rat model of transient, focal cerebral ischemia. Stroke 2009 Jun 18 (Epub ahead of print)Google Scholar
  207. 207.
    Huang WL, King VR, Curran OE, et al. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain 2007; 130:3004–3019PubMedCrossRefGoogle Scholar
  208. 208.
    King VR, Huang WL, Dyall SC, et al. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J Neurosci 2006; 26:4672–4680PubMedCrossRefGoogle Scholar
  209. 209.
    Peet M. Nutrition and schizophrenia: beyond omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 2004; 70:417–422PubMedCrossRefGoogle Scholar
  210. 210.
    Galletly C, Moran L, Noakes M, et al. Psychological benefits of a high-protein, low-carbohydrate diet in obese women with polycystic ovary syndrome – a pilot study. Appetite 2007; 49:590–593PubMedCrossRefGoogle Scholar
  211. 211.
    Weidner G, Connor SL, Gerhard GT, et al. The effects of dietary cholesterol-lowering on psychological symptoms: a randomised controlled study. Psychol Health Med 2009; 14:255–261PubMedCrossRefGoogle Scholar
  212. 212.
    Witte AV, Fobker M, Gellner R, et al. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci USA 2009; 106:1255–1260PubMedCrossRefGoogle Scholar
  213. 213.
    Duan W, Guo Z, Mattson MP. Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J Neurochem 2001; 76:619–626PubMedCrossRefGoogle Scholar
  214. 214.
    Araya AV, Orellana X, Espinoza J. Evaluation of the effect of caloric restriction on serum BDNF in overweight and obese subjects: preliminary evidences. Endocrine 2008; 33:300–304PubMedCrossRefGoogle Scholar
  215. 215.
    Wu A, Ying Z, Gomez-Pinilla F. The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat dieton synaptic plasticity and cognition. Eur J Neurosci 2004; 19:1699–1707PubMedCrossRefGoogle Scholar
  216. 216.
    Wu A, Molteni R, Ying Z, et al. A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. Neuroscience 2003; 119:365–375PubMedCrossRefGoogle Scholar
  217. 217.
    Molteni R, Barnard RJ, Ying Z, et al. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 2002; 112:803–814PubMedCrossRefGoogle Scholar
  218. 218.
    Casadesus G, Shukitt-Hale B, Stellwagen HM, et al. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutr Neurosci 2004; 7:309–316PubMedCrossRefGoogle Scholar
  219. 219.
    Williams CM, El Mohsen MA, Vauzour D, et al. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med 2008; 45:295–305PubMedCrossRefGoogle Scholar
  220. 220.
    Mead GE, Morley W, Campbell P, et al. Exercise for depression. Cochrane Database Syst Rev 2008; CD004366Google Scholar
  221. 221.
    Ng F, Dodd S, Berk M. The effects of physical activity in the acute treatment of bipolar disorder: a pilot study. J Affect Disord 2007; 101:259–62PubMedCrossRefGoogle Scholar
  222. 222.
    Kilbourne AM, Rofey DL, McCarthy JF, et al. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord 2007; 9:443–452PubMedCrossRefGoogle Scholar
  223. 223.
    Shah A, Alshaher M, Dawn B, et al. Exercise tolerance is reduced in bipolar illness. J Affect Disord 2007; 104:191–195PubMedCrossRefGoogle Scholar
  224. 224.
    Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 2003; 14:125–130PubMedCrossRefGoogle Scholar
  225. 225.
    Etnier JL, Nowell PM, Landers DM, et al. A meta-regression to examine the relationship between aerobic fitness and cognitive performance. Brain Res Rev 2006; 52:119–130PubMedCrossRefGoogle Scholar
  226. 226.
    Kubesch S, Bretschneider V, Freudenmann R, et al. Aerobic endurance exercise improves executive functions in depressed patients. J Clin Psychiatry 2003; 64:1005–1012PubMedCrossRefGoogle Scholar
  227. 227.
    Khatri P, Blumenthal JA, Babyak MA, et al. Effects of exercise training on cognitive functioning among depressed older men and women. J Aging Phys 2001; 9:43–57Google Scholar
  228. 228.
    Neeper SA, Gómez-Pinilla F, Choi J, et al. Exercise and brain neurotrophins. Nature 1995; 373:109PubMedCrossRefGoogle Scholar
  229. 229.
    Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004; 20:2580–2590PubMedCrossRefGoogle Scholar
  230. 230.
    Berchtold NC, Chinn G, Chou M, et al. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 2005; 133:853–861PubMedCrossRefGoogle Scholar
  231. 231.
    Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 1999; 21:679–682PubMedCrossRefGoogle Scholar
  232. 232.
    Russo-Neustadt AA, Beard RC, Huang YM, et al. Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 2000; 101:305–312PubMedCrossRefGoogle Scholar
  233. 233.
    Russo-Neustadt AA, Ha T, Ramirez R, et al. Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res 2001; 120:87–95PubMedCrossRefGoogle Scholar
  234. 234.
    Berchtold NC, Kesslak JP, Pike CJ, et al. Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci 2001; 14:1992–2002PubMedCrossRefGoogle Scholar
  235. 235.
    Kiraly MA, Kiraly SJ. The effect of exercise on hippocampal integrity: review of recent research. Int J Psychiatry Med 2005; 35:75–89PubMedCrossRefGoogle Scholar
  236. 236.
    van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular Med 2008; 10:128–140PubMedCrossRefGoogle Scholar
  237. 237.
    Black JE, Isaacs KR, Anderson BJ, et al. Learning causes synaptogenesis, whereas motor activity causes angiogenesis in cerebellar cortex of adult rats. Proc Natl Acad Sci USA 1990; 87:5568–5572PubMedCrossRefGoogle Scholar
  238. 238.
    Wang RY, Yang YR, Yu SM. Protective effects of treadmill training on infarction in rats. Brain Res 2001; 922:140–143PubMedCrossRefGoogle Scholar
  239. 239.
    Dietrich MO, Mantese CE, Porciuncula LO, et al. Exercise affects glutamate receptors in postsynaptic densities from cortical mice brain. Brain Res 2005; 1065:20–25PubMedCrossRefGoogle Scholar
  240. 240.
    Radak Z, Sasvari M, Nyakas C, et al. Single bout of exercise eliminates the immobilization-induced oxidative stress in rat brain. Neurochem Int 2001; 39:33–38PubMedCrossRefGoogle Scholar
  241. 241.
    Larsen JO, Skalicky M, Viidik A. Does long-term physical exercise counteract age-related Purkinje cell loss? A stereological study of rat cerebellum. J Comp Neurol 2000; 428:213–222PubMedCrossRefGoogle Scholar
  242. 242.
    Tillerson JL, Caudle WM, Reveron ME, et al. Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson’s disease. Neuroscience 2003; 119:899–911PubMedCrossRefGoogle Scholar
  243. 243.
    Scott J, Colom F, Vieta E. A meta-analysis of relapse rates with adjunctive psychological therapies compared to usual psychiatric treatment for bipolar disorders. Int J Neuropsychopharmacol 2007; 10:123–129PubMedCrossRefGoogle Scholar
  244. 244.
    Beynon S, Soares-Weiser K, Woolacott N, et al. Psychosocial interventions for the prevention of relapse in bipolar disorder: systematic review of controlled trials. Br J Psychiatry 2008; 192:5–11PubMedCrossRefGoogle Scholar
  245. 245.
    Johnson SL. Life events in bipolar disorder: towards more specific models. Clin Psychol Rev 2005; 25:1008–1027PubMedCrossRefGoogle Scholar
  246. 246.
    Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis, Am J Psychiatry 2000; 157:1243–1251PubMedCrossRefGoogle Scholar
  247. 247.
    Risch N, Herrell R, Lehner T, et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009; 301:2462–2471PubMedCrossRefGoogle Scholar
  248. 248.
    Ickes BR, Pham TM, Sanders LA, et al. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol 2000; 164:45–52PubMedCrossRefGoogle Scholar
  249. 249.
    Strasser A, Skalicky M, Hansalik M, et al. The impact of environment in comparison with moderate physical exercise and dietary restriction on BDNF in the cerebral parietotemporal cortex of aged Sprague-Dawley rats. Gerontology 2006; 52:377–381PubMedCrossRefGoogle Scholar
  250. 250.
    Zhu SW, Pham TM, Aberg E, et al. Neurotrophin levels and behaviour in BALB/c mice: impact of intermittent exposure to individual housing and wheel running. Behav Brain Res 2006; 167:1–8PubMedCrossRefGoogle Scholar
  251. 251.
    Li L, Tang BL. Environmental enrichment and neurodegenerative diseases. Biochem Biophys Res Commun 2005; 334:293–297PubMedCrossRefGoogle Scholar
  252. 252.
    Scaccianoce S, Del Bianco P, Paolone G, et al. Social isolation selectively reduces hippocampal brain-derived neurotrophic factor without altering plasma corticosterone. Behav Brain Res 2006; 168:323–325PubMedCrossRefGoogle Scholar
  253. 253.
    Koch JM, Hinze-Selch D, Stingele K, et al. Changes in CREB phosphorylation and BDNF plasma levels during psychotherapy of depression. Psychother Psychosom 2009; 78:187–192PubMedCrossRefGoogle Scholar
  254. 254.
    Kobayashi K, Shimizu E, Hashimoto K, et al. Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: as a biological predictor of response to group cognitive behavioral therapy. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:658–663PubMedCrossRefGoogle Scholar
  255. 255.
    Hirota T, Lewis WG, Liu AC, et al. A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3β. Proc Natl Acad Sci USA 2008; 105:20746–20751PubMedCrossRefGoogle Scholar
  256. 256.
    Iwahana E, Hamada T, Uchida A, et al. Differential effect of lithium on the circadian oscillator in young and old hamsters. Biochem Biophys Res Commun 2007; 354:752–756PubMedCrossRefGoogle Scholar
  257. 257.
    Iitaka C, Miyazaki K, Akaike T, et al. A role for glycogen synthase kinase-3beta in the mammalian circadian clock. J Biol Chem 2005; 280:29397–29402PubMedCrossRefGoogle Scholar
  258. 258.
    Padiath QS, Paranjpe D, Jain S, et al. Glycogen synthase kinase 3beta as a likely target for the action of lithium on circadian clocks. Chronobiol Int 2004; 21:43–55PubMedCrossRefGoogle Scholar
  259. 259.
    Iwahana E, Akiyama M, Miyakawa K, et al. Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. Eur J Neurosci 2004; 19:2281–2287PubMedCrossRefGoogle Scholar
  260. 260.
    Breggin P. Toxic Psychiatry: Why Therapy, Empathy and Love Must Replace the Drugs, Electroshock, and Biochemical Theories of the “New Psychiatry”. St. Martin’s Griffin, New York; 1994Google Scholar
  261. 261.
    Leo J, Lacasse J. The media and the chemical imbalance theory of depression. Society 2008; 45:35–45CrossRefGoogle Scholar
  262. 262.
    Mai L, Jope RS, Li X. BDNF-mediated signal transduction is modulated by GSK3beta and mood stabilizing agents. J Neurochem 2002; 82:75–83PubMedCrossRefGoogle Scholar
  263. 263.
    Tanabe M, Umeda M, Honda M, et al. Phenytoin and carbamazepine delay the initial depression of the population spike upon exposure to in vitro ischemia and promote its post-ischemic functional recovery in rat hippocampal slices. Eur J Pharmacol 2006; 553:104–108PubMedCrossRefGoogle Scholar
  264. 264.
    Ambrósio AF, Silva AP, Araújo I, et al. Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and two new putative antiepileptic drugs, BIA 2-093 and BIA 2-024. Eur J Pharmacol 2000; 406:191–201PubMedCrossRefGoogle Scholar
  265. 265.
    Koukopoulos A, Ghaemi SN. The primacy of mania: a reconsideration of mood disorders. Eur Psychiatry 2009; 24:125–134PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Director, Mood Treatment Center, Clinical Instructor in Psychiatry, Wake Forest University School of MedicineWinston-SalemUSA

Personalised recommendations