Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

Translational Psychiatry

Volumn 1, Issue , 2011, Pages

  Webhofer, C ^a,b   Gormanns, P ^a   Tolstikov, V ^c   Zieglgansberger W ^a,b   Sillaber, I ^a,d   Holsboer, F ^a   Turck, C W ^a,b  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Phenoquest AG   (Germany)

Author keywords

antidepressant; biomarker; metabolite profiling; novel antidepressant drug targets; paroxetine; pathway analysis

Indexed keywords

ANTIDEPRESSANT AGENT; BIOGENIC AMINE; BIOLOGICAL MARKER; PAROXETINE;

ANIMAL; ANIMAL BEHAVIOR; ARTICLE; BIOSYNTHESIS; COMPARATIVE STUDY; DBA MOUSE; DRUG ANTAGONISM; DRUG DELIVERY SYSTEM; DRUG EFFECT; HIPPOCAMPUS; MASS FRAGMENTOGRAPHY; METABOLISM; METABOLOME; METHODOLOGY; MOUSE;

ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; BEHAVIOR, ANIMAL; BIOGENIC MONOAMINES; BIOLOGICAL MARKERS; DRUG DELIVERY SYSTEMS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HIPPOCAMPUS; METABOLOME; MICE; MICE, INBRED DBA; PAROXETINE;

EID: 83755180488     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/tp.2011.56     Document Type: Article

References (57)

1. Burmeister M, McInnis MG, Zollner S. Psychiatric genetics: Progress amid controversy. Nat Rev Genet 2008; 9: 527-540. (Pubitemid 351972757)
2. World Health Organization. The World Health Report 2001 -Mental Health: New Understanding, New Hope; 2001.
3. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: A meta-analysis of efficacy and tolerability. J Affect Disord 2000; 58: 19-36. (Pubitemid 30173208)
4. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: Beyond monoamines. Nat Rev Neurosci 2006; 7: 137-151. (Pubitemid 43151600)
5. Wong ML, Licinio J. From monoamines to genomic targets: A paradigm shift for drug discovery in depression. Nat Rev Drug Discov 2004; 3: 136-151. (Pubitemid 38239775)
6. Delgado PL. How antidepressants help depression: Mechanisms of action and clinical response. J Clin Psychiatry 2004; 65(Suppl 4): 25-30.
7. Delgado PL. Depression: The case for a monoamine deficiency. J Clin Psychiatry 2000; 61(Suppl 6): 7-11. (Pubitemid 30217405)
8. Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: A meta-analysis of monoamine depletion studies. Mol Psychiatry 2007; 12: 331-359. (Pubitemid 46496835)
9. Nickel T, Sonntag A, Schill J, Zobel AW, Ackl N, Brunnauer A et al. Clinical and neurobiological effects of tianeptine and paroxetine in major depression. J Clin Psychopharmacol 2003; 23: 155-168. (Pubitemid 36368793)
10. Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: Implications for therapy. J Affect Disord 2001; 62: 77-91. (Pubitemid 32126613)
11. Michelson D, Galliven E, Hill L, Demitrack M, Chrousos G, Gold P. Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans. J Clin Endocrinol Metab 1997; 82: 2601-2606. (Pubitemid 27337880)
12. Brady LS, Gold PW, Herkenham M, Lynn AB, Whitfield Jr HJ. The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin- releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: Therapeutic implications. Brain Res 1992; 572: 117-125.
13. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-9110. (Pubitemid 32042912)
14. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805-809. (Pubitemid 36962615)
15. Vaidya VA, Duman RS. Depression -emerging insights from neurobiology. Br Med Bull 2001; 57: 61-79.
16. Binder EB, Nemeroff CB. The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol Psychiatry 2010; 15: 574-588.
17. Gilman AG. G proteins in signal transduction: Transducers of receptor-generated signals. Annu Rev Biochem 1987; 56: 615-649.
18. Birnbaumer L. G proteins in signal transduction. Annu Rev Pharmacol Toxicol 1990; 30: 675-705.
19. Gould TD, Manji HK. Signaling networks in the pathophysiology and treatment of mood disorders. J Psychosom Res 2002; 53: 687-697. (Pubitemid 36292448)
20. Schwaninger M, Schofl C, Blume R, Rossig L, Knepel W. Inhibition by antidepressant drugs of cyclic AMP response element-binding protein/cyclic AMP response elementdirected gene transcription. Mol Pharmacol 1995; 47: 1112-1118.
21. Shelton RC. Intracellular mechanisms of antidepressant drug action. Harv Rev Psychiatry 2000; 8: 161-174.
22. Sun MK, Alkon DL. Protein kinase C substrate activators: Potential as novel antidepressants. Drug Dev Res 2005; 65: 77-91.
23. Sillaber I, Panhuysen M, Henniger MS, Ohl F, Kuhne C, Putz B et al. Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine. Psychopharmacology (Berl) 2008; 200: 557-572.
24. McHugh PC, Rogers GR, Loudon B, Glubb DM, Joyce PR, Kennedy MA. Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. J Neurosci Res 2008; 86: 306-316. (Pubitemid 351196736)
25. Carboni L, Vighini M, Piubelli C, Castelletti L, Milli A, Domenici E. Proteomic analysis of rat hippocampus and frontal cortex after chronic treatment with fluoxetine or putative novel antidepressants: CRF1 and NK1 receptor antagonists. Eur Neuropsychopharmacol 2006; 16: 521-537. (Pubitemid 44376555)
26. Khawaja X, Xu J, Liang JJ, Barrett JE. Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies. J Neurosci Res 2004; 75: 451-460. (Pubitemid 38160706)
27. Fiehn O. Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol 2002; 48: 155-171.
28. Kaddurah-Daouk R, Krishnan KR. Metabolomics: A global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 2009; 34: 173-186.
29. Kaddurah-Daouk R, McEvoy J, Baillie RA, Lee D, Yao JK, Doraiswamy PM et al. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry 2007; 12: 934-945. (Pubitemid 47482696)
30. Su ZH, Li SQ, Zou GA, Yu CY, Sun YG, Zhang HW et al. Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats. J Pharm Biomed Anal 2011; 55: 533-539.
31. Dai Y, Li Z, Xue L, Dou C, Zhou Y, Zhang Y et al. Metabolomics study on the antidepression effect of xiaoyaosan on rat model of chronic unpredictable mild stress. J Ethnopharmacol 2010; 128: 482-489.
32. Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K et al. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: Pharmacometabolomics-informed pharmacogenomics. Clin Pharmacol Ther 2011; 89: 97-104.
33. Paige LA, Mitchell MW, Krishnan KR, Kaddurah-Daouk R, Steffens DC. A preliminary metabolomic analysis of older adults with and without depression. Int J Geriatr Psychiatry 2007; 22: 418-423. (Pubitemid 46831684)
34. Urayama S, Zou W, Brooks K, Tolstikov V. Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom 2010; 24: 613-620.
35. Xia J, Psychogios N, Young N, Wishart DS. MetaboAnalyst: A web server for metabolomic data analysis and interpretation. Nucleic Acids Res 2009; 37(Web Server issue): W652-W660.
36. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98: 5116-5121. (Pubitemid 32397092)
37. Wold S, Sjö ström M, Eriksson L. PLS-regression: A basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems 2001; 58: 109-130. (Pubitemid 33033283)
38. Hosack DA, Dennis Jr G, Sherman BT, Lane HC, Lempicki RA. Identifying biological themes within lists of genes with EASE. Genome Biol 2003; 4: R70.
39. Watkins SM, German JB. Metabolomics and biochemical profiling in drug discovery and development. Curr Opin Mol Ther 2002; 4: 224-228. (Pubitemid 35282867)
40. Scaini G, Maggi DD, De-Nes BT, Goncalves CL, Ferreira GK, Teodorak BP et al. Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants. Acta Neuropsychchiatrica 2011; 23: 112-118.
41. Scaini G, Santos PM, Benedet J, Rochi N, Gomes LM, Borges LS et al. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants. Brain Res Bull 2010; 82: 224-227.
42. Santos PM, Scaini G, Rezin GT, Benedet J, Rochi N, Jeremias GC et al. Brain creatine kinase activity is increased by chronic administration of paroxetine. Brain Res Bull 2009; 80: 327-330.
43. Moretti A, Gorini A, Villa RF. Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry 2003; 9: 773-785. (Pubitemid 37100711)
44. Lynch CJ, Hutson SM, Patson BJ, Vaval A, Vary TC. Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats. Am J Physiol Endocrinol Metab 2002; 283: E824-E835.
45. Lynch CJ, Patson BJ, Anthony J, Vaval A, Jefferson LS, Vary TC. Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue. Am J Physiol Endocrinol Metab 2002; 283: E503-E513. (Pubitemid 35230488)
46. Nishitani S, Ijichi C, Takehana K, Fujitani S, Sonaka I. Pharmacological activities of branched-chain amino acids: Specificity of tissue and signal transduction. Biochem Biophys Res Commun 2004; 313: 387-389. (Pubitemid 37543597)
47. Hoeffer CA, Klann E. mTOR signaling: At the crossroads of plasticity, memory and disease. Trends Neurosci 2010; 33: 67-75.
48. Lin CJ, Robert F, Sukarieh R, Michnick S, Pelletier J. The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling. Cancer Res 2010; 70: 3199-3208.
49. Cleary C, Linde JA, Hiscock KM, Hadas I, Belmaker RH, Agam G et al. Antidepressive-like effects of rapamycin in animal models: Implications for mTOR inhibition as a new target for treatment of affective disorders. Brain Res Bull 2008; 76: 469-473.
50. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010; 329: 959-964.
51. Murin R, Mohammadi G, Leibfritz D, Hamprecht B. Glial metabolism of valine. Neurochem Res 2009; 34: 1195-1203.
52. Murin R, Mohammadi G, Leibfritz D, Hamprecht B. Glial metabolism of isoleucine. Neurochem Res 2009; 34: 194-204.
53. Aquilani R, Boselli M, Boschi F, Viglio S, Iadarola P, Dossena M et al. Branchedchain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: A pilot study. Arch Phys Med Rehabil 2008; 89: 1642-1647.
54. Willner P. Chronic mild stress (CMS) revisited: Consistency and behaviouralneurobiological concordance in the effects of CMS. Neuropsychobiology 2005; 52: 90-110. (Pubitemid 41160326)
55. Kudryavtseva NN, Bakshtanovskaya IV, Koryakina LA. Social model of depression in mice of C57BL/6J strain. Pharmacol Biochem Behav 1991; 38: 315-320.
56. Rygula R, Abumaria N, Flügge G, Fuchs E, Rüther E, Havemann-Reinecke U. Anhedonia and motivational deficits in rats: Impact of chronic social stress. Behav Brain Res 2005; 162: 127-134. (Pubitemid 40731540)
57. Millstein RA, Holmes A. Effects of repeated maternal separation on anxiety-and depression-related phenotypes in different mouse strains. Neurosci Biobehav Rev 2007; 31: 3-17. (Pubitemid 44880075)