European Neuropsychopharmacology
Volume 20, Issue 5 , Pages 301-309 , May 2010

Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response in anxious depression

  • Katharina Domschke

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 251 8356601; fax: +49 251 8356612.
    • This is to indicate that both authors contributed equally to this work and therefore should both be considered first authors.
  • ,
  • Udo Dannlowski

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
    • This is to indicate that both authors contributed equally to this work and therefore should both be considered first authors.
  • ,
  • Christa Hohoff

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Patricia Ohrmann

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Jochen Bauer

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Harald Kugel

      Affiliations

    • Dept. of Clinical Radiology, University of Muenster, Germany
  • ,
  • Peter Zwanzger

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Walter Heindel

      Affiliations

    • Dept. of Clinical Radiology, University of Muenster, Germany
  • ,
  • Jürgen Deckert

      Affiliations

    • Dept. of Psychiatry, University of Wuerzburg, Germany
  • ,
  • Volker Arolt

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Thomas Suslow

      Affiliations

    • Dept. of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany
  • ,
  • Bernhard T. Baune

      Affiliations

    • Dept. of Psychiatry, James Cook University, Queensland, Australia

Received 18 May 2009 ,Revised 1 September 2009 ,Accepted 28 September 2009.

References 

  1. Bagby RM, Ryder AG, Cristi C. Psychosocial and clinical predictors of response to pharmacotherapy for depression. J. Psychiatry Neurosci. 2002;27:250–257
  2. Bannon AW, Seda J, Carmouche M, Francis JM, Norman MH, Karbon B, et al. Behavioral characterization of neuropeptide Y knockout mice. Brain Res. 2000;868:79–87
  3. Baune BT, Hohoff C, Berger K, Neumann A, Mortensen S, Roehrs T, et al. Association of the COMT val158met variant with antidepressant treatment response in major depression. Neuropsychopharmacology. 2008;33:924–932
  4. Benjamini Y, Hochberg Y. Controlling the false discovery rate — a practical and powerful approach to multiple testing. J. R. Stat. Soc. B. 1995;57:289–300
  5. Brett M, Anton JL, Valabregue R, Poline JB. Region of interest analysis using an SPM toolbox. NeuroImage. 2002;16:497
  6. Broqua P, Wettstein JG, Rocher MN, Gauthier-Martin B, Junien JL. Behavioral effects of neuropeptide Y receptor agonists in the elevated plus-maze and fear-potentiated startle procedures. Behav. Pharmacol. 1995;6:215–222
  7. Caberlotto L, Fuxe K, Overstreet DH, Gerrard P, Hurd YL. Alterations in neuropeptide Y and Y1 receptor mRNA expression in brains from an animal model of depression: region specific adaptation after fluoxetine treatment. Brain Res. Mol. Brain Res. 1998;59:58–65
  8. Caberlotto L, Jimenez P, Overstreet DH, Hurd YL, Mathé AA, Fuxe K. Alterations in neuropeptide Y levels and Y1 binding sites in the Flinders Sensitive Line rats, a genetic animal model of depression. Neurosci. Lett. 1999;265:191–194
  9. Cleary P, Guy W. Factor analysis of the Hamilton depression scale. Drugs Exp. Clin. Res. 1977;1:115–120
  10. Dannlowski U, Ohrmann P, Bauer J, Deckert J, Hohoff C, Kugel H, et al. 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology. 2008;33:418–424
  11. Dannlowski U, Ohrmann P, Bauer J, Kugel H, Arolt V, Heindel W, et al. a) Amygdala reactivity predicts automatic negative evaluations for facial emotions. Psychiatry Res. 2007;154:13–20
  12. Dannlowski U, Ohrmann P, Bauer J, Kugel H, Arolt V, Heindel W, et al. b) Amygdala reactivity to masked negative faces is associated with automatic judgmental bias in major depression: a 3T fMRI study. J. Psychiatry Neurosci. 2007;32:423–429
  13. Dannlowski U, Kersting A, Donges U, Lalee-Mentzel J, Arolt V, Suslow T. Masked facial affect priming is associated with therapy response in clinical depression. Eur. Arch. Psychiatry Clin. Neurosci. 2006;256:215–221
  14. Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol. Psychiatry. 2001;6:13–34
  15. Domschke, K., Deckert, J., Arolt, V., Baune, B., in press. Anxious versus non-anxious depression: difference in treatment outcome. J. Psychopharmacol. doi:10.1177/0269881108097723.
  16. Domschke K, Hohoff C, Jacob C, Maier W, Fritze J, Bandelow B, et al. a) Chromosome 4q31–34 panic disorder risk locus: association of neuropeptide Y Y5 receptor variants. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008;147B:510–516
  17. Domschke K, Hohoff C, Mortensen LS, Roehrs T, Deckert J, Arolt V, et al. b) Monoamine oxidase A variant influences antidepressant treatment response in female patients with major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2008;32:224–228
  18. Ekman P, Friesen WV. Pictures of Facial Affect. Palo Alto, CA, USA: Consulting Psychologists Press; 1976;
  19. Etkin A, Klemenhagen KC, Dudman JT, Rogan MT, Hen R, Kandel ER, et al. Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron. 2004;44:1043–1055
  20. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am. J. Psychiatry. 2007;164:1476–1488
  21. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Method. 2007;39:175–191
  22. Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am. J. Psychiatry. 2008;165:342–351
  23. Gauderman WJ. a) Sample size requirements for association studies of gene-gene interaction. Am. J. Epidemiol. 2002;155:478–484
  24. Gauderman WJ. b) Sample size requirements for matched case-control studies of gene–environment interaction. Stat. Med. 2002;21:35–50
  25. Hariri AR, Drabant EM, Weinberger DR. Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biol. Psychiatry. 2006;59:888–897
  26. Hasler G, Drevets WC, Manji HK, Charney DS. Discovering endophenotypes for major depression. Neuropsychopharmacology. 2004;29:1765–1781
  27. Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004;38:213–224
  28. Heilig M, McLeod S, Brot M, Heinrichs SC, Menzaghi F, Koob GF, et al. Anxiolytic-like action of neuropeptide Y: mediation by Y1 receptors in amygdala, and dissociation from food intake effects. Neuropsychopharmacology. 1993;8:357–363
  29. Heilig M, Söderpalm B, Engel JA, Widerlöv E. Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology. 1989;98:524–529
  30. Heilig M, Zachrisson O, Thorsell A, Ehnvall A, Mottagui-Tabar S, Sjögren M, et al. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J. Psychiatr. Res. 2004;38:113–121
  31. Husum H, Mikkelsen JD, Hogg S, Mathé AA, Mørk A. Involvement of hippocampal neuropeptide Y in mediating the chronic actions of lithium, electroconvulsive stimulation and citalopram. Neuropharmacology. 2000;39:1463–1473
  32. Itokawa M, Arai M, Kato S, Ogata Y, Furukawa A, Haga S, et al. Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans. Neurosci. Lett. 2003;347:202–204
  33. Kaabi B, Gelernter J, Woods SW, Goddard A, Page GP, Elston RC. Genome scan for loci predisposing to anxiety disorders using a novel multivariate approach: strong evidence for a chromosome 4 risk locus. Am. J. Hum. Genet. 2006;78:543–553
  34. Karl T, Burne TH, Herzog H. Effect of Y(1) receptor deficiency on motor activity, exploration, and anxiety. Behav. Brain Res. 2005;167:87–93
  35. Karlsson RM, Holmes A, Heilig M, Crawley JN. Anxiolytic-like actions of centrally-administered neuropeptide Y, but not galanin, in C57BL/6J mice. Pharmacol. Biochem. Behav. 2005;80:427–436
  36. Karvonen MK, Pesonen U, Koulu M, Niskanen L, Laakso M, Rissanen A, et al. Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels. Nat. Med. 1998;4:1434–1437
  37. Lindberg C, Koefoed P, Hansen ES, Bolwig TG, Rehfeld JF, Mellerup E, et al. No association between the −399 C>T polymorphism of the neuropeptide Y gene and schizophrenia, unipolar depression or panic disorder in a Danish population. Acta Psychiatr. Scand. 2006;113:54–58
  38. Lydiard RB, Brawman-Mintzer O. Anxious depression. J. Clin. Psychiatry. 1998;18:10–17
  39. Marcos P, Coveñas R, Narváez JA, Diaz-Cabiale Z, Aguirre JA, Tramu G, et al. Immunohistochemical mapping of enkephalins, NPY, CGRP, and GRP in the cat amygdala. Peptides. 1999;20:635–644
  40. Mathé AA, Jimenez PA, Theodorsson E, Stenfors C. Neuropeptide Y, neurokinin A and neurotensin in brain regions of Fawn Hooded “depressed”, Wistar, and Sprague Dawley rats. Effects of electroconvulsive stimuli. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1998;22:529–546
  41. Mathé AA, Husum H, El Khoury A, Jiménez-Vasquez P, Gruber SH, Wörtwein G, et al. Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role?. Physiol. Behav. 2007;92:226–231
  42. McDonald AJ, Pearson JC. Coexistence of GABA and peptide immunoreactivity in non-pyramidal neurons of the basolateral amygdala. Neurosci. Lett. 1989;100:53–58
  43. Morris JS, Frith CD, Perrett DI, Rowland D, Young AW, Calder AJ, et al. A differential neural response in the human amygdala to fearful and happy facial expressions. Nature. 1996;383:812–815
  44. Mottagui-Tabar S, Prince JA, Wahlestedt C, Zhu G, Goldman D, Heilig M. A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence. Alcohol. Clin. Exp. Res. 2005;29:702–707
  45. Nelson JC. Anxious depression and response to treatment. Am. J. Psychiatry. 2008;165:297–299
  46. Nikisch G, Agren H, Eap CB, Czernik A, Baumann P, Mathé AA. Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram. Int. J. Neuropsychopharmacol. 2005;8:403–410
  47. Obuchowicz E, Krysiak R, Herman ZS. Does neuropeptide Y (NPY) mediate the effects of psychotropic drugs?. Neurosci. Biobehav. Rev. 2004;28:595–610
  48. Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol. Psychiatry. 2003;54:515–528
  49. Primeaux SD, Wilson SP, Cusick MC, York DA, Wilson MA. Effects of altered amygdalar neuropeptide Y expression on anxiety-related behaviors. Neuropsychopharmacology. 2005;30:1589–1597
  50. Redrobe JP, Dumont Y, Fournier A, Quirion R. The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology. 2002;26:615–624
  51. Sajdyk TJ, Schober DA, Gehlert DR. Neuropeptide Y receptor subtypes in the basolateral nucleus of the amygdala modulate anxiogenic responses in rats. Neuropharmacology. 2002;43:1165–1172
  52. Sajdyk TJ, Vandergriff MG, Gehlert DR. Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. Eur. J. Pharmacology. 1999;368:143–147
  53. Serretti A, Kato M, Kennedy JL. Pharmacogenetic studies in depression: a proposal for methodologic guidelines. Pharmacogenomics J. 2008;8:90–100
  54. Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol. Psychiatry. 2001;50:651–658
  55. Silverstone PH, von Studnitz E. Defining anxious depression: going beyond comorbidity. Can. J. Psychiatry. 2003;48:675–680
  56. Skibola DR, Smith MT, Bracci PM, Hubbard AE, Agana L, Chi S. Polymorphisms in ghrelin and neuropeptide Y. Cancer Epidemiol. Biomarkers Prev. 2005;14:1251–1256
  57. Smoller JW, Gardner-Schuster E, Misiaszek M. Genetics of anxiety: would the genome recognize the DSM. Depress. Anxiety. 2008;25:368–377
  58. Sorensen G, Lindberg C, Wortwein G, Bolwig TG, Woldbye DP. Differential roles for neuropeptide Y Y1 and Y5 receptors in anxiety and sedation. J. Neurosci. Res. 2004;77:723–729
  59. Stenfors C, Theodorsson E, Mathé AA. Effect of repeated electroconvulsive treatment on regional concentrations of tachykinins, neurotensin, vasoactive intestinal polypeptide, neuropeptide Y, and galanin in rat brain. J. Neurosci. Res. 1989;24:445–450
  60. Stenfors C, Mathé AA, Theodorsson E. Repeated electroconvulsive stimuli: changes in neuropeptide Y, neurotensin and tachykinin concentrations in time. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1994;18:201–209
  61. Stogner KA, Holmes PV. Neuropeptide-Y exerts antidepressant-like effects in the forced swim test in rats. Eur. J. Pharmacol. 2000;387:9–10
  62. Tovote P, Meyer M, Beck-Sickinger AG, von Hörsten S, Ove Ogren S, Spiess J, et al. Central NPY receptor-mediated alteration of heart rate dynamics in mice during expression of fear conditioned to an auditory cue. Regul. Pept. 2004;120:205–214
  63. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage. 2002;15:273–289
  64. Wahlestedt C, Pich EM, Koob GF, Yee F, Heilig M. Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides. Science. 1993;259:528–531
  65. Whalen PJ, Rauch SL, Etcoff NL, McInerney SC, Lee MB, Jenike MA. Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J. Neurosci. 1998;18:411–418
  66. Widdowson PS, Ordway GA, Halaris AE. Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. J. Neurochem. 1992;59:73–80
  67. Widerlöv E, Lindström LH, Wahlestedt C, Ekman R. Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. J. Psychiatry Res. 1988;22:69–79
  68. Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M. SKID-I. Hogrefe, Göttingen: Strukturiertes Klinisches Interview für DSM-IV; 1997;
  69. Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D, Sinha R, et al. Genetic variation in human NPY expression affects stress response and emotion. Nature. 2008;452:997–1001

PII: S0924-977X(09)00236-3

doi: 10.1016/j.euroneuro.2009.09.006

European Neuropsychopharmacology
Volume 20, Issue 5 , Pages 301-309 , May 2010