Problems and solutions to filling the drying drug pipeline for psychiatric disorders: A report from the inaugural 2012 CINP Think Tank

International Journal of Neuropsychopharmacology

Volumn 17, Issue 1, 2014, Pages 137-148

  Dean, Brian ^a   Moller, Hans Jürgen ^b   Svensson, Torgny H ^c   Geyer, Mark A ^d,e   Rujescu, Dan ^f,g   Scarr, Elizabeth ^a   Millan, Mark J ^c  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b UNIVERSITY OF MUNICH   (Germany)

^c KAROLINSKA INSTITUTE   (Sweden)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^f MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^g INSTITUT DE RECHERCHES SERVIER   (France)

Author keywords

CINP Think Tank; drug development; neuropsychopharmacology

Indexed keywords

AGOMELATINE; BIOLOGICAL MARKER; CELECOXIB; CLOZAPINE; CYCLOSERINE; NORADRENALIN; SEROTONIN UPTAKE INHIBITOR; TRICYCLIC ANTIDEPRESSANT AGENT; VARENICLINE; VORTIOXETINE; XANOMELINE;

ACROPHOBIA; ARTICLE; BIPOLAR MANIA; DEPRESSION; DRUG EFFICACY; DRUG TREATMENT FAILURE; FINANCIAL MANAGEMENT; HUMAN; HUMAN GENOME; HUNTINGTON CHOREA; LEGAL ASPECT; MENTAL DISEASE; MODEL; NONHUMAN; PATENT; PHARMACOGENETICS; PHOBIA; PRIORITY JOURNAL; PSYCHOPHARMACOLOGY; REIMBURSEMENT; RISK BENEFIT ANALYSIS; SCHIZOPHRENIA; SOCIAL ASPECT; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; ANIMAL; DRUG DEVELOPMENT; GROUP PROCESS; MENTAL DISORDERS; PROCEDURES; TRENDS;

ANIMALS; DRUG DISCOVERY; GROUP PROCESSES; HUMANS; MENTAL DISORDERS; PSYCHOPHARMACOLOGY;

EID: 84888628095     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1017/S1461145713001077     Document Type: Article

References (116)

1. Aan Het RM, Zarate CA Jr., Charney DS, Mathew SJ (2012) Ketamine for depression: where do we go from here? Biol Psychiatry 72:537-547.
2. Abbott A (2011) Novartis to shut brain research facility. Nature 480:161-162.
3. Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang DR, Keilp J, Kochan L, Van Heertum R, Gorman JM, Laruelle M (2002) Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 22:3708-3719. (Pubitemid 37465776)
4. Adem A, Karlsson E (1997) Muscarinic receptor subtype selective toxins. Life Sci 60:1069-1076. (Pubitemid 27165577)
5. Alphs L, Benedetti F, Fleischhacker WW, Kane JM (2012) Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? Int J Neuropsychopharmacol 15:1003-1014.
6. Andersen MB, Fink-Jensen A, Peacock L, Gerlach J, Bymaster F, Lundbaek JA, Werge T (2003) The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. Neuropsychopharmacology 28:1168-1175.
7. Armstrong MJ, Miyasaki JM (2012) Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 79:597-603.
8. Baldessarini RJ (2013) Chemotherapy in psychiatry. New York: Springer.
9. Ballon J, Stroup TS (2013) Polypharmacy for schizophrenia. Curr Opin Psychiatry 26:208-213.
10. Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP, Deckersbach T, Kelly JF, Freudenreich O, Goff DC, Evins AE (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33:480-490.
11. Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39:17-23. (Pubitemid 46026496)
12. Birdsall NJ, Lazareno S, Popham A, Saldanha J (2001) Multiple allosteric sites on muscarinic receptors. Life Sci 68:2517-2524. (Pubitemid 32455690)
13. Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339-343. (Pubitemid 9016401)
14. Buchsbaum MS, Wu JC (1987) Hypofrontality in schizophrenia as assessed by PET. Am J Psychiatry 144:122-123.
15. Bymaster FP, Whitesitt CA, Shannon HE, DeLapp N, Ward JS, Calligaro DO, Shipley LA, Buelke-Sam JL, Bodick NC, Farde L, Sheardown MJ, Olesen PH, Hansen KT, Suzdak PD, Swedberg MDB, Sauerberg P, Mitch CH (1997) Xanomeline: a selective muscarinic agonist for the treatment of Alzheimer's disease. Drug Devel Res 40:158-170. (Pubitemid 27281623)
16. Bymaster FP, Felder C, Ahmed S, McKinzie D (2002) Muscarinic receptors as a target for drugs treating schizophrenia. Curr Drug Targets CNS Neurol Disord 1:163-181.
17. Cade JFJ (1949) Lithium salts in the treatment of psychotic excitement. Med J Aust 1:349-352.
18. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM (1999) Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 56:162-168. (Pubitemid 29081391)
19. Chan WY, McKinzie DL, Bose S, Mitchell SN, Witkin JM, Thompson RC, Christopoulos A, Lazareno S, Birdsall NJ, Bymaster FP, Felder CC (2008) Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia. Proc Natl Acad Sci USA 105:10978-10983.
20. Conn PJ, Christopoulos A, Lindsley CW (2009a) Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov 8:41-54.
21. Conn PJ, Jones CK, Lindsley CW (2009b) Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol Sci 30:148-155.
22. Davis M (2006) Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am Psychol 61:741-756. (Pubitemid 44789942)
23. de Bodinat C, Guardiola-Lemaitre B, Mocaer E, Renard P, Munoz C, Millan MJ (2010) Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov 9:628-642.
24. de Leon J (2006) AmpliChip CYP450 test: personalized medicine has arrived in psychiatry. Expert Rev Mol Diagn 6:277-286. (Pubitemid 44174334)
25. de Leon J (2009) Pharmacogenomics: the promise of personalized medicine for CNS disorders. Neuropsychopharmacology 34:159-172.
26. Dean B (2000) Signal transmission, rather than reception, is the underlying neurochemical abnormality in schizophrenia. Aust N Z J Psychiatry 34:560-569. (Pubitemid 30496904)
27. Dean B (2002) Changes in the molecular structure of the brain in bipolar disorder: findings using human postmortem brain tissue. World J Biol Psychiatry 3:125-132.
28. Dean B (2004) M1 receptor agonism, a possible treatment for cognitive deficits in schizophrenia. Neuropsychopharmacology 29:1583-1584.
29. Dean B (2011) Dissecting the syndrome of schizophrenia: progress toward clinically useful biomarkers. Schizophr Res Treatment 2011:614730.
30. Dean B (2013) Neurochemistry of schizophrenia and psychosis: the contribution of neuroimaging. Curr Top Med Chem 12:2375-2392.
31. Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E (2002) Decreased muscarinic(1) receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 7:1083-1091. (Pubitemid 36044267)
32. Delrieu J, Piau A, Vellas XX (2012) Drug development and Alzheimer's disease. In: Pathy's principles and practice of geriatric medicine, John Wiley and Sons Ltd, Chichester, UK, pp 923-941.
33. Drews J (1996) Genomic sciences and the medicine of tomorrow. Nat Biotechnol 14:1516-1518.
34. Englander MT, Dulawa SC, Bhansali P, Schmauss C (2005) How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing. J Neurosci 25:648-651.
35. Evers K (2009) Personalized medicine in psychiatry: ethical challenges and opportunities. Dialogues Clin Neurosci 11:427-434.
36. Floresco SB, Geyer MA, Gold LH, Grace AA (2005) Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia. Schizophr Bull 31:888-894. (Pubitemid 41437783)
37. Geyer MA (2006) The family of sensorimotor gating disorders: comorbidities or diagnostic overlaps? NeurotoxRes 10:211-220.
38. Geyer MA (2008) Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox Res 14:71-78.
39. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 156:117-154. (Pubitemid 32702206)
40. Goodman AB, Pardee AB (2000) Meeting report; "Molecular neurobiological mechanisms in schizophrenia: seeking a synthesis, " April 11-14, 1999. Biol Psychiatry 48:173-183. (Pubitemid 30618989)
41. Guilloux JP, Mendez-David I, Pehrson A, Guiard BP, Repérant C, Orvoën S, Gardier AM, Hen R, Ebert B, Miller S, Sanchez C, David DJ (2013) Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice. Neuropharmacology 28:147-159.
42. Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C (2002) Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 34:349-356. (Pubitemid 34465494)
43. Gusella JF, MacDonald ME (1995) Huntington's disease: CAG genetics expands neurobiology. Curr Opin Neurobiol 5:656-662.
44. Hambly K, Danzer J, Muskal S, Debe DA (2006) Interrogating the druggable genome with structural informatics. Mol Divers 10:273-281. (Pubitemid 44546682)
45. Harrison PJ, Law AJ (2006) Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol.Psychiatry 60:132-140.
46. Henry BL, Minassian A, Young JW, Paulus MP, Geyer MA, Perry W (2010) Cross-species assessments of motor and exploratory behavior related to bipolar disorder. Neurosci Biobehav Rev 34:1296-1306.
47. Huskamp HA (2003). Managing psychotropic drug costs: will formularies work? Health Aff (Millwood) 22:84-96. (Pubitemid 41388724)
48. Insel TR (2009) Disruptive insights in psychiatry: transforming a clinical discipline. J Clin Invest 119:700-705.
49. Insel TR, Voon V, Nye JS, Brown VJ, Altevogt BM, Bullmore ET, Goodwin GM, Howard RJ, Kupfer DJ, Malloch G, Marston HM, Nutt DJ, Robbins TW, Stahl SM, Tricklebank MD, Williams JH, Sahakian BJ (2013) Innovative solutions to novel drug development in mental health. Neurosci Biobehav Rev. S0149-7634(13)00082-1 [pii]; doi: 10.1016/j.neubiorev.2013.03.022.
50. Joers V, Seneczko K, Goecks NC, Kamp TJ, Hacker TA, Brunner KG, Engle JW, Barnhart TE, Nickles RJ, Holden JE, Emborg ME (2012) Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys. PLoS ONE 7:e35371.
51. Johansson D, Falk A, Marcus MM, Svensson TH (2012). Celecoxib enhances the effect of reboxetine and fluoxetine on cortical noradrenaline and serotonin output in the rat. Prog Neuropsychopharmacol Biol Psychiatry 39:143-148.
52. Kane JM (1992) Clinical efficacy of clozapine in treatment-refractory schizophrenia: an overview. Br J Psychiatry Suppl: 41-45.
53. Kefford RF (2012) Drug treatment for melanoma: progress, but who pays? Med J Aust 197:198-199.
54. Kemp AS, Schooler NR, Kalali AH, Alphs L, Anand R, Awad G, Davidson M, Dube S, Ereshefsky L, Gharabawi G, Leon AC, Lepine JP, Potkin SG, Vermeulen A (2010) What is causing the reduced drug-placebo difference in recent schizophrenia clinical trials and what can be done about it? Schizophr Bull 36:504-509.
55. Kinon BJ, Zhang L, Millen BA, Osuntokun OO, Williams JE, Kollack-Walker S, Jackson K, Kryzhanovskaya L, Jarkova N (2011) A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 31:349-355.
56. Lopez-Munoz F, Alamo C (2009) Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des 15:1563-1586.
57. Lopez-Munoz F, Alamo C, Cuenca E, Shen WW, Clervoy P, Rubio G (2005) History of the discovery and clinical introduction of chlorpromazine. Ann Clin Psychiatry 17:113-135. (Pubitemid 41176798)
58. Malhotra D, Sebat J (2012) CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 148: 1223-1241.
59. Markou A, Chiamulera C, Geyer MA, Tricklebank M, Steckler T (2009) Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology 34:74-89.
60. Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Weaver CD, Conn PJ (2009) Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharmacol 75:577-588.
61. Meltzer HY (2013) Update on typical and atypical antipsychotic drugs. Annu Rev Med 64:393-406.
62. Mentz RJ, Kaski JC, Dan GA, Goldstein S, Stockbridge N, Alonso-Garcia A, Ruilope LM, Martinez FA, Zannad F, Pitt B, Fiuzat M, O'Connor CM (2012) Implications of geographical variation on clinical outcomes of cardiovascular trials. Am Heart J 164:303-312.
63. Millan MJ (2006) Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 110:135-370.
64. Millan MJ (2009) Dual-and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs. Neurotherapeutics 6:53-77.
65. Millan MJ (2013) An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy. Neuropharmacology 68:2-82.
66. Millan MJ et al. (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11:141-168.
67. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, Clair DM, Muir WJ, Blackwood DH, Porteous DJ (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 9:1415-1423. (Pubitemid 30312490)
68. Moller HJ (2005) Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot. Eur Psychiatry 20:379-385.
69. Moller HJ (2008) Outcomes in major depressive disorder: the evolving concept of remission and its implications for treatment. World J Biol Psychiatry 9:102-114.
70. Moskvina V, Craddock N, Holmans P, Nikolov I, Pahwa JS, Green E, Owen MJ, O'Donovan MC (2009) Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol Psychiatry 14:252-260.
71. Nordberg A (2007) Amyloid imaging in Alzheimer's disease. Curr Opin Neurol 20:398-402. (Pubitemid 47051985)
72. O'Connor EC, Parker D, Rollema H, Mead AN (2010) The alpha4beta2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology (Berl) 208:365-376.
73. Perry W, Minassian A, Paulus MP, Young JW, Kincaid MJ, Ferguson EJ, Henry BL, Zhuang X, Masten VL, Sharp RF, Geyer MA (2009) A reverse-translational study of dysfunctional exploration in psychiatric disorders: from mice to men. Arch Gen Psychiatry 66:1072-1080.
74. Pfeiffer PN, Kim HM, Ganoczy D, Zivin K, Valenstein M (2013) Treatment-resistant depression and risk of suicide. Suicide Life Threat Behav 43:356-365.
75. Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, Fuxe K, Changeux JP (1998) Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173-177. (Pubitemid 28092475)
76. Pongrac J, Middleton FA, Lewis DA, Levitt P, Mirnics K (2002) Gene expression profiling with DNA microarrays: advancing our understanding of psychiatric disorders. Neurochem Res 27:1049-1063. (Pubitemid 35316102)
77. Pop M, Salzberg SL (2008) Bioinformatics challenges of new sequencing technology. Trends Genet 24:142-149.
78. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748-752.
79. Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR (2003) In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry 160:118-127. (Pubitemid 36042435)
80. Raedler TJ, Bymaster FP, Tandon R, Copolov D, Dean B (2007) Towards a muscarinic hypothesis of schizophrenia. Mol Psychiatry 12:232-246. (Pubitemid 46328501)
81. Rajji TK, Voineskos AN, Butters MA, Miranda D, Arenovich T, Menon M, Ismail Z, Kern RS, Mulsant BH (2013) Cognitive performance of individuals with schizophrenia across seven decades: a study using the MATRICS consensus cognitive battery. Am J Geriatr Psychiatry 21:108-118.
82. Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, Hodges L, Davis M (2004) Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 61:1136-1144. (Pubitemid 39463415)
83. Reynolds GP (1992) Developments in the drug treatment of schizophrenia. Trends Pharmacol Sci 13:116-121.
84. Rollema H, Shrikhande A, Ward KM, Tingley FD III, Coe JW, O'Neill BT, Tseng E, Wang EQ, Mather RJ, Hurst RS, Williams KE, de VM, Cremers T, Bertrand S, Bertrand D (2010) Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. Br J Pharmacol 160:334-345.
85. Rowe DL (2007) Off-label prescription of quetiapine in psychiatric disorders. Expert Rev Neurother 7:841-852. (Pubitemid 47037724)
86. Rujescu D, Genius J, Benninghoff J, Giegling I (2012) Current progress in the genetic research of schizophrenia: relevance for drug discovery? Curr Pharm Biotechnol 13:1614-1621.
87. Salah-Uddin H, Scarr E, Pavey G, Harris K, Hagan JJ, Dean B, Challiss RA, Watson JM (2009) Altered M(1) muscarinic acetylcholine receptor (CHRM1)-Galpha(q/11) coupling in a schizophrenia endophenotype. Neuropsychopharmacology 34:2156-2166.
88. Scarr E, Keriakous D, Crossland N, Dean B (2006) No change in cortical muscarinic M2, M3 receptors or [35S]GTPgammaS binding in schizophrenia. Life Sci 78:1231-1237. (Pubitemid 43176718)
89. Scarr E, Sundram S, Keriakous D, Dean B (2007) Altered hippocampal muscarinic m4, but not m1, receptor expression from subjects with schizophrenia. Biol Psychiatry 61:1161-1170. (Pubitemid 46669465)
90. Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B (2009) Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol Psychiatry 14:1017-1023.
91. Seeman P, Niznik HB (1990) Dopamine receptors and transporters in Parkinson's disease and schizophrenia. FASEB J 4:2737-2744.
92. Segal DS, Geyer MA (1985) Stimulant-induced psychoses: an evaluation of animal models. In: Psychobiological foundations of clinical psychiatry (Judd LL, Grove PM ed), pp 95-130. Philadelphia: Lippincott Co.
93. Shah L, Yadav S, Amiji M (2013) Nanotechnology for CNS delivery of bio-therapeutic agents. Drug Deliv and Transl Res 3:1-16.
94. Shekhar A, Potter WZ, Lightfoot J, Lienemann J, Dube S, Mallinckrodt C, Bymaster FP, McKinzie DL, Felder CC (2008) Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry 165:1033-1039.
95. Spedding M, Jay T, Costa e Silva Perret L (2005) A pathophysiological paradigm for the therapy of psychiatric disease. Nat Rev Drug Discov 4:467-476. (Pubitemid 40861989)
96. Stefansson H et al. (2002) Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71:877-892. (Pubitemid 135750519)
97. Stefansson H et al. (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455:232-236.
98. Stefansson H et al. (2009) Common variants conferring risk of schizophrenia. Nature 460:744-747.
99. Stocchi F, Olanow CW (2013) Obstacles to the development of a neuroprotective therapy for Parkinson's disease. Mov Disord 28:3-7.
100. Stuart H (2006) Media portrayal of mental illness and its treatments: what effect does it have on people with mental illness? CNS Drugs 20:99-106. (Pubitemid 43261695)
101. Sullivan PF et al. (2009) Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiatry 14:359-375.
102. Tamminga CA et al. (2002) Developing novel treatments for mood disorders: accelerating discovery. Biol Psychiatry 52:589-609. (Pubitemid 35284023)
103. Tseng CW, Brook RH, Keeler E, Mangione CM (2003) Impact of an annual dollar limit or "cap" on prescription drug benefits for Medicare patients. JAMA 290:222-227. (Pubitemid 37430061)
104. Tucker GJ (1998) Putting DSM-IV in perspective. Am J Psychiatry 155:159-161. (Pubitemid 28074274)
105. Valencia PM, Farokhzad OC, Karnik R, Langer R (2012) Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol 7:623-629.
106. van Nimwegen LJ, Storosum JG, Blumer RM, Allick G, Venema HW, de HL, Becker H, van AT, Ackermans MT, Fliers E, Serlie MJ, Sauerwein HP (2008) Hepatic insulin resistance in antipsychotic naive schizophrenic patients: stable isotope studies of glucose metabolism. J Clin Endocrinol Metab 93:572-577. (Pubitemid 351240833)
107. Walburn J, Gray R, Gournay K, Quraishi S, David AS (2001) Systematic review of patient and nurse attitudes to depot antipsychotic medication. Br J Psychiatry 179:300-307. (Pubitemid 32996038)
108. Walker DL, Davis M (2002) Quantifying fear potentiated startle using absolute vs. proportional increase scoring methods: implications for the neurocircuitry of fear and anxiety. Psychopharmacology (Berl) 164:318-328. (Pubitemid 35340999)
109. Wang Q, Jaaro-Peled H, Sawa A, Brandon NJ (2008) How has DISC1 enabled drug discovery? Mol Cell Neurosci 37:187-195. (Pubitemid 351173852)
110. Whitaker R (2011) Anatomy of an epidemic: magic bullets, psychiatric drugs, and the astonishing rise of mental illness in America. New York: Broadway Paperbacks.
111. Wiker C, Schilstrom B, Sandback C, Wadenberg ML, Svensson TH (2008) Adjunctive galantamine, but not donepezil, enhances the antipsychotic-like effect of raclopride in rats. Int J Neuropsychopharmacol 11:845-850.
112. Woodcock J, Woosley R (2008) The FDA critical path initiative and its influence on new drug development. Annu Rev Med 59:1-12. (Pubitemid 351287920)
113. Young JW, Light GA, Marston HM, Sharp R, Geyer MA (2009a) The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS ONE 4:e4227.
114. Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA (2009b) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 122:150-202.
115. Young JW, Zhou X, Geyer MA (2010) Animal models of schizophrenia. Curr Top Behav Neurosci 4:391-433.
116. Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS (2005) Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 25:7754-7762. (Pubitemid 41208646)