D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: A pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial

The Lancet Psychiatry

Volumn 2, Issue 5, 2015, Pages 403-412

  Kantrowitz, Joshua T ^a,b   Woods, Scott W ^c   Petkova, Eva ^a,d   Cornblatt, Barbara ^e   Corcoran, Cheryl M ^b   Chen, Huaihou ^f   Silipo, Gail ^a   Javitt, Daniel C ^a,b  

^a NATHAN S KLINE INSTITUTE FOR PSYCHIATRIC RESEARCH   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c YALE UNIVERSITY   (United States)

^d NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e ZUCKER HILLSIDE HOSPITAL   (United States)

^f UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEXTRO SERINE; GAMMA INTERFERON; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; PLACEBO; TUMOR NECROSIS FACTOR ALPHA; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; SERINE;

ADOLESCENT; ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; HIGH RISK PATIENT; HUMAN; KIDNEY DISEASE; MALE; MENTAL DISEASE ASSESSMENT; NEGATIVE SYNDROME; OUTCOME ASSESSMENT; PILOT STUDY; PLACEBO EFFECT; POSITIVE SYNDROME; PROTEIN BLOOD LEVEL; PROTEINURIA; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; SCALE OF PRODROMAL SYMPTOMS; SCHIZOPHRENIA; SIMPSON-ANGUS SCALE; AIRPLANE PILOT; PATHOPHYSIOLOGY; PHYSIOLOGY; RISK ASSESSMENT; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; PILOTS; RECEPTORS, N-METHYL-D-ASPARTATE; RISK ASSESSMENT; SCHIZOPHRENIA; SERINE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84933522572     PISSN: 22150366     EISSN: 22150374     Source Type: Journal    
DOI: 10.1016/S2215-0366(15)00098-X     Document Type: Article

References (60)

1. Piskulic D, Addington J, Cadenhead KS, et al. Negative symptoms in individuals at clinical high risk of psychosis. Psychiatry Res 2012, 196:220-224.
2. Corcoran CM, Kimhy D, Parrilla-Escobar MA, et al. The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis. Psychol Med 2011, 41:251-261.
3. van der Gaag M, Smit F, Bechdolf A, et al. Preventing a first episode of psychosis: meta-analysis of randomized controlled prevention trials of 12 month and longer-term follow-ups. Schizophr Res 2013, 149:56-62.
4. Javitt DC, Zukin SR Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991, 148:1301-1308.
5. Kantrowitz JT, Javitt DC N-methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia?. Brain Res Bull 2010, 83:108-121.
6. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994, 51:199-214.
7. Moghaddam B, Krystal JH Capturing the angel in "angel dust": twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophr Bull 2012, 38:942-949.
8. Coyle JT NMDA receptor and schizophrenia: a brief history. Schizophr Bull 2012, 38:920-926.
9. Balla A, Schneider S, Sershen H, Javitt DC Effects of novel, high affinity glycine transport inhibitors on frontostriatal dopamine release in a rodent model of schizophrenia. Eur Neuropsychopharmacol 2012, 22:902-910.
10. Javitt DC, Balla A, Burch S, Suckow R, Xie S, Sershen H Reversal of phencyclidine-induced dopaminergic dysregulation by N-methyl-D-aspartate receptor/glycine-site agonists. Neuropsychopharmacology 2004, 29:300-307.
11. Hashimoto K, Fujita Y, Horio M, et al. Co-administration of a D-amino acid oxidase inhibitor potentiates the efficacy of D-serine in attenuating prepulse inhibition deficits after administration of dizocilpine. Biol Psychiatry 2009, 65:1103-1106.
12. Javitt DC, Schoepp D, Kalivas PW, et al. Translating glutamate: from pathophysiology to treatment. Sci Transl Med 2011, 3:102mr2.
13. Weiser M, Heresco-Levy U, Davidson M, et al. A multicenter, add-on randomized controlled trial of low-dose D-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry 2012, 73:e728-e734.
14. D'Souza DC, Gil R, Cassello K, et al. IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Biol Psychiatry 2000, 47:450-462.
15. Leiderman E, Zylberman I, Zukin SR, Cooper TB, Javitt DC Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial. Biol Psychiatry 1996, 39:213-215.
16. Tsai G, Yang P, Chung LC, Lange N, Coyle JT D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 1998, 44:1081-1089.
17. Heresco-Levy U, Javitt DC, Ebstein R, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry 2005, 57:577-585.
18. Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol 2010, 13:451-460.
19. Tsai GE, Yang P, Chang YC, Chong MY D-alanine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 2006, 59:230-234.
20. Kantrowitz JT, Malhotra AK, Cornblatt B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res 2010, 121:125-130.
21. Schobel SA, Chaudhury NH, Khan UA, et al. Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a driver. Neuron 2013, 78:81-93.
22. Schobel SA, Lewandowski NM, Corcoran CM, et al. Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry 2009, 66:938-946.
23. Gozzi A, Herdon H, Schwarz A, et al. Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology (Berl) 2008, 201:273-284.
24. Woods SW, Walsh BC, Hawkins KA, et al. Glycine treatment of the risk syndrome for psychosis: report of two pilot studies. Eur Neuropsychopharmacol 2013, 23:931-940.
25. Behrens MM, Sejnowski TJ Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?. Neuropharmacology 2009, 57:193-200.
26. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry 2015, 2:258-270.
27. Upthegrove R, Manzanares-Teson N, Barnes NM Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res 2014, 155:101-118.
28. McGlashan TH, Miller TJ, Woods SW, Hoffman RE, Davidson L Instrument for the assessment of prodromal symptoms and states. Early Intervention in psychotic disorders 2001, 135-149. Kluwer Academic Publishers, Netherlands. M. Miller, T.H. McGlashan (Eds.).
29. McGlashan T, Walsh B, Woods S The Psychosis-risk Syndrome: Handbook for Diagnosis and Follow-up 2010, Oxford University Press, New York.
30. Simpson GM, Angus JWS A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970, 212(suppl):11-19.
31. Addington D, Addington J, Atkinson M A psychometric comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale. Schizophr Res 1996, 19:205-212.
32. Nuechterlein KH, Green MF MATRICS Consensus Cognitive Battery 2006, MATRICS Assessment, Inc, Los Angeles.
33. Cannon TD, Chung Y, He G, et al. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry 2015, 77:147-157. the North American Prodrome Longitudinal Study Consortium.
34. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989, 28:193-213.
35. Levine J, Schooler NR SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull 1986, 22:343-381.
36. Schwarz G Estimating the dimension of a model. Ann Stat 1978, 6:461-468.
37. Spiegelhalter DB, Best NG, Carlin BP, van der Linde A Bayesian measures of model complexity and fit. J R Stat Soc B 2002, 64:583-639.
38. Cohen J Statistical Power Analysis for the Behavioral Sciences 1988, Lawrence Erlbaum Assoc, Hillsdale. 2nd edn.
39. Ruhrmann S, Schultze-Lutter F, Salokangas RK, et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 2010, 67:241-251.
40. Singh SP, Singh V Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 2011, 25:859-885.
41. Tsai GE, Lin PY Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Curr Pharm Des 2010, 16:522-537.
42. Umbricht D, Alberati D, Martin-Facklam M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry 2014, 71:637-646.
43. Buchanan RW, Javitt DC, Marder SR, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 2007, 164:1593-1602.
44. Arango C, Nasrallah AT, Lawrie S, et al. Efficacy and safety of adjunctive bitopertin (5 and 10 mg) versus placebo in subjects with persistent predominant negative symptoms of schizophrenia treated with antipsychotics - Results from the phase III DayLyte study. Schizophr Res 2014, 158:e1.
45. Blaettler T, Bugarski-Kirola D, Fleishhacker WW, et al. Efficacy and safety of adjunctive bitopertin (10 and 20 mg) versus placebo in subjects with persistent predominant negative symptoms of schizophrenia treated with antipsychotics - Results from the Phase III FlashLyte Study. Schizophr Res 2014, 158:e2-e3.
46. Bugarski-Kirola D, Wang A, Abi-Saab D, Blättler T A phase II/III trial of bitopertin monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia-results from the CandleLyte study. Eur Neuropsychopharmacol 2014, 24:1024-1036.
47. Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 2010, 67:146-154.
48. Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008, 64:361-368.
49. Lavoie S, Murray MM, Deppen P, et al. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 2008, 33:2187-2199.
50. Meyer EC, Carrión RE, Cornblatt BA, et al. The relationship of neurocognition and negative symptoms to social and role functioning over time in individuals at clinical high risk in the first phase of the North American Prodrome Longitudinal Study. Schizophr Bull 2014, 40:1452-1461. the NAPLS group.
51. Lin CH, Huang CL, Chang YC, et al. Clinical symptoms, mainly negative symptoms, mediate the influence of neurocognition and social cognition on functional outcome of schizophrenia. Schizophr Res 2013, 146:231-237.
52. Valmaggia LR, Stahl D, Yung AR, et al. Negative psychotic symptoms and impaired role functioning predict transition outcomes in the at-risk mental state: a latent class cluster analysis study. Psychol Med 2013, 43:2311-2325.
53. Nelson B, Yuen HP, Wood SJ, et al. Long-term follow-up of a group at ultra high risk ("prodromal") for psychosis: the PACE 400 study. JAMA Psychiatry 2013, 70:793-802.
54. Gonzalez-Burgos G, Lewis DA NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia. Schizophr Bull 2012, 38:950-957.
55. Stojanovic A, Martorell L, Montalvo I, et al. Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology 2014, 41:23-32.
56. Perkins DO, Jeffries CD, Addington J, et al. Towards a psychosis risk blood diagnostic for persons experiencing high-risk Symptoms: preliminary results from the NAPLS project. Schizophr Bull 2015, 41:419-428.
57. Kinon BJ, Gómez JC Clinical development of pomaglumetad methionil: a non-dopaminergic treatment for schizophrenia. Neuropharmacology 2013, 66:82-86.
58. Adams DH, Zhang L, Millen BA, Kinon BJ, Gomez JC Pomaglumetad methionil (LY2140023 Monohydrate) and aripiprazole in patients with schizophrenia: a phase 3, multicenter, double-blind comparison. Schizophr Res Treatment 2014, 2014:758212.
59. Kinon BJ, Millen BA, Zhang L, McKinzie DL Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor against pomaglumetad methionil in schizophrenia. Biol Psychiatry 2015, published online online March 19. 10.1016/j.biopsych.2015.03.016.
60. Javitt DC Glycine transport inhibitors for the treatment of schizophrenia: symptom and disease modification. Curr Opin Drug Discov Devel 2009, 12:468-478.