Antiherpes virus-specific treatment and cognition in schizophrenia: A test-of-concept randomized double-blind placebo-controlled trial

Schizophrenia Bulletin

Volumn 39, Issue 4, 2013, Pages 857-866

  Prasad, Konasale M ^a   Eack, Shaun M ^a,b   Keshavan, Matcheri S ^a,c   Yolken, Robert H ^d   Iyengar, Satish ^b   Nimgaonkar, Vishwajit L ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cognitive impairments; herpes simplex virus; neurotropic viruses; psychosis; therapeutics; valacyclovir

Indexed keywords

IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; PLACEBO; VALACICLOVIR;

ADULT; AKATHISIA; ANTIVIRAL THERAPY; ARTICLE; BLOATING; COGNITION; CONSTIPATION; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; FEMALE; FOLLOW UP; HERPES SIMPLEX; HUMAN; HYPERSALIVATION; INSOMNIA; LEARNING; LEG CRAMP; LIBIDO; MAJOR CLINICAL STUDY; MALE; MINIMUM INHIBITORY CONCENTRATION; MOTION SICKNESS; MUSCLE TIGHTNESS; NEGATIVE SYNDROME; PILOT STUDY; POSITIVE SYNDROME; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPONSE TIME; SCHIZOPHRENIA; SENSITIVITY AND SPECIFICITY; SIDE EFFECT; STOMACH PAIN; TREATMENT DURATION; TREMOR; VERBAL MEMORY; WORKING MEMORY;

EID: 84879324491     PISSN: 05867614     EISSN: 17451701     Source Type: Journal    
DOI: 10.1093/schbul/sbs040     Document Type: Article

References (43)

1. Elvevag B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol. 2000; 14: 1-21. (Pubitemid 32193047)
2. Green MF, Nuechterlein KH. Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull. 1999; 25: 309-319. (Pubitemid 29272507)
3. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996; 153: 321-330. (Pubitemid 26074706)
4. Murray CJL, Lopez AD. Evidence-based health policy - lessons from the global burden of disease study. Science. 1996; 274: 740-743. (Pubitemid 26398244)
5. Meltzer HY, McGurk SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull. 1999; 25: 233-255. (Pubitemid 29272503)
6. Shirts BH, Prasad KM, Pogue-Geile MF, Dickerson F, Yolken RH, Nimgaonkar VL. Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia. Schizophr Res. 2008; 106: 268-274.
7. Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Ruslanova I, Yolken RH. Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. Arch Gen Psychiatry. 2003; 60: 466-472. (Pubitemid 36539055)
8. Yolken RH, Torrey EF, Lieberman JA, Yang S, Dickerson FB. Serological evidence of exposure to Herpes Simplex Virus type 1 is associated with cognitive deficits in the CATIE schizophrenia sample. Schizophr Res. 2011; 128: 61-65.
9. Schretlen DJ, Vannorsdal TD, Winicki J, et al. Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia. Schizophr Res. 2010; 118: 224-231.
10. Prasad KM, Shirts BH, Yolken RH, Keshavan MS, Nimgaonkar VL. Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia. Mol Psychiatry. 2007; 12: 105-113. (Pubitemid 44973667)
11. Pandurangi AK, Pelonero AL, Nadel L, Calabrese VP. Brain structure changes in schizophrenics with high serum titers of antibodies to herpes virus. Schizophr Res. 1994; 11: 245-250. (Pubitemid 24063744)
12. Prasad KM, Eack SM, Goradia DD, et al. Progressive grey matter loss and changes in cognitive functions associated with exposure to HSV1 in schizophrenia: a longitudinal study. Am J Psychiatry. 2011; 168: 822-830.
13. Markoula S, Giannopoulos S, Pelidou SH, Argyropoulou M, Lagos G, Kyritsis AP. MRI deterioration in herpes simplex encephalitis despite clinical recovery. Neurologist. 2009; 15: 223-226.
14. Daheshia M, Feldman LT, Rouse BT. Herpes simplex virus latency and the immune response. Curr Opin Microbiol. 1998; 1: 430-435. (Pubitemid 128423258)
15. Cleator GM, Klapper PE. Herpes simplex. In: Zuckerman AJ, Banatvala JE, Pattison JR, eds. Principles and Practice of Clinical Virology. 5th ed. New York, NY: John Wiley and Sons, Ltd; 2004: 27-51.
16. Margolis TP, Elfman FL, Leib D, et al. Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory ganglia. J Virol. 2007; 81: 11069-11074. (Pubitemid 47536079)
17. Orvedahl A, Levine B. Autophagy and viral neurovirulence. Cell Microbiol. 2008; 10: 1747-1756.
18. Hayden FG. Antiviral agents (nonretroviral). In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's The Phamacological Basis of Therapeutics. 11th ed. New York, NY: McGraw Hill; 2006.
19. Wagstaff AJ, Faulds D, Goa KL. Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994; 47: 153-205. (Pubitemid 24032382)
20. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13: 261-276. (Pubitemid 18039085)
21. First MB. The Structured Clinical Interview for DSM-IV for Axis I disorders: Clinical Version, Administration Booklet. Washington, DC: American Psychiatric Press; 1997.
22. Hollingshead AB. Four-Factor Index of Social Status. New Haven, CT: Yale University; 1975.
23. Lycke J, Malmestrom C, Stahle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003; 47: 2438-2441. (Pubitemid 36919441)
24. Gur RC, Ragland JD, Moberg PJ, et al. Computerized neurocognitive scanning: II. The profile of schizophrenia. Neuropsychopharmacology. 2001; 25: 777-788. (Pubitemid 32995960)
25. Prasad KM, Almasy L, Gur RC, et al. RGS4 polymorphisms associated with variability of cognitive performance in a familybased schizophrenia sample. Schizophr Bull. 2010; 36: 983-990.
26. Gur RE, Nimgaonkar VL, Almasy L, et al. Neurocogntive endophenotypes in a multiplex multigenerational family study of schizophrenia. Am J Psychiatry. 2007; 164: 813-819. (Pubitemid 46808537)
27. Hamer RM, Simpson PM. Last observation carried forward versus mixed models in the analysis of psychiatric clinical trials. Am J Psychiatry. 2009; 166: 639-641.
28. Rubin DB. Multiple imputation after 18+ years. J Am Statist Assoc. 1996; 91: 473-489.
29. Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York, NY: Wiley; 1987.
30. Valtrex Package Insert. Full Prescribing Information. Durham, NC: Glaxo Smith Kline; 2008.
31. Schreppel TJ, Pauli P, Ellgring H, Fallgatter AJ, Herrmann MJ. The impact of prefrontal cortex for selective attention in a visual working memory task. Int J Neurosci. 2008; 118: 1673-1688.
32. Ando Y, Kitayama H, Kawaguchi Y, Koyanagi Y. Primary target cells of herpes simplex virus type 1 in the hippocampus. Microbes Infect. 2008; 10: 1514-1523.
33. Elion GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977; 74: 5716-5720.
34. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res. 2005; 79: 231-238. (Pubitemid 41457263)
35. Arias I, Sorlozano A, Villegas E, et al. Infectious agents associated with schizophrenia: a meta-analysis. Schizophr Res. 2012; 136: 128-136.
36. Prasad KM, Watson AMM, Dickerson FB, Yolken RH, Nimgaokar VL. Exposure to herpes simplex virus type 1 and cognitive impairment in individuals with schizophrenia. Schizophr Bull. In Press.
37. Dickerson FB, Boronow JJ, Stallings CR, Origoni AE, Yolken RH. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia. Am J Psychiatry. 2003; 160: 2234-2236. (Pubitemid 39619620)
38. DeLisi LE, Goldin LR, Nurnberger JI, Simmons-Alling S, Hamovit J, Dingman CW. Failure to alleviate symptoms of schizophrenia with the novel use of an antiviral agent, acyclovir (Zovirax). Biol Psychiatry. 1987; 22: 216-220. (Pubitemid 17222135)
39. Frith CD. Functional brain imaging and the neuropathology of schizophrenia. Schizophr Bull. 1997; 23: 525-527. (Pubitemid 27427993)
40. Addington J, Addington D, Maticka-Tyndale E. Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophr Res. 1991; 5: 123-134.
41. Schillinger JA, Xu F, Sternberg MR, et al. National seroprevalence and trends in herpes simplex virus type 1 in the United States, 1976-1994. Sex Transm Dis. 2004; 31: 753-760. (Pubitemid 39557424)
42. Gur RC, Ragland JD, Moberg PJ, et al. Computerized neurocognitive scanning: I. Methodology and validation in healthy people. Neuropsychopharmacology. 2001; 25: 766-776. (Pubitemid 32995959)
43. Buchanan RW, Keefe RS, Lieberman JA, et al. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry. 2011; 69: 442-449.