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Letters to the Editor   |    
Natural Antiviral Cellular Defense in Relation to Positive and Negative Symptoms of Schizophrenia?
Andrei Vedeniapin, M.D.
Am J Psychiatry 2010;167:1276-1276. doi:10.1176/appi.ajp.2010.10040535
View Author and Article Information

accepted for publication in June 2010

The author reports no financial relationships with commercial interests.

Accepted June , 2010.

Copyright © American Psychiatric Association

To the Editor: The review article by Alan S. Brown, M.D., M.P.H., and Elena J. Derkits, B.A. (1), published in the March 2010 issue of the Journal, provided further evidence of a possible role of prenatal infection and maternal immune response in the etiology of schizophrenia. The authors also emphasized the importance of gene-environment interplay in neurodevelopmental disturbance leading to schizophrenia. However, the hypothesis of the single prenatal viral or immunological effect on the developing brain as a predisposing factor to schizophrenia cannot explain the variable long-term course of the illness.

A recent discovery of intracellular RNA-based gene inactivation machinery (short interfering RNA-induced silen cing complex) (2) suggested a mechanism of the natural defense against neurotropic viruses. RNA-induced silencing complex is the natural mechanism that prevents viruses from producing functional proteins. Such cellular defense can inhibit production of HIV and poliovirus (23). In some cases, the viral infection can be cleared; in other cases a virus can escape (4).

A hypothetical genetic variation in RNA-induced silencing complex may explain a variability of illness progression in schizophrenia: in some affected individuals, RNA-induced silencing complex controls an expression of schizovirus, while in others genetic polymorphism in RNA-induced silencing complex may lead to overstimulation of the cellular defense with temporary silencing of both schizoviral RNA and some host cell RNAs. Such dysregulation in the RNA-induced silencing complex response may increase dopamine production in affected neurons and lead to transient positive symptoms of schizophrenia, a clinical presentation consistent with "cycloid psychosis"(5). In some other patients, the underresponsive defense leads to a fast progression of neuronal damage and early development of deficit schizophrenia (6). In a majority of cases, overstimulation of RNA-induced silencing complex and eventual viral escape from the short interfering RNA inhibition is represented by often intermittent positive psychotic symptoms and progression of negative symptoms. Thus, suggested polymorphisms in the RNA-induced silencing complex genes may be related to genetic vulnerability to schizophrenia and a progression of the disease.

There is a lack of studies of RNA-induced silencing complex activity in humans. It is tempting, however, to suggest that a study of intracellular RNA defense may help to identify infectious agents, predisposing to schizophrenia, and that a development of short interfering RNA therapy may potentially cure some schizophrenia spectrum disorders.

Brown  AS;  Derkits  EJ:   Prenatal infection and schizophrenia: a review of epidemiologic and translational studies.  Am J Psychiatry 2010; 167:261—280
[CrossRef] | [PubMed]
 
Gitlin  L;  Karelsky  S;  Andino  R:   Short interfering RNA confers intracellular antiviral immunity in human cells.  Nature 2002; 418:430 —434
[CrossRef] | [PubMed]
 
Hu  WY;  Myers  CP;  Kilzer  JM;  Pfaff  SL;  Bushman  FD:   Inhibition of retroviral pathogenesis by RNA interference.  Curr Biol 2002; 12:1301—1311
[CrossRef] | [PubMed]
 
Gitlin  L;  Stone  JK;  Andino  R:   Poliovirus escape from RNA interference: short interfering RNA-target recognition and implications for therapeutic approaches.  J Virol 2005; 79:1027—1035
[CrossRef] | [PubMed]
 
Salvatore  P;  Bhuvaneswar  C;  Ebert  D;  Maggini  C;  Baldessarini  RJ:   Cycloid psychoses revisited: case reports, literature review, and commentary.  Harv Rev Psychiatry 2008; 16:167—180
[CrossRef] | [PubMed]
 
Kirkpatrick  B;  Galderisi  S:   Deficit schizophrenia: an update.  World Psychiatry 2008; 7:143—147
[PubMed]
 
References Container
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References

Brown  AS;  Derkits  EJ:   Prenatal infection and schizophrenia: a review of epidemiologic and translational studies.  Am J Psychiatry 2010; 167:261—280
[CrossRef] | [PubMed]
 
Gitlin  L;  Karelsky  S;  Andino  R:   Short interfering RNA confers intracellular antiviral immunity in human cells.  Nature 2002; 418:430 —434
[CrossRef] | [PubMed]
 
Hu  WY;  Myers  CP;  Kilzer  JM;  Pfaff  SL;  Bushman  FD:   Inhibition of retroviral pathogenesis by RNA interference.  Curr Biol 2002; 12:1301—1311
[CrossRef] | [PubMed]
 
Gitlin  L;  Stone  JK;  Andino  R:   Poliovirus escape from RNA interference: short interfering RNA-target recognition and implications for therapeutic approaches.  J Virol 2005; 79:1027—1035
[CrossRef] | [PubMed]
 
Salvatore  P;  Bhuvaneswar  C;  Ebert  D;  Maggini  C;  Baldessarini  RJ:   Cycloid psychoses revisited: case reports, literature review, and commentary.  Harv Rev Psychiatry 2008; 16:167—180
[CrossRef] | [PubMed]
 
Kirkpatrick  B;  Galderisi  S:   Deficit schizophrenia: an update.  World Psychiatry 2008; 7:143—147
[PubMed]
 
References Container
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