Viruses and schizophrenia: a focus on herpes simplex virus.
Various factors have been implicated in the pathogenesis of schizophrenia. Evidence for an infectious cause includes the 5-8% increased risk among those born in the winter-spring months, when infectious diseases are more prevalent and at times when other infections (measles, varicella, poliomyelitis) show increased activity. Herpes simplex virus (HSV) has been implicated in schizophrenia as it has a tropism for the nervous system and is capable of replication in the brain. Although post-mortem studies of brain tissue of schizophrenic patients have failed to detect the virus, these studies have been hampered by the unknown cellular localization of HSV genomes and by attempting to detect the virus years after the symptom onset. A more recent, nested, case-control study evaluated pregnant women between 1959 and 1966 and identified 27 surviving offspring who were later diagnosed with schizophrenia. Analysis of stored blood samples showed an association between high levels of maternal antibody to HSV-2 and subsequent development of adult psychosis. No association was found between HSV-1 infection and psychosis. There is also evidence that human endogenous retroviruses (HERVs) may play a role in schizophrenia, as antibodies to these agents have been found at a greater frequency in the sera of affected individuals compared with controls. This is supported by the presence of reverse transcriptase, a retroviral marker, at levels four times higher in the cerebrospinal fluid (CSF) of people with recent onset schizophrenia compared with controls, and by its elevated presence in long-term schizophrenic patients. Further research to investigate the relationship between virus infection and schizophrenia is warranted.
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-4933, USA. yolken@mail.jhmi.edu
Robert
R
Yolken
D006801:Humans; D012559:Schizophrenia / Q000821:virology*; D018139:Simplexvirus / Q000302:isolation & purification*