An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease

Abstract

SynopsisIn experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (Huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2½ years.Analysis of variance on data obtained from behavioural observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2½ years after injection by automated activity monitoring.There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation.Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.

A re-investigation of the behavioural effects of intracerebral injection in marmosets of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease

“…Behavioural observations were made on the animals during a period of 2\ years prior to injection and for 2 | years after injection. In an earlier study (Baker et al 1983/)) we found that animals injected with CPE + ve CSF became progressively more inactive when compared with those injected with non-cytopathic (CPE -ve) CSF from control patients. In the present study we were unable to replicate this finding.…”

“…It should be noted, however, that two studies conducted independently using coded CSF samples have shown that the CPE is a reproducible phenomenon even after the samples have been stored for several years over liquid nitrogen (Tyrrell et al 1983;Taylor et al 1985 c). Also, cell death has been implicated in all the neuropsychiatric diseases which have provided cytopathic CSF and is particularly marked in Huntington's disease where 50 % of CSF samples were found to be cytopathic in tissue culture (Crow et al 1979;Baker et al 1983 a). The nature of the agent in CSF from patients with Huntington's disease and schizophrenia responsible for the cytopathic effect in cell culture remains obscure.…”

“…1968; Himmelhoch et al 1970;Petrov, 1970; CSF from a similar proportion of patients with Misra & Hay, 1971; Rzewuska-Szatkowska, serious and progressive neurological disease (e.g 1972) or as a late sequela of viral infection Huntington's disease, multiple sclerosis), how- (Jelliffe, 1927;Hendrick, 1928; McGowan & ever, was also cytopathic in tissue culture Cook, 1928;Hall, 1929;Von Economo, 1931). although only occasional samples from patients Seasonal trends in the onset of schizophrenia with other medical, but non-neurological con- (Abe, 1963;Hare & Walter, 1978) and the ditions were cytopathic (Tyrrell et al 1979; tendency for those who later become schizo- Crow et al 1979;Baker et al 1983 a). The phrenic to have been born in the winter months cytopathic effect (CPE) could have been due to (Hare, 1975) suggest that exposure, either the presence of a virus or virus-like agent (VLA), perinatally or later, to an agent with a seasonal although attempts at serial passage of the CPE prevalence may be important.…”

Schizophrenia and Multiple Sclerosis

“…Tyrrell et al (1979) described a cytopathic effect on human embryonic fibroblasts of CSF from schizophrenic patients and from individuals with a number of neurodegenerative disorders, but were unable to passage the agent or inhibit its effect with metabolic or DNA and RNA antagonists. Intracerebral inoculation of marmosets with the cytotoxic CSF reportedly caused behavioral changes (Baker et al 1983). Cytopathic effects of schizophrenic CSF were also reported by Libikova (1983).…”

Stalking the Schizovirus

“…Baker et al (1983) in England reported that CSF from schizophrenic patients which caused CPE in cell cultures produced behavioral alterations when injected intracerebrally into marmosets. In collaboration with the Laboratory of Central Nervous System Studies, National Institute of Neurological and Communicative Disorders and Stroke (NINCDS), attempts were undertaken by Kaufmann et al (in press) to study laboratory animals into which post-mortem schizophrenic brain tissue had been intracerebrally injected.…”