Christine L. Miller

Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition--i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Miller C (PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ, UK), Farrington C P and Harbert K. The epidemiology of subacute sclerosing panencephalitis in England and Wales 1970–1989. International Journal of Epidemiology 1992 21: 998–1006. Two hundred and ninety cases of subacute sclerosing panencephalitis (SSPE) registered in England and Wales from 1970 to 1989 were followed at 6-monthly intervals. Male to female ratio was 2.8:1. Age at onset increased significantly over the period. Measles was recorded for 81% of cases; in nearly half this had occurred under 2 years. Measles vaccine was documented in 20 cases; in 10 measles was also documented and it could not be positively excluded in the remainder. The calculated risk of SSPE following measles was 4.0/100000 cases compared with the risk after vaccine of 0.14/100 000 doses. Measles under 1 year carried a risk 16 times greater than measles over 5 years. There was an excess of cases in third and subsequent children. The incidence was higher in the northwest than in the southeast of the country. Survival time varied from 4 weeks to 16 years and was shorter when measles had occurred over the mean age of 2.5 years. Of the cases 9% had a history of mental retardation before the onset of SSPE. The incidence of SSPE has fallen following the reduction in measles resulting from vaccination. However, because of the median 8-year interval between measles and onset of SSPE, further cases arising from measles during the study period must still be expected, particularly in adolescents.