MESOPONTINE NEURONS IN SCHIZOPHRENIA

Findings reported here show that there is a significant increase in th e number of neurons in the pedunculopontine nucleus in most schizophre nic patients compared to age-matched controls. Nicotinamide adenine di nucleotide phosphate diaphorase histochemistry was used to label putat ive cholinergic neurons in the pedunculopontine nucleus acid laterodor sal tegmental nucleus, while noradrenergic locus coeruleus neurons wer e labeled immunocytochemically using an antibody to tryosine hydroxyla se. Cell counts of these neuronal groups were carried out using a Biog raphies image analysis system. We found significantly increased cell n umbers in the pedunculopontine nucleus of schizophrenic patients compa red to controls. The number of laterodorsal tegmental nucleus neurons was increased but this was not statistically significant. However, the total cell counts for pedunculopontine and laterodorsal tegmental nuc lei were significantly higher in schizophrenic subjects. The number of locus coeruleus noradrenergic neurons was similar in both groups. The se results implicate the brainstem reticular formation as a pathophysi ological site in at least some patients with schizophrenia. In additio n, these findings suggest a developmental etiology for the disease and account for some, but not all, of the symptoms of schizophrenia, incl uding sensory gating abnormalities, sleep-wake disturbances and, perha ps, hallucinations. Overdriving of thalamic and substantia nigra funct ion by cholinergic afferents from the midbrain may account for some of the symptoms seen in schizophrenia. These findings suggest that, at l east in some schizophrenic patients, there is an increased number of n eurons in the cholinergic arm of the reticular activating system. This may explain some of the symptoms of schizophrenia and points to a pre natal disturbance as one of the possible causes of the disease.