Lamina-specific deficits in parvalbumin-immunoreactive varicosities in the prefrontal cortex of subjects with schizophrenia: Evidence for fewer projections from the thalamus

Objective: Neuronal number in the mediodorsal thalamic nucleus, the principal source of thalamic projections to the prefrontal cortex, has been reported to be lower in subjects with schizophrenia. The authors tested the hypothesis that schizophrenia is associated with a selective deficit in a marker of thalamic axon terminals in the middle layers of the prefrontal cortex, the primary zone of termination of thalamic axons. Method: The densities of parvalbumin-immunoreactive varicosities (putative axon terminals) were determined in the superficial and middle layers of prefrontal cortex area 9 from 20 matched pairs of subjects with schizophrenia and normal comparison subjects. In order to determine the specificity of these observations, similar studies were conducted in subjects with major depressive disorder and in monkeys after 9-12 months of haloperidol treatment. Results: The relative densities of parvalbumin-immunoreactive varicosities did not differ between schizophrenic and comparison subjects in the superficial layers. However, in the middle layers, mean varicosity density was significantly lower (24% difference) in the subjects with schizophrenia. In contrast, neither subjects with major depressive disorder nor haloperidol-treated monkeys exhibited a middle-layer density of parvalbumin-immunoreactive varicosities that was lower than that of their matched comparison groups. Conclusions: Although not definitive, these findings are consistent with the hypothesis of fewer projections from the mediodorsal thalamic nucleus to the prefrontal cortex in schizophrenic subjects and thus converge with other lines of evidence demonstrating an abnormality in thalamo-prefrontal cortical circuitry in persons with schizophrenia.