Increased volume and glial density in primate prefrontal cortex associatedwith chronic antipsychotic drug exposure

Background: Long term medication with antipsychotic drugs is known to produ ce changes in neurotransmitter levels and receptor sensitivity in the corte x; however, the anatomic consequences of chronic antipsychotic exposure are not well established. Methods: Accordingly, rhesus monkeys were given daily oral doses of typical or atypical antipsychotic drugs (TAP or AAP) or a placebo for 6 months. Af ter treatment, a stereologic method was used to assess neuronal and glial d ensity and cortical thickness in prefrontal area 46. Results: Neuronal density in drug-treated monkeys and controls did not diff er in any cortical layer. Glial density was elevated in monkeys that receiv ed antipsychotic medications: as much as 33% in layers that receive dense e xcitatory, afferents (layers I in TAP monkeys and IV in AAP monkeys). In ad dition, layer V was wider in all drug-treated monkeys. Conclusions: Our findings indicate that glial proliferation and hypertrophy of the cerebral cortex is a common response to antipsychotic drugs. We hyp othesize that these responses play a regulatory role in adjusting neurotran smitter levels or metabolic processes. Finally, the negative results with r espect to neuronal density indicate that the elevated neuronal density foun d in the schizophrenic cortex is unlikely to be a medication effect. (C) 19 99 Society of Biological Psychiatry.