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

Background: Long term medication with antipsychotic drugs is known to produce changes in neurotransmitter levels and receptor sensitivity in the cortex; 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. After treatment, a stereologic method was used to assess neuronal and glial density and cortical thickness in prefrontal area 46. Results: Neuronal density in drug-treated monkeys and controls did not differ in any cortical layer. Glial density was elevated in monkeys that received antipsychotic medications: as much as 33% in layers that receive dense excitatory afferents (layers I in TAP monkeys and IV in AAP monkeys). In addition, 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 hypothesize that these responses play a regulatory role in adjusting neurotransmitter levels or metabolic processes. Finally, the negative results with respect to neuronal density indicate that the elevated neuronal density found in the schizophrenic cortex is unlikely to be a medication effect.