Latent inhibition in drug naive schizophrenics: relationship to duration of illness and dopamine D2 binding using SPET

Abstract

The dual aims of the study were (1) to examine the effect of neuroleptic medication on the expression of latent inhibition (LI) by studying LI in drug naive schizophrenic patients, and (2) to investigate the relationship between LI and dopamine D2 receptor binding in the basal ganglia using single photon emission tomography (SPET). Subjects constituted a sub-set of patients investigated in a major study of in vivo D2 receptor binding in schizophrenia (Pilowsky et al., 1993). Striatal D2 receptor binding was assessed in 15 neuroleptic naive schizophrenic patients and 13 healthy volunteers. The performance of subjects on a within-subject auditory latent inhibition paradigm was also assessed. There was found to be no significant difference in LI between schizophrenic patients and normal controls, both groups showing a strong within-subject LI effect. There was also found to be no association between LI and dopamine D2 receptor binding in either the left or the right basal ganglia. This lack of association indicates that LI is not directly related to post-synaptic D2 receptor levels in the striatum. LI was, however, found to be correlated with duration of illness in the schizophrenic group. Patients with a relatively short duration of illness (< 12 months) tended to show reversed, or absent, LI whereas patients with a longer illness duration (> 12 months) showed intact LI. The effect on LI of duration of illness is consistent with previous findings that LI is disrupted specifically in acute, but not chronic, schizophrenia. Previous studies have assumed that this pattern of results is due to the stabilising effect of long-term neuroleptic medication. The present findings in a sample of neuroleptic naive schizophrenic patients indicate that this is unlikely to be the case. Rather, it appears that the reinstatement of LI in schizophrenic patients over time is due to a factor(s) intrinsic to the evolution of the schizophrenic illness.