Schizophrenic Patients Taking Antipsychotic Drugs

~ ! , -" .~ link these neuropathologic findings to pathogenic processes and the clinical dimensions of the disease. Two questions that have not been resolved, however, are 1) whether some of the neuropathologic findings associated with schizophrenia are a consequence of the disease or of the substantial treatment that most patients receive in the course of their illness and 2) whether the neuropathologic process is, in some regions, progressive. Since the major pharmacologic action of antipsychotic drugs is in the dopamine neurons that project to the basal ganglia nuclei-including the caudate nucleus, globus pallidus, and putamen-and produce extrapyramidal side effects as a consequence of this action, if drugs can affect brain morphology, these structures might be particularly susceptible. In this context, recent post-mortem and magnetic resonance imaging (MRI) studies that have reported increased striatal and lenticular nuclei volumes in schizophrenic patients (4-8) are of 'interest. These findings are in contrast to the usual pattern of neuropathology in schizophrenia, in which reduction in the size of soft-tissue brain structures and enlargement of fluid-containing structures are characteristically seen (1, 2). In a post-mortem study, Heckers et al. (5) reported significant increases in left striatal Obiective: This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure. Method: Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment. Results: Caudate volumes increased 5. 7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts ofantipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume. Conclusions: Caudate enlargement occurs early in the course oftreatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients. ' (Am J Psychiatry 1994; 151:1430-1436) Increase in Caudate Nuclei Volumes of First~Episode Schizophrenic Patients Taking Antipsychotic Drugs