Final Activity Report Summary - SCHIZOPHRENIA/ MOTOR (Motor disorder and its relationship to frontal/executive dysfunction) Current theoretical approaches to schizophrenia invoke dysfunction in fronto-striatal circuits. The proposed study aimed to examine the 'frontostriatal' hypothesis in the disorder, from clinical, neuropsychological and functional imaging standpoints. The study aimed especially, but not exclusively, to explore the hypothesis that frontostriatal dysfunction would be more evident in patients who show clinical evidence of basal ganglia dysfunction, in the form of schizophrenia-associated motor disorder, tardive dyskinesia and catatonia. Study 1. The relationship of catatonia, and extrapyramidal motor disorder in schizophrenia A sample of 162 patients meeting diagnostic criteria for chronic schizophrenia were collected. The relationship of catatonia (motor disorder intrinsic to schizophrenia) to extrapyramidal disorder (drug related, but also partly intrinsic in the case of tardive dyskinesia) was examined using latent class analysis, which provided a stable solution at 3 pure types in this chronic schizophrenic population. The types found consisted of an aysmptomatic type, a type with probabilities purely on tardive dyskinesia, and a type with high probabilities of showing tardive dyskinesia, catatonia and Parkinsonism. This result provides experimental justification to Rogers' (1985) clinical observation that there exist chronic schizophrenic patients who present a mixture of both extrapyramidal and catatonic symptoms which are impossible to disentangle from each other. Study 2. The relationship of motor disorder in schizophrenia to executive impairment 92 intellectually preserved chronic schizophrenic were administered an executive test battery (the BADS) and also non-executive control tests. Normal controls (N = 37) were also tested. Both patient groups performed more poorly than the normal controls on the executive test. However, no difference in executive test performance was found between patients with and without motor disorder, either total (extrapyramidal and catatonic), or tardive dyskinesia alone. These findings support the hypothesis of specific executive impairment in schizophrenia, but provide no support for the hypothesis that patients with motor disorder will also show more executive impairment than those without. Study 3. Prefrontal cortex abnormality on functional imaging in schizophrenic patients with and without motor disorder For this study, 47 intellectually preserved patients with schizophrenia and 35 controls underwent fMRI during performance of a working memory task (n-back) and under baseline conditions. The patients showed a highly significant pattern of differential activation from controls, this took the form of a reduced activation in the main areas related to working memory performance such as DLPC, both basal ganglia, inferio-parietal, temporal, precentral areas, supplementary premotor area and cerebellum. Also, a noteworthy finding was a failure to deactivate ventral and medial prefrontal regions in the schizophrenic patients compared to the control group. Patients with and without motor disorder showed no differences in patterns of activation. Study 4. Basal ganglia abnormality on functional imaging in schizophrenic patients with and without motor disorder For this study, 35 intellectually preserved patients with schizophrenia and 34 controls underwent fMRI during performance of a procedural learning task (serial reaction time task) known to activate basal ganglia in normal subjects. The patients showed a highly significant pattern of differential activation from controls. Here, reduced activation in both basal ganglia was the principal finding in the schizophrenic group compared to healthy subjects. Patients with and without motor disorder showed no differences in the degree of under-activation in the basal ganglia.
