Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.
Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major depressive and generalised anxiety disorders were more frequent in patients with lateral compared with medial lesions at 2 weeks but not at 3 months. At 3 months, however, patients with lateral damage showed greater severity of depressive symptoms, and greater impairment in both activities of daily living and social functioning. At initial evaluation depressed mood and slowness were more frequent, whereas at 3 months slowness, lack of energy, and social unease were more frequent in the lateral than the medial group. Patients with lateral lesions showed greater reduction of emotion and motivation (apathy) during both examinations. Medial frontal injury may fail to produce emotional dysregulation or may inhibit experience of mood changes, anxiety, or apathy. Lateral prefrontal damage may disrupt mood regulation and drive while leaving intact the ability to experience (negative) emotions. (J Neurol Neurosurg Psychiatry 1999;67:664-667)
Both anaesthetists and surgeons overestimated their patients' preoperative anxiety by a wide margin and poorly predicted their patients' feared conditions and their desire for relief of anxiety.
Although there have been several case reports suggesting the beneficial effect of acetylcholinesterase inhibitors in the cognitive deficits seen in schizophrenia, controlled studies have revealed contradictory results. The aim of this study was to investigate if donepezil could improve cognitive functions in schizophrenia. Twelve schizophrenic patients, who were diagnosed according to DSM-IV criteria and who had been on a stable dose of a high-potency typical antipsychotic for a minimum period of 3 months, participated in this 12-wk double-blind, placebo controlled, cross-over study of donepezil adjunctive treatment. Patients were randomly assigned under double-blind conditions to receive 5 mg/d donepezil or placebo for 6 wk, and then were crossed over to the alternate condition for 6 additional weeks. At baseline, 6 and 12 wk, patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, the Wechsler Memory Scale Revised (WMS-R), a test for Verbal Fluency, Trail Making Test, Parts A and B, and Wisconsin Card Sorting Test (WCST). Treatment effect was not significant in any of the cognitive measures. There were also no significant changes in the PANSS and depression scores. Nicotinic receptor desensitization may cause non-responsiveness to acetylcholine as previously suggested, but the most likely explanation appears to be that defects in other neurotransmitter systems account for the cognitive deficits seen in schizophrenic patients.
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