Celeste Johns

Hippocampus-Amygdala Volumes and Psychopathology in Chronic Schizophrenia

Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age-matched healthy controls using T1-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11%), with significant reductions in both left (-20%) and right (-15%) hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rhos = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure.

Pharmacologic studies of tardive dyskinesia.

Based on the results of two preliminary studies, we concluded that late-developing persistent drug-induced movement disorders are pharmacologically heterogeneous, and this heterogeneity is seen between individual patients (and groups of patients) as well as within body areas of individual patients; dystonic pathology has a distinct and more consistent response to pharmacologic stimulation than does nondystonic tardive dyskinesia (TD); and, although disturbances in dopamine and acetylcholine appear to be involved in these disorders, they do not in all cases exist in functionally opposite relationships. The observed pharmacologic heterogeneity in TD response reflects the limitations of the dopamine/acetylcholine model of TD, which oversimplifies the neuroanatomy of the basal ganglia and the pathophysiology of TD. The chemical and anatomical complexity of this region suggests that other neurotransmitter systems and neuronal circuits within and extending from the basal ganglia may be disturbed in the pathogenesis of TD.

Hormonal response to fenfluramine challenges in clozapine-treated schizophrenic patients

Clozapine is a dibenzodiazepine derivative with proven antipsychotic efficacy in treatme_nt-refractory schizophrenic patients (Kane et a11988). It is considered an atypical neuroleptic due to its low incidence of extrapyramidal side effects (Kane et a11988), its inability to produce catalepsy (Biirki et al 1975) or block apomorphine-induced stercotypy in animals (Ljungberg and Ungerstedt 1978), and its failure to significantly elevate serum prolactin (Prl) levels (Meltzer et al 1979). Serotonin (5-hydroxytryptamine [5-HT]) agonists are known to stimulate Prl release (Martin and Reichlin 1987). This effect is blocked by 5-HT antagonist agents (Martin and Reichlin 1987). PreclinicaI studies suggest that clozapine is a potent 5-HT antagonist (Fink et al 1984; Lee and Tang 1984). We chose a neuroendocrine strategy to study clozapines effect on the serotonergic system of schizophrenic patients. Fentturamine, a 5-HT agonist, was used as a serotonergic probe. Clozapines ability to inhibit the Prl response to fenfluramine would suggest 5-HT antagonistic properties in humans.