Search

The purpose of this study was to investigate the neurofunctional substrate of verbal learning and memory impairments in schizophrenic patients. In this pilot study, our aim was to compare the memory disturbance of schizophrenic patients to the subcortico-frontal memory profile of Parkinson's disease (PD) patients. The California Verbal Learning Test, a verbal episodic memory test, was administered to 60 subjects, 20 patients with schizophrenia, 20 patients with PD and 20 healthy control subjects. All subjects were aged between 50 and 70 years and all patients were in a stable phase. Like the Parkinson patients, the schizophrenic patients showed a major deficit of retrieval characterized by deficit of recalls but contrarily to PD patients, schizophrenic patients' encoding scores were altered. These impairments in episodic memory could suggest a dysfunction of the subcortico-frontal circuits in schizophrenic patients. However, they demonstrated an additional encoding deficit associated with probable frontal in situ alteration.

The aim of this study was to determine whether executive/attentional cognitive performances could be considered as markers of vulnerability to schizophrenia. The Stroop Color Word and fluency tests were significantly impaired in schizophrenic patients and their parents compared to controls matched on age and sex while performances on Nelson's Modified Card Sorting Test and the Trail Making Test did not differ. The impairments on the Stroop and fluency could be considered as endophenotypic markers of schizophrenia.

The central benzodiazepine receptor occupancy by zolpidem in man is unknown. The present study used positron emission tomography (PET) and [11C]flumazenil to assess in five healthy volunteers, central benzodiazepine receptor occupancy in brain regions with high receptor densities 1 h following an acute oral administration of twice the usual hypnotic dose of zolpidem (20 mg). Receptor occupancy was measured in five discrete structures (middle frontal gyrus, middle temporal gyrus, posterior occipital cortex, lateral parietal cortex, and cerebellar cortex) and in a large neocortical area as the fractional change in the [11C]flumazenil bound/free ratio for the interval 15-40 min post-administration of the radiotracer. The free-radioligand concentration was estimated from the pons, a reference structure virtually devoid of central benzodiazepine receptor. With individual pons values, mean occupancy was about 21% but with spurious inter-subject variability. With pons values averaged across the five subjects and separately for control and treated condition, the occupancy was (mean +/- S.D.) 27 +/- 11% for the whole neocortex, and ranged from 26 to 29% in the five discrete structures (P < 0.01). By showing hypnotic effect at moderate occupancies, this study directly provides evidence for the full-agonist properties of zolpidem in human.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.