Biomedical subjects

M Saoud

Publications and source records attributed to M Saoud.

22 records · Page 2Linked to original sources

PubMedDate not supplied

[Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine].

Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in schizophrenia pathophysiology. Post-mortem studies have revealed a lower density of glutamatergic receptors in patients with schizophrenia. Other studies of cerebrospinal fluid reported lower levels of glutamate in patients with schizophrenia in healthy comparison subjects. The most compelling evidence is provided by the psychomimetic effects of the NMDA antagonists phencyclidine and ketamine. Recently, much interest has been given to the study related to the role of NMDA receptor in pathophysiology of schizophrenia by administration of sub-anesthetic doses of ketamine. A phencyclidine hydrochloride derivate, ketamine, is a dissociative anesthetic and a non competitive antagonist of the NMDA receptor. In healthy subjects, ketamine produces: 1) positive symptoms of psychosis, such as illusions, thought disorder and delusions; 2) negative symptoms similar to those associated with schizophrenia including blunted emotional responses, emotional detachment, and psychomotor retardation; 3) cognitive impairments, in particular impairments on tests of frontal cortical function including increased distractibility, reduced verbal fluency and poorer performance on the Wisconsin Card Sorting Test. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities which are among the characteristics of schizophrenia. In patients with schizophrenia, the administration of ketamine produces an activation of their psychotic symptoms, which have striking similarities to symptoms of their usual psychotic episodes. Ketamine effects on memory and other cognitive functions in schizophrenic patients are controversial. The psychomimetic effects of ketamine are transitional, reversible and influenced by time, dose and administration conditions. Susceptibility to the psychotomimetic effects of ketamine is minimal or absent in children and becomes maximal in early adulthood. The similarity between ketamine effects and endogenous psychoses created interest in the capacity of antipsychotic medications to block ketamine effects. Haloperidol failed to block this ketamine-induced psychomimetic effects in healthy subjects and in schizophrenic patients. However, clozapine, the prototype of atypical antipsychotic agents significantly reduced the ketamine-induced increase in positive symptoms in schizophrenic patients. Recently, lamotrigine significantly decreased ketamine-induced positive and negative symptoms in healthy subjects. Brain regions responsible for NMDA-mediated psychosis have not been established. Using positron emission tomography and [18F] fluorodeoxyglucose, the sub-anesthetic ketamine administration produces bilateral increases in metabolic activity in the prefrontal cortex. In a [15O] H2O positron emission tomography study, ketamine selectively increases cerebral blood flow in the anterior cingulate cortex and reduces cerebral blood flow in the hippocampus and primary visual cortex. The mechanism of neuropsychiatric effects of sub-anesthetic ketamine is not clear. A dysfunction in glutamate-dopaminergic interactions has been suggested as a mechanism for these effects of ketamine. Ketamine has been reported to primarily block NMDA receptor complex giving support to a glutamate deficiency hypothesis in schizophrenia. In addition, ketamine caused increases in cortical and striatal synaptic dopamine concentrations. The effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

Brain↗

PubMedDate not supplied

[Pharmacological modulation of the effects induced by ketamine at subanesthetic doses].

The similarity between ketamine effects and endogenous psychoses has created interest in the capacity of antipsychotic medications to block ketamine effects. In healthy subjects, a sub-anaesthetic single dose of lorazepam, typical neuroleptics, such as haloperidol, and atypical neuroleptics, such as clozapine and olanzapine, failed to block ketamine-induced positive and negative symptoms resembling schizophrenia. However, haloperidol is able to decrease ketamine-induced impairment in executive cognitive functions. Recently, lamotrigine reduced ketamine-induced psychotic symptoms, perceptual alterations, and cognitive impairments. In schizophrenic subjects, single doses of olanzapine do not decrease the effects of ketamine. However, long term treatment with clozapine has been reported to decrease ketamine-induced positive symptoms. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

Anesthetics, Dissociative↗

PubMedDate not supplied

[Vulnerability to schizophrenia. I: Familial nature of of neuropsychologic indicators].

The existence of a genetic background is now a well admitted notion in schizophrenia, but some individuals at genetic risk for that disease could never manifest it at a clinical level. However, several vulnerability models could help us to identify such individuals. According to them, when similar perturbations at a given test are observed both in clinically stable schizophrenics and their nonschizophrenic first degree relatives, this test could be qualify as an indicator of the vulnerability to schizophrenia. In literature, that seems the case for several neuropsychological tasks, exploring attentional abilities (degraded version of the Continuous Performance Task [DS-CPT], and Span Of Apprehension task [SOA]) and executive functions (Wisconsin Card Sorting Test [WCST]). Our study was undertaken to replicate literature data and to further explore the relationship between these three neuropsychological markers. For that purpose, performances at DS-CPT, SOA and WCST were assessed among 18 clinically stable schizophrenics, 18 of their biological full siblings and 15 unrelated control subjects matched with the two others groups for several socio-demographic factors. Comparisons were performed by non parametric analysis (Kruskal-Wallis one way ANOVA, and Mann-Whitney). Compared to controls, the siblings group performances were significantly impaired on the three tasks, while they did not statistically differ from the schizophrenic ones. No relationship was observed between the markers, except for the "d'" index at DS-CPT and the number of successfully performed categories at the WCST. Results from the sibling group suggested that the observed impaired neuropsychological performances may actually represent indicators of the genetic vulnerability to schizophrenia. Moreover, the generally admitted relationship between WCST poor performances and an impairment of the prefrontal cortex, lead us to hypothesize some role of this brain area in schizophrenia vulnerability.

Adult↗

PubMedDate not supplied

[Basic cognitive-perceptive module in schizophrenics].

A specific deficit in gaze discrimination has been hypothesized for schizophrenic patients (Rosse et al., 1994). Gaze discrimination is a basic ability for animals as well as for human beings. It plays an important role in mutual control of social interactions. According to Baron-Cohen (1995), sensitivity to eye gaze relies on a specific cognitive module, the Eye Direction Detector (EDD). The author distinguishes three basic functions of the EDD; first, the EDD is involved in eyes detection; second, the EDD is used in order to establish direction of gaze, and specially to compute whether the eyes one is looking at are directed to the subject or somewhere else; third, the EDD is implied in interpretation of gaze as seeing. Rosse et al. (1994) tested subjective impressions concerning gaze discrimination in a group of schizophrenic patients. Schizophrenics reported the subjective impression of being looked at by the portraits significantly more often than controls. The authors concluded that a specific impairment in gaze detection is present in the patients, and that it may be responsible for the paranoid symptoms often reported in schizophrenia. However, it seems difficult to assert that a response bias in schizophrenics toward perceiving faces as looking at them results from the deficit of an elementary perceptual module responsible for the detection of eye-direction. Rather we suspect such a bias to be the consequence of an impairment of the more complex level of mindreading, responsible for the interpretation of gaze as seeing in terms of mental states. The aim of the present experiment was to test in a more specific way the elementary gaze discrimination system. A series of portraits of models looking at five different directions (-30 degrees, -15 degrees, 0 degree, 15 degrees, 30 degrees), have been presented to 22 schizophrenic patients and 36 normal control subjects. In each trial one portrait was presented. Subjects were asked to determine the direction of its gaze by pressing the "z-key" (left side of the keyboard) if the portrait was looking to the left, and the "/-key" (right side of the keyboard) if the portrait was looking to the right. For each trial, we recorded both the side of the response (left key or right key) and the corresponding reaction time (RT). For the purpose of the analysis, the mean numbers of left responses were computed for each subject. The mean numbers of left responses recorded for each direction of gaze did not significantly differ between patients and controls. That is schizophrenic patients are not impaired in the gaze discrimination task used in the present study. In Rosse's experiment, subjects were required to decide whether the portrait on the screen was looking at them or not. On the contrary, in our task, subjects were simply required to state whether gaze was directed to the right or to the left. No explicit judgment was required as to whom or what gaze was directed. Therefore, we can assume that the present paradigm investigated the functioning of a more basic process than that tested by Rosse et al. Our data are consistent with those reporting that basic cognitive processes are unimpaired in schizophrenia, whereas explicit processes are extensively affected.

Adult↗