Need for a new framework to understand the mechanism of all antipsychotics.
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Biomedical subjects
Publications and source records attributed to E Stip.
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The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown.
UNLABELLED: To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. DESIGN: a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). SETTING: Inpatient and outpatient units, Institute of Psychiatry. PATIENTS: Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. INTERVENTIONS: New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). OUTCOME MEASURES: a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. RESULTS: A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. CONCLUSION: Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.
BACKGROUND: In his or her practice, a psychiatrist must often deal with patients who refuse treatment. In 1990, Quebec radically changed this situation by introducing a Civil Code provision imposing judicial intervention to treat an individual deemed unfit to consent, against his or her will. This paper presents an assessment and survey of patients and attending psychiatrists who have used this Code provision. METHOD: Thirty-nine subjects who explicitly refused treatment were brought to court. We asked a subgroup of these patients to be interviewed, using the Drug Attitude Inventory (DAI), the Clinical Global Impression (CGI), and 2 questionnaires specifically considering the court experience of patients and attending psychiatrists. RESULTS: The results of the survey show that patients remember their experience in court as rather uncomfortable. However, the therapeutic alliance remained unchanged, even after the legal procedure. Physicians agreed that patients would not have been clinically well enough to leave the hospital if they had not received the drug regimen resulting from the court decision. The dissociation between the perceptions of patients and physicians is compared with that found in previous studies in the United States. CONCLUSION: Even with a limited sample, this study addresses a delicate, difficult situation that professionals are increasingly likely to confront. It also proposes further research on alternatives to judicial intervention.
OBJECTIVE: To review the literature on the permanent neurological sequelae resulting from acute lithium poisoning. METHOD: Sixty-six articles were reviewed in English and in French. They were accessed through Medline and cover the period from 1968 to 1997. RESULTS: Fifty-nine case studies were broken down into 3 groups: lithium intoxications without a neuroleptic that has provoked a cerebellar syndrome; those in which there was a neuroleptic; and those with diverse neurological consequences, with or without a neuroleptic. CONCLUSIONS: Lithium has an intrinsic toxicity for the central nervous system and provokes a tropism specific to the cerebellum. The association with neuroleptics appears to increase toxicity as well as some associated factors, including infections and the rapid correction of the lithium level in the blood. We discuss the psychopathological mechanisms invoked to explain lithium's neurotoxicity.
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An important issue regarding the neural basis of major depression is whether the functional brain changes associated with the affect disturbance seen in this syndrome are similar to those that accompany transient sadness in normal subjects. To address this question, we carried out an fMRI study using an emotional activation paradigm. Brain activity associated with passive viewing of an emotionally laden film clip aimed at inducing a transient state of sadness was contrasted with that associated with passive viewing of an emotionally neutral film clip in patients suffering from unipolar depression and in normal control subjects. Results showed that transient sadness produced significant activation in the medial and inferior prefrontal cortices, the middle temporal cortex, the cerebellum and the caudate in both depressed and normal subjects. They also revealed that passive viewing of the emotionally laden film clip produced a significantly greater activation in the left medial prefrontal cortex and in the right cingulate gyrus in depressed patients than in normal control subjects. These findings suggest that these two cortical regions might be part of a neural network implicated in the pathophysiology of major depression. Taken together, these results strongly support the view that activation paradigms represent an extremely useful and powerful way of delineating the functional anatomy of the various symptoms that characterize major depression.
This study explored the mechanisms underlying the hypermnesia of an autistic savant (NM) through three experiments. The first two served to assess whether absence of interference was responsible for NM's exceptional list memory. The third investigated the type of cues used in recall. Results indicated absence of retroactive interference but presence of slight proactive interference in list recall of proper names. Normal interference effects were found, however, in list recall of common nouns. Exceptional performance was also demonstrated in a missing-name task involving spatial and verbal recall cues. The findings suggest that the outstanding episodic memory presented by some savant persons with autism might be related to an abnormally high resistance to interference.
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Lithium is a neurotoxin with a particular affinity for the cerebellum. The risk of permanent neurotoxic sequelae of lithium is increased by the concomitant use of certain conventional neuroleptics. We report two new cases of lithium neurotoxicity; one received lithium alone, not in combination with a neuroleptic. Both cases showed severe cerebellar atrophy on brain CT and MRI. Additional factors such as dehydration, systemic infection, other medications, or rapid correction of frequently-coexisting hyponatremia may contribute to the risk of lithium neurotoxicity. We discuss possible pathophysiologic mechanisms and preventive measures.
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The case study of an autistic "savant" subject with person names hypermnesia is presented. NM's performance in memorizing person names is compared to that of normal controls, IQ-matched controls, and one overtrained control. The data show a selective hypermnesia for both the free recall of person names and the recognition of faces. Recall of common names and of biographical informations linked to faces is unremarkable. NM's hypermnesia is restricted to list learning as low performance is observed in face-name learning tasks. A comparison of the data with that of the overtrained control indicates that training is not responsible for NM's pattern of results. These findings, when combined with previous results involving proper names, demonstrate a double dissociation between proper names and other types of semantic and referential information. However, aspects of NM's performance pattern are more compatible with a network model of proper names than with a sequential model. We propose that the contextual regularity of proper names in ecological situations can be responsible for their high memorization by NM.
OBJECTIVE: to trace the evolution of hypotheses concerning Capgras' syndrome. METHODS: The data consist of slightly over 60 studies published between 1866 and 1994 which were selected in terms of their innovative nature and relevance to the clinical description of the syndrome and to psychodynamic, neurological and neuropsychological interpretations. RESULTS: Two partially overlapping major stages can be identified in the evolution of hypotheses regarding the mechanisms of the syndrome. The 1st, beginning in 1923, is characterized by the predominance of psychodynamic interpretations. The 2nd, resulting from the observation of organic dysfunctions in a high percentage of cases, is distinguished by the advent of neurological interpretations, and by a few mixed hypotheses. CONCLUSIONS: Overall, this review highlights the broad diversity of viewpoints concerning the syndrome. It will be used as a basis for the following study, which is designed to show that it is possible to test each of the viewpoints experimentally.
OBJECTIVE: To examine the way in which certain concepts regarding the physiopathology of Capgras' syndrome (1) have been tested neuropsychologically. METHODS: Data consist of approximately 30 studies selected for their relevance to the cerebral stages of face processing in patients with schizophrenia, patients with Capgras' syndrome and normal subjects. RESULTS: Study of this work shows: a) that with respect to patients, authors have focused on the stage of treatment corresponding to the facial recognition phase per se; b) but that it is also possible to study the phase corresponding to knowledge and beliefs relative to individuals and to evaluate the existence of the cleavage proposed by numerous psychodynamicians. CONCLUSIONS: Views from the field of neuropsychology, like those from the field of psychodynamics, can therefore be tested. By offering a means of developing testable predictions in experimental protocols, cognitive neuropsychology methods will, in short, make it possible to reject erroneous concepts and demonstrate accurate ones. Limited here to the example of Capgras' syndrome, we advocate that the same methods be applied to Capgras' syndrome as to each symptom of schizophrenia.
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