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Emmanuel Stip

Publications and source records attributed to Emmanuel Stip.

17 recordsLinked to original sources

Self-assessed cognitive dysfunction and objective performance in outpatients with schizophrenia participating in a rehabilitation program.

OBJECTIVE: To explore the pattern of associations between self-assessed and objective neuropsychological performance in a sample of outpatients with schizophrenia participating in a rehabilitation program. METHOD: The Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) [Compr. Psychiatry 44 (2003) 331] was used to assess cognitive complaints in 73 subjects with schizophrenia. Visuo-spatial tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) [Cogn. Neuropsychiatry 3 (1998) 45] were administered as objective measures. RESULTS: Cognitive complaints in several cognitive domains were mainly correlated with a true difficulty in memory. Higher SSTICS attention scores, i.e. increased complaints, were associated with poorer CANTAB explicit visual memory and planning performances. Higher SSTICS executive functioning scores were associated with poorer CANTAB explicit visual memory scores. CONCLUSION: These findings suggest that outpatients with schizophrenia express some cognitive difficulties. However, the cognitive nature of these subjective complaints does not strictly correspond with objective performances. These results also suggest that theoretical constructs of cognitive functions do not always have ecological validity. Thus, subjective cognitive complaints should be taken into account in assessment of patient well-being, but cannot be used as a substitute to objective cognitive measures. The simultaneous use of subjective and objective measures of cognitive dysfunction may provide a more complete picture of individual rehabilitation targets in patients with schizophrenia.

Adult↗

Genes and memory: the neuroanatomical correlates of emotional memory in monozygotic twin discordant for schizophrenia.

BACKGROUND: Brain morphology and physiological measures in schizophrenia have yielded inconsistent results. This may be due in part to difficulties in ascertaining precisely to what degree each measure deviates from its genetically and environmentally determined potential level. We attempted to surmount this problem in a paradigm involving monozygotic twin pair discordant for schizophrenia. In this paradigm, the difference score and reaction time between the unaffected member and affected member of a twin pair should represent the degree of pathologic involvement irrespective of actual level. METHOD: We investigated, using fMRI, the neural substrate underlying encoding and retrieval of aversive and neutral IAPS pictures. RESULTS: An ANOVA on reaction time (RT) between schizophrenia patient (J) and normal sister (D) significant difference, (F = 5.2, p < or = .02) for J had less RT than D. Conversely, the ANOVA for the correct pictures retrieved was insignificant (F = 1.8, p < or = .2). When the brain activity associated with the encoding and retrieval of the aversive pictures was subtracted (J-D and D-J) from that associated with the neutral ones, significant loci of activation were found. During encoding: for J-D the right fusiform gyrus was significantly activated (p < .0001) and for D-J the orbitofrontal cortex was significantly activated (p < .05). During retrieval: for J-D the right anterior cingulate (p < .0001) was activated and the dorsolateral prefrontal cortex (p < .002). For D-J only the cerebellum showed activation (p < .0001). CONCLUSION: Results indicated subtle attenuations in some aspects of memory, thus providing another evidence for cognitive markers of a genetic component in schizophrenia. New approaches in neuropsychiatry-based on genetic methodologies should further define the cerebral physiology responsible for schizophrenia.

Adult↗

ERP study of pre-attentive auditory processing in treatment-refractory schizophrenia.

Event-related potential (ERP) studies have demonstrated impaired auditory sensory processing in patients with schizophrenia, as reflected in abnormal mismatch negativity (MMN). We sought to extend this finding by evaluating MMN in 13 treatment-refractory patients with schizophrenia, and 14 age- and gender-matched healthy controls. Subjects responded to infrequent visual stimulation while ignoring binaurally presented auditory tones. The amplitude and topographical pattern of the MMN were analyzed. The control group presented the expected reduction in the amplitude of the MMN from frontal to central and parietal locations. In comparison, the MMN amplitude was not reduced in the treatment-refractory patients, and was largest at the central-posterior electrode location. In addition, patients displayed larger negativities at left frontal, and left- and right-temporal electrode locations than the control subjects. These findings are consistent with pre-attentive abnormalities in treatment-refractory patients with schizophrenia.

Adult↗

Cognitive function and depression in symptom resolution in schizophrenia patients treated with an atypical antipsychotic.

OBJECTIVE: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. DESIGN: A prospective open trial with an atypical antipsychotic (olanzapine). PATIENTS: One hundred and thirty-four patients meeting diagnostic criteria for schizophrenia, schizophreniform or schizoaffective disorder began an 8-week open-label olanzapine treatment at a dose of 5 mg/day which was increased to 10 mg/day after one week. INTERVENTIONS: Olanzapine during 8 weeks. Patients were considered as responders if their BPRS score decreased of at least 20% (n = 96) and non-responders if it did not (n = 38). Neuropsychological assessments were carried out at baseline, at four and at eight weeks. RESULTS: Neurocognitive measures were analyzed for discriminate factors between responder and non-responder groups. A regression analysis was applied to explain the effects of depression on each cognitive variable. Depression was found to be a weak discriminant factor, however this finding could not firmly establish that depression is a potential factor in explaining deficits and improvements in cognition.

Affective Symptoms↗

Long-term effect of prefrontal lobotomy on verbal fluency in patients with schizophrenia.

OBJECTIVE: This study investigated the long-term effects of bilateral prefrontal leukotomy on lexical abilities in schizophrenia subjects. METHOD: we compared performances of leukotomized (LSP), non-leukotomized schizophrenia patients (NLSP) and normal controls, using a test of verbal fluency. Multiple case and triple comparison design were implemented. i.e., the performance of each LSP was compared to that of NLSP and that of a normal control. The sample consisted of four LSP, four NLSP, and four normal subjects. Subjects were matched in sex, age, handedness, and schooling. In Addition, schizophrenia groups were matched in diagnosis and years of hospitalization. Quantitative and qualitative analyses of generated words and errors produced by subjects were carried out. RESULTS: A deficiency in both groups of schizophrenia was observed, although a better performance in LSP patients was detected. CONCLUSION: Intact Lexical ability in LSP indicates its poor relation to the frontal lobe.

Aged↗

Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments.

BACKGROUND: Conventional and atypical antipsychotics have different affinities for D2 receptors, and these receptors are principally located in the striatum. Given that this cerebral structure was previously found to play a major role in procedural learning, the antipsychotic treatment in schizophrenia may be determinant for the procedural learning profile of these patients. OBJECTIVE: The current study was aimed at verifying whether procedural learning differs in patients with schizophrenia treated with conventional antipsychotics and patients treated with atypical antipsychotics. METHOD: Forty-five patients with schizophrenia were divided into 3 different groups according to their pharmacologic treatment: (1) haloperidol, a classical neuroleptic with high D2 receptor affinity; (2) clozapine, an atypical neuroleptic with practically no D2 receptor affinity; and (3) risperidone, an atypical neuroleptic that nevertheless shows high D2 receptor affinity. Patients were compared to 35 control subjects on a visuomotor procedural learning task (mirror drawing). RESULTS: All patients were able to learn the task. However, those treated with haloperidol showed some degree of learning impairment, while those treated with clozapine or risperidone did not show this impairment. In addition, performance per se, regardless of the learning, was found to be affected in the haloperidol and risperidone, but not in the clozapine groups. CONCLUSION: Procedural learning in schizophrenia may be differentially affected, depending on the pharmacologic profiles of the antipsychotics used for the treatment of this illness.

Adult↗

[Antipsychotic drugs. Risk factors for diabetes].

ANTIPSYCHOTICS AND DIABETES: After 50 years' use of antipsychotics, it is pertinent to draw-up a circumspect review of the side effects of these psychotropic agents. Moreover, few articles have attempted to elucidate the relationship between the monitoring of carbohydrate metabolism and the prescription of this type of medication. SEVERAL MECHANISMS AT THE ORIGIN OF AN IMBALANCE IN GLYCAEMIA: Antipsychotics, notably the atypical forms, represent an additional factor of risk for developing diabetes. The weight gain secondary to this treatment plays an important part in this imbalance, but other mechanisms may also contribute. DEPENDING ON THE TYPE OF ANTIPSYCHOTIC: Our present knowledge is insufficient to be able to quantify the effect of each atypical antipsychotic on diabetes. The only tendency that has been reproduced in several studies concerns the increased risk associated with dibenzodiazepine antipsychotics (clozapine and olanzapine), compared with the other antipsychotics.

Antipsychotic Agents↗

[Diabetes and schizophrenia, which links?].

UNLABELLED: WHAT IS OBSERVED: Epidemiology and clinical practice show an increased prevalence of diabetes in schizophrenic patients, preceding even the use of antipsychotics. Several patho-physiological mechanisms have been proposed to explain the phenomenon, although none is completely satisfactory. SEVERE CONSEQUENCES: Diabetic schizophrenics exhibit a significantly greater number of other physical diseases than non-diabetic schizophrenic patients. These diseases are at the origin of early mortality and reduced quality of life. THE NEED FOR SCREENING: Schizophrenic patients should be included in the groups of those at risk for diabetes, together with patients treated with anti-psychotics. Diabetes is diagnosed if fasting blood sugar is>7.0 mmol/L and a glucose tolerance test>11,1 mmol/L. IN PRACTICE: The epidemiology and extent of the impact on mortality and morbidity of the association between schizophrenia and diabetes mellitus requires particular attention of the practitioners and the screening for diabetes, its prevention and treatment must be conducted according to regularly updated guidelines.

Comorbidity↗

Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia.

The goal of the present study was to characterize sleep organization in first episode and neuroleptic-naive patients with schizophrenia and to evaluate relationships between those sleep parameters and clinical symptoms. Eleven patients with acute schizophrenia never treated with neuroleptics were compared to 11 healthy controls. Sleep stages and phasic events (sleep spindles and rapid-eye-movements during REM sleep (REMs) were visually identified. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Compared to controls, patients with schizophrenia had difficulty initiating sleep, decreased stage 4 duration, reduced rapid eye movement (REM) sleep latency, and normal sleep spindles and REMs densities. Positive symptoms correlated negatively with REM sleep latency. The BPRS total score correlated negatively with REM sleep duration and REMs density. The present results indicate that first episode and neuroleptic-naive patients with schizophrenia have difficulties initiating, but not maintaining, sleep. These results also confirm that the duration of stage 4 and REM sleep latency are reduced in first episode and neuroleptic-naive patients with schizophrenia. The fact that measures of REM sleep correlate with clinical scales of schizophrenia suggests that REM sleep physiology shares common substrates with symptoms of this disease.

Acute Disease↗

Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol.

RATIONALE: First generation antipsychotics induce extrapyramidal motor symptoms (EPS), presumably through dopamine D(2) receptor blockade at the dorsal striatum. This may also produce impairment of cognitive processes, such as procedural learning, that are dependent on this region. Haloperidol and, to a lesser extent, risperidone, are active in the dorsal striatum and may induce EPS and impairment of procedural learning. In contrast, the prototypical second-generation antipsychotic, clozapine, is less active in the dorsal striatum and does not induce EPS or impair procedural learning. Olanzapine is pharmacologically similar to clozapine and has a low incidence of EPS induction. OBJECTIVES: To assess the hypothesis that olanzapine would not have a deleterious effect on procedural learning. METHODS: Thirty-nine subjects with early phase schizophrenia were randomly assigned to double blind treatment with haloperidol, risperidone, or olanzapine. They were administered the Tower of Toronto test at an unmedicated baseline and again following 6 weeks and 6 months of treatment. RESULTS: Procedural learning, defined as the improvement observed between two blocks of five trials of the Tower of Toronto, was preserved after 6 weeks of all three treatments but showed a substantial decline after 6 months of treatment with haloperidol or risperidone. CONCLUSIONS: These data are consistent with the differential activity of the three medications in dorsal striatum structures and suggest that the advantages of olanzapine over haloperidol and risperidone in relation to extrapyramidal syndromes may also generalize to procedural learning. The results also suggest that the procedural learning disadvantages of haloperidol and risperidone accrue slowly but are apparent after 6 months of treatment.

Adolescent↗

A Canadian multicenter trial assessing memory and executive functions in patients with schizophrenia spectrum disorders treated with olanzapine.

Serial verbal learning task (explicit long-term memory) and verbal fluency (generation of a response) are tests that are usually severely impaired in schizophrenia. Despite the growing literature supporting the clinical efficacy of olanzapine, psychiatrists still question its cognitive consequences. This study assessed the efficacy of olanzapine on neurocognitive functioning. Patients (N = 134) meeting diagnostic criteria for schizophrenia, schizophreniform, or schizoaffective disorders began an 8-week, open-label olanzapine treatment at a dose of 5 mg/d, which was increased to 10 mg/d after 1 week. Daily dosage was subsequently adjusted between 5 and 20 mg/d based on individual clinical status. All previous antipsychotics were tapered and discontinued during the first 2 weeks of the study. Neuropsychologic assessments were carried out at baseline and at 4 and 8 weeks. Explicit long-term memory was assessed with the Rey Auditory-Verbal Learning Test: the average immediate recall score significantly improved (P < 0.001), as did the delayed recall score (P < 0.001). The average total score on category fluency improved from 34.6 words at baseline to 37.6 words at end point (P < 0.0001). Time on both Trail A and B making tasks significantly decreased (P < 0.0001). Lack of a control arm makes it impossible to exclude a practice effect as an explanation for the enhanced cognitive performance, although the Word List Recall test represents one of the better resources to avoid a practice effect. After switching to olanzapine, there was a statistically significant improvement of cognitive function in the 3 main domains tested and no significant worsening of any memory or executive function measure.

Acoustic Stimulation↗

Clozapine, quetiapine and olanzapine among addicted schizophrenic patients: towards testable hypotheses.

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.

Affect↗

Mild procedural learning disturbances in neuroleptic-naive patients with schizophrenia.

This study investigated whether drug-naive patients with schizophrenia present procedural learning disturbances, given that this function is known to involve the striatum and that structural abnormalities of the striatum have been described in these patients. Eleven neuroleptic-free schizophrenic patients were compared with 11 healthy control subjects on a visuomotor procedural learning task (the Mirror Drawing Test). Average performance and learning rate did not differ between the two groups. However, schizophrenia patients were lower in learning smoothness (the consistency with which performance improves from trial to trial), which would indicate difficulty in benefiting from past experience to perform better on a current task. Because low smoothness has recently been found to be associated with striatal dysfunction, these results might indicate a premature dysfunction of the striatum in young drug-naive patients with schizophrenia. However, this dysfunction is not severe enough to prevent learning.

Adult↗

Happy birthday neuroleptics! 50 years later: la folie du doute.

Given that we are celebrating the 50th birthday of neuroleptics introduction in psychiatry, the author proposes to take a look at certain results related to therapeutic practice. After a brief chronological literature review of the clinical practices and theoretical models that have controlled drug treatment of schizophrenia, the author presents a critical review of four meta-analyses. Since Delay, Deniker and Harl's initial report, the story of neuroleptics comprises several periods. In 1963, the hyper-dopaminergic theory of psychoses was proposed. Another period began with models mainly based on the serotonin/dopamine relative blockade receptor hypothesis. More recently, a new framework to understand the differential effect of antipsychotics is related to the appropriate modulation (e.g., fast dissociation) of the D2 receptor alone. The concept of atypicality has become a new vista for research and to market new compounds. However, after 50 years of neuroleptic drugs, are we able to answer the following simple questions: Are neuroleptics effective in treating schizophrenia? Is there a difference between atypical and conventional neuroleptics? How do the efficacy and safety of newer antipsychotic drugs compare with those of clozapine? Actually, the answers yielded by these simple questions by meta-analysis should elicit in us a good deal of humility. If we wish to base psychiatry on evidence-based medicine, we run a genuine risk in taking a closer look at what has long been considered fact. Each psychiatrist must continue to be critical, sceptical, optimistic (not overoptimistic) and to learn in order to integrate the positive aspects of our growing knowledge base.

Antipsychotic Agents↗

Cerebral activity associated with auditory verbal hallucinations: a functional magnetic resonance imaging case study.

Among the many theories that have been advanced to explain the mechanism by which auditory verbal hallucinations (AVH) arise, 2 that have received a degree of empirical support are: the hypothesis that AVHs arise from misinterpreted inner speech and the proposal that they arise from aberrant activation of the primary auditory cortex. To test these hypotheses, we were fortunate to be able to study the interesting and rare case of a woman with schizophrenia who experienced continuous AVH which disappeared when she listened to loud external speech. Functional magnetic resonance imaging (fMRI) was used to measure the patient's brain activity in the temporal and inferior frontal regions during the AVHs and while the she was listening to external speech. The brain activity of a matched control subject was also recorded under the same experimental conditions. AVHs were associated with increased metabolic activity in the left primary auditory cortex and the right middle temporal gyrus. Our results suggest a possible interaction between these areas during AVHs and also that the hypotheses of defective internal monitoring and aberrant activation are not mutually exclusive. Potential limitations to the generalization of our results are discussed.

Adult↗