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To evaluate the long-term clinical benefit and effectiveness of switching to once-daily quetiapine extended release (XR) from an oral antipsychotic in patients with schizophrenia. Reasons for switching included insufficient efficacy, tolerability, and/or non-acceptability. The primary endpoint was the percentage of patients achieving an improvement in Clinical Global Impression - Clinical Benefit (CGI-CB) scale scores.A 24-week, international, multicentre, open-label, prospective study ( www.clinicaltrials.gov : NCT00640601). After a 7-14 day enrolment period (depending whether prior antipsychotic mono- or combination therapy), all patients received quetiapine XR 300 mg once daily (day 1), 600 mg/day (day 2), 600-800 mg/day (day 3) and 400-800 mg/day thereafter, with down-titration and discontinuation of prior antipsychotic by day 4.A total of 62% of patients completed the study and 56.9% (LOCF, ITT) achieved a significant improvement in CGI-CB (95% CI [0.51, 0.63]; p = 0.02). Switches due to insufficient efficacy showed a significant improvement (60%, 95% CI [0.51, 0.68]; p = 0.02), compared to 54.4% ([0.44, 0.64]; p = 0.38) and 52.4% ([0.36, 0.68]; p = 0.76) of switches due to insufficient tolerability and non-acceptability respectively (both p = ns). Patients previously on olanzapine and quetiapine IR showed a significant improvement in CGI-CB (62.6% [p = 0.02] and 61.2% [p = 0.04], respectively). Somnolence (18.0%) and dizziness (14.6%) were the main adverse events. Anticholinergic use decreased from 7.1 to 2.7%. Overall mean weight gain was 0.4 kg; 12.9% of patients experienced a weight gain of ≥7% and 15% experienced a clinically relevant shift in triglycerides from baseline.A majority of patients switched from other antipsychotics to quetiapine XR experienced clinical benefit. This was supported by all other efficacy outcomes regardless of the reason for switching. Safety data confirmed quetiapine XR was safe and well tolerated. The open-label design and lack of a placebo group represent limitations.

ResumenDado que celebramos el quicuagésimo cumpleaños de la introducción de los neurolépticos en psiquiatría, el autor propone echar un vistazo a algunos resultados relacionados con la práctica terapéutica. Después de una breve revisión cronológica de las publicaciones de las prácticas clínicas y los modelos teóricos que han controlado el tratamiento farmacológico de la esquizofrenia, el autor presenta una revisión crítica de cuatro meta-análisis. Desde el informe inicial de Delay, Deniker y Harl, la historia de los neurolépticos comprende varios períodos. En 1963 se propuso la teoría hiperdopaminérgica de la psicosis. Otro período comenzó con los modelos basados principalmente en la hipótesis del bloqueo relativo de los receptores de serotonina/dopamina. Más recientemente, un nuevo marco para comprender el efecto diferencial de los antipsicóticos se relaciona con la modulación apropiada (por ejemplo, la disociación rápida) del receptor D2 solo. El concepto de atipicidad se ha convertido en una nueva perspectiva para la investigación y para comercializar nuevos compuestos. Sin embargo, después de 50 años de fármacos neurolépticos, ¿podemos responder a las simples preguntas siguientes?: ¿Son los neurolépticos eficaces en el tratamiento de la esquizofrenia? ¿Hay diferencias entre los neurolépticos atípicos y los convencionales? ¿Cuál es la eficacia y la seguridad de los nuevos medicamentos antipsicóticos comparado con la eficacia y la seguridad de la clozapina? En realidad, las respuestas que los meta-análisis dan a estas simples preguntas deberían provocar en nosotros una gran humildad. Si deseamos basar la psiquiatría en la medicina basada en la evidencia, corremos un riesgo real al mirar más de cerca a lo que durante mucho tiempo se han considerado hechos. Cada psiquiatra debe continuar siendo crítico, escético y (no excesivamente) optimista y aprender para integrar los aspectos positivos de nuestra base creciente de conocimientos.

Given the extent, magnitude and functional significance of the neurocognitive deficits of schizophrenia, growing attention has been paid recently to patients' self-awareness of their own deficits. Thus far, the literature has shown either that patients fail to recognize their cognitive deficits or that the association between subjective and objective cognition is weak in schizophrenia. The reasons for this lack of consistency remain unexplained but may have to do, among others, with the influence of potential confounding clinical variables and the choice of the scale used to measure self-awareness of cognitive deficits. In the current study, we sought to examine the relationships between subjective and objective cognitive performance in schizophrenia, while controlling for the influence of sociodemographic and psychiatric variables.Eighty-two patients with a schizophrenia-spectrum disorder (DSM-IV criteria) were recruited. Patients' subjective cognitive complaints were evaluated with the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), the most frequently used scale to measure self-awareness of cognitive deficits in schizophrenia. Neurocognition was evaluated with working memory, planning and visual learning tasks taken from Cambridge Neuropsychological Tests Automated Battery. The Stroop Color-Word test was also administered. Psychiatric symptoms were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. The relationships between subjective and objective cognition were evaluated with multivariate hierarchic linear regression analyses, taking into consideration potential confounders such as sociodemographic and psychiatric variables. Finally, a factor analysis of the SSTICS was performed.For the SSTICS total score, the regression analysis produced a model including two predictors, namely visual learning and Stoop interference performance, explaining a moderate portion of the variance. Visual learning performance was the most consistent predictor of most SSTICS subscores (e.g. episodic memory, attention, executive functioning, language and praxis). Modest associations were found between the PANSS cognitive factor and objective cognition (e.g. Stroop interference, visual learning, and working memory). Finally, the factor analysis revealed a 6-factor solution that echoes the classification of the items of the SSTICS based on the neuropsychological literature.Using a scale having good internal validity, as shown by the factor analysis, the current study highlighted modest associations between subjective and objective cognitive performance, which suggests that schizophrenia patients are only partially aware of their own cognitive deficits. The results also showed a lack of correspondence between the impaired cognitive domain and the domain of cognitive awareness. It should be noted that clinicians were not better than patients at evaluating their cognitive deficits. Future research will need to determine if the observations reported here are schizophrenia-specific or not.

Background: Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium. The aim of the study was to look at the effect of lithium in normal subjects (N=30) taking lithium for 3 weeks. A comprehensive battery was used to assess attention and memory. Methods: Subjects were randomized to double-blind treatment with either lithium (N=15) or placebo (N=15) for a 3-week period. Thirteen participants in the lithium group and 15 in the placebo group completed the study. The lithium and placebo were administered twice daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The initial daily dose was calculated according to the Pepin formula to achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive performance (attention, memory) was assessed in each subjects during three periods, i.e. at baseline, after 3 weeks of lithium or placebo, and 2 weeks after discontinuation of study medication. Results: In short-term memory tasks, the performance of subjects in the lithium group was worst 3 weeks after lithium treatment compared to 2 weeks after discontinuation. In long-term memory, a significantly higher number of words was recalled by the placebo group but not the lithium group. Conclusions. Lithium may have an effect on learning when long-term explicit memory test are administered repeatedly. It means that the practice effect when a subject performs the same task several times is less in the lithium-treated group than in the placebo group. This practice effect is related to the learning of a task.

ResumenIdentificar qué mejoras en la función cognitiva se asocian con la resolución de los síntomas en pacientes esquizofrénicos tratados con antipsicóticos atípicos. Diseño: un ensayo abierto prospectivo con neuroléptics atípicos (risperidona, clozapina, quetiapina). Entorno: Unidades de pacientes hospitalizados y ambulatorios. Pacientes: Se incluyeron 39 pacientes con esquizofrenia según los criterios del DSM-IV. La evaluación clínica y cognitiva se hizo en la línea de base (T0) y de nuevo después de seis meses de tratamiento (T2). Veinticinco pacientes completaron el ensayo. Intervenciones: Antipsicóticos de nueva generación durante seis meses. Se consideraba que los pacientes respondían si su puntuación de la PANSS disminuía el 20% al menos (n= 15), y que no respondían si no lo hacía (n= 10). Medidas de evolución: una evaluación cognitiva informatizada comprendía pruebas de memoria a corto plazo (amplitud de dígitos), memoria explícita a largo plazo explícita (aprendizaje de pares de palabras), atención dividida, atención selectiva y fluidez verbal (ortográfica y semántica). La evaluación clínica incluía la PANSS y la ESRS. Resultados: Se realizó un análisis de función discriminante para determinar qué cambios en el rendimiento cognitivo predecían la condición de respuesta de los síntomas. La fluidez semántica y la fluidez ortográfica fueron predictores significativos. Juntos, predecían correctamente la condición de respuesta en el 88% de los casos. La memoria no fue un predictor significativo de la respuesta de los síntomas. Conclusión: la fluidez verbal discriminó al grupo de pacientes con respuesta del grupo de los pacientes sin ella durante un tratamiento farmacológico.

Background In much of the world, general practitioners (GPs) are the health professionals most frequently initially contacted when a young person is developing psychosis. However little is known about their expertise in assessing psychosis and its risk. Methods To assess the diagnostic patterns and treatment practices related to psychosis of GPs working in a range of health care systems, questionnaires were mailed to 12,516 randomly selected GPs in seven countries: Canada, Australia, New Zealand, England, Norway, Austria and the Czech Republic. Sites were defined as gatekeeping or non-gatekeeping, based on the primary care health system in effect at each site. A gatekeeping system (GK) is one which mandates that patients see a GP before in order to be referred to a specialist. By contrast, in a non-gatekeeping (nGK) system, individuals can seek help directly from specialists without authorization by a GP. Results Twenty-two percent (n = 2784) GPs responded to the mailed questionnaire. They reported low prevalence of early psychosis seen in general practice. Using awareness of functional decline as a prognostic sign as a proxy, gatekeeping (GK) GPs were found to be superior in their knowledge of the signs and symptoms of early psychosis than were non-gatekeeping GPs. GP's with less knowledge as to early psychosis were more likely to refer individuals with suspected psychosis to specialists. GP's reported a preference for access to specialized outpatient services as compared with obtaining continuous medical education relevant to early psychosis. The duration of maintenance treatment recommended by GP's was less than that recommended in international guidelines. GP's also underestimated the risk for relapse after a first episode of psychosis. Conclusions As GPs were largely unaware of features of early psychosis, such as functional decline, this should be the target of educational programs for GP's. However, the incidence of psychosis is low and GP's express a preference for access to appropriate referral over continuing medical education. Therefore, the development of specializ ed services for the assessment and care of patients who are in the early stages of developing schizophrenia may be warranted.

This article reviews the cognitive phenomenology of delusional disorders (DD) and examines the current cognitive models. Some case studies have shown considerable promise concerning the utilisation of cognitive behavioral therapy (CBT) for the treatment of DD, even if this approach is in its infancy. Although the stages of CBT to treat DD are very similar to that of other psychotic disorders, there are also considerable differences. However, it is essential to combine several strategies in order to modify inferences specific to DD. The clinical evaluation of delusions as well as the application of CBT as a treatment is illustrated in two cases with a diagnosis of DD with persecutory subtype. The cases required different time periods for different stages of CBT and highlight the importance of tailoring CBT according to need.

Cognitive therapies of delusions and hallucinations are increasingly common and offer a complementary or interesting alternative to neuroleptic medication. But then again must these therapeutic approach relie on an explanatory neuropsychological basis. According to many observers, the study of the cardinal symptoms of schizophrenia is the " royal path " leading to the elucidation of this disabling and chronic illness affecting around 0,5% to 1% of the population. In this perspective, auditory hallucinations are one of the major symptoms of schizophrenia found in 50% to 80% of cases. Recently, experimental data drawn from cognitive neuropsychology and functional magnetic resonance imaging studies have allowed the elaboration of many models regarding this symptomatic manifestation. This article proposes a literature review on the subject of psychopathology and neurobiological bases of auditory hallucinations in schizophrenia and aims at proposing some leads that could contribute to a better undertanding of this phenomenon.

Cognitive impairments are a core feature in schizophrenia. They impact several cognitive abilities but most importantly attention, memory and executive functions, consequently leading to great difficulties in everyday life. Most schizophrenia patients need assurance and require assistance and help from care workers, family members and friends. Family members taking care of a patient have additional daily work burden, and suffer psychological anguish and anxiety. Therefore, improving cognitive functions in schizophrenia patients is essential for the well-being of patients and their relatives. Reducing these deficits may decrease the economic burden to the health care system through lower numbers of hospital admissions and shorter hospitalisation periods, for example. Cognitive rehabilitation was developed to address the limited benefits of conventional treatments on cognitive deficits through the use of assistive technology as a means of enhancing memory and executive skills in schizophrenia patients.To provide clinicians with comprehensive knowledge on cognitive trainings, programs of remediation, and cognitive assistive technologies.Literature review. A search in the electronic databases (PubMed, EMBASE, Index Medicus) for recent articles in the last 10 years related to cognitive remediation published in any language using the words: cognitive and remediation or rehabilitation and schizophrenia, and a search for chapters in psychiatry and rehabilitation textbooks.We found 392 articles and 112 review paper mainly in English. First, we identified cognitive remediation programs that were beneficial to schizophrenia patients. Programs available in French (IPT, RECOS, and RehaCom) and others (CET, NET, CRT, NEAR, APT and CAT) were identified. In addition, since memory and executive function impairments could be present in people without schizophrenia, we reviewed inventories of cognitive assistive technologies proven to enhance cognitive skills in other populations. Finally, we present a review of recent studies testing innovative devices developed to assist schizophrenia patients.First, we found several cognitive programs proven to be effective with schizophrenia patients, but only three were validated in French. It could be useful to adapt other programs for French-speaking populations. Unfortunately, we found that very few of the existing cognitive assistive technologies are proposed to be used with schizophrenia patients. In fact, most of the available cognitive orthoses were tested primarily in people with neurological injuries (for example, various memory impairments caused by traumas), and in elderly illnesses (like Alzheimer disease). Devices for patients with mental deficits (e.g., mental retardation) were developed later, and only very recently explored for use in schizophrenia. As a result of an international collaboration between France and Canada, currently a tool called MOBUS is being tested. This technology aims at improving the autonomy of schizophrenia patients, by helping them plan and remember their daily activities. Furthermore, it encourages patient-caregiver communication, and permits monitoring patients' subjective reports of their symptoms. The use of cognitive assistive technologies is not meant to isolate patients by replacing the human element of relatives and caregivers by a machine. On the contrary, they offer a sense of security and they improve interpersonal relationships by permitting enhanced autonomy and greater self-confidence. Finally, a literature review of cognitive remediation in schizophrenia emphasizes the importance of a structured application of the technique in order for it to succeed. First, it is crucial to detect the impairments that will be targeted in each patient presenting a specific pattern of impairments. For this purpose, validated and customised neuropsychological tests are required. Then, cognitive remediation programs must be customised to each patient's needs in order to motivate the patient to participate. Finally, long-term effects must be assessed in order to verify whether reinforcement is needed. Following these steps, most of the studies show an improvement in the well-being of patients with schizophrenia. These recommendations are also suitable for the cognitive remediation programs, as for treatments with cognitive assistive devices. An important hurdle facing the advance of cognitive assistive technology programs is that different research groups work individually without a coordinated effort to improve and validate the existing programs.Schizophrenia treatments must take into account not only patients' symptoms, but also the associated cognitive deficits which constitute an important factor in their social problems. It has been shown that several cognitive remediation programs are efficient in schizophrenia. New technologies complement the benefits of such programs, and support pharmacological treatments and psychotherapies.

In this review, we conclude that cognitive impairments are as important as positive and negative symptoms in the clinical assessment and management of patients with schizophrenia. This is not a comprehensive review, considering that the new Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) model will soon provide valuable data. It is however a product of the collective efforts of a French Canadian clinical research team that proposes a synthesis of data of pragmatic interest to clinicians. Medication with improved safety and cognition profile, gene-rally lead to better outcomes by facilitating compliance with drug regimens and rehabilitation programs. In addition, measures of attention and executive function (EF) appear to improve with novel antipsychotics when compared to traditional neuroleptics. Nevertheless, evaluating cognitive performance is not a routine procedure outside the domain of research. For example, procedural learning (PL) -- an important measure of cognitive function -- refers to cognitive and motor learning processes in which execution strategies cannot be explicitly described (ie learning by doing). These actions or procedures are then progressively learned through trial and error until automation of optimal performance is established. Procedural learning is rarely assessed in clinical practice. Inconsistent findings regarding the effects of neuroleptic drugs on PL have been reported.Trials using acute administration of chlorpromazine in normal subjects induced PL deficits, suggesting the direct effect of neuroleptics, presumably via a D(2) dopamine blockade in the striatum. In a recent study by our group, schizophrenia patients, divided into three groups according to their pharmacological treatment (haloperidol, clozapine and risperidone) were compared to normal controls on two PL tasks; a visuomotor learning task (mirror drawing) and a problem solving learning task (Tower of Toronto). No deficits were detected in patients receiving clozapine, while haloperidol was associated with deleterious effects in both tasks. Risperidone, however, produced different effects depending on the task performed. Another 6-month double-blind Canadian study confirmed the beneficial effect of olanzapine on PL compared to haloperidol and risperidone. The differential effects of drugs on the striatal D(2) receptors, -irrespective of their classification as conventional or atypical neuroleptics and the specific process implicated in each of these PL tasks may explain these results. Tracer studies using radioactive benzamides (IBZM) specific to striatal D receptors determined a relationship between striatal D(2) receptor occupancy and PL performance such as the mirror drawing task. Using this method, data obtained in Montreal on schizophrenia patients receiving olanzapine and haloperidol have shown that the coefficient of determination in a visuomotor PL task varied inversely with D2 receptor saturation.This review probes the effect of impaired cognitive functions on schizophrenia patients' quality of life. Cognitive deficits found in schizophrenia affect planning, along with the aptitude to initiate and -regulate a goal-directed behaviour. These impairments have been repeatedly, yet inconclusively, attributed to frontal lobe dysfunction. Morphological findings obtained from neuroimaging studies remain inconsistent, some noting no differences between patients and controls while others observing reduced prefrontal volumes in schizophrenia patients. Conversely, functional neuroimaging (fMRI) demonstrated reduced frontal blood flow relative to global cerebral perfusion in schizophrenia patients. Overall, neuroimaging literature provides reliable evidence of frontal impairments in schizophrenia, although the average magnitude of difference between patients and controls is insufficient to defend a frontal lobe dysfunction hypo-thesis, as far as brain volume, resting cerebral metabolism or blood flow are concerned. The only measurement clearly distinguishing between patients and controls is fMRI of the frontal lobe while performing an experimentally controlled task. Here, schizophrenia patients fail to activate their frontal cortex when required. Sensitive to frontal lobe dysfunction are Neuropsychological tests of executive function.A study conducted in Montreal assessed the relation between EF impairments and difficulties in planning daily activities in schizophrenia patients scoring more than 3 on at least 4 items of the PANSS negative subscale. Performances on EF, memory and script generation were measured and compared to controls. Script production task required that subjects recite 10-20 actions that would normally be carried out for during daily life activity (going to a restaurant, buying groceries, etc.). Patients' performances were significantly lower with higher perserveration and sequencing impairments. Routine activities such as the ability to cook a meal were similarly investigated. Patients were videotaped in a kitchen while preparing a specific meal.Optimal sequence of micro- and macro-steps necessary to prepare the meal in a minimal time were measured. Sequencing errors, repetitions and omissions were significantly higher compared to controls. In addition, temporal organization was positively correlated with negative symptoms and low EF performance on neuro-psychological tasks. Thus concluding that EF impairment interferes with basic routine activities in schizophrenia patients, notably those with negative symptoms. Last but not least, we assessed the progress of patients' subjective complaints with regards to their cognitive functions using tests such as the SSTICS, specifically developed to address subjective cognitive complaints and insight.This review concludes that from now on cognitive deficit should be recognized as a major element in social and professional integration of schizophrenia patients, and should become a standardized assessment approach in clinical practice.

The main goal of this functional Magnetic Resonance Imaging (fMRI) study was to verify the hypothesis that seriously violent persons with Sz and the co-morbid diagnoses of an Antisocial Personality Disorder (APD) and a Substance Use Disorder (Sz+APD+SUD) would present a different pattern of prefrontal functioning than seriously violent persons with Sz only. In support with the main hypothesis, frontal basal cortices were significantly less activated in persons with Sz+APD+SUD during the execution of a go/no-go task than in persons with Sz only and non-violent persons without a mental illness. In contrast, significantly higher activations in frontal motor, premotor and anterior cingulate regions were observed in the Sz+APD+SUD group than in the Sz-only group.

Despite immense importance of auditory verbal hallucinations (AVHs) in the phenomenology of schizophrenia, the neurocognitive and neurophysiological bases of AVHs remain obscure. On the neurocognitive level, it has been proposed that AVHs arise from the disordered monitoring manifested by patients' inability to recognize their inner speech as being their own. On the neurophysiological level, the AVHs have been attributed to the aberrant activity in the primary auditory cortex (Heschl's gyrus). Although interesting, these models cannot account for the very specific and restricted content of AVHs in individual patients. The specific content of AVHs persists across different psychotic episodes even after extended periods of remission. Furthermore, the AVHs are usually triggered by emotionally charged and stressful situations.We hypothesized that even during absence of AVHs, when patients are in remission, the verbal content remains present in the latent, pre-clinical form. In order to elucidate potential cerebral substrates of the dormant AVHs content, we employed functional magnetic resonance imaging (fMRI) in 6 schizophrenia patients in total remission of AVHs for at least 12 months, during listening to the words hallucinated by them in the past. Specifically, we created the list of previously hallucinated words for each patient and matched the words in terms of length, structure, emotional valence, semantic category and frequency of usage with the non-hallucinated words. Moreover, each patient was paired demographically with the control participant who was presented with the same words. We predicted that exposure to the hallucinated versus non-hallucinated words would result in increased activation in cerebral areas associated with cognitive and emotional content of previously experienced AVHs in patients, whereas the same comparison will not produce any significant changes in blood oxygen level-dependent (BOLD) signal in control participants. In addition, based on existing neuroimaging data obtained during experience of AVHs, we hypothesized that previously hallucinated words may elicit greater activation in the primary auditory cortex than the non-hallucinated words in patients. Each pair of participants was analyzed separately.The most consistent finding in patients, absent in all control participants, was significant activation in the orbitofrontal and medial prefrontal cortex (PFC) during listening to previously hallucinated versus non-hallucinated words. The orbitofrontal and medial PFC are both part of corticolimbic system and play an important role in cognitive control of emotion processing.Thus, present results imply that previously hallucinated words, even in remission, are associated with inappropriate emotional response on neurophysiological level in schizophrenia patients. The relative hyperactivation of orbitofrontal and medial PFC in patients may stem from and/or may contribute to anomalous neural plasticity and disordered connectivity in the corticolimbic circuitry. This in turn could lead to attribution of excessive emotional salience to normally neutral stimuli and over time via process of sensitization could result in hallucinations. Potential normalization of this dysfunction could reduce patients' susceptibility to experience AVHs in stressful situations. In addition to observed hyperactivations in the PFC, some schizophrenia patients exhibited anomalous BOLD signal in other regions of the corticolimbic system such as anterior cingulate gyrus and parahippocampal gyrus. These additional anomalies could be related to greater affective sensitivity to the hallucinated versus non-hallucinated words in some patients.Finally, in contrast to our initial hypothesis we did not observe any significant differences between processing of the hallucinated versus non-hallucinated words in the primary auditory cortex. In retrospect, this result is not surprising because patients did not experience internally generated AVHs while in the scanner, but instead were exposed exclusively to externally generated stimuli.

Despite the fact that most researchers acknowledge the high prevalence of comorbid substance abuse among schizophrenic patients, there is no common agreement regarding the etiology of this serious public health problem. At the center of this debate though, Khantzian's self-medication hypothesis has captured most of the attention. In the present literature review, the authors evaluate this hypothesis in the light of our current knowledge. Formulated in a clinical context, in reaction to the psychoanalytic interpretation of addiction as a pleasure seeking pathology, Khantzian's hypothesis holds that schizophrenic patients use psychoactive substances to relieve their symptoms. Properly understood, this conjecture presupposes that, with the relief of certain target symptoms, substance use would no more be a necessity. But in reality, the use of psychoactive substances usually leads to a general deterioration of the patients' condition. Pharmacodependent schizophrenic patients relapse more often, they are more frequently hospitalized, they show more violent behaviors, and they are more frequently homeless. In particular, the positive symptoms of these patients are generally exacerbated by the psychoactive drugs--with the possible exception of opiates. This observation is in lign with the fact that psychostimulants (cocaine, amphetamines), anesthesic dissociatives (PCP, ketamine) as well as hallucinogens (cannabis, LSD) are all known to exert psychotomimetic effects. As for negative symptoms, the reality is more complex. Preliminary results certainly suggest that stimulants (minor or major) relieve these symptoms, but in the case of the other psychoactive substances, empirical evidence remains fragmentary. Still, the properties of psychoactive substances invite to pay close attention, among the negative symptoms, to the cognitive deficits, the social inaptitudes and the hedonic deficits of these patients. Unsatisfied with the self-medication hypothesis, an increasing number of researchers hypothesize that schizophrenic patients abuse drugs in hope to relieve the negative affects (stress, depression) that commonly accompany their symptomatology. Interestingly, increasing data link these negative manifestations and substance abuse among schizophrenic patients. But these same data do not elucidate whether these manifestations are primary or secondary to drug abuse. For the moment, these findings must be replicated. Furthermore, it remains to be clarified what negative affect is involved here. Is it stress, anxiety or, as commonly thought, depression? Other paths aim in the direction of personality traits and dissociation. The first path is suggested by recent studies demonstrating that pharmacodependent schizophrenic patients differ from non-abusing schizophrenics in that their personality is characterized by traits such as sensation seeking and impulsivity. As for the second path, it is suggested by a recurrent observation in addictive medicine practice, that is: alcohol, cannabis, ketamine, LSD, opiates, PCP, all these substances can induce dissociative states (depersonalization, derealization, etc.). Surprisingly, most of the hypotheses advanced so far have been formulated without reference to neuroscience. However, from a biological perspective, substance abuse among schizophrenic patients appears paradoxical: while the positive symptoms of schizophrenia might involve an hyperactivity of the reward system, the drugs of abuse all seem to increase dopamine release in that same system. That very paradox further casts some doubt on the self-medication hypothesis. And it opens an alternative: schizophrenic patients might be biologically vulnerable to the rewarding effects of drugs abuse. On the therapeutic level finally, the authors argue that polypharmacy medications such as clozapine and quetiapine, known to act on the reward system preferentially to the extrapyramidal system and known to dissociate fastly from the dopamine-D2 receptor, could simplify clinical intervention.

Background. High expressed emotion (EE) in families reliably predicts relapse in schizophrenia leading to the assumption that high EE stresses patients and is the cause of relapse. Attempts at validating the stressful properties of high EE using autonomic skin conductance measures have been inconclusive. Since memory loaded vigilance tasks are sensitive to stress, we used a memory loaded version of the Continuous Performance Test (CPT) to see if test performance would change in the presence and absence of high or low EE relatives. If high EE was stressful, performance should decline in their presence of high EE relatives. If low EE was protective against stress performance should improve in the presence of low EE relatives.Methods. The CPT was administered to 41 schizophrenic and 51 normal control participants. CPT testing was conducted in the absence, then presence, then absence of high or low EE relatives.Results. Control participants had significantly greater CPT scores than schizophrenic participants; there was no effect of the relative's presence or absence on CPT performance for either the high or low EE group. Schizophrenic participants from high EE homes demonstrated significantly better, rather than worse, CPT scores than those in low EE homes.Conclusions. These findings fail to support the notion of high EE as stressor, but show that high EE and low EE patient groups perform a vigilance task significantly differently. We propose that patients from low EE groups may be underaroused relative to their high EE counterparts and that this underarousal leads to less than optimal performance on the CPT.

Cognitive deficits in schizophrenia have been observed with neuropsychological tests of executive function, traditionally considered sensitive to frontal lobe damage. These impairments affect planning abilities, as well as the aptitude to initiate and regulate a goal-directed behaviour. On the other hand, negative symptoms of schizophrenia are widely suspected to reflect a frontal lobe dysfunction. Based on a review of a hundred papers, the present article analyses the anatomical and neuropsychological evidence of disturbed frontal lobe functioning in patients with negative schizophrenic symptoms. The phenomenological similarity of some schizophrenic symptoms to the clinical features of patients with prefrontal injury inspired the hypothesis of damaged frontal lobe in the former disorder. The morphological findings of neuroimaging studies brought inconsistent conclusions, with some researchers noting no differences between patients and control subjects while others observing reduced prefrontal volumes in schizophrenia. The functional neuroimaging demonstrated a reduced frontal blood flow relative to the general cerebral perfusion in patients with schizophrenia. Even though the overall neuroimaging literature provides reliable evidence of frontal impairment in schizophrenia, the average magnitude of the difference between patients and healthy controls is insufficient to defend the hypothesis of frontal lobe dysfunction, as far as brain volume, resting metabolism or blood flow are concerned. The only measure, which clearly distinguishes between the patients' and controls' distributions, is the functional neuroimaging of the frontal lobe while subjects are performing an experimentally controlled task. Schizophrenic patients fail to activate their frontal cortex when the task requires it. Analysing executive abilities in relation to symptom expression leads to recognising the fact that frontal dysfunction is a characteristic of only a sub-syndrome of schizophrenia. The factor analysis of the clinical features consistently reveals three syndromes in schizophrenia, termed disorganisation, positive and negative syndromes. The substantial body of evidence that patients exhibit more than one syndrome indicates these are dimensions within a single illness rather than discrete diseases. Liddle labelled the negative syndrome as "psychomotor poverty" and associated it with malfunction of the neuronal projections from dorsal prefrontal cortex to thalamus via striatum, connections involved in the initiation of mental activity. His hypothesis was supported by the work of other, independent research groups. The patients with negative symptoms, in contrast with the nonnegative symptom group, tend to demonstrate reduced neuronal activation of the frontal cortex during executive task realisation. The nonnegative patients are indistinguishable from the healthy control subjects in this region. Neuropsychological studies reveal that severity of psychomotor poverty is associated with slowing of mental processing and deficits in tasks that require planning abilities. These frontal functions are identified with the selection, the initiation and monitoring of a wide variety of behavioural processes. It was hypothesised that executive dysfunction will appear through different patterns across symptom subtypes, but few studies sought to validate this assumption. Finally, researchers make little effort to develop theoretical conceptualisations of the aetiology of negative schizophrenic symptoms, despite the growing body of evidence on its resemblance to the dorsolateral frontal lobe syndrome. Frith proposes that defects in the initiation of spontaneous action underlie these clinical phenomena, but his definition is not specific enough to be confronted to existing literature, neither has been empirically tested. Disturbed executive functioning has detrimental impact on the quality of daily living in patients with schizophrenia. Indirect observation of the latter accounts for defective long-term adaptation, which has been correlated to severity of negative symptoms and, although not consistently, to executive deficit as assessed by neuropsychological testing. Unfortunately, this area of research lacks ecologically valid studies. Measuring executive dysfunction as it occurs in the natural setting of the patient and validating dissocialbility of frontal deficits with respect to the schizophrenic symptomatology could lead to greater individualization of treatment plans and therefore to more efficient therapy outcome.

Two case studies were conducted of patients suffering from paranoid schizophrenia with glossomanic schizophasia. Their dictation-taking performance was assessed via a comprehensive standardized neuropsychological test battery following a protocol specifically designed for the purpose (Lecours, 1996.). The patients' performance was compared with normative data from the general population. The results show that the patients committed graphemic paragraphias, that is, they replaced target graphemes with others representative of the corresponding phoneme (ph and f for/f/, in French) or with graphemes representative of a similar phoneme (v for/f/). These errors suggest that components of a cognitive model of writing are dysfunctional.

The study compared controlled and automatic processing in 17 people diagnosed with chronic tic disorder (CTD), 20 with habit disorder (HT), and 30 screened controls. Using a countermanding paradigm, time to initiate a response (GO-time) was compared with time taken to inhibit a response (STOP-time) under automated and controlled response conditions. The signals were 2 sets of traffic-light-like computer displays with ready, go, and stop lights. The automated response was a repetitive series of taps and the controlled response was a morse code pattern of taps. There were no group differences in GO time under any conditions. The control group but not the HD or CTD groups showed a significant practice effect over time. The CTD group was significantly slower to STOP the automated than the controlled response. The results suggest that the CTD group had specifically, greater difficulty inhibiting automated than controlled actions.

The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia.Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment.The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test.These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.

In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in schizophrenia, which appears before the introduction of neuroleptics. The attention performance was also shown to present some association to clinical symptoms.

To review the literature on the permanent neurological sequelae resulting from acute lithium poisoning.Sixty-six articles were reviewed in English and in French. They were accessed through Medline and cover the period from 1968 to 1997.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.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.

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.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.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.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.

The aim of this study was to examine selective attention in patients with chronic and refractory schizophrenia who had been exposed for six months to atypical neuroleptic medications: risperidone or clozapine.17 patients satisfying DSM III-R criteria for schizophrenia were assessed according to BPRS and PANSS and abnormal involuntary movements to ESRS. Selective attention tasks were performed before treatment with risperidone or clozapine and at two times during the treatment (6 weeks, T1, and 24 weeks, T2). Patients' performance data were compared to data from a group of general population at T1. Selective attention refers to the ability to discriminate relevant information from irrelevant one. This was measured by a visual search task. Subjects had to search for a target specified by a conjunction of features (color and shape). The target was a black X, while the distracters were white X's, black O's and white O's. The stimuli were displayed on a Macintosh SE computer. A two-button response box was used for response production and the experiment was run in a dimly lit room. A white-fixation stimulus was shown at the center of the display screen between trials. The number of stimuli displayed on a single trial was 1, 4, 7 or 10. The median RTs and error rates of subjects were computed for each factor (target presence and number of stimuli).A Group X Number of items X Presence of target ANOVA applied on median correct RTs revealed a significant Group X Presence interaction [F(1,176) = 60.433, p.0001]. Performances improved with the time (F2, p.01). Correlations were found between positive score on PANSS and performance on selective attention (r39 = -.391).Atypical neuroleptic do not have a deleterious effect on selective attention but a favorable effect on the schizophrenic patients' performance.

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.

To examine the way in which certain concepts regarding the physiopathology of Capgras' syndrome (1) have been tested neuropsychologically.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.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.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.

In cognitive science, lexical decision task is used to investigate visual word recognition and lexical access. The issue of whether or not individuals who are depressed differ in their access to affectively laden words and specifically to words that have negative affect was examined. Based on some aspects of the Resource Allocation Model (Ellis), it was postulated that patients suffering from depression take more time to recognize items from an affective-loaded list. In order to compare their behavior in a lexical decision task, patients suffering from depression and healthy controls were studied. We hoped to find an interaction between the mood state of subjects and the categories (affective or neutral) of words. Two groups of right-handed adults served as subjects in our experiment. The first group consisted of 11 patients suffering from depression (mean age: 40.2; sd: 6.8). All of this group met the DSM-III-R and the Research Diagnostic Criteria for major depressive disorder. Severity of their disease was rated using the 24-item Hamilton Depressive Rating Scale. All patients suffering from depression were without psychotropic medication. The control group was composed of 24 subjects (mean age: 32.7; sd: 7.9). A depressive word-list and a neutral word-list were built and a computer was used for the lexical-decision task. A longer reaction time to detect the non-word stimuli (F1,33 = 11.19, p < 0.01) was observed with the patients by comparison to the normal subjects. In the analysis of the word stimuli, a group by list interaction (F1,33 = 7.18, p < 0.01) was found.(ABSTRACT TRUNCATED AT 250 WORDS)

This study focuses on a sample of 35 patients who had recently suffered an attack of multiple sclerosis. They were first subjected to the so-called life stress method in order to look for a connection between life stresses and the attacks of multiple sclerosis. The sample was compared with a paired control population composed of patients recruited from admission departments and medical emergency departments. The AMDP psychopathological evaluation method was applied to the sample, to establish a characteristic mental profile of these patients. Three types of results are highlighted. First, the comparison of the event scores shows a significant difference between the population of patients suffering from an outbreak of multiple sclerosis and the control population. A connection between "life stresses" and the triggering of the outbreaks of multiple sclerosis is therefore mentioned and discussed. Second, the application of the system of the Association de méthodologie et de documentation psychiatrique brings out a mental profile common to patients suffering from multiple sclerosis, consisting of a very specific association of mood disorders: dysphoria, euphoria and mania on the one hand, and depression, anxiety and dramatization on the other, with relative anosognosia. The correlation between dysphoria, the syndrome's principal characteristic, and the event score adds another argument in favour of the connection between life stresses and the evolution of the disease. The main components of this mental profile are primarily correlated with the existence of a neuropsychology suggestive of a medial basal frontal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

According to the Resource Allocation Model, it is logical to think that emotional mood states modulate the allocation of capacity, most cognitive tasks require some allocation of capacity, and in many instances there is a positive correlation between effort and memory. In cognitive science, the experimental paradigm of lexical decision task is used to investigate visual words recognition and lexical access. According to the Resource Allocation Model, we postulated that depressed patients take more time to recognize items from an affective loaded list. In order to compare their behavior in lexical decision task in this study, depressed patients and healthy controls were studied. We hoped to find an interaction between the mood state of subjects and the categories (affective or neutral) of words. This kind of interaction is expected to figure among the cognitive markers of depression. Two groups of right-handed adults served as subjects in our experiment. The subjects were living in the north west region of Quebec. The first group consisted of 11 depressed patients (mean age: 40.2; SD: 6.8). All of them met the DSM III criteria for major depressive disorder and the RDC. Patients were rated using the 24-item Hamilton Depression Rating Scale (HDRS). All depressed patients were without medications. The control group was composed with 24 subjects (mean age: 32.7; SD: 7.9). We built a depressive word-list (Mood-list) and a neutral word-list (Neutral-list) and used a computer for the lexical-decision task. We noted a significant interaction [F(1.33) = 10,035, p0.001] between the subjects group (depression vs control) and the words category (Moodlist vs Neutral-list).(ABSTRACT TRUNCATED AT 250 WORDS)

Psychiatry in Communist China is at a delicate phase where it is drawn both to modern Western medicine and to the wealth of traditional medicine. This is conveyed through accounts of some present-day situations as seen by the author during stays in Peking and Shanghai. After the treatment provided in various hospitals for acute-care and chronic-care patients is described, we are introduced to the organization of mental health at the various levels of hospital and external structures. A general survey of the research being done in epidemiology, neurology and traditional medicine at the Peking Research Centre is also presented. The novel nosography reveals one particular entity: phasophrenia, described as a stereotyped and recurring acute psychotic episode that responds poorly to neuroleptic chemotherapy. Finally, the medico-legal aspects of psychiatry and the effects of the new birth-rate policy are briefly discussed.