Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set.

OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.

[Autobiographical memory and self-disorders in schizophrenia]. / Les troubles de la mémoire autobiographique et du self dans la schizophrénie.

OBJECTIVES: Disorders of self in schizophrenia have been considered as the core feature of the illness since its early clinical description. However, until recently, the understanding of these disorders referred mostly to philosophical considerations. The aim of this work is to examine how the various aspects of autobiographical memory deficits may be considered as possible cognitive mechanisms accounting for self-disorders in patients. METHODS: We performed a theoretical review of the literature on autobiographical memory studies in schizophrenia. Our approach of cognitive psychopathology was grounded in the model of the Self-Memory System put forward by Conway (2005), which posits reciprocal relationships between autobiographical memory and the self. This model stresses the distinction between the working-self and the autobiographical memory knowledge base. The latter contains all autobiographical information stored in our life and is organized according to the specificity of this information. The role of the working-self is to maintain the coherence of the self and to control the access to autobiographical memories and corresponding memory details. The working-self supports an experiential or phenomenological dimension of the self, especially when a highly detailed autobiographical memory is retrieved, and a past event is re-experienced by the rememberer. The working-self also entails a conceptual part, the conceptual self, which contains self-knowledge and self-images. RESULTS: Our review showed that autobiographical memories of patients with schizophrenia are less specific and contain fewer phenomenological details than those of healthy participants. Patients also have difficulty assessing the subjective temporal distance of past events, and their ability to re-experience unique past personal events is affected as shown by a reduced conscious recollection and a smaller frequency of Field visual perspective during recall of autobiographical memories. This global alteration of all phenomenological characteristics of autobiographical memories strongly suggests an alteration of the phenomenological dimension of the self in schizophrenia. Since some of these alterations are also found in patients when they plan for future personal events, the ability to mentally travel in time is reduced in patients and reflects an impaired sense of self across time. The literature also shows that self-images are more passive, less coherent and less stable in time in patients compared to healthy participants. These results point to an alteration of the conceptual dimension of the self in schizophrenia. This may be partly explained by a weaker connection between the self and autobiographical memory and by other alterations of autobiographical memories closely linked to the self. In fact, the reminiscence bump is disorganized in patients and comprises poorly detailed memories. Memories grounding self-images are less organized and weakly connected to self-images. Finally, patients have an impaired ability to give a meaning to or to draw lessons from self-defining memories of their life. CONCLUSION: Based on these results, we discuss current and future therapeutic interventions including both cognitive remediation methods and cognitive psychotherapy applied to autobiographical memory. These methods appear relevant to help patients improve both the sense of self associatied with their autobiographical memory retrieval and the coherence and stability of the self.

Grasping the mechanisms of narratives' incoherence in schizophrenia: an analysis of the temporal structure of patients' life story.

OBJECTIVE: Life narratives of patients with schizophrenia are characterized by impaired coherence so that the listener has often difficulties to grasp the life trajectory of the patients. In order to better understand what causes this reduced temporal coherence, we investigated the temporal structure of patients' life narratives through different temporal narrative elements (elaboration of beginnings and endings, local temporal indicators and temporal deviations from a linear order), across two complementary studies. METHODS: Life narratives were collected by means of two different methods; a free recall in study 1 and a more structured protocol, aiming at reducing the cognitive task demands in study 2. All narratives from the two studies were analyzed using the same validated method. RESULTS: Both studies showed that global temporal coherence is significantly reduced in patients with schizophrenia (ps.02). This is mainly due to their stronger tendency to temporally deviate from a linear temporal order without marking the deviation as such. We also observed significant correlations in the patient groups between global temporal coherence and executive dysfunction (p=.008) or their higher tendency to temporally deviate from a linear temporal order in their life narratives (p<.001). CONCLUSIONS: These results shed light on narrative correlates of temporal narrative incoherence in schizophrenia and highlight the central role of executive dysfunction in this incoherence.

Self-continuity across time in schizophrenia: An exploration of phenomenological and narrative continuity in the past and future.

BACKGROUND: Disorders of the self, such as a reduced sense of personal continuity in time, are a core symptom of schizophrenia, but one that is still poorly understood. In the present study, we investigated two complementary aspects of self-continuity, namely phenomenological and narrative continuity, in 27 patients with schizophrenia, and compared them with 27 control participants. METHODS: Participants were asked to identify important past events and to narrate a story from their life that included these events. They were also asked to imagine important events that might happen in their personal future and to build a narrative of their future life. The vividness of these important life events and the proportion of self-event connections in the narratives were used as a measure of phenomenological and narrative continuity, respectively. RESULTS: Our study showed patients with schizophrenia experienced less vivid representations of personally significant events (p = .02) for both temporal directions (past and future) (p < .001). In addition, their ability to make explicit connections between personal events and self-attributes in life narratives was also impaired (p = .03), but only in the case of past narratives (p < .001). CONCLUSIONS: These results shed new light on the cognitive mechanisms underlying self-disorders in schizophrenia. The clinical and therapeutic implications of these findings are discussed.

[Theoretical reflection on the place of memory and temporal cognitive mechanisms in addictive disorders]. / Réflexion théorique sur la place des mécanismes cognitifs mnésiques et temporels dans l'addiction.

INTRODUCTION: Addictions can be regarded as cognitive disorders related to neurobiological impairments. On the one hand, some cognitive impairments occur as a result of substance intake and withdrawal upon stopping intake, while, on the other hand, cognitive mechanisms are responsible for initiating and maintaining addiction. In this review, we detail the memory and temporal mechanisms involved in this pathology. METHODOLOGY: We reviewed the literature dedicated to the mechanisms of conditioning association between a substance and a context, and the memory and temporal mechanisms involved in the maintenance of addiction. Cognitive impairments in this context are accompanied by both short-term and long-term neurobiological disorders. RESULTS: Drug-context conditioning is dependent on learning abilities in rats and humans, and it is the first step towards the development of an addiction. In fact, with the beginning of an addiction, it is the context associated with the substance intake, which determines the reinforcing factors (such as pleasure in the case of drug consumption) for the development of an addiction. Maintenance of addiction is related to the persistence of this association between context and substance. Furthermore, the impulsiveness of patients renders them unable to delay their gratification. Consequently, even if delayed gratifications are more valuable, patients prefer immediate gratification such as substance use. DISCUSSION: The memory and temporal mechanisms of addiction are central to the initiation and maintenance of drug addiction. They also affect patients' ability to develop projects for the future. The salience of the memory association between drug and context is accompanied by a decline in autobiographical memories, which become poor and lacking in detail. It is probably these impairments which are responsible for the difficulty that the patients have while investigating their story during psychotherapy. On the other hand, given that even though delayed gratification is greater patients prefer immediate gratification, they have difficulty making plans for the future and constructing their own personality. These cognitive impairments are sustained by neurobiological correlates such as dopamine dysregulation in the short-term and changes in neural plasticity in the cortico-meso-limbic system in the long term. CONCLUSION: We reviewed full arguments which highlight that addiction is mediated by cognitive mechanisms which are related on the one hand to clinical symptoms and, on the other hand, to neurobiological alterations. According to the literature, memory and time mechanisms seem to be central to the initiation and maintenance of addictive behaviours. More research is needed to improve our knowledge of the cognitive mechanisms of addiction and to develop new tools for treating patients.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Rumination and autobiographical memory impairment in patients with schizophrenia.

Although patients with schizophrenia exhibit autobiographical memory impairment, which is considered to be a limiting factor in their daily life, the mechanisms underlying such impairment have been rarely studied. In the current study, we investigate whether rumination and, in particular, brooding, which is a form of maladaptive repetitive thinking, may be linked to the difficulty that patients with schizophrenia experience when attempting to access specific autobiographical memories. Our results indicate that patients reported less specific autobiographical memories compared to control participants. Patients also displayed a higher level of brooding and had more depressive symptoms. According to the CaR-FA-X model (Williams et al., 2007), depression and brooding were associated with memory specificity in control participants. In contrast, neither depression nor brooding was correlated with memory specificity in patients. These results suggest that depression and rumination may not be directly related to patients' difficulty to recall specific memories and that other factors, such as metacognitive deficits, must first be considered when seeking interventions aimed to improve autobiographical memory in patients with schizophrenia.

Rehabilitation of executive functions in a real-life setting: goal management training applied to a person with schizophrenia.

The aim was to assess the efficacy of a modified version of Goal Management Training (GMT) in a person with schizophrenia who had difficulties in attaining the final goal for new and multitasking daily-life situations. GMT is designed to improve abilities in establishing goal-directed plans and carrying them out effectively. Beneficial effects of GMT were measured for several clinical questionnaires, laboratory tasks, and three real-life situations: meal preparation (trained, familiar); washing (nontrained, familiar); meeting preparation (nontrained, unfamiliar). The results revealed improvement in planning and on trained laboratory and meal preparation tasks and a generalization of GMT effects on nontrained laboratory and everyday tasks. Self-esteem also improved. Finally, a two-year followup indicated the durability of the beneficial effects.

An individualized and everyday life approach to cognitive rehabilitation in schizophrenia: a case illustration.

Objective. The effectiveness of an individualized and everyday approach to cognitive rehabilitation for schizophrenia was examined in a case study. Method. After cognitive and functional assessment, concrete objectives were targeted for the person's everyday complaints. Strategies were constructed based on an analysis of the cognitive profile, daily life functioning, and processes involved in activities. They included a memory strategy for reading, a diary to compensate memory difficulties, and working memory exercises to improve immediate processing of information when reading and following conversations. Efficacy was assessed with outcome measures. Results. The program had beneficial effects on the person's cognitive and everyday functioning, which persisted at a 3-year follow-up. Conclusion. Findings provide suggestive evidence that an individualized and everyday approach may be a useful alternative in order to obtain a meaningfully lasting transfer of training to daily life, compared to the nomothetic ones which dominate the field.

Prefrontal cortex recruitment during naturalistic remote memory: a factorial block-event fMRI study.

Most classical neuroimaging studies of human memory require the subject to follow task instructions, discriminate stimuli, make a decision and, finally, press a button to respond. To which extent does such a cognitive sequence influence neural correlates of recognition memory especially with respect to the prefrontal cortex (PFC) is not clear yet. We set up a naturalistic recognition task. Personal photographs were mixed with photographs from family albums of people who were not known to the participant. The subjects alternated a recognition task (recognition and response) with a mere observational one (simple recognition). This factorial block-event functional MRI design allowed us to disentangle the regions related to memory (personal photographs vs. distracters under both conditions) from those related to the response (responding vs. observing) as well as to examine the interaction between the two factors. Only medial and left orbito-frontal regions were transiently active during successful recognition in the two task conditions. Memory and responding interacted in the left lateral PFC within the middle and inferior gyrus. These regions were more active for personal photographs than for distracters only when the subject had to respond. Sustained activations spread bilaterally whatever the task. Such a design that encompasses personal photographs, an observation period for recognition as well as a mixed-design may have led to a better isolation of the neural network underlying remote autobiographical memory. Recruitment within the PFC during retrieval was only limited to its medial and left anterior parts. Sustained activation did not differ between the discrimination and the observation period. This original design might be valuable for further dissociation between decision, self, autobiographical memory and the PFC.

Cognitive rehabilitation of the updating sub-component of working memory in schizophrenia: a case study.

Working memory problems have been identified as a core cognitive deficit in schizophrenia. In this paper, we present the results of a cognitive rehabilitation programme (Duval & Coyette, 2005) administered to a schizophrenia patient, and specifically designed to improve the updating sub-component of working memory. The original feature of this programme was that it involved two types of updating exercises: cognitive and ecological. The purpose was to enable the patient to acquire cognitive strategies that alleviate the mental load of the central executive and to transfer them to daily life. The specificity and efficacy of the programme were assessed with multiple (cognitive, ecological and non-target) baseline measurements. In addition, several questionnaires were administered to assess the effect of the programme on subjective cognitive complaints affecting daily life, psychiatric symptoms and self-esteem. The results demonstrated the efficacy of the rehabilitation programme on the updating function and the generalisation of these beneficial effects to daily life. A significant decrease in both subjective cognitive complaints and psychiatric symptoms was also observed. However, the patient's self-esteem did not improve.

[Functioning of memory in subjects with autism]. / Fonctionnement de la mémoire chez les sujets avec autisme.

INTRODUCTION: Autism is an early developmental disorder with cognitive impairments that leads to learning and social integration disabilities. The characterization of memory functions in individuals with autism has been the subject of numerous investigations, with widely varying conclusions. The notable differences between these studies can be attributed to variations in the age, intelligence and level of severity of the participants with autism. LITERATURE FINDINGS: The purpose of our review of the recent literature is to describe the memory function of individuals with autism. Some of the different memory subtypes are intact, others are impaired. Short-term memory (digit span) is not impaired while working memory is impaired in some of its components, but the findings are inconsistent. More recent studies demonstrate reduced spatial working memory abilities in autism and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory. Episodic long-term memory, as measured by free recall, cued recall or recognition tasks, is intact, but participants with autism perform significantly less well than controls as the complexity of the verbal or visual material to be recalled increases. Source or contextual memory involves a variety of characteristics specifying the conditions under which specific items or facts are acquired: it has been investigated in individuals with autism with different methods. Deficits in source memory for temporal information have been found, but there were no reality monitoring deficits. Recent findings indicate that the nature of source memory confusion in autism does not appear to reflect a generalized deficit in attaching context to memories, but rather is dependant on the specific to-be-remembered information that involves social aspects of context. The self-reference effect is missing, with individuals with autism recalling events performed by themselves less well than the events performed by a peer, suggesting they have difficulties in relation to processes involving the self. Studies involving assessment of subjective states of awareness during recognition show less conscious recollection and more feelings of familiarity. Recent investigations are consistent in demonstrating memory impairments related to the failure of subjects with autism to use organizing strategies or meaning to support memory, an effect which grows with the increasing complexity of the material. Memory deficits in autism may be related more to retrieval and less to encoding, as deficit in source memory in participants with autism is largely eliminated when source was supported at test. DISCUSSION: The neuroanatomical basis of the specificities of memory impairment in autism is still uncertain, but it is suggested that autism involves an impairment in the conversion of limbic inputs into medial prefrontal outputs. Memory deficits found in individuals with autism may explain some of the clinical symptoms. Failure to encode all the information, especially its social aspects, may therefore contribute to dysfunction in the social, communication, and reasoning domains. Abnormal memory functioning in autism is also related to more general cognitive impairments, including executive function deficits and central coherence weakness. Evidence of the normality of certain memory capacities, at least in individuals with moderate autistic symptomatology, is encouraging for adaptive improvements in cognitive functioning.

Functional integration in schizophrenia: too little or too much? Preliminary results on fMRI data.

The disconnectivity hypothesis proposes that schizophrenia results from poor or miswired anatomical connections. Theoretically, its functional counterpart should be disintegration. Integration is thought to allow segregated neurons to interact as a coherent whole, referred to as the "core", while the non-interacting part of the brain is referred to as the "rest". In this study, it is suggested that schizophrenia is the result of rest noise interfering with core activity. Two possible causes are assessed: (i) defective core integration, making the core more vulnerable to noise from the rest, or (ii) the rest being too highly integrated, meaning that it can interfere with the core. These hypotheses were tested using fMRI data acquired from 13 stabilized medicated schizophrenic subjects compared to 11 matched controls. Subjects were required to perform a series of lexical decision and retrieval tasks in separate sessions. The brain was divided into 90 components. Integration was defined as the amount of information shared between the components of a sub-system. An iterative aggregation procedure made it possible to identify a core on the basis of the functional clustering index, which assesses the integration of the core relative to its integration with the rest. Correlation of component-pairs within the core was also compared between the two groups. This procedure was repeated for each subject and for each task. Cores did not differ between the two groups, either in terms of integration or in terms of functional clustering index. However, the core was still highly integrated with the rest and the rest was overly integrated in schizophrenic subjects. Both anomalies were correlated with the negative symptoms. These findings were consistent regardless of the task considered. Furthermore, within the core, anterior-posterior correlations were lower in patients (between the frontal and the parietal and posterior cingulate cortices), whereas frontal left-right correlations were excessive. No significant correlation was found with the medication. Thus, it appears that schizophrenia entails a deleterious combination of too much "noisy" integration (from the rest) and too little "significant" integration (anterior-posterior functional connectivity).

Lorazepam, sedation, and conscious recollection: a dose-response study with healthy volunteers.

The role of sedation in the benzodiazepine-induced impairment of conscious recollection is still subject to debate. The aim of this study was to investigate further the role of sedation using the Remember-Know procedure and a physiological measure of sedation based on pupillography in addition to standard measures of sedation and attention (digit-symbol substitution task, symbol cancellation task, self-rated sedation). Twelve subjects were tested after the intake of placebo, lorazepam 0.026 mg/kg and lorazepam 0.038 mg/kg, administered in a randomized order, with a minimum interval of 8 days between each administration. On a recognition memory task, they were asked to give 'Remember', 'Know' or 'Guess' responses to items that were recognized on the basis of conscious recollection, familiarity, or guessing, respectively. Lorazepam selectively impaired recognition based on 'Remember' responses. This impairment was greater in the lorazepam 0.038 mg/kg than in the lorazepam 0.026 mg/kg groups. Measures of sedation were not correlated with the proportion of 'Remember' responses. These results suggest that sedation alone cannot account for the impairment of conscious recollection induced by lorazepam.

Defective relationship between subjective experience and behavior in schizophrenia.

OBJECTIVE: The relationship between subjective experience and behavior abnormalities in schizophrenia was investigated. METHOD: Eighteen patients with schizophrenia and 18 normal comparison subjects completed a general knowledge task with two incentive conditions to measure monitoring effectiveness, control sensitivity, and response criterion setting. RESULTS: The patients' levels of monitoring effectiveness and control sensitivity were lower than those of the comparison subjects. The effect of incentives on response criterion values was similar in the two groups. CONCLUSIONS: Patients were impaired in subjectively assessing the correctness of their knowledge, and their behavior was less determined by subjective experience than that of normal subjects. The patients' intact sensitivity to incentives has implications for cognitive remediation.

[Apropos of atypical melancholia with Sustiva (efavirenz)]. / A propos d'un état mélancolique atypique sous Sustiva (Efavirenz).

The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV-infected person presented with two severe melancholic episodes associated with marked cognitive disorders which resisted two successive antidepressant treatments (viloxazine and citalopram, respectively) prescribed at effective doses and for sufficient time duration. Mister H. had no personal or family psychiatric antecedent. His psychic condition improved only when efavirenz was discontinued. However, drug discontinuation may not be an obligatory step to improve the patient's condition since antidepressant treatment has been found effective in some similar situations. Actually, each case should be discussed with the clinicians taking care of the patient.

Intact implicit learning in schizophrenia.

OBJECTIVE: Schizophrenia impairs performance on explicit, but not implicit, memory tasks, indicating that conscious awareness at retrieval is a critical determinant of impaired memory. The authors investigated implicit learning, i.e., knowledge acquisition in the absence of conscious awareness, in patients with schizophrenia. METHOD: An artificial grammar learning task was used to assess implicit learning in 48 patients with schizophrenia and 24 healthy comparison subjects. The subjects were first presented with letter strings that were generated according to the rules of a finite-state grammar paradigm. They were then required to indicate whether new letter strings were "grammatical," depending on whether or not the strings corresponded to the rules. IQ, working memory, explicit memory, verbal fluency, and speed of processing were also assessed. RESULTS: Patients performed significantly worse than the comparison subjects on cognitive tasks that assessed episodic memory, verbal fluency, working memory, and speed of processing. In contrast, patients classified as being correct more grammatical than nongrammatical letter strings, and the magnitude of the difference was similar to that observed in healthy comparison subjects. CONCLUSIONS: Implicit learning, as assessed with an artificial grammar learning task, is intact in patients with schizophrenia. Conscious awareness might be a critical determinant of memory impairment both at encoding and at retrieval.

Effects of lorazepam on vision and oculomotor balance.

BACKGROUND: Previous studies have shown an effect of the tranquilizer lorazepam on visual perception. We explored the effects of the drug on binocular vision, visual acuity and accommodation. SUBJECTS AND METHODS: Twenty-four paid healthy volunteers (13 women, 11 men) were recruited from the University of Strasbourg (mean age: 23.6 years, mean weight: 66.8 Kg). They were randomly assigned to one of two parallel groups of 12 subjects each (a placebo group and a lorazepam 0.038 mg/kg group). Visual acuity was measured for each eye separately (Snellen chart and Parinaud scale). Binocular vision was studied using the cover tests, measurement of the fusional amplitudes (with Berens prisms), and the Duane Scale Test (near point rule) measuring convergence and/or accommodation in centimeters or diopters as a function of age. RESULTS: Regarding vision, there was no lorazepam effect, at either 33 cm or 5 m. An esophoria was observed after the intake of lorazepam (0Delta before intake and 2.8Delta after intake, p=0.001). Both fusional convergence and fusional divergence amplitudes decreased by lorazepam, (p=0.008, and p=0.002). Lorazepam also impaired the near point of convergence but did not affect accommodation. CONCLUSION: A single dose of lorazepam induces an esophoric oculomotor imbalance and impaired fusional convergence and divergence amplitudes without impairing visual acuity or accommodation.

Lorazepam and diazepam impair true, but not false, recognition in healthy volunteers.

RATIONALE: The deleterious effects of benzodiazepine on memory are well documented. However, their effects on false memories are unknown. OBJECTIVE: The aim of this study was to investigate the effects of lorazepam and diazepam on false memories and related states of awareness in healthy volunteers. METHODS: The Deese/Roediger-McDermott procedure was used in 36 healthy volunteers randomly assigned to one of three parallel groups (placebo, diazepam 0.3 mg/kg, lorazepam 0.038 mg/kg). Subjects studied lists of words semantically related to a non-presented theme word (critical lure). On a recognition memory task with both previously presented words and non presented critical lures, they were asked to give Remember, Know or Guess responses to items that were recognized on the basis of conscious recollection, familiarity, or guessing, respectively. RESULTS: The proportions of studied words correctly recognized and the proportions of Remember responses associated with true recognition were lower in the benzodiazepine groups than in the placebo group. In contrast, benzodiazepines did not significantly influence the proportions of critical lures falsely recognized or the proportions of Remember responses associated with false recognition. CONCLUSION: These results indicate that diazepam and lorazepam impair conscious recollection associated with true, but not false, memories.