Effects of amisulpride, risperidone and chlorpromazine on auditory and visual latent inhibition, prepulse inhibition, executive function and eye movements in healthy volunteers.

In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.

Teaching and cognitive outcomes in A-levels and Advanced GNVQ's: Case studies from Science and Business Studies Classrooms

The purpose of the paper is to demonstrate how a research diary methodology, designed to analyse A-level and GNVQ classrooms, can be a powerful tool for examining pedagogy and quality of learning at the level of case study. Two subject areas, science and business studies, are presented as cases. Twelve teachers and thirty-four students were studied over a four-week period in May 1997 and contrasts were drawn between lessons from three A-level physics teachers/three Advanced GNVQ science teachers and two A-level business/economics teachers/four Advanced GNVQ business teachers. Lessons were analysed within a cognitive framework which distinguishes between conceptual and procedural learning and emphasizes the importance of metacognition and epistemological beliefs. Two dimensions of lessons were identified: pedagogical activities (e.g. teacher-led explanation, teacher-led guidance on a task, question/answer sessions, group discussions, working with IT) and cognitive outcomes (e.g. structuring and memorizing facts, understanding concepts and arguments, critical thinking, problem-solving, learning core skills, identifying values). Immediately after each lesson, teachers and students (three per class) completed structured research diaries with respect to the above dimensions. Data from the diaries reveal general and unique features of the lessons. Time-ofyear effects were evident (examinations pending in May), particularly in A-level classrooms. Students in business studies classes reported a wider range of learning activities and greater variety in cognitive outcomes than did students in science classes. Science students self-rating of their ability to manage and direct their own learning was generally low. The phenomenological aspects of the classrooms were consistently linked to teachers' lesson plans and what their teaching objectives were for those particular students at that particular time of the year.

A 6-month open-label study of the effectiveness and tolerability of galantamine in patients with Alzheimer's disease

The objective of this study was to assess the effectiveness and tolerability of galantamine in patients with mild-to-moderate Alzheimer's disease (AD) in everyday clinical practice. Patient selection was made on 36 sequential patients attending Belfast City Hospital Memory Clinic between December 2000 and June 2001. Patients were treated with galantamine for 6 months, starting from 4 mg twice daily increasing to 8 mg twice daily and then to 12 mg twice daily at 4-weekly intervals. Patients (25 females, 11 males), mean age 78 years (59-90), were diagnosed with probable AD and had a mini-mental state examination (MMSE) score of 10-26. Efficacy was assessed using the MMSE, neuropsychiatric inventory (NPI), neuropsychiatric inventory caregiver distress (NPI-D) scale and the Bristol activities of daily living (B-ADL) scale at baseline and after 3 and 6 months of treatment. Mean improvements were noted on all four measures of efficacy at 3 and 6 months; improvements were significant on the MMSE, NPI and NPI-D at 3 months and on the NPI-D at 6 months. Galantamine was overall well tolerated. The most common adverse events were gastrointestinal, particularly nausea. Four patients stopped treatment due to adverse events, and seven were stabilised on 8 mg twice daily as they were unable to tolerate the target dose. This naturalistic study confirms clinical trial data, which shows galantamine improves cognition and behavioural symptoms and is overall well tolerated. © 2004 Blackwell Publishing Ltd.

Genetically increased risk of sleep disruption in alzheimer's disease

STUDY OBJECTIVES: To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD). DESIGN: A case-control association analysis. SETTING: Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A). PATIENTS: Patients with AD diagnosed according to standard criteria. INTERVENTIONS: Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods. MEASUREMENTS AND RESULTS: Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype. CONCLUSIONS: We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.

Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behavours in rats

Angiotensin converting enzyme inhibitors (ACEis) are widely used anti-hypertensive agents that are also reported to have positive effects on mood and cognition. The present study examined the influence of the ACEi, perindopril, on cognitive performance and anxiety measures in rats. Two groups of rats were treated orally for one week with the ACEi, perindopril, at doses of 0.1 and 1.0mg/kg/day. Learning was assessed by the reference memory task in the water maze, comparing treated to control rats. Over five training days both perindopril-treated groups learnt the location of the submerged platform in the water maze task significantly faster than control rats. A 60s probe trial on day 6 showed that the 1.0mg/kg/day group spent significantly longer time in the training quadrant than control rats. This improved performance in the swim maze task was not due to the effect of perindopril on motor activity or the anxiety levels of the rats as perindopril-treated and control animals behaved similarly in activity boxes and on the elevated+maze. These results confirm the anecdotal human studies that ACEis have a positive influence on cognition and provide possibilities for ACEis to be developed into therapies for memory loss.

The fall of kinship - towards an epidemiological explanation

Kinship used to be described as what anthropologists do. Today, many might well say that it is what anthropologists do not do. One possible explanation is that the notion of kinship fell off anthropology's radar due to the criticisms raised by Needham and Schneider among others, which supposedly demonstrated that kinship is not a sound theoretical concept. Drawing inspiration from epidemiological approaches to cultural phenomena, this article aims to enrich this explanation. Kinship became an unattractive theoretical concept in the subculture of anthropology not simply because of problems with kinship theory per se, but also on account of fundamental changes in the very conception of anthropological knowledge and the impact of these changes on the personal identity of anthropologists.

Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats.

The extensive clinical experience of angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists as antihypertensive agents provide numerous examples of anecdotal evidence of improvements in cognition and mood. This study aimed to determine the effect of chronic treatment with the angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT(1) receptor antagonist, candesartan, on central neurotransmitter levels in the rat. Perindopril (1.0mg/kg/day) or candesartan (10mg/kg/day) was administered via the drinking water at for 1 week, while controls received water alone. At the end of treatment rats were sacrificed, brains removed and discrete regions dissected and analysed for noradrenaline, dopamine and its major metabolites, and serotonin content. As shown previously we found an increase in striatal dopamine levels after perindopril treatment, though this did not extend to the mesolimbic system with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and frontal cortex. Conversely, candesartan administration produced no change in dopamine, but significant decreases in both DOPAC and HVA in the striatum. In addition chronic candesartan infusion produced a significant increase in the levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin content. These results demonstrate that while angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists act as antihypertensives by affecting the renin-angiotensin system, they have divergent actions on brain neurochemistry.

Manual asymmetries in the preparation and control of goal-directed movements

The primary purpose of this experiment was to determine if left hand reaction time advantages in manual aiming result from a right hemisphere attentional advantage or an early right hemisphere role in movement preparation. Right-handed participants were required to either make rapid goal-directed movements to small targets or simply lift their hand upon target illumination. The amount of advance information about the target for a particular trial was manipulated by precuing a subset of potential targets prior to the reaction time interval. When participants were required to make aiming movements to targets in left space, the left hand enjoyed a reaction advantage that was not present for aiming in right space: or simple finger lifts. This advantage was independent of the amount or type of advance information provided by the precue. This finding supports the movement planning hypothesis. With respect to movement execution, participants completed their aiming movements more quickly when aiming with their right hand, particularly in right space. This right hand advantage in right space was due to the time required to decelerate the movement and to make feedback-based adjustments late in the movement trajectory. (C) 2001 Academic Press.

Bimanual coordination in chronic schizophrenia

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia. a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees) and out-of-phase movements (hands separated by 180 degrees) at both speeds with an external cue on or off. All participants performed the in-phase movements well. irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved. (C) 2001 Academic Press.

Patterns of neurocognitive impairment in first-episode bipolar disorder and schizophrenia.

BACKGROUND:
Researching psychotic disorders in unison rather than as separate diagnostic groups is widely advocated, but the viability of such an approach requires careful consideration from a neurocognitive perspective.
AIMS:
To describe cognition in people with bipolar disorder and schizophrenia and to examine how known causes of variability in individual's performance contribute to any observed diagnostic differences.
METHOD:
Neurocognitive functioning in people with bipolar disorder (n = 32), schizophrenia (n = 46) and healthy controls (n = 67) was compared using analysis of covariance on data from the Northern Ireland First Episode Psychosis Study.
RESULTS:
The bipolar disorder and schizophrenia groups were most impaired on tests of memory, executive functioning and language. The bipolar group performed significantly better on tests of response inhibition, verbal fluency and callosal functioning. Between-group differences could be explained by the greater proclivity of individuals with schizophrenia to experience global cognitive impairment and negative symptoms.
CONCLUSIONS:
Particular impairments are common to people with psychosis and may prove useful as endophenotypic markers. Considering the degree of individuals' global cognitive impairment is critical when attempting to understand patterns of selective impairment both within and between these diagnostic groups.

When some is actually all: Scalar inferences in face-threatening contexts

Accounts of the scalar inference from 'some X-ed' to 'not all X-ed' are central to the debate between contemporary theories of conversational pragmatics. An important contribution to this debate is to identify contexts that decrease the endorsement rate of the inference. We suggest that the inference is endorsed less often in face-threatening contexts, i.e., when X implies a loss of face for the listener. This claim is successfully tested in Experiment 1. Experiment 2 rules out a possible confound between face-threatening contexts and lower-bound contexts. Experiment 3 shows that whilst saying 'some X-ed' when one knew for a fact that all X-ed is always perceived as an underinformative utterance, it is also seen as a nice and polite thing to do when X threatens the face of the listener. These findings are considered from the perspective of Relevance Theory as well as that of the Generalized Conversational Inference approach. (C) 2009 Elsevier B.V. All rights reserved.

Temporal Decentering and the Development of Temporal Concepts

This article reviews some recent research on the development of temporal cognition, with reference to Weist's (1989) account of the development of temporal understanding. Weist's distinction between two levels of temporal decentering is discussed, and empirical studies that may be interpreted as measuring temporal decentering are described. We argue that if temporal decentering is defined simply in terms of the coordination of the temporal locations of three events, it may fail to fully capture the properties of mature temporal understanding. Characterizing the development of mature temporal cognition may require, in addition, distinguishing between event-dependent and event-independent thought about time. Experimental evidence relevant to such a distinction is described; these findings suggest that there may be important changes between 3 and 5 years in children's ability to think about points in time independently of the events that occur at those times.

Deciding between theories of how reasoning develops is hard

Although Sloutsky agrees with our interpretation of our data, he argues that the totality of the evidence supports his claim that children make inductive generalisations on the basis of similarity. Here we take issue with his characterisation of the alternative hypotheses in his informal analysis of the data, and suggest that a thorough Bayesian analysis, although practically very difficult, is likely to result in a more finely balanced outcome than he suggests. (c) 2008 Elsevier B.V. All rights reserved.

Do development and learning really decrease memory? On similarity and category-based induction in adults and children

In a recently published study, Sloutsky and Fisher [Sloutsky, V. M., & Fisher, A.V. (2004a). When development and learning decrease memory: Evidence against category-based induction in children. Psychological Science, 15, 553-558; Sloutsky, V. M., & Fisher, A. V. (2004b). Induction and categorization in young children: A similarity-based model. Journal of Experimental Psychology: General, 133, 166-188.] demonstrated that children have better memory for the items that they generalise to than do adults. On the basis of this finding, they claim that children and adults use different mechanisms for inductive generalisations;whereas adults focus on shared category membership, children project properties on the basis of perceptual similarity. Sloutsky & Fisher attribute children's enhanced recognition memory to the more detailed processing required by this similarity-based mechanism. In Experiment I we show that children look at the stimulus items for longer than adults. In Experiment 2 we demonstrate that although when given just 250 ms to inspect the items children remain capable of making accurate inferences, their subsequent memory for those items decreases significantly. These findings suggest that there are no necessary conclusions to be drawn from Sloutsky & Fisher's results about developmental differences in generalisation strategy. (C) 2007 Elsevier B.V. All rights reserved.