Cognitive deficits in first-episode psychosis: A population-based study in Sao Paulo, Brazil

Background: Studies conducted in high-income countries have reported significant cognitive deficits in first on set schizophrenia subjects relative to asymptotic controls, and it has been suggested that the severity of such deficits could be directly related to the duration of untreated psychosis (DUP). It is relevant to conduct similar studies in developing countries, given the supposedly better outcome for schizophrenia patients living in the latter environments.

Methods: We applied verbal fluency and digit span tests to an epidemiological-based series of patients with first-onset psychoses (n = 179) recruited in the city of Sao Paulo, and compared the findings with those from non-psychotic control subjects randomly selected from the same geographical areas (n=383).

Results: Psychosis subjects showed lower scores on the three tests relative to controls, with greatest between-group differences for the backward digit span task (p < 0.0001). There were no significant differences between subjects with affective and schizophreniform psychosis. Cognitive performance indices were negatively correlated with the severity of negative symptoms, but showed no relation to DUP.

Conclusion: We found significant cognitive deficits in patients investigated early during the course of psychotic disorders in an environment that is distinct from those where the subjects investigated in previous studies have been drawn from. We found no support to the hypothesis of an association between greater cognitive deficits and a longer DUP. (c) 2006 Published by Elsevier B.V.

Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137

Objective: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. Method: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). Results: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. Conclusion: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted. © 2012 Elsevier Ireland Ltd.

Agility and search and rescue training differently affects pet dogs' behaviour in socio-cognitive tasks

Both genetic factors and life experiences appear to be important in shaping dogs' responses in a test situation. One potentially highly relevant life experience may be the dog's training history, however few studies have investigated this aspect so far. This paper briefly reviews studies focusing on the effects of training on dogs' performance in cognitive tasks, and presents new, preliminary evidence on trained and untrained pet dogs' performance in an 'unsolvable task'. Thirty-nine adult dogs: 13 trained for search and rescue activities (S&R group), 13 for agility competition (Agility group) and 13 untrained pets (Pet group) were tested. Three 'solvable' trials in which dogs could obtain the food by manipulating a plastic container were followed by an 'unsolvable' trial in which obtaining the food became impossible. The dogs' behaviours towards the apparatus and the people present (owner and researcher) were analysed. Both in the first 'solvable' and in the 'unsolvable' trial the groups were comparable on actions towards the apparatus, however differences emerged in their human-directed gazing behaviour. In fact, results in the 'solvable' trial, showed fewer S&R dogs looking back at a person compared to agility dogs, and the latter alternating their gaze between person and apparatus more frequently than pet dogs. In the unsolvable trial no difference between groups emerged in the latency to look at the person however agility dogs looked longer at the owner than both pet and S&R dogs; whereas S&R dogs exhibited significantly more barking (always occurring concurrently to looking at the person or the apparatus) than both other groups. Furthermore, S&R dogs alternated their gaze between person and apparatus more than untrained pet dogs, with agility dogs falling in between these two groups. Thus overall, it seems that the dogs' human-directed communicative behaviours are significantly influenced by their individual training experiences. © 2009 Elsevier B.V. All rights reserved.

Apolipoprotein E e4 allele influences aggressive behaviour in Alzheimer's disease

The rising number of people with cognitive impairment is placing health care budgets under significant strain. Dementia related behavioural change is a major independent risk factor for admission to expensive institutional care, and aggressive symptoms in particular are poorly tolerated by carers and frequently precipitate the collapse of home coping strategies. Aggressive change may result from known genetic risk factors for Alzheimer's disease (AD) and therefore accompany conventional markers such as apolipoprotein E (ApoE). We tested this hypothesis in 400 moderately to severely affected AD patients who were phenotyped for the presence of aggressive or agitated behaviour during the month prior to interview using the Neuropsychiatric Inventory with Caregiver Distress. The proportion of subjects with aggression/agitation in the month prior to interview was 51.8%. A significantly higher frequency of the e4 allele was found in individuals recording aggression/agitation in the month prior to interview (chi2 = 6.69, df = 2, p = 0.03). The additional risk for aggression/agitation conferred by e4 was also noted when e4 genotypes were compared against non-e4 genotypes (chi2 = 5.45, df = 1, p = 0.02, OR = 1.60, confidence interval (CI) 1.06 to 2.43). These results indicate that advanced Alzheimer's disease patients are at greater risk of aggressive symptoms because of a genetic weakness in apolipoprotein E.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

Cognitive inhibition and interference in dissociative indentity disorder: the effects of anxiety on specific executive functions:The effects of anxiety on specific executive functions

Using an experimentally based, computer-presented task, this study assessed cognitive inhibition and interference in individuals from the dissociative identity disorder (DID; n=12), generalized anxiety disorder (GAD; n=12) and non-clinical (n=12) populations. Participants were assessed in a neutral and emotionally negative (anxiety provoking) context, manipulated by experimental instructions and word stimuli. The DID sample displayed effective cognitive inhibition in the neutral but not the anxious context. The GAD sample displayed the opposite findings. However, the interaction between group and context failed to reach significance. There was no indication of an attentional bias to non-schema specific negative words in any sample. Results are discussed in terms of the potential benefit of weakened cognitive inhibition during anxious arousal in dissociative individuals.

The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.

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.