Objectives
Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) ...Targeting Cognition Task Force aimed to develop consensus‐based clinical recommendations on whether, when and how to assess and address cognitive impairment.
Methods
The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face‐to‐face meeting, telephone conference call and email exchanges. Consensus‐based recommendations were achieved through these exchanges with no need for formal consensus methods.
Results
The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy‐to‐administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence‐based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments.
Conclusions
This task force paper provides the first consensus‐based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients’ functional recovery and improve their quality of life.
The aim of this study was to derive new spirometric reference equations for the English population, using the 1995/1996 Health Survey for England, a large nationally representative cross-sectional ...study. The measurements used were the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of a sample of 6,053 "healthy" (nonsmokers with no reported diagnosis of asthma or respiratory symptoms) White people aged > or = 16 yrs. Multiple regression analysis, with age and height as predictors, was carried out to estimate prediction equations for mean FEV1, FVC and FEV1/FVC, separately for males and females. A method based on smoothing multiple estimates of the fifth percentiles of residuals was used to derive prediction equations for the lower limit of normal lung function. The new equations fit the current English adult population considerably better than the European Coal and Steel Community equations, and the proportions of people with "low" (below the fifth percentile) lung function are closer to those expected throughout the whole adult age range (16 to > 75 yrs). For the age ranges the studies share in common, the new equations give estimates close to those derived from other nonlinear equations in recent studies. It is, therefore, suggested that these newly developed prediction equations be used for the White English population in both epidemiological studies and clinical practice.
There are no tested methods for conducting epidemiological studies of autism spectrum disorders (ASDs) in adult general population samples. We tested the validity of the Autism Diagnostic Observation ...Schedule module-4 (ADOS-4) and the 20-item Autism-Spectrum Quotient (AQ-20).
Randomly sampled adults aged ≥16 years were interviewed throughout England in a general population multi-phase survey. The AQ-20 was self-completed by 7353 adults in phase 1. A random subset completed phase 2, ADOS-4 assessments (n=618); the probability of selection increased with AQ-20 score. In phase 3, informant-based Diagnostic Interview Schedule for Social and Communication Disorders (DISCO) and Autism Diagnostic Interview-Revised (ADI-R) developmental assessments were completed (n=56). Phase 1 and 2 data were presented as vignettes to six experienced clinicians (working in pairs). The probability of respondents having an ASD was compared across the three survey phases.
There was moderate agreement between clinical consensus diagnoses and ADOS-4. A range of ADOS-4 caseness thresholds was identified by clinicians: 5+ to 13+ with greatest area under the curve (AUC) at 5+ (0.88). Modelling of the presence of ASD using 56 DISCO assessments suggested an ADOS-4 threshold in the range of 10+ to 13+ with the highest AUC at ADOS 10+ to 11+ (0.93-0.94). At ADOS 10+, the sensitivity was 1 95% confidence interval (CI) 0.59-1.0 and the specificity 0.86 (95% CI 0.72-0.94). The AQ-20 was only a weak predictor of ADOS-4 cases.
Clinically recommended ADOS-4 thresholds are also recommended for community cases: 7+ for subthreshold and 10+ for definite cases. Further work on adult population screening methods is needed.
In response to the growing need for functional analysis of the human genome, we have developed a platform for high-throughput functional screening of genes overexpressed from lentiviral vectors. ...Protein-coding human open reading frames (ORFs) from the Mammalian Gene Collection were transferred into lentiviral expression vector using the highly efficient Gateway recombination cloning. Target ORFs were inserted into the vector downstream of a constitutive promoter and upstream of an IRES controlled GFP reporter, so that their transfection, transduction and expression could be monitored by fluorescence. The expression plasmids and viral packaging plasmids were combined and transfected into 293T cells to produce virus, which was then used to transduce the screening cell line. We have optimised the transfection and transduction procedures so that they can be performed using robotic liquid handling systems in arrayed 96-well microplate, one-gene-per-well format, without the need to concentrate the viral supernatant. Since lentiviruses can infect both dividing and non-dividing cells, this system can be used to overexpress human ORFs in a broad spectrum of experimental contexts. We tested the platform in a 1990 gene pilot screen for genes that can increase proliferation of the non-tumorigenic mammary epithelial cell line MCF-10A after removal of growth factors. Transduced cells were labelled with the nucleoside analogue 5-ethynyl-2'-deoxyuridine (EdU) to detect cells progressing through S phase. Hits were identified using high-content imaging and statistical analysis and confirmed with vectors using two different promoters (CMV and EF1α). The screen demonstrates the reliability, versatility and utility of our screening platform, and identifies novel cell cycle/proliferative activities for a number of genes.
The syndrome of schizophrenia often includes negative symptoms and severe cognitive deficits that are resistant to change with conventional pharmacotherapy. The efficacy of clozapine in the reduction ...of the negative syndrome has prompted a series of studies implicating circumscribed cognitive improvements. Restrictions on the use of clozapine have encouraged the development and introduction of novel compounds with a clinical efficacy profile similar to clozapine that are hoped also to have beneficial cognitive effects. The present review summarizes studies of the cognitive efficacy of novel antipsychotic medications, particularly in regard to issues in experiment design and study implementation that might facilitate additional research. Although preliminary support exists for relatively circumscribed improvement of cognitive status with the use of clozapine and risperidone—and more general improvement with the use of olanzapine—specific inferences relating cognitive change to particular treatments will remain speculative until more sophisticated investigations are completed. The present review emphasises the most relevant design limitations in past studies to provide practical suggestions for the implementation of subsequent investigations. Previous results have established the possibility of a medication-based change in cognitive status in schizophrenia. Future research will determine the validity of these changes, the cerebral mechanism involved, and their significance to improved prognosis.
To assess the efficacy of quetiapine, a recently introduced second generation antipsychotic medication, in reducing cognitive impairment in patients with schizophrenia.
Prospective, randomized, ...double-blind clinical trial.
25 patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited from 3 Canadian hospitals.
After a 48-hour washout period, 25 patients with schizophrenia were randomly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms, mood and extrapyramidal side effects, as well as standardized neuropsychological measures sensitive to 6 cognitive domains: fine motor skill, attention span, verbal reasoning and fluency, visuospatial construction and fluency, executive skills and visuomotor tracking, and immediate recall of verbal and nonverbal materials. The measures were repeated 8 weeks and 6 months after treatment was initiated.
Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine also had beneficial effects on cognitive skills, particularly verbal reasoning and fluency skills and immediate recall, with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment. Patients taking haloperidol showed improvements in general clinical status, but no specific improvements on the positive syndrome, the negative syndrome, depression ratings or cognitive skills.
These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic.
Uni-rhinal olfactory acuity in schizophrenia was investigated in two experiments. The first assessed the presence of a predicted atypical asymmetry of nostril laterality and the second assessed the ...effect of antipsychotic treatment on the asymmetry. Although olfactory identification impairment has been well documented in schizophrenia, olfactory acuity has been neglected. This may be an oversight as cerebral structures of the mesial temporal lobe important to olfactory perception have often been implicated in the pathophysiology of schizophrenia and it is thus reasonable to postulate a primary impairment of olfactory acuity in schizophrenia. In addition, unmedicated patients with schizophrenia have exhibited asymmetrical laterality favouring the right over the left hemisphere in studies of visual, haptic, and auditory perception, and the few published prospective treatment studies have suggested a reversal of this asymmetry with first generation neuroleptic treatments. In experiment 1 a generalization of the perceptual asymmetry to olfactory acuity was examined by measurement of n-butanol olfactory thresholds with the Connecticut Chemosensory Perception Exam (CCPE) in an unmedicated sample of 17 patients with schizophrenia and 17 age, gender, and handedness matched normal controls. The patient sample showed an asymmetrical impairment of the left nostril that was not apparent in the normal control sample. In experiment 2, the CCPE was administered to a new sample of 10 patients with schizophrenia before and after neuroleptic treatment. The asymmetry observed in experiment 1 was replicated, and the relative advantage of the right nostril shifted to a relative advantage of the left nostril over the course of 8
weeks of treatment. Results are discussed in relation to cerebral aspects of schizophrenia and potential implications to cognitive change from treatment.
Cognitive impairment is central to many psychiatric conditions and is a determinant factor of functioning. The evaluation of cognition is time-consuming and recourse to it limited by cost, ...accessibility of expertise, and, in the case of computerized batteries, equipment. The SCIP is a 15 minute paper and pencil evaluation of cognitive function which can be integrated into clinical practice. It is thus a tool which can assist in determining which patients require a more extensive evaluation and can inform the elaboration of a personalized treatment plan. Our group (Groupe Comorbidité psychiatrique et Dimensions) has validated a french translation of the SCIP and is testing the acceptability of its integration into clinical practice in selected clinical populations. We will present preliminary data regarding the use of the SCIP in adult attention deficit disorder. Forty adult patients with attention deficit disorder were invited to participate in the study. In order to maintain a sample representative of clinical practice the only exclusion criteria were inability to speak french and inability to give informed consent. Demographic characteristics were collected, and a multiaxial DSM-IV diagnosis determined by the treating physician, SCIP was administered. The time to administer the SCIP was recorded, and a qualitative questionnaire of patient impressions was completed. We will present preliminary results of this study.
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