Evidence that GABA rho subunits contribute to functional ionotropic GABA receptors in mouse cerebellar Purkinje cells

Ionotropic gamma-amino butyric acid (GABA) receptors composed of heterogeneous molecular subunits are major mediators of inhibitory responses in the adult CNS. Here, we describe a novel ionotropic GABA receptor in mouse cerebellar Purkinje cells (PCs) using agents reported to have increased affinity for rho subunit-containing GABA(C) over other GABA receptors. Exogenous application of the GABA(C)-preferring agonist cis-4-aminocrotonic acid (CACA) evoked whole-cell currents in PCs, whilst equimolar concentrations of GABA evoked larger currents. CACA-evoked currents had a greater sensitivity to the selective GABA(C) antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) than GABA-evoked currents. Focal application of agonists produced a differential response profile; CACA-evoked currents displayed a much more pronounced attenuation with increasing distance from the PC soma, displayed a slower time-to-peak and exhibited less desensitization than GABA-evoked currents. However, CACA-evoked currents were also completely blocked by bicuculline, a selective agent for GABA(A) receptors. Thus, we describe a population of ionotropic GABA receptors with a mixed GABA(A)/GABA(C) pharmacology. TPMPA reduced inhibitory synaptic transmission at interneurone-Purkinje cell (IN-PC) synapses, causing clear reductions in miniature inhibitory postsynaptic current (mIPSC) amplitude and frequency. Combined application of NO-711 (a selective GABA transporter subtype 1 (GAT-1) antagonist) and SNAP-5114 (a GAT-(2)/3/4 antagonist) induced a tonic GABA conductance in PCs; however, TPMPA had no effect on this current. Immunohistochemical studies suggest that rho subunits are expressed predominantly in PC soma and proximal dendritic compartments with a lower level of expression in more distal dendrites; this selective immunoreactivity contrasted with a more uniform distribution of GABA(A) alpha 1 subunits in PCs. Finally, co-immunoprecipitation studies suggest that rho subunits can form complexes with GABA(A) receptor alpha 1 subunits in the cerebellar cortex. Overall, these data suggest that rho subunits contribute to functional ionotropic receptors that mediate a component of phasic inhibitory GABAergic transmission at IN-PC synapses in the cerebellum.

Learning and memory in holocaust survivors with posttraumatic stress disorder

Background: Impairments in explicit memory have been observed in Holocaust survivors with posttraumatic stress disorder. Methods: To evaluate which memory components are preferentially affected, the California Verbal Learning Test was administered to Holocaust survivors with (n = 36) and without (n = 26) posttraumatic stress disorder, and subjects not exposed to the Holocaust (n = 40). Results: Posttraumatic stress disorder subjects showed impairments in learning and short-term and delayed retention compared to nonexposed subjects; survivors without posttraumatic stress disorder did not. Impairments in learning, but not retention, were retained after controlling fir intelligence quotient. Older age was associated with poorer learning and memory performance in the posttraumatic stress disorder group only. Conclusions: The most robust impairment observed in posttraumatic stress disorder was in verbal learning, which may be a risk factor for or consequence of chronic posttraumatic stress disorder. The negative association between performance and age may reflect accelerated cognitive decline in posttraumatic stress disorder.

Predicting violence in schizophrenia: a prospective study

Background: People with schizophrenia are more violent than the general population, but this increased risk is attributable to the actions of a small subgroup. Identifying those at risk has become an essential part of clinical practice. Aims: To estimate the risk factors for assault in patients with schizophrenia. Methods: Two hundred seventy-one patients with schizophrenia were interviewed using an extensive battery of instruments. Assault was measured from multiple data sources over the next 2 years and criminal records were obtained. Multiple sociodemographic and clinical variables measured at baseline were examined as possible predictors of assault during follow-up. Results: Sixty-nine (25%) patients committed assault during the 2-year followup. The model that best predicted assault included a history of recent assault (OR 2.33, 95% CI 1.17-4.61), a previous violent conviction (OR 2.02, 95% CI 1.04-3.87), having received special education (OR 2.76, 95% CI 1.22-6.26) and alcohol abuse (OR 3.55, 95% CI 1.24-10.2). Conclusions: Previously established risk factors including a history of violence and alcohol abuse are replicated in this study. Although low premorbid IQ did not predict violence, a need for special education did. (C) 2003 Published by Elsevier B.V.

Is NHS Direct meeting the needs of mental health callers?

Background: NHS Direct is a new service that offers 24-hour advice from trained nurses. The National Service Framework for Mental Health and the National Strategy for Carers both mention NHS Direct as an important source of support for people with mental health problems. Aims: This paper reports findings from an evaluation of the Department of Health's NHS Direct mental health initiative. This initiative was established to ensure that NHS Direct can meet the needs of callers with mental health problems by offering additional training to all staff and improving the database of mental health services. Method: The findings reported here are based on routine computer data provided by 12 out of 17 NHS Direct sites, 552 data forms completed by nurse advisers from the 17 sites, and 111 questionnaires administered over the telephone with callers to the 17 sites. Results: Mental health calls accounted for 3% of NHS Direct's workload, although these calls were often longer and more complex than other calls. The majority of callers to the service were in touch with other services for their mental health problems (59%), typically their GP. Most callers had 'moderate' mental health problems, as indicated by the Global Assessment of Functioning Scale. Generally callers were satisfied with the service they received, although satisfaction was lower in some areas than previous studies of NHS Direct. Conclusions: Improvements could be made in the mechanisms for referring callers on to other services, and training to increase nurse advisers' knowledge of mental health problems.

Intensive case management for severe psychotic illness: is there a general benefit for patients with complex needs? A secondary analysis of the UK700 trial data

The UK700 trial failed to demonstrate an overall benefit of intensive case management (ICM) in patients with severe psychotic illness. This does not discount a benefit for particular subgroups, and evidence of a benefit of ICM for patients of borderline intelligence has been presented. The aim of this study is to investigate whether this effect is part of a general benefit for patients with severe psychosis complicated by additional needs. In the UK700 trial patients with severe psychosis were randomly allocated to ICM or standard case management. For each patient group with complex needs the effect of ICM is compared with that in the rest of the study cohort. Outcome measures are days spent in psychiatric hospital and the admission and discharge rates. ICM may be of benefit to patients with severe psychosis complicated by borderline intelligence or depression, but may cause patients using illicit drugs to spend more time in hospital. There was no convincing evidence of an effect of ICM in a further seven patient groups. ICM is not of general benefit to patients with severe psychosis complicated by additional needs. The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available.

A review of instruments developed to measure outcomes for carers of people with mental health problems

Objective: Community-based care for mental disorders places considerable burden on families and carers. Measuring their experiences has become a priority, but there is no consensus on appropriate instruments. We aimed to review instruments carers consider relevant to their needs and assess evidence for their use. Method: A literature search was conducted for outcome measures used with mental health carers. Identified instruments were assessed for their relevance to the outcomes identified by carers and their psychometric properties. Results: Three hundred and ninety two published articles referring to 241 outcome measures were identified, 64 of which were eligible for review (used in three or more studies). Twenty-six instruments had good psychometric properties; they measured (i) carers' well-being, (ii) the experience of caregiving and (iii) carers' needs for professional support. Conclusion: Measures exist which have been used to assess the most salient aspects of carer outcome in mental health. All require further work to establish their psychometric properties fully.

The effect of intensive case management on the relatives of patients with severe mental illness

Objective: Relatives play a vital role in caring for patients with severe mental illness but receive inadequate support from psychiatric services. Evidence suggests that although intensive case management is directed primarily at patients, relatives may benefit a's well. This study examined whether relatives of patients who were receiving intensive case management had more contact with mental health professionals than relatives of patients who were receiving standard case management. It also examined whether relatives of patients receiving intensive case management appraised caregiving less negatively and experienced less psychological distress than relatives of patients receiving standard case management. Methods: The sample was drawn from the pool of patients participating in the UK700 randomized controlled trial of intensive case management. Prospective data on contact between case managers and the relatives of 146 patients were collected over a two-year period. At a two-year follow-up assessment, relatives of 116 patients were. interviewed with the Experience of Caregiving Inventory and the 12-item General Health Questionnaire. Results: Considerably more relatives of patients receiving intensive case management had contact with a case manager during the study period than relatives of patients receiving standard case management (70 percent compared with 45 percent). However, relatives of patients receiving intensive case management did not-appraise caregiving less negatively or experience less psychological distress than relatives of patients who were receiving. standard case management. Conclusions: Reducing case managers' caseloads alone. will not guarantee adequate support for relatives.. Instead, providing more support will need to be an explicit aim, and staff will require specific additional training to achieve it.

Relatives of patients with severe mental disorders: unique traits and experiences of primary, nonprimary, and lone caregivers

The authors examined caregivers' characteristics and experiences. Previously suggested principles for identifying the primary caregiver in 22 multiple-caregiver families were assessed, but none reliably distinguished the primary caregiver. The authors then compared primary (n = 22), nonprimary (n = 22), and lone caregivers' (n = 43) appraisals of caregiving and psychological distress. Lone and primary caregivers' experiences were similar. but nonprimary caregivers' experiences were less adverse. Despite these findings, greater psyhcological distress in primary caregivers indicated greater psychological distress in nonprimary caregivers.

Input and output modality effects in immediate serial recall

In immediate recall tasks, visual recency is substantially enhanced when output interference is low (Cowan, Saults, Elliott, & Moreno, 2002; Craik, 1969) whereas auditory recency remains high even under conditions of high output interference. Ibis auditory advantage has been interpreted in terms of auditory resistance to output interference (e.g., Neath & Surprenant, 2003). In this study the auditory-visual difference at low output interference re-emerged when ceiling effects were accounted for, but only with spoken output. With written responding the auditory advantage remained significantly larger with high than with low output interference. These new data suggest that both superior auditory encoding and modality-specific output interference contribute to the classic auditory-visual modality effect.

Local, national and imported foods: a qualitative study

The UK government is currently attempting to encourage consumers to buy more locally produced food. It is hoped that this will provide economic, environmental and social benefits to local areas, leading to more sustainable patterns of consumption. This qualitative study looks at the views and behaviour of consumers towards local foods with a particular focus on the barriers that prevent greater uptake of local produce. In total, four focus groups (n = 33) were conducted. Content analysis identified six relevant themes in relation to local, national and imported foods. These were cost, lifestyle, food quality, consumer ethnocentrism, choice and farmers. Overall, although participants reported buying few local products currently, there was widespread enthusiasm across socio-economic groups for local foods, with participants perceiving them as being of a higher quality than imported foods. They also generally endorsed the idea of supporting local farmers and their own national economy. The main barriers preventing participants from buying more local products were price and inconvenience. The results are discussed in relation to developing future strategies for encouraging people to buy more local food products. (c) 2007 Elsevier Ltd. All rights reserved.

Forty-eight hour access to primary care: practice factors predicting patients' perceptions

Background: The government has proposed a 48-hour target for GP availability. Although many practices are moving towards delivering that goal, recent national patient surveys have reported a deterioration in patients' reports of doctor availability. What practice factors contribute to patients' perceptions of doctor availability? Method: A cross sectional patient survey (11 000 patients from 54 inner London practices, 7247 (66%) respondents) using the General Practice Assessment Survey. We asked patients how soon they could be seen in their practice following non-urgent consultation requests and related their aggregated responses to the characteristics of their practice. Results: Three factors relating to practice administration and appointments systems operation independently predicted patients' reports of doctor availability. These were the proportion of patients asked to attend the surgery and wait to be seen, the proportion of patients seen using an emergency surgery arrangement, and the extent of practice computerization. Conclusion: Some practices may have difficulty in meeting the target for GP availability. Meeting the target will involve careful review of practice administrative procedures.

Perceptions of psychological content in the GP consultation - the role of practice, personal and prescribing attributes

Objective: The aim of the present study was to determine the relationship between the characteristics of general practices and the perceptions of the psychological content of consultations by GPs in those practices. Methods: A cross-sectional survey was conducted of all GPs (22 GPs based in nine practices) serving a discrete inner city community of 41 000 residents. GPs were asked to complete a log-diary over a period of five working days, rating their perception of the psychological content of each consultation on a 4-point Likert scale, ranging from 0 (no psychological content) to 3 (entirely psychological in content). The influence of GP and practice characteristics on psychological content scores was examined. Results: Data were available for every surgery-based consultation (n = 2206) conducted by all 22 participating GPs over the study period. The mean psychological content score was 0.58 (SD 0.33). Sixty-four percent of consultations were recorded as being without any psychological content; 6% were entirely psychological in content. Higher psychological content scores were significantly associated with younger GPs, training practices (n = 3), group practices (n = 4), the presence of on-site mental health workers (n = 5), higher antidepressant prescribing volumes and the achievement of vaccine and smear targets. Training status had the greatest predictive power, explaining 51% of the variation in psychological content. Neither practice consultation rates, GP list size, annual psychiatric referral rates nor volumes of benzodiazepine prescribing were related to psychological content scores. Conclusion: Increased awareness by GPs of the psychological dimension within a consultation may be a feature of the educational environment of training practices.