Effects of cognitive remediation on negative symptoms dimensions: exploring the role of working memory.

BACKGROUND: Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement. METHOD: Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests. RESULTS: Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = -0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation. CONCLUSIONS: The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

Cognitive remediation for individuals with psychosis: efficacy and mechanisms of treatment effects.

BACKGROUND: The popularity of cognitive remediation (CR) interventions for individuals with psychosis is in part based on the well-established link between cognition and functioning and the assumption that by targeting cognition, function can improve. While numerous trials have reported CR's efficacy, it is still not considered an evidence-based treatment. Importantly, little is known about the mechanisms through which it may affect functioning. METHOD: In this study, we evaluated CR's proximal and distal effects, and examined potential mechanisms. A total of 75 individuals with psychotic disorders were randomized to a combination of strategy-based and drill-and-practice CR or wait-list control, with assessments of training task performance, neurocognition, functional capacity, symptoms and functioning conducted at baseline, end of the 2-month intervention, and 2-month follow-up. RESULTS: Compared with treatment as usual, CR was associated with large post-training improvements on training tasks targeting attention, visuospatial memory, and verbal learning and memory, with persisting group differences at the 2-month follow-up. These generalized to mostly large improvements on neuropsychological measures targeting visuospatial memory, verbal learning and memory, delayed verbal memory and verbal working memory. While there were no CR-associated improvements on measures of functional capacity, symptoms, or a self-report measure of independent living skills, there was an effect on an interviewer-rated measure of functioning (Quality of Life Scale), which appeared primarily driven by the Intrapsychic Foundations subscale. Finally, for those randomized to CR, there were significant, medium-sized correlations between training task improvement, neuropsychological improvement and functioning measures. CONCLUSIONS: This suggests a complex, multifactorial relationship between CR, and cognitive and functional change.

Quality and outcomes in anaesthesia: lessons from litigation.

Healthcare litigation in the UK continues to grow at an alarming rate, with claims against anaesthetists and critical care physicians increasing each year. This has led to a huge financial burden for the taxpayer and a sharp increase in professional indemnity fees for individual doctors. Although such litigation should provide valuable information to educate practitioners and reduce future similar claims, there appear to be significant barriers preventing important lessons from being learned. Detailed learning opportunities are available only to the healthcare providers being sued or the expert witnesses employed to analyse the claims. Most practitioners have to rely on indemnifiers' case reports, closed-claim analyses, and ad hoc publications for information. In this review, we suggest ways in which important lessons from litigation could be brought to the attention of all clinicians. Currently, most clinicians are unable to determine whether key components of their practice such as consent, clinical decision-making, and documentation are of an acceptable standard for legal scrutiny. By reporting outcomes of Coroners' inquests, clinical and criminal negligence cases, and referrals to the General Medical Council, it would be hoped that more explicit standards of performance could be derived. Ultimately, this may not only improve patient safety, but protect practitioners from unjustifiable claims. Finally, given the critical importance of experts in the above process, we believe that a system for professional registration and regulation should be explored to ensure that they offer accurate, representative, and unbiased opinions and have the appropriate expertise in the subject matter to be analysed.

Toward the improvement of total nitrogen deposition budgets in the United States.

Frameworks for limiting ecosystem exposure to excess nutrients and acidity require accurate and complete deposition budgets of reactive nitrogen (Nr). While much progress has been made in developing total Nr deposition budgets for the U.S., current budgets remain limited by key data and knowledge gaps. Analysis of National Atmospheric Deposition Program Total Deposition (NADP/TDep) data illustrates several aspects of current Nr deposition that motivate additional research. Averaged across the continental U.S., dry deposition contributes slightly more (55%) to total deposition than wet deposition and is the dominant process (>90%) over broad areas of the Southwest and other arid regions of the West. Lack of dry deposition measurements imposes a reliance on models, resulting in a much higher degree of uncertainty relative to wet deposition which is routinely measured. As nitrogen oxide (NOx) emissions continue to decline, reduced forms of inorganic nitrogen (NHx = NH3 + NH4+) now contribute >50% of total Nr deposition over large areas of the U.S. Expanded monitoring and additional process-level research are needed to better understand NHx deposition, its contribution to total Nr deposition budgets, and the processes by which reduced N deposits to ecosystems. Urban and suburban areas are hotspots where routine monitoring of oxidized and reduced Nr deposition is needed. Finally, deposition budgets have incomplete information about the speciation of atmospheric nitrogen; monitoring networks do not capture important forms of Nr such as organic nitrogen. Building on these themes, we detail the state of the science of Nr deposition budgets in the U.S. and highlight research priorities to improve deposition budgets in terms of monitoring and flux measurements, leaf- to regional-scale modeling, source apportionment, and characterization of deposition trends and patterns.

Safety in anaesthesia: a study of 12,606 reported incidents from the UK National Reporting and Learning System.

The incident reporting database at the National Patient Safety Agency was interrogated on the nature, frequency and severity of incidents related to anaesthesia. Of 12,606 reports over a 2-year period, 2842 (22.5%) resulted in little harm or a moderate degree of harm, and 269 (2.1%) resulted in severe harm or death, with procedure or treatment problems generating the highest risk. One thousand and thirty-five incidents (8%) related to pre-operative assessment, with harm occurring in 275 (26.6%), and 552 (4.4%) related to epidural anaesthesia, with harm reported in 198 (35.9%). Fifty-eight occurrences of anaesthetic awareness were also examined. This preliminary analysis is not authoritative enough to warrant widespread changes of practice, but justifies future collaborative approaches to reduce the potential for harm and improve the submission, collection and analysis of incident reports. Practitioners, departments and professional bodies should consider how the information can be used to promote patient safety and their own defensibility.

Inflammation in the nervous system.

Earlier studies on inflammation in the CNS have largely focused on conditions with an immune component. Recent evidence has emerged, however, that the innate, acute inflammatory response in the CNS parenchyma is quite unlike that in other tissues. The meninges and ventricular compartments show more typical responses, as does the parenchyma of the brain in immature animals. It is becoming apparent that the cells of the mononuclear phagocyte lineage dominate inflammatory responses in the CNS parenchyma.

Impact of intellectual status on response to cognitive task training in patients with schizophrenia.

Cognitive remediation is a promising rehabilitation procedure for people with schizophrenia, but very little is known about who can benefit. In the current analyses, we examined the role of pre-morbid and morbid intellectual function in predicting response to cognitive remediation in a sample of 152 patients diagnosed with schizophrenia or schizoaffective disorder. They were participants in a trial of work therapy and cognitive remediation and had been randomized to receive either Neurocognitive Enhancement Therapy with Work Therapy (NET+WT) or Work Therapy only (WT only). For the current analyses, patients were divided into three intellectual subgroups based on their pattern of premorbid and morbid deficits (preserved intelligence, compromised intelligence, and deteriorated intelligence), and their cognitive remediation outcomes were examined. Cognitive remediation response was measured in two ways: normalization of performance on a computerized training task, and pre-post neuropsychological test performance. Subjects in NET+WT showed greater improvement in cognition than those in WT only, but response differed by intellectual group. For patients in the compromised group, those in NET+WT showed a significantly higher proportion of task normalization than those in the WT only condition, but no such differences were found with the preserved and deteriorated intellectual groups. For patients in the preserved and deteriorated intellectual groups, those in the NET+WT condition showed significantly greater improvement in the analysis of pre-post neuropsychological test performance, but this difference was not found in the compromised intellectual group. These findings suggest that the compromised intellectual group, which had the lowest frequency of normal performers at intake, benefited from NET by achieving dramatic increases in normalization, but that they had difficulty in generalizing these gains to untrained tasks. Those in the preserved and deteriorated intellectual groups were more successful in generalizing their training.

Emergency medicine, organ donation and the Human Tissue Act.

The Human Tissue Act 2004, which governs all activity relating to the human body, organs or tissues, is grounded in the principle of fully informed consent in line with societal expectations. The associated intention to deal with the current deficit of transplantable organs has paradoxically been translated into the legitimisation of non-consensual organ preservation manoeuvres after death. The procurement strategy targeted under this new statute is "uncontrolled" non-heart-beating donation, and the clinical arenas would be accident and emergency departments and acute medical wards. Practitioners in these fields need to have an understanding of the process and the associated ethical, logistical and legal hurdles to defensible implementation. In the light of these hurdles, there is an obvious need for more widespread professional and public consultation before adoption of this programme.

Unusual aspects of inflammation in the nervous system: Wallerian degeneration.

Wallerian degeneration in the PNS is accompanied by the rapid recruitment of monocytes, but monocytes do not invade CNS fibre tracts undergoing Wallerian degeneration. In recent years it has become apparent that the acute inflammatory response to cell degeneration in the CNS is unlike that in other tissues. We have been interested to learn why Wallerian degeneration does not provoke a typical inflammatory response. We investigated whether the vascular endothelial cells express adhesion molecules during Wallerian degeneration in PNS and CNS. We found that in the degenerating sciatic nerve there was upregulation of ICAM-1 and VCAM-1 expression on endothelial cells in the distal stump of the injured nerve as well as at the site of the lesion. However, in the degenerating optic nerve, the endothelium failed to upregulated these molecules in the distal stump of the nerve and ICAM-1 expression was only increased in the crush site. The lack of adhesion molecule expression on CNS endothelium molecules may be an explanation for the poor leukocyte recruitment during Wallerian degeneration in CNS when compared with PNS.

Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines.

Following the intracranial injection of lipopolysaccharide or during acute neuronal degeneration, there is a paucity of polymorphonuclear leukocyte recruitment to the brain parenchyma and a delay in monocyte recruitment. The present study investigates whether the injection of specific leukocyte chemoattractants into the murine central nervous system can override this intrinsic resistance. Recombinant alpha-(IL-8/NAP-1 MIP-2, IP-10) and beta-chemokines (MCP-1, RANTES) were injected into the murine hippocampus and leukocyte recruitment was assessed histologically. Injections were also made into the dermis of the hind flank for comparison. At doses of 1 microgram, MCP-1 was found to be the most potent monocyte chemoattractant in the brain parenchyma and skin with IP-10 and RANTES producing minimal monocyte recruitment to both sites. In contrast IL-8, and MIP-2 provoked dramatic polymorphonuclear leukocyte recruitment in both the central nervous system and skin. The polymorphonuclear leukocyte recruitment was associated with a breaching of the blood brain barrier that was particularly severe after MIP-2. Both L-8 and MIP-2 induced blood brain barrier breakdown could be attenuated by prior depletion of the circulating leukocytes. The regulation of polymorphonuclear leukocyte chemoattractants in the brain parenchyma during injury and infection is an important area for future studies.

Clinical benefits of paid work activity in schizophrenia: 1-year followup.

In a previous article in the Schizophrenia Bulletin (Vol. 22, No. 1, 1996), we presented findings of a study on the clinical and rehabilitative effects of work activity on 150 subjects diagnosed with schizophrenia or schizoaffective disorder. Subjects were randomly assigned to either a Pay ($3.40/hr) or No-Pay group and given 6-month work placements in a Department of Veterans Affairs medical center. At the 5-month followup, Pay subjects had worked more hours and earned more money (from any employment) than No-Pay subjects. Pay subjects also had significantly greater improvement in symptoms and lower rehospitalization rates. Clinical improvement was closely linked to amount of participation. We concluded that pay increased participation. The current study examined clinical and rehabilitative outcomes at 1-year followup, 6 months after the conclusion of the work program. Results indicated that the Pay subjects had a significant decrease in work activity once they had completed the work program. However, 75 percent of those who had fully participated in the program continued working during the subsequent 6 months, either as volunteers or for pay. Clinical outcomes for subjects in the Pay condition were attenuated at 1-year followup but still significantly better than for subjects in the No-Pay condition. More than 40 percent of participants continued to be "much improved" on total symptoms, and more than 50 percent were "much improved" on positive symptoms. Discussion focuses on the importance and limitations of work for pay as a clinical intervention and concludes that continuous work services are necessary and beneficial for many people with schizophrenia.

Work rehabilitation in schizophrenia: does cognitive impairment limit improvement?

Cognitive impairments may be an important contributor to disability in schizophrenia and may limit the rate of improvement in work rehabilitation. Thirty-three outpatients with schizophrenia or schizoaffective disorder who participated in a 6-month work rehabilitation program were assessed for symptom severity and administered neuropsychological testing at intake. Their work performance was evaluated biweekly using the Work Behavior Inventory. On each of five domains of work performance, 76 to 91 percent of subjects reached proficiency or improved significantly over 26 weeks. Individual differences in rate of improvement were robustly predicted by neuropsychological variables: Work Habits, r2 = 0.79; Personal Presentation, r2 = 0.73; Cooperativeness, r2 = 0.67; Work Quality, r2 = 0.56; Social Skills, r2 = 0.27; Total, r2 = 0.44. Neuropsychological measures had differential relationships to work domains. Individual differences in improvement were not predicted by symptom measures. These findings link cognitive impairment to disability and suggest that remediating or accommodating such deficits may be necessary for successful rehabilitation.

Clinical benefits of paid work activity in schizophrenia.

Although indirect support can be found for the clinical benefits of work, it has not been studied in randomized designs, nor have critical variables been manipulated. One such variable is pay incentive. The authors present a study of 150 subjects with schizophrenia or schizoaffective disorder who were randomized into Pay ($3.40/hour) and No-Pay conditions and offered 6-month work placements within a Department of Veterans Affairs medical center. Subjects participated in a work-related support group and were evaluated weekly on symptom measures. Results indicated that Pay subjects worked more hours and earned more money than No-Pay subjects. Pay subjects showed more total symptom improvement at followup, and more improvement, particularly on positive and emotional discomfort symptoms. They also had a significant lower rate of rehospitalization than No-Pay subjects. Participation in work activity was closely associated with symptom improvement. Participators showed more total symptom improvement at followup than partial participators or nonparticipators, and more improvement, particularly on positive, hostility, and emotional discomfort symptoms. We concluded that pay increased participation and that, in this study, participation in work activity was primarily responsible for symptom reduction.

Central nervous system tuberculosis in HIV-infected patients: clinical and radiographic findings.

PURPOSE: To characterize the radiographic findings on neuroimaging of 25 human immunodeficiency virus (HIV)-seropositive patients with proved central nervous system tuberculosis and to correlate those findings with clinical data. METHODS: Twenty-five HIV-seropositive patients with central nervous system tuberculosis were identified, and their imaging studies (CT and, in some cases, MR) and medical records were reviewed. The diagnosis of central nervous system tuberculosis was based on cerebrospinal fluid culture (n = 20), biopsy (n = 4), and/or autopsy (n = 5), with a clinical diagnosis of central nervous system tuberculosis in one additional patient. Results also were correlated with CD4 counts and chest x-ray findings. RESULTS: Nine (36%) of 25 patients demonstrated meningeal enhancement. Eleven (44%) of 25 demonstrated enhancing parenchymal lesions; 6 patients had tuberculomata, and 5 had tuberculous abscesses. Communicating hydrocephalus was present in 8 (32%) of 25, and infarction was seen in 9 (36%) of 25. Fifteen of 23 chest x-rays were suggestive of pulmonary tuberculosis. Mean CD4 count was 162. Nine (38%) of 24 patients had a history of pulmonary tuberculosis, and 5 (21%) of 24 had no history of tuberculosis or any other opportunistic infection. Overall mortality was 79%. CONCLUSION: Central nervous system tuberculosis has a very high mortality among HIV-infected patients. Because cerebrospinal fluid cultures can take 6 to 8 weeks, the neuroradiologist can play a critical role in patient treatment by suggesting the correct diagnosis based on characteristic imaging findings. Radiographic clues include multiloculated abscess, cisternal enhancement, basal ganglia infarction, and communicating hydrocephalus, which are not findings associated with the more commonly encountered central nervous system lymphoma or toxoplasma encephalitis. Central nervous system tuberculosis may be the initial presentation of acquired immunodeficiency syndrome. In patients with suspected central nervous system tuberculosis, chest x-ray may provide additional support for the diagnosis of tuberculosis.

Personality and psychosocial dysfunction in schizophrenia: the association of extraversion and neuroticism to deficits in work performance.

Research on vocational dysfunction in schizophrenia has as yet only examined associated features of illness. We hypothesized that personality variables may be also associated with work function. We reasoned that higher levels of extraversion and neuroticism would predict poor function by virtue of the social support seeking and passive/avoidant coping styles associated with each. To test this, multiple regressions were conducted in which measures of extraversion and neuroticism predicted work performance among 43 subjects with schizophrenia or schizoaffective disorder. Higher levels of extraversion and neuroticism significantly predicted poorer function, accounting for between 7% and 27% of the variance in global cooperativeness, work quality, work habits and personal presentation measures of work behavior. The potential importance of assessing personality in rehabilitation is discussed.

Five-component model of schizophrenia: assessing the factorial invariance of the positive and negative syndrome scale.

A five-component model of schizophrenia has been presented by Kay and Sevy based upon an analysis of the Positive and Negative Syndrome Scale. Kay and Sevy found factorial validity for negative and positive syndromes, and they identified excitement, depressive, and cognitive components as well. They suggested that subtypes and syndromes can be mapped along dimensions presented in their model. The present study compares the five-component solution for a new sample of 146 subjects to a reanalysis of the Kay and Sevy data. Despite divergent demographic characteristics, the two samples produce similar dimensions. Correlations of component loadings and subject scores as well as confirmatory factor analysis are presented. Discussion focuses on points of agreement and important differences in the symptoms assigned to each component. How the dimensions relate to rationally derived models of positive and negative syndromes is reviewed, and implications for subtyping and other methods of examining the heterogeneity of schizophrenia are considered.