Road to full recovery: longitudinal relationship between symptomatic remission and psychosocial recovery in first-episode psychosis over 7.5 years.

BACKGROUND: In recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables. METHOD: Altogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR. RESULTS: Remission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators. CONCLUSIONS: These findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery.

Immunocompromised children and young people are at no increased risk of severe COVID-19.

OBJECTIVES: We aimed to prospectively describe the incidence and clinical spectrum of SARS-CoV-2 infection in immunocompromised paediatric patients in the UK. METHODS: From March 2020 to 2021 weekly questionnaires were sent to immunocompromised paediatric patients or their parents. Information, including symptom presentation and SARS-CoV-2 PCR test results, was collected from 1527 participants from 46 hospitals. Cross-sectional serology was investigated in February and March 2021. RESULTS: Until the end of September 2020, no cases were reported. From September 28th 2020 to March 2021 a total of 38 PCR-detected SARS-CoV-2 infections were reported. Of these, four children were admitted to hospital but none had acute severe COVID-19. Increasing age in association with immunodeficiency increased reporting of SARS-CoV-2 infection. Worsening of fever, cough, and sore throat were associated with participants reporting SARS-CoV-2 infection. Serology data included 452 unvaccinated participants. In those reporting prior positive SARS-CoV-2 PCR, there were detectable antibodies in 9 of 18 (50%). In those with no prior report of infection, antibodies were detected in 32 of 434 (7•4%). CONCLUSIONS: This study shows SARS-CoV-2 infections have occurred in immunocompromised children and young people with no increased risk of severe disease. No children died.

Analysis of interleukin-2-activated killer cells of rhesus monkeys: striking resemblance to the human system.

We have found numerous and exquisite homologies between the interleukin-2 (IL-2)-activated killing systems of rhesus monkeys and humans. Lymphocytes with high oncolytic and proliferative activity were generated from peripheral blood, spleen, and bone marrow of monkeys after culture with IL-2. The distribution of lymphocyte subsets in IL-2 cultures closely paralleled that seen in humans, including a decrease in CD4+ and increase in CD8+, CD38+, and CD25+ lymphocytes and an increase in density of CD2 molecules. We also describe three distinct subsets of monkey lymphocytes, CD16+,56-, CD16+,56+"dim", and CD16-,56+"bright", and show that the CD56+"bright" subset is substantially increased (to as high as 79%) after IL-2 activation. Furthermore, as in humans, the cells with oncolytic activity were characterized as CD56+, CD16+/-, and CD8+. This strong homology with humans indicates that the rhesus monkey may be a valuable preclinical model for evaluation of therapeutically relevant biological response modifiers.

Spurious precision: procedural validity of diagnostic assessment in psychotic disorders.

OBJECTIVE: Very few studies have quantified the level of agreement among alternative diagnostic procedures that use a common set of fixed operational criteria. The authors examined the procedural validity of four independent methods of assigning DSM-III-R diagnoses of psychotic disorders. METHOD: The research was conducted as a satellite study to the DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders. The setting was the National Health and Medical Research Council Schizophrenia Research Unit's Early Psychosis Prevention and Intervention Centre, which focuses on first-episode psychosis. Consecutively admitted patients (N = 50) were assessed by independent raters who used four different procedures to determine a DSM-III-R diagnosis. These procedures were 1) the diagnostic instrument developed for the DSM-IV field trial, 2) the Royal Park Multidiagnostic Instrument for Psychosis, 3) the Munich Diagnostic Checklists, and 4) a consensus DSM-III-R diagnosis assigned by a team of clinician researchers who were expert in the use of diagnostic criteria. RESULTS: Concordance between pairs of diagnostic procedures was only moderate. Corresponding levels of percent agreement, however, ranged from 66% to 76%, with converse misclassification rates of 24%-34% (assuming one procedure to be "correct"). CONCLUSIONS: These findings have significant research and clinical implications. Despite the introduction of operationally defined diagnoses, there remained an appreciable level of differential classification or misclassification arising from variability in the method of assigning the diagnostic criteria rather than the criteria themselves. Such misclassification may impede neurobiological research and have harmful clinical effects on patients with first-episode psychosis.

Prediction of employability in schizophrenic patients.

This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview-based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements.

Facial affect and affective prosody recognition in first-episode schizophrenia.

Individuals with schizophrenia experience problems in the perception of emotional material; however, the specificity, extent, and nature of the deficits are unclear. Facial affect and affective prosody recognition were examined in representative samples of individuals with first-episode psychosis, assessed as outpatients during the early recovery phase of illness, and non-patients. Perception tasks were selected to allow examination of emotion category results across face and voice modalities. Facial tasks were computerised modifications of the Feinberg et al. procedure (Feinberg, T.E., Rifkin, A., Schaffer, C., Walker, E., 1986. Arch. Gen. Psychiatry 43, 276--279). Prosody tasks were developed using four professional actors, and item selections were based on responses of undergraduates. Participant groups did not differ in their understanding of the words used to describe emotions. Findings supported small but consistent deficits in recognition of fear and sadness across both communication channels for the combined schizophrenia (n=29) and other psychotic disorders (n=28) groups as compared to the affective psychoses (n=23) and non-patients (n=24). A diagnostic effect was evident that was independent of the contribution of intelligence. The detection of emotion recognition impairments in first-episode schizophrenia suggests a trait deficit. The pattern of results is consistent with amygdala dysfunction in schizophrenia and related psychoses.

Depression, negative and positive symptoms, and the DST in schizophrenia.

It has been suggested that the presence of depression is a major determinant of abnormal dexamethasone suppression in patients with schizophrenia. It has been reported that negative symptoms in patients with schizophrenia are associated with increased rates of nonsuppression. In this study of schizophrenic inpatients, the Dexamethasone Suppression Test (DST), depression and negative and positive symptom ratings were carried out in two phases of the acute episode, in the second week after administration to, and in the week prior to discharge from, hospital. There was no association between depression and cortisol nonsuppression or between negative and positive symptoms and cortisol nonsuppression either early or late in the acute episode. It is concluded that the DST has no clinical utility in identifying the non-melancholic depression which occurs commonly in schizophrenia.

Social skill as determinant of social networks and perceived social support in schizophrenia.

Factors influencing supportive social networks of people with schizophrenia are little understood. Data from 46 outpatients with schizophrenia were analysed using structural equation modelling to test plausible sets of inter-relationships between social skill, social networks, and social support. The data supported a tentative model about the causal relationships between variables. Paths showed that people with greater social skill had larger social networks, but did not necessarily perceive greater support from these networks. Negative symptoms accounted for some of the effect of social skill on social networks. Whereas groups of single-admission and multiple-admission participants did not differ in terms of social skill, social networks, or support, the age of the participants influenced their social skill and the size of their social networks. Younger participants had greater social skill and larger social networks. The results appear to suggest the importance of early intervention for young people with first-episode psychosis.

Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia?

Prodromal symptoms and other variables for a sample of 200 young people who had experienced a first-onset functional psychosis, were analyzed to examine their diagnostic efficiency and predictive power in relation to a diagnosis of schizophrenia. Two different techniques were utilized to generate optimal cut-off points for a number of prodromal symptoms, and optimal decision rules to maximize diagnostic efficiency. The product of the chance-corrected sensitivity and specificity, or the area under the QROC curve, was used to assess the predictive efficiency of a number of prodromal variables, DSM-III-R prodromal variables, pre-psychotic deterioration, pre-morbid functioning, and prodromal duration. The SPAN technique generated a decision rule that performed equivalently to the single variable 'duration of prodrome'. Implications of these results for future research are discussed.

Positive and negative symptoms in the psychoses: multidimensional scaling of SAPS and SANS items.

Recently, the validity of the simple dichotomy between positive and negative symptoms in psychosis has been questioned. A newly admitted group of 114 DSM-III patients with psychotic disorder were assessed using Andreason's positive and negative symptoms scales. Multidimensional scaling, augmented by cluster analysis, was applied to the full item set of these scales and showed clearly that there are three major, independent groups of symptoms: Hallucinations/Delusions, Positive Thought Disorder and Negative Symptoms. Within the Hallucinations/Delusions and Negative Symptoms groups there was some additional structure which does not conform to the SAPS and SANS sub-scales. In particular there was considerable heterogeneity within the Hallucinations/Delusions group, and delusions of persecution may represent a fourth independent dimension of psychopathology which is under-represented in these scales.

Is social skills performance a correlate of schizophrenia subtypes?

53 inpatients with a DSM-III diagnosis of schizophrenia were assessed in the week prior to discharge from hospital on measures of social skills performance and on severity of positive and negative symptoms. A cluster analysis based on the total positive and negative symptom scores resulted in three groups. The group with the least negative symptoms exhibited the best social skills performance. The findings add a further dimension to the validity of the subtyping of schizophrenia on the basis of positive and negative symptoms.

Negative symptoms and social skills performance in schizophrenia.

The present study aimed to determine whether the negative symptoms of patients with schizophrenia were better predictors of social competence than a range of other variables pertaining to demographics, illness, hospitalization, and premorbid functioning. Independent raters assessed social skills performance on a video-taped role-play test and 5 min conversation in 53 inpatients with a DSM-III diagnosis of schizophrenia. Patients' social skills were also assessed by ward nurses. Project clinicians assessed depression, medication side effects and positive and negative symptoms. Multiple-regression analyses demonstrated that, generally, negative symptoms were the best predictors of social skills performance.

EPPIC: an evolving system of early detection and optimal management.

Early intervention at the onset of psychotic disorders is a highly attractive theoretical notion that is receiving increasing international interest. In practical terms, it amounts to first deciding when a psychotic disorder can be said to have commenced and then offering potentially effective treatment at the earliest possible point. A second element involves ensuring that this intervention constitutes best practice for this phase of illness and is not merely the translation of standard treatments developed for later stages and the more persistently ill subgroups of the disorder. Furthermore, it means ensuring that this best practice model is actually delivered to patients and families. The relative importance of these elements in relation to outcome has not yet been established. This article outlines a framework for preventive intervention in early psychosis, based on more than a decade of experience initially gained within a first-generation model. This experience has been followed, after a prolonged gestation, by the birth of the Early Psychosis Prevention and Intervention Centre (EPPIC), a comprehensive "real-world" model of care targeting the multiple clinical foci underpinning the preventive task. Data are reported to illustrate the topography and impact of delay in treatment in our regional setting, and the results of an initial evaluation of the EPPIC model are presented. The latter demonstrate a significant improvement in symptomatic and functional outcome when the second-generation model is contrasted with the first. The implications of these findings and future developments are discussed.

Monitoring and care of young people at incipient risk of psychosis.

This article describes the theoretical background, origins, and development of a new clinical service for intervention in the putatively prodromal phase of schizophrenia and other psychotic disorders. Establishing such a service required examination of conceptual issues such as the meaning of the prodrome in psychosis and its association with risk of subsequent psychosis, and of practical issues related to identifying prodromal patients in the community and engaging them in monitoring and treatment. Patients' needs, timing, and mode of treatment had to be considered. Preliminary data from the service's 20-month pilot phase are presented to help inform these issues.

Tumoricidal effect of interleukin-2-activated killer cells in canines.

We investigated the effect of both partially purified (TCGF) and recombinant interleukin-2 (rIL-2) on the tumor-directed cytotoxic activity of canine peripheral blood mononuclear cells (PBMC) using three normal canines. No cytotoxic activity was displayed by unstimulated effector cells at 3 h of incubation; however, the cytotoxic effect was observed in a 16-h assay. PBMC of all canines displayed significant levels of lytic activity after stimulation for 4 to 7 days with both types of IL-2 against a variety of allogeneic and xenogeneic neoplastic cells in 3-h 51Cr release assay. The cytotoxic activity of cultured cells increased proportionally in the 16-h assays. Morphological examination of the May-Grünwald and Giemsa stained cytocentrifuged slides of cultured cells on each day of assay showed an increase in large granular lymphocytes (LGLs) beginning on day 4 and reaching a peak on day 7 of culture.

Understanding pre- and post-hysterectomy levels of negative affect: a stress moderation model approach.

Before and after hysterectomy, 60 women completed self-report questionnaires. Measures of personality (NEO-Five Factor Inventory, NEO-FFI), coping (Coping Inventory for Stressful Situations, CISS), and procedure appraisal were completed pre-operatively. Measures of depression and anxiety were completed pre- and post-operatively. Pre-op, 34% of women reported depression at clinical levels, and 29% reported clinical anxiety. The prevalence of depression fell to 8% 3-months post-op although clinical levels of anxiety persisted post-op in 22% of women. Regression analyses revealed that the principal risk factors for post-op negative affect were pre-op levels of depression and concerns about hysterectomy outcome. In assessing proposed models of post-hysterectomy outcome, structural equational modelling revealed the key position of neuroticism and extraversion, which were both directly and indirectly related to pre- and post-operative depression and anxiety. The mediating variables in this model included coping dispositions and procedure appraisal. It is concluded that the variables contained within stress moderation models provide a useful framework for understanding the processes that may lead to elevated levels of negative affect both before and after hysterectomy. Such an approach may prove beneficial for other surgical-outcome studies.

The reduction of stereotypic screaming in a severely retarded boy through a visual screening procedure.

The stereotypic screaming of a 4.2 yr old severely retarded boy was successfully reduced with a visual screening procedure in both school and home settings. Treatment gains were maintained over time and there was some evidence of treatment generalizing across time and persons. Social validation ratings confirmed the effectiveness of the program.

Reducing chronic drooling in a retarded female using a multi-treatment package.

Functional control over chronic drooling in a retarded female was demonstrated through the use of an ABAB design. An early decrease in drooling during baseline showed that the nature of the observation procedure produced a reactive effect, though this was only temporary. While the basic treatment package greatly reduced incidences in wetness and eliminated incidences in soaking, the addition of cognitive self-instructions (SI) led to almost complete elimination of the target behavior. These results were maintained at 2 and 6 month follow-ups.

Social skills training and negative symptoms.

Schizophrenic patients with severe negative symptoms may have an impaired capacity to benefit from social skills training (SST), and their negative symptoms may show little change as a result of SST. The present study, employing a multiple-baseline design across-behaviors with three patients who had prominent negative schizophrenic symptoms, combined nonverbal skills training with the Stacking the Deck social skills game. Further, the study examined changes in both social skills (assessed using role-play and conversation tests) and negative symptoms. Depression, extrapyramidal side effects, and positive symptoms were also monitored. Modest improvements in social skills and negative symptoms were achieved. There was little evidence of a training effect. The unstable baselines may have contributed to this finding. It is important for further research to employ comprehensive patient-assessment procedures.

Prediction of psychosis. A step towards indicated prevention of schizophrenia.

BACKGROUND: The identification of people at high risk of becoming psychotic within the near future creates opportunities for early intervention prior to the onset of psychosis to prevent or minimise later ill-health. The present study combines current knowledge about risk factors for schizophrenia with our knowledge of psychotic prodromes in an attempt to identify a group particularly vulnerable to impending psychosis. We wanted to identify people with high likelihood of transition to psychosis within a follow-up period of 12 months, and to determine the rate of transition to psychosis in this group. METHOD: Various state and trait risk factors for psychosis were used alone and in combination to operationally define a putatively high-risk group. Operationalised criteria for onset of psychosis were established. The individuals were assessed monthly on measures of psychopathology for six months. RESULTS: Eight out of 20 people made the transition to frank psychosis within a six-month follow-up period. Follow-up of this group is still in progress, and the 12 month transition rate might prove to be higher still. CONCLUSIONS: We have demonstrated that it is possible to identify individuals with a high likelihood of onset of psychosis within a brief follow-up period. This lays the foundation for early treatment in an attempt to prevent, delay or minimise the severity of first onset of schizophrenia.