Systematic review of early warning signs of relapse and behavioural antecedents of symptom worsening in people living with schizophrenia spectrum disorders.

BACKGROUND: Identification of the early warning signs (EWS) of relapse is key to relapse prevention in schizophrenia spectrum disorders, however, limitations to their precision have been reported. Substantial methodological innovations have recently been applied to the prediction of psychotic relapse and to individual psychotic symptoms. However, there has been no systematic review that has integrated findings across these two related outcomes and no systematic review of EWS of relapse for a decade. METHOD: We conducted a systematic review of EWS of psychotic relapse and the behavioural antecedents of worsening psychotic symptoms. Traditional EWS and ecological momentary assessment/intervention studies were included. We completed meta-analyses of the pooled sensitivity and specificity of EWS in predicting relapse, and for the prediction of relapse from individual symptoms. RESULTS: Seventy two studies were identified including 6903 participants. Sleep, mood, and suspiciousness, emerged as predictors of worsening symptoms. Pooled sensitivity and specificity of EWS in predicting psychotic relapse was 71% and 64% (AUC value = 0.72). There was a large pooled-effect size for the model predicting relapse from individual symptom which did not reach statistical significance (d = 0.81, 95%CIs = -0.01, 1.63). CONCLUSIONS: Important methodological advancements in the prediction of psychotic relapse in schizophrenia spectrum disorders are evident with improvements in the precision of prediction. Further efforts are required to translate these advances into effective clinical innovations.

Sleep duration and psychotic experiences in patients at risk of psychosis: A secondary analysis of the EDIE-2 trial.

Sleep disturbance is common among individuals at risk of psychosis, yet few studies have investigated the relationship between sleep disturbance and clinical trajectory. The Early Detection and Intervention Evaluation (EDIE-2) trial provides longitudinal data on sleep duration and individual psychotic experiences from a cohort of individuals at risk of psychosis, which this study utilises in an opportunistic secondary analysis. Shorter and more variable sleep was hypothesised to be associated with more severe psychotic experiences and lower psychological wellbeing. Mixed effect models were used to test sleep duration and range as predictors of individual psychotic experiences and psychological wellbeing over the 12-24 months (with assessments every 3 months) in 160 participants. Shorter sleep duration was associated with more severe delusional ideas and hallucinations cross-sectionally and longitudinally. The longitudinal relationships did not remain significant after conservative controls were added for the previous severity of psychotic experiences. No significant relationships were found between the sleep variables and other psychotic experiences (e.g. cognitive disorganisation), or psychological wellbeing. The results support a relationship between shorter sleep duration and delusional ideas and hallucinations. Future studies should focus on improving sleep disturbance measurement, and test whether treating sleep improves clinical trajectory in the at-risk group.

Negative cognition, affect, metacognition and dimensions of paranoia in people at ultra-high risk of psychosis: a multi-level modelling analysis.

BACKGROUND: Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between 'poor me' and 'bad me' paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness). METHOD: We used data from 117 participants from the Early Detection and Intervention Evaluation for people at risk of psychosis (EDIE-2) trial of cognitive­behaviour therapy, comparing them with samples of psychiatric in-patients and healthy students from a previous study. Multi-level modelling was utilized to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness. RESULTS: Our sample of at-risk mental state participants was not as paranoid, but reported higher levels of 'bad-me' deservedness, compared with psychiatric in-patients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness. CONCLUSIONS: This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis.

Insight, duration of untreated psychosis and attachment in first-episode psychosis: prospective study of psychiatric recovery over 12-month follow-up.

BACKGROUND: Increasing evidence shows attachment security influences symptom expression and adaptation in people diagnosed with schizophrenia and other psychoses. AIMS: To describe the distribution of secure and insecure attachment in a cohort of individuals with first-episode psychosis, and to explore the relationship between attachment security and recovery from positive and negative symptoms in the first 12 months. METHOD: The study was a prospective 12-month cohort study. The role of attachment, duration of untreated psychosis (DUP), baseline symptoms and insight in predicting and mediating recovery from symptoms was investigated using multiple regression analysis and path analysis. RESULTS: Of the 79 participants, 54 completed the Adult Attachment Interview (AAI): 37 (68.5%) were classified as insecure, of which 26 (48.1%) were insecure/dismissing and 11 (20.4%) insecure preoccupied. Both DUP and insight predicted recovery from positive symptoms at 12 months. Attachment security, DUP and insight predicted recovery from negative symptoms at 12 months. CONCLUSIONS: Attachment is an important construct contributing to understanding and development of interventions promoting recovery following first-episode psychosis.

A systematic review of attachment and psychosis: measurement, construct validity and outcomes.

OBJECTIVE: This review sought to identify, summarise and critically evaluate studies that investigated attachment amongst individuals with psychosis. METHOD: The following computerised databases searched were CINAHL<1980 to December 2012; EMBASE<1980 to December 2012; Ovid MEDLINE (R)<1980 to December 2012; PsychINFO<1980 to December 2012; and Google Scholar<1980 to December 2012. RESULTS: We identified 22 papers describing 21 studies comprising 1453 participants, with a mean age of 35.0 years (range of 12-71 years), of whom 68.4% (n=994) were male. Of our sample, 1112 (76.5%) had a diagnosis of schizophrenia. We found small to moderate associations between greater attachment insecurity (as reflected in anxiety and avoidance) and poorer engagement with services, more interpersonal problems, more avoidant coping strategies, more negative appraisals of parenting experiences and more severe trauma. We also found small to modest associations between attachment insecurity and more positive and negative symptoms and greater affective symptom problems. CONCLUSION: Attachment theory may be useful as a means of understanding the developmental and interpersonal basis of recovery and adaptation in the context of psychosis. However, further research comprising more representative samples in their first episode and using prospective designs is required.

Social cognition and metacognition in schizophrenia: evidence of their independence and linkage with outcomes.

OBJECTIVE: Research suggests that many with schizophrenia experience deficits in the ability to make discrete judgments about the thoughts and feelings of others as well as to form larger integrated representations of themselves and others. Little is known about whether these difficulties may be distinguished from one another and whether they are linked with different outcomes. METHOD: We administered three assessments of social cognition which tapped the ability to identify emotions and intentions and two metacognitive tasks which called for the formation of more integrated and flexible representations of the self and others. We additionally assessed symptoms, social functioning and neurocognition. Participants were 95 individuals with a schizophrenia spectrum disorder. RESULTS: A principle components analysis followed by a varimax rotation revealed two factors which accounted for 62% of the variance. The first factor was comprised of the three social cognition tests and the second of two tasks that tapped the ability to create representations of oneself and others which integrate more discreet information. The first factor was uniquely correlated with negative symptoms, and the second was uniquely correlated with social function. CONCLUSION: Results suggest that deficits in social cognition and metacognition represent different forms of dysfunction in schizophrenia.

Intolerance of uncertainty and distress associated with the experience of psychosis.

There is growing research interest in the role of worry processes in psychosis. This study investigated associations between intolerance of uncertainty, meta-cognitive beliefs about hallucinations and paranoia, and distress in 27 individuals with psychosis. Results suggest that intolerance of uncertainty may represent an important factor in emotional adaptation following psychosis.

Cognitive behaviour therapy for violent men with antisocial personality disorder in the community: an exploratory randomized controlled trial.

BACKGROUND: Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive. METHOD: This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning. RESULTS: The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others. CONCLUSIONS: CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.

Premorbid adjustment, symptom development and quality of life in first episode psychosis: a systematic review and critical reappraisal.

OBJECTIVE: To systematically review the relationship of premorbid adjustment to symptomatology in first episode psychosis (FEP), taking into account the influence of duration of untreated psychosis (DUP). METHOD: Electronic databases were searched to identify relevant studies. RESULTS: A variety of approaches to the reporting of premorbid adjustment were identified. There was no significant association between premorbid adjustment and DUP, supporting the proposition that they are independent constructs. The effect of premorbid adjustment upon positive symptomatology was negligible. Premorbid adjustment had a modest effect upon negative symptoms and quality of life, increasing over duration of follow-up. CONCLUSION: Premorbid adjustment remains a valid construct in the study of FEP. Both premorbid adjustment and DUP confer independent effects on aspects of symptomatology in FEP. Results for premorbid adjustment are similar to previous findings in more chronic samples. The potential for conceptualizing premorbid functioning by developmental, academic/social and typological approaches is currently underexploited.

The development and validation of the Pre-operative Intrusive Thoughts Inventory (PITI).

Pre-operative anxiety is common and influences postoperative pain, hospital stay and patient satisfaction. We set out to explore anxiety content and develop a tool to evaluate patient anxiety at the pre-operative assessment clinic. We recruited 128 day surgery patients. Pre-operative anxiety content was explored and six factors (themes) were identified: 'preoccupation', 'outcome concerns', 'being unconscious', 'loss of control', 'dependence on others' and 'pain/discomfort'. The Pre-operative Intrusive Thoughts Inventory (PITI) was constructed and evaluated using exploratory and confirmatory factor analysis. The PITI demonstrated internal consistency for the full scale (Cronbach's alpha = 0.91) and for the subscales (Cronbach's alpha 0.74-0.85) as well as sensitivity (0.88) and specificity (0.60) to clinically significant anxiety assessed using the Hospital Anxiety and Depression Scale. The properties of the PITI suggest that it has potential as an additional tool for the evaluation of pre-operative anxiety.

Young people with intellectual disabilities attending mainstream and segregated schooling: perceived stigma, social comparison and future aspirations.

BACKGROUND: Mainstream schooling is a key policy in the promotion of social inclusion of young people with learning disabilities. Yet there is limited evidence about the school experience of young people about to leave mainstream as compared with segregated education, and how it impacts on their relative view of self and future aspirations. METHODS: Sixty young people with mild to moderate intellectual disabilities in their final year of secondary school participated in this study. Twenty-eight individuals came from mainstream schools and 32 attended segregated school. They completed a series of self-report measures on perceptions of stigma, social comparison to a more disabled and non-disabled peer and the likelihood involved in attaining their future goals. RESULTS: The majority of participants from both groups reported experiencing stigmatized treatment in the local area where they lived. The mainstream group reported significant additional stigma at school. In terms of social comparisons, both groups compared themselves positively with a more disabled peer and with a non-disabled peer. While the mainstream pupils had more ambitious work-related aspirations, both groups felt it equally likely that they would attain their future goals. Although the participants from segregated schools came from significantly more deprived areas and had lower scores on tests of cognitive functioning, neither of these factors appeared to have an impact on their experience of stigma, social comparisons or future aspirations. CONCLUSIONS: Irrespective of schooling environment, the young people appeared to be able to cope with the threats to their identities and retained a sense of optimism about their future. Nevertheless, negative treatment reported by the children was a serious source of concern and there is a need for schools to promote the emotional well-being of pupils with intellectual disabilities.

Long-term outcome of cognitive behaviour therapy clinical trials in central Scotland.

OBJECTIVES: To establish the long-term outcome of participants in clinical trials of cognitive behaviour therapy (CBT) for anxiety disorders and psychosis, examining the effectiveness and cost-effectiveness associated with receiving CBT in comparison with alternative treatments. DESIGN: An attempt was made to contact and interview all of the participants in eight randomised, controlled, clinical trials of CBT for anxiety disorders and two randomised, controlled, clinical trials of CBT for schizophrenia conducted between 1985 and 2001. Case note reviews of healthcare resources used in the 2 years prior to entering the trials and the 2 years prior to follow-up interview were undertaken. SETTING: Mixed rural and urban settings in five localities in central Scotland. Anxiety disorder trials were conducted mainly in primary care and included three with generalised anxiety disorder, four with panic disorder and one with post-traumatic stress disorder (PTSD). The psychosis studies (one on relapse prevention and one with chronic disorder) were conducted in secondary care. PARTICIPANTS: Of the 1071 entrants to the 10 studies, 489 agreed to participate (46% of original entrants, 52% of those available to contact). INTERVENTIONS: Follow-up interviews took place between 1999 and 2003, 2-14 years after the original treatment. Interviews for Trials 1-8 were conducted by a research psychologist blind to original treatment condition. Interviews for Trials 9 and 10 were conducted by community psychiatric nurses also blind to treatment condition. Case note reviews were completed following the interview. MAIN OUTCOME MEASURES: For Trials 1-8 the main interview-based outcome measures were: Anxiety Disorders Interview Schedule-DSM-IV for diagnosis and co-morbidity, Clinical Global Severity (0-8) and the Hamilton Anxiety Rating Scale. The main patient-rated measures were: Brief Symptom Inventory, SF-36 II, Clinical Global Improvement (1-7), and the Positive and Negative Affect Scale. For Trials 9 and 10 the primary outcome measure was the interview-based Positive and Negative Syndrome Scale (PANSS). RESULTS: For the anxiety disorder studies (Trials 1-8), over half of the participants (52%) had at least one diagnosis at long-term follow-up, with significant levels of co-morbidity and health status scores comparable to the lowest 10% of the general population. Only 36% reported receiving no interim treatment for anxiety over the follow-up period with 19% receiving almost constant treatment. Patients with PTSD did particularly poorly. There was a 40% real increase in healthcare costs over the two time periods, mainly due to an increase in prescribing. A close relationship was found between poor mental and physical health for those with a chronic anxiety disorder. Treatment with CBT was associated with a better long-term outcome than non-CBT in terms of overall symptom severity but not with regard to diagnostic status. The positive effects of CBT found in the original trials were eroded over longer time periods. No evidence was found for an association between more intensive therapy and more enduring effects of CBT. Long-term outcome was found to be most strongly predicted by the complexity and severity of presenting problems at the time of referral, by completion of treatment irrespective of modality and by the amount of interim treatment during the follow-up period. The quality of the therapeutic alliance, measured in two of the studies, was not related to long-term outcome but was related to short-term outcome. The cost-effectiveness analysis showed no advantages of CBT over non-CBT. The cost of providing CBT in the original trials was only a very small proportion (6.4%) of the overall costs of healthcare for this population, which are high for both physical and mental health problems. In the psychosis studies (Trials 9 and 10), outcome was generally poor with only 10% achieving a 25% reduction in total PANSS scores from pretreatment to long-term follow-up, also cost-effectiveness analysis showed no advantages of CBT over non-CBT, although healthcare costs fell over the two time periods mainly owing to a reduction in inpatient costs. CONCLUSIONS: Psychological therapy services need to recognise that anxiety disorders tend to follow a chronic course and that good outcomes with CBT over the short term are no guarantee of good outcomes over the longer term. Clinicians who go beyond standard treatment protocols of about 10 sessions over a 6-month period are unlikely to bring about greater improvement. Poor outcomes over the long term are related to greater complexity and severity of presenting problems at the time of referral, failure to complete treatment irrespective of modality and the amount of interim treatment during the follow-up period. The relative gains of CBT are greater in anxiety disorders than in psychosis. Longitudinal research designs over extended periods of time (2-5 years), with large numbers of participants (500+), are required to investigate the relative importance of patient characteristics, therapeutic alliance and therapist expertise in determining the cost-effectiveness of CBT in the longer term.

Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy.

BACKGROUND: The paper describes a randomized controlled trial of targeting cognitive behavioural therapy (CBT) during prodromal or early signs of relapse in schizophrenia. We hypothesized that CBT would result in reduced admission and relapse, reduced positive and negative symptoms, and improved social functioning. METHOD: A total of 144 participants with schizophrenia or a related disorder were randomized to receive either treatment as usual (TAU) (N = 72) or CBT+TAU (N = 72). Participants were prospectively followed up between entry and 12 months. RESULTS: At 12 months, 11 (15.3%) participants in the CBT group were admitted to hospital compared to 19 (26.4%) of the TAU group (hazard ratio = 0.53, P = 0.10, 95% CI 0.25, 1.10). A total of 13 (18.1%) participants in CBT relapsed compared to 25 (34.7%) in TAU (hazard ratio = 0.47, P < 0O05, 95% CI 0.24, 0.92). In addition, the CBT group showed significantly greater improvement in positive symptoms, negative symptoms, global psychopathology, performance of independent functions and prosocial activities. CONCLUSIONS: The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia. The results are discussed in context of the study's methodological limitations.

Cold shock proteins and cold acclimation proteins in the psychrotrophic bacterium Pseudomonas putida Q5 and its transconjugant.

The production of cold shock proteins (csps) and cold acclimation proteins (caps) was characterized in the psychrotrophic bacterium Pseudomonas putida Q5 and its transconjugant P. putida Q5T which contains the toluene-degradative TOL (pWWO) plasmid, using two-dimensional gel electrophoresis and computing scanning laser densitometry. Similar growth rates for the psychrotrophic bacterium P. putida Q5 and the transconjugant were found at temperatures ranging from 30 to 0 degree C. Sixteen proteins were quantified and compared in P. putida Q5 and P. putida Q5T following a 25 to 5 degrees C cold shock or constant growth at 5 degrees C. During constant growth at 25 degrees C, a decrease in the synthesis of various proteins occurred in the transconjugant. Following cold shock to 5 degrees C or constant growth at 5 degrees C, csps and caps were produced with a greater number occurring in the transconjugant. This may suggest an additional stress response in the transconjugant owing to metabolic load exerted by the TOL plasmid. Growth of P. putida Q5T with toluate produced seven proteins that appeared to be TOL-plasmid mediated and of which some were also designated as caps.