Stress sensitivity in paranoia: poor-me paranoia protects against the unpleasant effects of social stress.

BACKGROUND: The attributional theory of paranoia suggests that paranoid beliefs may protect individuals from low self-esteem and distress (Bentall et al. 2001). The current study tested this theory by investigating a hypothesis that paranoid beliefs in combination with low perceived deservedness of persecution (poor-me beliefs) confer protection against the distress caused by social but not activity related stress. METHODS: Paranoid symptoms, perceived deservedness of persecution, self-esteem, mood, and stress levels of individuals diagnosed with schizophrenia spectrum disorders (N = 91) and healthy controls (N = 52) were assessed in the context of daily life using the experience sampling method. RESULTS: Individuals holding poor-me beliefs (poor-me individuals) showed blunted sensitivity to social but not activity stress. In contrast, individuals holding paranoid beliefs in combination with high perceived deservedness of persecution (bad-me individuals) showed heightened sensitivity to social stress. No consistent differences in reactions to activity stress emerged. Although both poor-me and bad-me individuals reported low self-esteem, this disturbance was particularly characteristic of bad-me individuals. CONCLUSIONS: The results suggest that poor-me paranoid beliefs may protect individuals against the distress associated with unpleasant social situations. The specificity of reactions to social stress is discussed in the context of wider literature. Future directions for research are suggested.

Systematic review: psychological morbidity in young people with inflammatory bowel disease - risk factors and impacts.

BACKGROUND: Psychological morbidity in young people aged 10-24 years, with inflammatory bowel disease (IBD) is increased, but risk factors for and impacts of this are unclear. AIM: To undertake a systematic literature review of the risk factors for and impact of psychological morbidity in young people with IBD. METHODS: Electronic searches for English-language articles were performed with keywords relating to psychological morbidity according to DSM-IV and subsequent criteria; young people; and IBD in the MEDLINE, PsychInfo, Web of Science and CINAHL databases for studies published from 1994 to September 2014. RESULTS: One thousand four hundred and forty-four studies were identified, of which 30 met the inclusion criteria. The majority measured depression and anxiety symptoms, with a small proportion examining externalising behaviours. Identifiable risk factors for psychological morbidity included: increased disease severity (r(2) = 0.152, P < 0.001), lower socioeconomic status (r(2) = 0.046, P < 0.001), corticosteroids (P ≤ 0.001), parental stress (r = 0.35, P < 0.001) and older age at diagnosis (r = 0.28, P = 0.0006). Impacts of psychological morbidity in young people with IBD were wide-ranging and included abdominal pain (r = 0.33; P < 0.001), sleep dysfunction (P < 0.05), psychotropic drug use (HR 4.16, 95% CI 2.76-6.27), non-adherence to medication (12.6% reduction) and negative illness perceptions (r = -0.43). CONCLUSIONS: Psychological morbidity affects young people with IBD in a range of ways, highlighting the need for psychological interventions to improve outcomes. Identified risk factors provide an opportunity to develop targeted therapies for a vulnerable group. Further research is required to examine groups under-represented in this review, such as those with severe IBD and those from ethnic minorities.

The role of collaboration in the cognitive development of young children: a systematic review.

BACKGROUND: Collaboration is a key facilitator of cognitive development in early childhood; this review evaluates which factors mediate the impact of collaborative interactions on cognitive development in children aged 4-7 years. METHODS: A systematic search strategy identified relevant studies (n = 21), which assessed the role of ability on the relationship between collaboration and cognitive development. Other factors that interact with ability were also assessed: gender, sociability/friendship, discussion, age, feedback and structure. RESULTS: Immediate benefits of collaboration on cognitive development are highlighted for same-age peers. Collaborative interactions are beneficial for tasks measuring visual perception, problem-solving and rule-based thinking, but not for word-reading and spatial perspective-taking. Collaboration is particularly beneficial for lower-ability children when there is an ability asymmetry. High-ability children either regressed or did not benefit when paired with lower-ability participants. CONCLUSIONS: Overall, the studies included within this review indicate that brief one-off interactions can have a significant, positive effect on short-term cognitive development in children of infant school age. The longer-term advantages of collaboration are still unclear. Implications for practice and future research are discussed.

The experience of hepatitis C treatment for people with a history of mental health problems: An interpretative phenomenological analysis.

This qualitative study explores the experience of hepatitis C virus treatment for people with pre-existing mental health problems within a large city hospital. Four men and four women with pre-existing mental health problems who had received hepatitis C virus treatment took part in semi-structured interviews which were analysed using interpretative phenomenological analysis. A central theme of 'Self, stigma and change' was identified which interlinked with three other main themes of 'Coping and responding to treatment', 'Connectedness to others' and 'The impact of information'. These themes and their sub-themes are discussed in relation to existing literature and clinical practice guidelines.

Experience Sampling Methodology studies of depression: the state of the art.

BACKGROUND: Experience Sampling Methodology (ESM) is ideally suited to test the predictions, and inform the development of contemporary cognitive models of depression. Yet there has been no systematic examination of ESM in depression research. METHOD: A search of databases (PsychARTICLES, PsycINFO, AMED, Ovid Medline and CINAHL) was conducted to identify studies published within the last 25 years investigating major depressive disorder (MDD) using ESM. RESULTS: Altogether, 19 studies using ESM, or comparable methodologies, with clinically depressed individuals were identified and critically reviewed. The identified studies examined six aspects of MDD: methodological issues; positive and negative affect; cortisol secretion; antidepressant treatment; work performance; genetic risk factors. CONCLUSIONS: Despite some methodological limitations of existing studies, ESM has made a significant contribution to our current understanding of depression by consolidating existing theories, uncovering new and clinically relevant findings and identifying questions for future research. This review concludes by introducing the possibility of using ESM as an intervention tool in clinical practice and proposing that ESM could be useful for furthering knowledge of the causes of MDD.

A transdiagnostic investigation of 'theory of mind' and 'jumping to conclusions' in patients with persecutory delusions.

BACKGROUND: A tendency to make hasty decisions on probabilistic reasoning tasks and a difficulty attributing mental states to others are key cognitive features of persecutory delusions (PDs) in the context of schizophrenia. This study examines whether these same psychological anomalies characterize PDs when they present in the context of psychotic depression. METHOD: Performance on measures of probabilistic reasoning and theory of mind (ToM) was examined in five subgroups differing in diagnostic category and current illness status. RESULTS: The tendency to draw hasty decisions in probabilistic settings and poor ToM tested using story format feature in PDs irrespective of diagnosis. Furthermore, performance on the ToM story task correlated with the degree of distress caused by and preoccupation with the current PDs in the currently deluded groups. By contrast, performance on the non-verbal ToM task appears to be more sensitive to diagnosis, as patients with schizophrenia spectrum disorders perform worse on this task than those with depression irrespective of the presence of PDs. CONCLUSIONS: The psychological anomalies associated with PDs examined here are transdiagnostic but different measures of ToM may be more or less sensitive to indices of severity of the PDs, diagnosis and trait- or state-related cognitive effects.

Residential rehabilitation for drug users: a review of 13 months' intake to a therapeutic community.

BACKGROUND: Residential rehabilitation based on 'therapeutic community' treatment for drug users is a treatment option which is attractive to GPs and others referring drug users for treatment. Whilst there is evidence that maintenance-based programmes for drug users are effective, there have been fewer attempts to evaluate the effectiveness of abstinence-based programmes which are relatively more intensive and expensive interventions. OBJECTIVE: This paper reports and evaluates the outcomes for 13 months' intake of 138 drug users to a residential community. METHODS: We carried out a retrospective cohort study using existing clinical and residential record data. The setting is a residential rehabilitation centre run by the charity Phoenix House in Sheffield, UK, offering a 1-year programme for heroin addicts including community detoxification overseen by primary care specialist doctors and residential rehabilitation. Participants were all patients who entered treatment between 1 February 1998 and 28 February 1999 inclusive. An analysis was carried out of clinical records and other records kept by clinicians and staff at the centre. Outcome measures were numbers of days of retention in treatment and reasons for departure, categorized as completed treatment, planned or unplanned departure and expulsion from the programme. For patients who underwent in-house detoxification, a further outcome measure was whether or not detoxification was complete at discharge. RESULTS: Heroin was the main drug of abuse in 85% of admissions. Mean length of time for which individuals had been drug dependent was 8 years (range 1.3-20.1 years). The mean length of stay was 80.2 days (range 1-394, 95% confidence interval 61.8-98.6). Thirty-four individuals (25%) completed 90 days or more. No association was found between length of stay and age, sex, route of administration, polydrug use, length of time addicted or age of first addiction. Sixty-five per cent of those who received in-house detoxification completed the detoxification period. When patients were classified as 'successes' or 'failures' by reason for departure from the programme, 94 (68.1%) were classified as failures and 18 (13.0%) as successes. Data were unavailable for 26 patients. Success was not associated with any characteristic at entry apart from being drug free as opposed to requiring detoxification (P = 0.048, chi-square = 6.06, df = 2). CONCLUSION: This study shows overall low levels of programme completion and high levels of unplanned departure and eviction from the programme amongst these long-term drug users. On the other hand, the importance of abstinence for those who achieve it in residential rehabilitation should not be underestimated, nor should the possibility that long-term outcomes are influenced by the learning process involved in the intervention. It may be possible to operate better selection procedures in order to optimize outcomes.

Deaths from drugs of abuse in Sheffield, 1998: the role of prescribed medication.

Characteristics of recent drug abuse-related deaths in the city of Sheffield were examined from the coroner's records. Almost all of those who died of poisoning from a drug of abuse were known to be dependent on heroin yet less than half were receiving treatment. Benzodiazepines were frequently detected alongside opiates during toxicology, the source of which was likely to be the deceased's own prescription.

Geriatric assessment in primary care: formulating best practice.

Comprehensive geriatric assessment (CGA) is a structured approach to measuring physical, mental and social functioning of older people to identify needs and to plan care. Meta-analysis of trials of CGA suggest that it is cost-effective, but there is no agreed approach to its implementation in primary care. Our aim was to develop a best-practice model for geriatric assessment in primary care. We took an iterative approach to development, combining expert and local stakeholder opinion, and using semi-structured interviews to assess patient and practitioner experience in nine general practices in Sheffield. Patients were aged 75 and over, living at home. The best-practice model was the use of a standardized instrument (EASY-Care) to unselected patients aged 75 years and over living at home or in residential care, administered by a practice nurse in the context of an over-75s health check. There was high patient and practitioner acceptability, and significant cost savings were noted. Key beneficial features were the assessment of mental health and sources of support; goal-setting; generation of a disability score; and high patient satisfaction from contact with nursing staff. We conclude that geriatric assessment in primary care is feasible, economical and beneficial to patients and practitioners. Nursing staff are central to successful implementation of geriatric assessment in primary care.

Keeping families of heroin addicts together: results of 13 months' intake for community detoxification and rehabilitation at a family centre for drug users.

BACKGROUND: Heroin addiction is a major public health problem affecting both the addicted individuals and their children, who have been shown to have poor social, educational and health status and to be at higher risk of abuse than their peers. Whilst the antenatal effects of parental drug use and the overall poor outcomes for these children have been widely studied, there has been little emphasis on the effectiveness of treatment interventions and even less emphasis on evaluating the effect on children of the standard treatments aimed at their parents' drug use. OBJECTIVES: The aim of the present study was to evaluate the effect on heroin-addicted parents and their children of a family-based drug treatment intervention using a records-based methodology, and to identify any factors at admission which may influence outcome. This study is a pilot for a prospective Europe-wide study using a similar methodology prospectively in several treatment modalities. METHODS: A retrospective cohort study was carried out using existing clinical and residential record data. The setting was a residential family centre run by the charity Phoenix House in Sheffield, UK, offering a 6-month (180 days) family-based programme for heroin addicts including community detoxification overseen by primary care specialist doctors and residential rehabilitation. All adults and children who entered the centre between July 1997 and July 1998 were included in the study (26 adults and 33 children, in 23 family groups). An analysis was made of clinical records and records kept on the adults and children by the clinicians and staff at the centre. The main outcome measures for the adults were length of stay and reason for departure (treatment complete, early planned discharge, unplanned discharge, eviction); and for the children were reason for departure and discharge destination (with parent or taken into care). RESULTS: Mean length of stay was 110 days, and only 11 children (33%) and nine adults (35%) completed 150 days or more. Length of stay was found to be significantly correlated with parental age at admission (P < 0.01). Twelve children (37%) and nine adults (35%) were deemed to have completed treatment successfully. Of the remainder, 14 children (42%) and 11 adults (42%) left because of definite treatment failure. Successful treatment completion was found to be correlated with increased parental age (Pearson's r = 0.612, P = 0. 001). Poly-drug users were significantly less likely to complete treatment successfully (Fisher's exact test, P = 0.012). Twenty children were in the care of their parents on admission, and 24 were able to go home with their parents. There was no association between residence with parents pre- and post-admission (McNemar's chi-squared test = 1.6, P > or = 0.1). CONCLUSIONS: Whilst overall high rates of treatment success are not expected in abstinence-based programmes, the outcomes for the adults in this setting are comparable with published results in other residential settings, and there is some evidence that some families may have stayed together who might otherwise have been separated. Older adults who were not poly-drug users had significantly better outcomes. The records-based methodology proved successful, but centres need to keep detailed and preferably long-term records on children if their outcomes are to be evaluated more fully.

Getting the questions right: an example of loss of validity during transfer of a brief screening approach for depression in the elderly.

Screening for depression in the elderly has been advocated to improve detection and management. This article summarises the trend towards briefer screening instruments, and the integration of mental health screening with other assessments. The study aimed to validate a single question depression screen which has previously shown adequate sensitivity and specificity in a new context: a multi-faceted assessment instrument used by nurse practitioners within a community sample of over 75 year olds. The GMS-AGECAT computerised interview assessment was used as a 'gold standard' to determine the accuracy of the depression question in this new setting. Three hundred and twenty-eight patients were screened by their own nurse practitioners, of whom 100 consenting patients underwent a further interview with a research assistant using the GMS-AGECAT. The prevalence of depression was 30%, the sensitivity of the question was 67%, and its specificity 60% (compared with 88% and 71% previously). Responses indicating disability and loneliness were more closely correlated with depression than the depression screen itself. Relevant factors may include: the derivation of the question, the effect of a different sample, altered reliability when used by multiple interviewers, differing patient expectations, and the wording and context of the question within the multi-faceted screening instrument. Depression screening questions need repeated validation when used in different contexts. Patient and staff expectations may influence how screening instruments are used in practice in a way that may also alter reliability. Further studies are needed to establish the causes of loss of validity when screening approaches are used in new settings.

Can methadone maintenance for heroin-dependent patients retained in general practice reduce criminal conviction rates and time spent in prison?

A retrospective analysis was made of the criminal records of 57 patients successfully retained in methadone maintenance at two general practices in Sheffield. Their criminal conviction rates and time spent in prison per year were compared for the periods before and after the start of their methadone programme. Overall, patients retained on methadone programmes in the general practices studied had significantly fewer convictions and cautions, and spent significantly less time in prison than they had before the start of treatment.

Passively transferred anti-MUC1 antibodies cause neither autoimmune disorders nor immunity against transplanted tumors in MUC1 transgenic mice.

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to investigate the autoimmune consequences of producing MUC1 tumor immunity in an animal that expresses MUC1 as a self-protein on normal ductal epithelia. Previous work showed that MUC1.Tg mice challenged with MUC1-bearing syngeneic tumors (B16.MUC1) developed progressively growing MUC1-expressing tumors and no detectable MUC1-specific antibody (Ab) response. In contrast, wild-type C57BL/6 (wt) mice developed MUC1-negative tumors at a significantly slower rate and produced approximately 50 microg IgG1 Ab reactive with the MUC1 tandem repeat (TR)/ml of sera. One milliliter of these sera was administered passively to MUC1.Tg or wt mice and the concentration of the MUC1 TR-reactive IgG1 Abs was monitored over time. The results indicate that circulating MUC1-reactive Abs were detectable in MUC1.Tg mice and that significant amounts of these Abs were not absorbed by organs that endogenously express MUC1. No evidence of autoimmune disease, either gross or histological, was observed in the MUC1.Tg recipients of sera suggesting that MUC1, an organ-specific protein expressed primarily by secretory epithelia, is inaccessible to circulating MUC1 -reactive Abs. Additional studies showed that polyclonal sera containing IgG1 Abs reactive with MUC1 TR were unable to provide protection against the growth of syngeneic tumors expressing MUC1 in the MUC1.Tg animal model.

CD4+ lymphocytes provide MUC1-specific tumor immunity in vivo that is undetectable in vitro and is absent in MUC1 transgenic mice.

A C57BL/6 mouse transgenic for human MUC1 (MUC1.Tg) was developed to evaluate MUC1-specific tumor immunity in an animal that expresses MUC1 as a normal self protein. Previous studies showed that MUC1.Tg mice, challenged with syngeneic tumors expressing MUC1 (B16.MUC1), developed progressively growing MUC1-positive tumors, whereas wild-type C57BL/6 (wt) mice developed MUC1-negative tumors at a significantly slower rate. The results of a limiting dilution CTL frequency assay were not informative, in that similar numbers of MUC1-specific CTL precursors (CTL) were detected in MUC1.Tg and wt mice. Tumor immunity in vivo was characterized by an adoptive transfer method to evaluate the degree of MUC1 or non-MUC1 tumor immunity in wt or MUC1.Tg mice. The results revealed that wt mice developed protective tumor immunity mediated by MUC1-specific CD4+ lymphocytes, while MUC1.Tg mice were functionally tolerant to MUC1 in vivo. The potential of adoptive immunotherapy to provide immunity to tumors expressing MUC1 and to produce undesirable autoimmunity in recipient MUC1.Tg mice expressing MUC1 as a self Ag was evaluated. Adoptive transfer of immune cells from wt mice primed in vivo with B16.MUC1 tumor cells into MUC1.Tg recipients resulted in significant increases in the survival of MUC1.Tg recipients compared with unmanipulated control MUC .Tg mice challenged with B16.MUC1 tumor cells. This response was specific for MUC1 since control tumors developed at equivalent rates in recipient or control MUC1.Tg mice. No gross or histologic evidence of autoimmunity was observed in recipient MUC1.Tg mice, indicating that tumor immune responses mediated by MUC1-specific CD4+ lymphocytes spare nontransformed epithelia-expressing MUC1.

Genetic modulation of neu proto-oncogene-induced mammary tumorigenesis.

Modulation of oncogene-induced carcinogenesis by secondary mutation or genetic background may be an important factor in determining the expression of the tumor phenotype. We have investigated the role of loss of function mutations and strain-specific genetic elements in the modulation of oncogene-induced breast cancer using a murine model. FVB female mice transgenic for the rat neu proto-oncogene [mouse mammary tumor virus (MMTV)-neu] developed mammary tumors between 7 and 12 months of age, whereas FVB x C57Bl/6 (F1) MMTV-neu mice had tumor latencies greater than 18 months. The expression level of the neu transgene was equivalent in tumor tissue from both FVB and F1 mice. Furthermore, increased tumor latency did not appear to be associated with a decrease in expression of the neu transgene in the normal mammary gland of F1 mice because immunohistochemical staining for neu expression in the mammary glands of 3-month-old virgin female mice revealed similar levels of protein expression in FVB and F1 animals. When F1 animals were backcrossed one generation onto the FVB strain ([FVB x B6] F1 x FVB), a subset of the resulting offspring developed tumors with a latency equivalent to that of the pure-strain FVB mice. Statistical analysis of the genetic variability in mammary tumor latency indicated that approximately three independent genes were involved in the latency effect. Interestingly, when tumor growth rates were compared in these same animals, F1 mice had significantly faster tumor growth rates compared with FVB mice.

Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells.

Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.

Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model.

The human epithelial mucin, MUC1, is a large transmembrane glycoprotein that is expressed on most simple epithelia. It is overexpressed and aberrantly glycosylated on many human epithelial tumors, including more than 90% of human breast cancers. MUC1 is of interest as an immunotherapy target because patients with breast, ovarian, and pancreatic cancers have T lymphocytes in their tumor-draining lymph nodes that can be induced to recognize and lyse MUC1-expressing tumor cells. We have produced a transgenic mouse model that expresses the human MUC1 molecule on an inbred C57Bl/6 background to investigate the effect of endogenous expression of MUC1 on the ability of mice to generate antitumor immunity to MUC1-expressing tumors. Transgenic mice expressed the human transgene in a pattern and level consistent with that observed in humans. Transgenic mice were tolerant to stimulation by MUC1 as evidenced by the ability of MUC1-expressing tumor cells to grow in these mice, whereas MUC1-expressing cells were eliminated from wild-type mice. Moreover, transgenic mice immunized with MUC1 peptides failed to exhibit immunoglobulin class switching to the IgG subtypes. These data suggest that endogenous expression of MUC1 protein by MUC1 transgenic mice induces T-cell tolerance to stimulation by MUC1. The transgenic mice will provide a useful model to investigate the mechanisms that regulate immunological tolerance to tumor antigens and will facilitate the investigation of anti-MUC1 immunotherapy formulations.

Loss of heterozygosity analysis in primary mammary tumors and lung metastases of MMTV-MTAg and MMTV-neu transgenic mice.

Loss of heterozygosity (LOH) analysis has been used in many types of human cancer to localize putative tumor suppressor genes important in carcinogenesis. However, this approach has only recently been applied to transgenic mouse tumor models, which offer greater opportunity for detailed molecular genetic analysis of tumor initiation and progression. To explore the possible role of secondary genetic events in transgenic mouse mammary tumor development, we performed microsatellite-based allelotypes on primary mammary adenocarcinomas and lung metastases arising in mice transgenic for the polyomavirus middle T antigen under the control of the mouse mammary tumor virus promoter/enhancer (MMTV-MTAg mice) and on primary mammary adenocarcinomas arising in mice transgenic for the neu proto-oncogene (MMTV-neu mice). We examined a total of 80 microsatellite loci distributed throughout the mouse genome for LOH and observed high rates of specific chromosomal loss but very low rates of background allelic loss in these tumors. For the MMTV-MTAg mice, no individual chromosomes showed rates of LOH significantly above the background rates. For MMTV-neu mice, markers on chromosome 4 showed LOH in 82% of mammary tumors, whereas markers on chromosome 3 showed loss in 29% of tumors. These data suggest that the middle T antigen transgenic mice do not undergo whole chromosome loss or large genomic deletions as common mechanisms of tumor formation and that chromosomes 3 and 4 may contain tumor suppressor gene loci that play important roles in the development of neu-mediated mouse mammary tumors.