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.

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.

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.

Role of natural killer cells in psychosocial stressor-induced changes in mouse mammary tumor growth.

We have shown that social housing conditions affect the growth rate of the androgen-responsive Shionogi mouse mammary tumor (SC115) and differentially stimulate splenic natural killer (NK) cell activity. Mice reared in a social group and then singly housed (GI) following tumor cell injection have increased tumor growth rates and increased NK cell activity, whereas mice reared individually and then group housed following tumor cell injection have decreased tumor growth rates and decreased NK cell activity compared to that in mice remaining in their rearing group. The present study was undertaken to determine whether NK cells are involved in mediating the effects of social housing conditions on SC115 tumor growth rates. We demonstrate that the presence of the SC115 tumor significantly stimulates the activity of NK cells at the tumor site in the first 7 days after tumor cell injection, and that, consistent with the data on splenic NK cells, mice of the GI group (largest tumors) have significantly greater levels of NK cell activity than mice reared individually and then group housed (smallest tumors). We further demonstrate that in mice of the GI group, in vivo stimulation of NK cell activity by polyinosinic:polyCMP correlates with a corresponding increase in tumor growth rate. These findings suggest that NK cell activity may play a role in mediating the increased tumor growth rate observed in mice of the GI housing condition.

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.

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.

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.

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 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.

Endocrine mediation of psychosocial stressor effects on mouse mammary tumor growth.

We have demonstrated that differential housing alters the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma (SC115). In the present study we wished to determine if changes in plasma levels of hormones or a shift in the responsiveness of the tumor cells to hormones was responsible for the differential tumor growth rates observed. Plasma testosterone and corticosterone levels were assayed 24 h, 3 days and 1 week post tumor cell/vehicle injection. Also 3 weeks post injection androgen and glucocorticoid receptor binding capacity (Bmax) and binding affinity (Kd) and the in vitro responsiveness of tumor cells to dihydrotestosterone and hydrocortisone were measured. At 24 h post injection, plasma testosterone levels were significantly increased in mice with large tumors, but remained low in mice with small tumors. Plasma corticosterone levels were significantly elevated in mice with small tumors compared to those of mice with large tumors at all time points measured. Androgen and glucocorticoid receptor binding capacity and binding affinity of tumor cells did not differ among groups. Further, all groups tested had the ability to respond to dihydrotestosterone and hydrocortisone in vitro. These data indicate that an effect of housing condition on plasma levels of steroid hormones may, in part, mediate the differential tumor growth rates observed in this model.

Alterations in splenic natural killer cell activity induced by the Shionogi mouse mammary tumor.

We have previously demonstrated that differential housing conditions alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study was undertaken to determine if natural killer (NK) cells are involved in mediating the effects of differential housing on SC115 tumour growth rate. Splenic NK cell activity was assayed at 24 h, 3 days and 1 week post-injection in both tumour- and vehicle-injected animals. Significant stimulation of splenic NK cell activity occurred 3 days post-injection of SC115 cells. However, no correlation was observed between the level of splenic NK cell activity and tumour growth rate induced by housing condition. We conclude that either splenic NK cell activity does not accurately reflect NK cell activity at the tumour site or that NK cells are not a significant regulator of the differential tumour growth rates seen in this model.

A histological study of the Shionogi adenocarcinoma 115 grown in male and female mice.

We have previously demonstrated that growth rate and morphology differ between androgen-responsive Shionogi mouse mammary tumours maintained in male and female mice. Furthermore, we can modulate the growth rate of these tumours in male mice by exposing the mice to psychosocial stressors. In the present study, we were interested in determining if tumours in male mice with a comparable growth rate to that in females, also had a morphology similar to that in females. SC115 tumours were examined using histochemical and immunohistochemical techniques. Tumours in male mice were easily distinguishable from tumours in female mice regardless of growth rate. Tumours maintained in female mice contained osteoid-like regions which stained positive for sialic acid and sulphate moieties. No such regions were observed in any of the tumours from male mice. In addition, although all tumours contained MSA (muscle specific actin)-positive and S100 protein-positive cells, these regions were more extensive in the tumours of female mice. This study suggests that tumour growth rate and morphology are independently regulated by the host environment.

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.

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.

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.

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.