Someone is to blame: the impact of suicide on the mind of the bereaved (including clinicians).

This paper presents an emerging understanding of the psychodynamics of suicide loss, derived from over 1500 accounts of suicide bereavement shared by families, friends and clinicians. It identifies clear patterns in the responses of the bereaved, particularly the formation of delusional narratives that often place them at the centre of blame for the death. These narratives have a profound impact on well-being, increase the risk of mental illness and elevate the likelihood of death by suicide. They not only cause harm to the bereaved but also permeate and distort our systemic and societal responses. Understanding why suicide unleashes such painful and dangerous forces helps mitigate the widespread harm and distress that often follows such a death. This knowledge also enables us to effectively and compassionately support those bereaved.

Experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide.

AIMS AND METHOD: To investigate the experiences and support needs of consultant psychiatrists following a patient-perpetrated homicide, an anonymous online survey was sent to all consultant psychiatrists registered as members of the UK's Royal College of Psychiatrists. RESULTS: Of the 497 psychiatrists who responded, 165 (33%) had experienced a homicide by a patient under their consultant care. Most respondents reported negative impacts on their clinical work (83%), mental and/or physical health (78%) or personal relationships (59%), and for some (9-12%) these were severe and long lasting. Formal processes such as serious incident inquiries were commonly experienced as distressing. Support was mainly provided by friends, family and colleagues rather than the employing organisation. CLINICAL IMPLICATIONS: Mental health service providers need to provide support and guidance to psychiatrists following a patient-perpetrated homicide to help them manage the personal and professional impact. Further research into the needs of other mental health professionals is needed.

Eight 'truths' about suicide.

This paper summarises themes that have emerged from 14 years of study of suicide and work with those bereaved. It is based on a talk given in many clinical settings over the past 10 years. I describe my own emotional journey following impactful deaths and summarise personal 'truths' about suicide that have emerged over time. Case studies used for illustration are composites taken from clinical practice; accounts of relatives and other survivors of suicide; and data taken from many sources including suicide audits in mental health organisations, the police and transport services, and from the examination of coroners' records. The intention is to assist open dialogue about the nature of suicide, to contribute to the understanding of the impact on those bereaved and to encourage open-hearted clinical engagement with those who are suicidal.

Parity of esteem within the biopsychosocial model: is psychiatry still a psychological profession?

In recent years, the Royal College of Psychiatrists has been engaged in activities to ensure parity of esteem for mental health within the National Health Service, seeking to bring resources and services more in line with those available for physical health conditions. Central to this has been the promotion of psychiatry as a profession that takes a biopsychosocial approach, considering all aspects of the patient's presentation and history in the understanding and treatment of mental disorders. However, there has been a drift away from considering the psychological aspects of the patient's difficulties in recent years. This potentially has profoundly negative consequences for clinical care, training, workforce retention and the perception of our identity as psychiatrists by our colleagues, our patients and the general public. This editorial describes this issue, considers its causes and suggests potential remedies. It arises from an overarching strategy originating in the Royal College of Psychiatrists Medical Psychotherapy Faculty to ensure parity of esteem for the psychological within the biopsychosocial model.

Effects of patient deaths by suicide on clinicians working in mental health: A survey.

In the UK, at least a quarter of suicides occurs in patients whilst under the care of mental health services. This study investigated the effects of such deaths on non-medical mental health clinicians. An online survey was conducted within a single NHS mental health Trust to elicit both quantitative and qualitative responses from staff across a range of professions. The survey focused on personal and professional impacts and available support. Participants reported significant negative emotional and professional effects that were long-lasting for some. These included mental health difficulties, loss of confidence regarding clinical responsibilities, and actual or contemplated career change. However, there was also some evidence of positive effects and professional growth. Support from colleagues and line managers is clearly important following deaths of patients by suicide. Clinicians' experiences of the support they had received in the workplace were polarized, suggesting that there is no single nor ideal approach that will meet everyone's needs. Participants made recommendations for the types of support that may be helpful. Most commonly, clinicians desired opportunities for focused reflection and support and help with the formal processes following the death. Sensitivity around how clinicians are notified about the death was highlighted as being particularly important. Conclusions are drawn as to how training institutions and employers can help staff to be better prepared for the potential occurrence of patient suicides and the formal processes that follow, with a view to mitigating risks of more serious harm to staff and hence indirectly to patients, and potential loss of highly trained clinicians to the workforce.

Psychiatrists' Experience of a Peer Support Group for Reflecting on Patient Suicide and Homicide: A Qualitative Study.

There is a lack of support for mental health professionals who experience a patient suicide or homicide. This is despite a high likelihood of such an occurrence and the heavy professional and personal toll the experience can take. We conducted 15 interviews with members of a facilitated peer support group run for consultant psychiatrists who have experienced a patient homicide or suicide. Our interviews explored the trauma of the experience as well as the effectiveness of the group in helping the clinician heal. Our results echoed previous research that the experience can be profoundly traumatic. A professionally facilitated, consultant-only peer group specifically dedicated to suicide and homicide were the key components helping participants to process their grief. Mental health trusts should consider setting up facilitated peer support groups for clinicians who experience patient suicide or homicide.

After a patient dies by suicide: an illustrative case for trainee psychiatrists and trainers.

One of the most challenging experiences psychiatrists will face in their careers may well be the death of a patient by suicide. This is likely to happen at least once during a psychiatrist's career, and often more. It can be an intensely complex and painful event with a wide range of emotional responses. Reflecting on the death and accessing good support helps clinicians process the emotional impact. It can also increase their resilience in the longer term by giving them a greater understanding of both their own and their patients' limitations, and in this way strengthen their capacity for compassion as clinicians. Using an illustrative case study, this article provides an insight into the experience of losing a patient to suicide and signposts to sources of support.

The Maristán stigma scale: a standardized international measure of the stigma of schizophrenia and other psychoses.

BACKGROUND: People with schizophrenia face prejudice and discrimination from a number of sources including professionals and families. The degree of stigma perceived and experienced varies across cultures and communities. We aimed to develop a cross-cultural measure of the stigma perceived by people with schizophrenia. METHOD: Items for the scale were developed from qualitative group interviews with people with schizophrenia in six countries. The scale was then applied in face-to-face interviews with 164 participants, 103 of which were repeated after 30 days. Principal Axis Factoring and Promax rotation evaluated the structure of the scale; Horn's parallel combined with bootstrapping determined the number of factors; and intra-class correlation assessed test-retest reliability. RESULTS: The final scale has 31 items and four factors: informal social networks, socio-institutional, health professionals and self-stigma. Cronbach's alpha was 0.84 for the Factor 1; 0.81 for Factor 2; 0.74 for Factor 3, and 0.75 for Factor 4. Correlation matrix among factors revealed that most were in the moderate range [0.31-0.49], with the strongest occurring between perception of stigma in the informal network and self-stigma and there was also a weaker correlation between stigma from health professionals and self-stigma. Test-retest reliability was highest for informal networks [ICC 0.76 [0.67 -0.83]] and self-stigma [ICC 0.74 [0.64-0.81]]. There were no significant differences in the scoring due to sex or age. Service users in Argentina had the highest scores in almost all dimensions. CONCLUSIONS: The MARISTAN stigma scale is a reliable measure of the stigma of schizophrenia and related psychoses across several cultures. A confirmatory factor analysis is needed to assess the stability of its factor structure.

B7-H1 signaling is integrated during CD8(+) T cell priming and restrains effector differentiation.

A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cells is integrated during priming of naïve CD8(+) T cells and functions to limit the differentiation of effector T cell responses. CD8(+) T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN-γ, enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8(+) T cells primed by B7-H1-deficient dendritic cells. Based on these findings, we suggest that early blockade of B7-H1 signaling should be investigated as a strategy to improve dendritic cell-based anti-tumor immunotherapy.

Endogenous tumor-reactive CD8+ T cells are differentiated effector cells expressing high levels of CD11a and PD-1 but are unable to control tumor growth.

Immunotherapies aimed at enhancing natural or endogenous antitumor T-cell immunity in patients affected by advanced malignancies are currently being implemented in the clinic with promising results. In order to optimize therapeutic protocols and monitor the effectiveness of such therapies, reliable biomarkers are needed. We used CD11a, an integrin that is upregulated on the surface of effector and memory CD8+ T cells, and PD-1, an immunoregulatory receptor expressed by activated T cells, as biomarkers to identify, quantify and monitor endogenous tumor-reactive cytotoxic T lymphocytes (CTLs) in two mouse tumor models and in the peripheral blood of 12 patients affected by Stage IV melanoma. High expression levels of CD11a and PD-1 were detected among CD8+ T cells residing within primary and metastatic murine tumor sites, as well as in spontaneous murine breast cancer tissues. In the peripheral blood of melanoma patients, tumor antigen-specific CD8+ T cells were associated with a population of CD11ahigh CD8+ T cells that co-expressed high levels of PD-1. Healthy donors exhibited a comparatively much lower frequency of such PD-1+CD11ahighCD8+ T cells. Phenotypic analyses demonstrated that CD11ahighCD8+ T cells are proliferating (Ki67+) and activated (CD62L-CD69+). Increased CD11ahighCD8+ T cells and delayed tumor growth were observed in PD-1 deficient mice, suggesting that the antitumor effector functions of CD8+ T cells is compromised by an elevated expression of PD-1. The CD11ahighCD8+ T-cell population expresses high levels of PD-1 and presumably constitutes the cellular target of PD-1 blockade therapy. The expression level of CD11a and PD-1 by CD8+ T cells may therefore represent a novel biomarker to identify and monitor endogenous tumor-reactive CTLs. This may not only provide an immunological readout for evaluating the efficacy of immunotherapy but also contribute to the selection of cancer patients who are likely to benefit from anti-PD-1 therapy.

Tropism and pathological findings associated with canine respiratory coronavirus (CRCoV).

Canine infectious respiratory disease (CIRD) occurs frequently in densely housed dog populations. One of the common pathogens involved is canine respiratory coronavirus (CRCoV), however little is known regarding its pathogenesis and the role it plays in the development of CIRD. The pathogenesis of five geographically unrelated canine respiratory coronavirus (CRCoV) isolates was investigated. Following experimental infection in dogs, all five CRCoV isolates gave rise to clinical signs of respiratory disease consistent with that observed during natural infection. The presence of CRCoV was associated with marked histopathological changes in the nares and trachea, with loss and damage to tracheal cilia, accompanied by inflammation. Viral shedding was readily detected from the oropharynx up to 10 days post infection, but there was little or no evidence of rectal shedding. The successful re-isolation of CRCoV from a wide range of respiratory and mucosal associated lymphoid tissues, and lung lavage fluids demonstrates a clear tropism of CRCoV for respiratory tissues and fulfils the final requirement for Koch's postulates. By study day 14 dogs had seroconverted to CRCoV and the antibodies raised were neutralising against both homologous and heterologous strains of CRCoV in vitro, thus demonstrating antigenic homogeneity among CRCoV strains from the two continents. Defining the role that CRCoV and other agents play in CIRD is a considerable, but important, challenge if the disease is to be managed, treated and prevented more successfully. Here we have successfully developed a model for studying the pathogenicity and the role of CRCoV in CIRD.

B7-H1 limits the entry of effector CD8(+) T cells to the memory pool by upregulating Bim.

Protective T­cell immunity against cancer and infections is dependent on the generation of a durable effector and memory T­cell pool. Studies from cancer and chronic infections reveal that B7-H1 (PD-L1) engagement with its receptor PD-1 promotes apoptosis of effector T cells. It is not clear how B7-H1 regulates T­cell apoptosis and the subsequent impact of B7-H1 on the generation of memory T cells. In immunized B7-H1-deficient mice, we detected an increased expansion of effector CD8(+) T cells and a delayed T­cell contraction followed by the emergence of a protective CD8(+) T­cell memory capable of completely rejecting tumor metastases in the lung. Intracellular staining revealed that antigen-primed CD8(+) T cells in B7-H1-deficient mice express lower levels of the pro-apoptotic molecule Bim. The engagement of activated CD8(+) T cells by a plate-bound B7-H1 fusion protein led to the upregulation of Bim and increased cell death. Assays based on blocking antibodies determined that both PD-1 and CD80 are involved in the B7-H1-mediated regulation of Bim in activated CD8(+) T cells. Our results suggest that B7-H1 may negatively regulate CD8(+) T­cell memory by enhancing the depletion of effector CD8(+) T cells through the upregulation of Bim. Our findings may provide a new strategy for targeting B7-H1 signaling in effector CD8(+) T cells to achieve protective antitumor memory responses.

A new model for quality improvement in acute inpatient psychiatry: observational data from an acute assessment unit.

OBJECTIVES: There is little research into the constituents of effective psychiatric inpatient care. The aim of this study was to assess the effectiveness of a newly adopted model of inpatient care; the acute assessment ward. DESIGN: Review of data collected over a year-long period. SETTING: Acute assessment ward in North London. PARTICIPANTS: All Admissions between 8 October 2009 and 7 October 2010. MAIN OUTCOME MEASURES: Duration of stay, need for readmission, patient satisfaction and frequency of conflict behaviours. RESULTS: A total of 485 admissions over the yearlong study period. The median stay to discharge from the assessment ward was 6 days, whereas in those transferred it was 19 days. Readmission within 28 days following discharge from the assessment ward was 13.9%, whereas those discharged from other wards was 9.2% (P = 0.1). Patient satisfaction was no lower, for all domains, than for other wards in the trust. Frequency of conflict behaviour was equal to previous studies,(1) but self harm was significantly less common (P = 0.01). CONCLUSIONS: Our data show that focusing on the 'point of entry' to inpatient services means that some admission times can be reduced without an increase in 28-day readmission rates or conflict behaviours. The acute assessment model attempts to address the need for the NHS to deliver more for less, whilst remaining focused on service-user and staff satisfaction. Research into which areas of this complex intervention are effective is challenging, but we would urge others who run services with novel structures to publish data about their functioning.

B7-h1 expressed by activated CD8 T cells is essential for their survival.

An immunoinhibitory role of B7 homologue 1 (B7-H1) expressed by non-T cells has been established; however, the function of B7-H1 expressed by T cells is not clear. Peak expression of B7-H1 on Ag-primed CD8 T cells was observed during the contraction phase of an immune response. Unexpectedly, B7-H1 blockade at this stage reduced the numbers of effector CD8 T cells, suggesting B7-H1 blocking Ab may disturb an unknown function of B7-H1 expressed by CD8 T cells. To exclusively examine the role of B7-H1 expressed by T cells, we introduced B7-H1 deficiency into TCR transgenic (OT-1) mice. Naive B7-H1-deficient CD8 T cells proliferated normally following Ag stimulation; however, once activated, they underwent more robust contraction in vivo and more apoptosis in vitro. In addition, B7-H1-deficient CD8 T cells were more sensitive to Ca-dependent and Fas ligand-dependent killing by cytotoxic T lymphocytes. Activation-induced Bcl-x(L) expression was lower in activated B7-H1-deficient CD8 T cells, whereas Bcl-2 and Bim expression were comparable to the wild type. Transfer of effector B7-H1-deficient CD8 T cells failed to suppress tumor growth in vivo. Thus, upregulation of B7-H1 on primed T cells helps effector T cells survive the contraction phase and consequently generate optimal protective immunity.

Immunity after natural exposure to enteric canine coronavirus does not provide complete protection against infection with the new pantropic CB/05 strain.

Recently, an outbreak of fatal infection caused by a pantropic variant (strain CB/05) of canine coronavirus (CCoV) has been reported. In this study, evidence is provided that immunity induced by natural exposure to enteric CCoV is not fully protective against strain CB/05. Twenty-two, 10-week-old beagles with a recent natural infection by enteric CCoV were randomly distributed in two experimental groups of eight (groups A and B) and one control group of six (group C) dogs. Dogs in groups A and B were inoculated oronasally with different doses (4 x 10(5) or 4 x 10(3)TCID(50)) of the pantropic strain CB/05, whereas dogs in group C were used as negative controls. Clinical, post-mortem and virological investigations showed that, despite the high serum antibody titres induced by the prior natural infection with enteric CCoV, dogs were susceptible to experimental infection with strain CB/05. This was shown by the occurrence of faecal shedding, and dogs displaying moderate clinical signs, mainly vomiting and diarrhoea. Involvement of the lymphoid tissues was evident as demonstrated by the acute lymphopenia (below 70% of the initial counts), gross lesions in spleen and lymph nodes and detection of CB/05 RNA in thymus, spleen and lymph nodes of some infected dogs. The presence of viral RNA in lymphoid tissues was observed only in dogs euthanised in the early stages of infection and the clinical course of the infection was unrelated to the viral dose administered. The present study demonstrates that strain CB/05 is able to induce infection and disease in dogs seropositive to enteric CCoV, thus highlighting the need for extensive epidemiological investigation and for the possible development of novel antigenically relevant vaccines.

Identification of functional alpha2- and beta-adrenergic receptors in mammalian spermatozoa.

BACKGROUND: A recent study of several compounds, structurally related to amphetamine, provided evidence that mammalian spermatozoa might have adrenergic receptors able to regulate cAMP production. The present study investigated this possibility using physiological and immunochemical analyses of mouse and human spermatozoa. METHODS: Antibodies specific for different receptor subtypes were used for Western blotting of mouse and human sperm lysates and for immunocytochemical evaluation of whole mouse and human spermatozoa. Uncapacitated and capacitated mouse spermatozoa were incubated with specific agonists and antagonists for alpha2-, beta1-, beta2- and beta3-adrenergic receptors for approximately 35 min and then assessed using chlortetracycline (CTC) fluorescence. RESULTS: Western blotting revealed proteins of the correct size for all these receptors; immunolocalization indicated their presence on the head, especially acrosomal and neck regions, and flagellum of both mouse and human spermatozoa. CTC results indicated significant responses to agonists for all of the beta-receptors in uncapacitated cells, with agonist effectiveness being beta1 > beta2 > beta3; relevant antagonists blocked responses. In contrast, an agonist and antagonist for alpha2-receptors acted only on capacitated spermatozoa. CONCLUSION: These experiments provide the first good evidence that mammalian spermatozoa have both beta-adrenergic receptors, known to stimulate cAMP production by membrane-associated adenylyl cyclases (mACs), and alpha2-adrenergic receptors, known to inhibit cAMP production by mACs. Responses are capacitation state dependent and provide a mechanism for inhibiting spontaneous acrosome reactions and helping to maintain fertilizing ability. These results suggest that the use of amphetamine-related compounds, either for medical or for social reasons, might have an unexpected positive impact on fertility.

Regulation of mammalian sperm capacitation by endogenous molecules.

Capacitation in vitro in mammalian spermatozoa can be regulated by a number of first messengers, including fertilization promoting peptide, adenosine, calcitonin and angiotensin II, all of which are found in seminal plasma. The responses appear to involve several separate signal transduction pathways that have a common end point. These seminal-plasma derived first messengers can bind to specific receptors and directly or indirectly modulate the activity of membrane-associated adenylyl cyclase isoforms and production of the second messenger cAMP. Responses to all of these except angiotensin II involve initial acceleration of cAMP production and capacitation followed by inhibition of both cAMP production and spontaneous acrosome loss, resulting in maintenance of fertilizing potential. Appropriate G proteins and various phosphodiesterase isoforms also appear to be involved. The transition from stimulatory to inhibitory responses involves loss of decapacitation factors (DF) from receptors (DF-R) on the external surface; a DF-R present on both mouse and human spermatozoa has recently been identified as phosphatidylethanolamine-binding protein 1. The presence/absence of DF appears to cause changes in the plasma membrane that then alter the functionality of various membrane-associated proteins, including receptors. Since spermatozoa contact these first messengers at ejaculation, it is plausible that their actions observed in vitro also occur in vivo, allowing these molecules to play a pivotal role in enhancing the chances of successful fertilization.

A mouse sperm decapacitation factor receptor is phosphatidylethanolamine-binding protein 1.

Capacitation is a pivotal event for mammalian spermatozoa, involving the loss of surface proteins known as decapacitation factors (DF) and consequent acquisition of fertilizing ability. Earlier studies showed that a mouse sperm DF binds to a receptor, DF-R, whose attachment to the sperm plasma membrane appears to involve a glycosylphosphatidylinositol (GPI) anchor. In the present study, purification and subsequent sequencing of DF-R has identified this approximately 23 kDa protein as phosphatidylethanolamine-binding protein 1 (PEBP 1). To obtain functional evidence that supports sequence homology data, purified recombinant PEBP 1 and PEBP 2 were evaluated for biological activity. While PEBP 1 was able to remove DF activity in solution at concentrations above approximately 1 nmol/l, PEBP 2 was ineffective, even at 600 nmol/l; this confirmed that DF-R is PEBP 1. Anti-PEBP 1 antiserum recognized recombinant PEBP 1 and a approximately 23 kDa protein in both mouse and human sperm lysates. Immunolocalization studies revealed that DF-R/PEBP 1 is located on the acrosomal cap, the post-acrosomal region and the flagellum of both mouse and human spermatozoa, with epitope accessibility being capacitation state-dependent and reversible. Treatment of cells with a phospholipase able to cleave GPI anchors essentially abolished immunostaining, thus confirming the extracellular location of DF-R/PEBP 1. We suggest that DF-R/PEBP 1 plays its fundamental role in capacitation by causing alterations in the sperm plasma membrane in both head and flagellum, with functional consequences for membrane-associated proteins. Obtaining more detail about DF <--> DF-R interactions could lead to useful applications in both fertility treatments and new contraceptive approaches.