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Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

Purpose The aim of this study was to identify the most appropriate measure of quality of life (QoL) for patients living with and beyond cancer. Methods One hundred eighty-two people attending cancer clinics in Central London at various stages post-treatment, completed a series of QoL measures: FACT-G, EORTC QLQ-C30 , IOCv2 (positive and negative subscales) and WEMWBS, a wellbeing measure. These measures were chosen as the commonest measures used in previous research. Correlation tests were used to assess the association between scales. Participants were also asked about pertinence and ease of completion. Results There was a significant positive correlation between the four domain scores of the two health-related QoL measures (.32 ≤ r ≤ .72, P < .001), and a significant large negative correlation between these and the negative IOCv2 subscale scores (− .39 ≤ r ≤ − .63, P < .001). There was a significant moderate positive correlation between positive IOCv2 subscale and WEMWBS scores (r = .35, P < .001). However, neither the FACT-G nor the EORTC showed any significant correlation with the positive IOCv2 subscale. Participants rated all measures similarly with regards to pertinence and ease of use. Conclusion There was little to choose between FACT-G, EORTC, and the negative IOC scales, any of which may be used to measure QoL. However, the two IOCv2 subscales capture unique aspects of QoL compared to the other measures. The IOCv2 can be used to identify those cancer survivors who would benefit from interventions to improve their QoL and to target specific needs thereby providing more holistic and personalised care beyond cancer treatment.

BackgroundTargeting modifiable risk factors may have a role in the prevention of Alzheimer’s disease. However, the mechanisms by which these risk factors influence Alzheimer’s risk remain incompletely understood. Genomic structural equation modelling can reveal patterns of shared genetic architecture that provide insight into the pathophysiology of complex traits.MethodsWe identified genome-wide association studies for Alzheimer’s disease and its major modifiable risk factors: less education, hearing loss, hypertension, high alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, type 2 diabetes, sleep disturbance and socioeconomic deprivation. We performed linkage disequilibrium score regression among these traits, followed by exploratory factor analysis, confirmatory factor analysis and structural equation modelling.ResultsWe identified complex networks of linkage disequilibrium among Alzheimer’s disease risk factors. The data were best explained by a bi-factor model, incorporating a Common Factor for Alzheimer’s risk, and three orthogonal sub-clusters of risk factors, which were validated across the two halves of the autosome. The first sub-cluster was characterised by risk factors related to sedentary lifestyle behaviours, the second by traits associated with reduced life expectancy and the third by traits that are possible prodromes of Alzheimer’s disease. Alzheimer’s disease was more genetically distinct and displayed minimal shared genetic architecture with its risk factors, which was robust to the exclusion of APOE.ConclusionShared genetic architecture may contribute to epidemiological associations between Alzheimer’s disease and its risk factors. Understanding the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.

Major depressive disorder (MDD) is a prevalent disorder with moderate heritability. Both MDD and interpersonal adversity, including childhood maltreatment, have been consistently associated with elevated inflammatory markers. We investigated interaction between exposure to childhood maltreatment and extensive genetic variation within the inflammation pathway (CRP, IL1b, IL-6, IL11, TNF, TNFR1, and TNFR2) in relation to depression diagnosis. The discovery RADIANT sample included 262 cases with recurrent DSM-IV/ICD-10 MDD, and 288 unaffected controls. The replication Münster cohort included 277 cases with DSM-IV MDD, and 316 unaffected controls. We identified twenty-five single nucleotide polymorphisms (SNPs) following multiple testing correction that interacted with childhood maltreatment to predict depression in the discovery cohort. Seven SNPs representing independent signals (rs1818879, rs1041981, rs4149576, rs616645, rs17882988, rs1061622, and rs3093077) were taken forward for replication. Meta-analyses of the two samples presented evidence for interaction with rs1818879 (IL6) (RD=0.059, SE=0.016, p < 0.001), with the replication Münster sample approaching statistical significance in analyses restricted to recurrent MDD and controls following correction for multiple testing (q=0.066). The CRP locus (rs3093077) showed a similar level of evidence for interaction in the meta-analysis (RD=0.092, SE=0.029, p=0.002), but less compelling evidence in the replication sample alone (recurrent MDD q=0.198; all MDD q=0.126). Here we present evidence suggestive of interaction with childhood maltreatment for novel loci in IL-6 (rs1818879) and CRP (rs3093077), increasing risk of depression. Replication is needed by independent groups, targeting these specific variants and interaction with childhood maltreatment on depression risk.

Highlights • Hippocampal volume and depression risk have been linked to reproductive hormones. • We generated polygenic risk scores (PRS) for four reproductive hormones. • PRS for higher estradiol predicted smaller hippocampal subfield volumes. • None of the PRSs predicted postpartum or major depression risk., Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS) for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD) cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD) cases (68.6% female, mean age: 46.9 years old) and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation.

Objective Cancer has been reported to trigger symptoms of post-traumatic stress disorder (PTSD) in a substantial proportion of individuals. Despite the significant burden associated with these symptoms, there are as yet no therapeutic guidelines. This systematic review aims to evaluate the effectiveness of interventions for cancer-related post-traumatic stress in order to provide an evidence base for developing appropriate clinical practice. Methods Databases searched until April 2018 included Psych INFO, EMBASE, Medline, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). No restrictions to study design were applied. Participants aged 18 years or older who received their cancer diagnosis in adulthood and had symptoms of cancer-related PTSD were included. Because of significant clinical heterogeneity, a meta-analysis was not performed. Results Of 508 unique titles, eight studies met study inclusion criteria: five randomised controlled trials (RCTs), one before-and-after study, one case series, and one case study. Interventions were predominately psychological and were administered to patients with a range of cancer types. Eye movement desensitisation and reprocessing and cognitive behavioural therapy-based interventions were associated with reduced symptomatology; however, overall the methodological quality of studies had limitations. Conclusions At present, there is only weak evidence available for the effectiveness of psychological interventions in reducing symptoms of cancer-related PTSD. The majority of interventions were administered to all cancer patients regardless of whether they showed pretreatment levels of post-traumatic stress. Future studies would be better targeted towards patients with a diagnosis of cancer and who have significant levels of cancer-related post-traumatic symptoms. Higher quality trials are also needed before treatment recommendations can be made.

24-hour oesophageal multichannel impedance and pH monitoring is the gold standard in the diagnostic process of gastroesophageal reflux disease. Together with oesophagogastroduodenoscopy, it enables to distinguish different kinds of this disease and implement appropriate treatment. Recently, thanks to impedance, it was attempted to evaluate new parameters that could be helpful in diagnosis of gastroesophageal reflux disease and its differentiation from functional heartburn. One of these parameters is baseline impedance. It is measured when no swallows and refluxes occur in the oesophagus, i.e. when the oesophageal wall stays still. Postreflux swallow-induced peristaltic wave (PSPW) index is another parameter measured in 24-hour oesophageal multichannel intraluminal impedance and pH-monitoring. It is a quotient of the number of reflux episodes with postreflux swallow-induced peristaltic wave and the total number of reflux episodes. It was proven that baseline impedance and postreflux swallow-induced peristaltic wave index are correlated with oesophageal mucosa integrity. Values of these parameters differ in healthy volunteers, patients with functional heartburn as well as with erosive and nonerosive gastroesophageal reflux disease. They may be useful in the diagnosis, but also in making decisions about pharmacological or surgical treatment. These parameters are not evaluated during 24-hour oesophageal multichannel impedance and pH-monitoring on a routine basis. Since the available studies have been carried out on small groups of patients, there is a need for further investigation to assess the diagnostic value of baseline impedance and PSPW.

Zakazenie Helicobacter pylori jest powszechne. Światowa Organizacja Zdrowia szacuje, ze zainfekowanych tą bakterią jest okolo 70% ludzi w krajach rozwijających sie i okolo 30% w krajach rozwinietych. Zakazenie szerzy sie przez kontakty miedzyludzkie. Dochodzi do niego na drodze: oralno-oralnej, gastro-oralnej oraz fekalno-oralnej. W 80–90% przypadkow infekcja H. pylori ma charakter bezobjawowy. W diagnostyce zakazenia tym drobnoustrojem stosuje sie metody inwazyjne i nieinwazyjne. Wybor metody uwarunkowany jest aktualną sytuacją kliniczną oraz koniecznością wykonania badania endoskopowego gornego odcinka przewodu pokarmowego. Wobec znacznego rozpowszechnienia i duzej czestości rozpoznawania zakazenia H. pylori testy na obecnośc tej bakterii nalezy wykonywac tylko w sytuacji, gdy planowane jest wlączenie odpowiedniego schematu leczenia eradykacyjnego. Zgodnie z wytycznymi Grupy Roboczej Polskiego Towarzystwa Gastroenterologii w leczeniu eradykacyjnym stosuje sie schematy wielolekowe uwzgledniające inhibitory pompy protonowej, antybiotyki i cytrynian bizmutu. Wszystkie wymienione leki powinny byc stosowane przez okres 10–14 dni. Z uwagi na narastającą w Polsce opornośc na klarytromycyne antybiotyk ten nie powinien byc wykorzystywany w leczeniu pierwszego wyboru. Optymalną ocene skuteczności terapii przeciwbakteryjnej przeprowadza sie na podstawie testu oddechowego, lecz z powodu ceny i dośc trudnej dostepności nie jest to podstawowe narzedzie diagnostyczne. Z kolei dostepne dośc szeroko i niezbyt drogie testy serologiczne nie nadają sie do oceny skuteczności eradykacji. Na uwage zasluguje wiec oznaczanie antygenu H. pylori w kale, bedące niezbyt drogim badaniem, dostepnym, charakteryzującym sie wysoką czulością i swoistością, siegającymi 90%. Slowa kluczowe: Helicobacter pylori, zakazenie, diagnostyka, eradykacja, skutecznośc leczenia Helicobacter pylori infection is common. The World Health Organization estimates that about 70% of people in developing countries and 30% in developed countries are infected with this bacterium. The infection spreads through personal contacts via an oral-oral, gastro-oral and faecal-oral route of transmission. Helicobacter pylori infection is asymptomatic in 80–90% of cases. Both invasive and non-invasive methods are used in the diagnosis of this infection. The choice of the method depends on the current clinical condition and the necessity to perform endoscopy of the upper gastrointestinal tract. Since the incidence and prevalence of Helicobacter pylori infection are high, H. pylori detection tests should be performed only when eradication therapy is planned. According to the guidelines of the Working Group of the Polish Society of Gastroenterology, eradication treatment involves a multidrug therapy with proton pump inhibitors, antibiotics and bismuth citrate. All of these drugs should be used for a period of 10–14 days. Clarithromycin should not be used as the first choice treatment because of increasing resistance in Poland. A breath test is an optimal way to evaluate the effectiveness of the antibacterial therapy but is rarely performed due to high price and low availability. Serology tests are available and cheap, but are not suitable to assess the efficacy of eradication. Helicobacter pylori antigen detection in stool is therefore important in the diagnosis. The test is not very expensive, available and characterised by very high sensitivity and specificity of up to 90%.

Head and neck cancer (HNC) diagnosis and treatment are distressing and have immediate detrimental impacts on functioning and quality of life (QoL). Nevertheless, little is known about long-term psychosocial effects. The aim of this study was to determine the prevalence and correlates of clinical post-traumatic stress disorder (PTSD) and subclinical post-traumatic stress symptoms (PTSS) in HNC patients surviving more than 2 years since treatment and in their partners.HNC survivors identified from the cancer registry of a London hospital and their partners completed measures of PTSS, depression and anxiety, fear of cancer recurrence, social support, appearance concerns and health-related QoL. Data regarding their clinical and demographic characteristics were also collected. Correlations, as well as linear and logistic regression coefficients, were calculated to estimate associations with PTSS scores.In this analysis of 93 HNC survivors, at a mean of 6 years (SD = 4) after treatment, 33.4% reported PTSS and 11.8% met the criteria for post-traumatic stress disorder (PTSD). Fear of cancer recurrence was independently associated with PTSS (p .01). In subgroup analyses of patient-partner dyads, 15.4% of patients and 12.8% of partners reported PTSD, with a further 33.3% of patients and 25.7% of partners demonstrating PTSS. Patients' and partners' scores did not differ significantly (p .05).This is the first examination of post-traumatic stress in survivors of HNC and shows that high levels of cancer-related PTSS exist for many years after diagnosis in both patients and their partners.

Background People who experience physical trauma face a range of psychosocial outcomes. These may be overlooked by busy clinicians. While some risk factors are understood, understanding of the psychological effects of violent injury remains limited, particularly in UK settings. This study compared psychological outcomes following interpersonal violence and accidental injury, including the persistence of psychological distress. Methods A questionnaire survey was carried out at two time points of patients admitted to a large teaching hospital in London between July 2012 and April 2014. Participants were consecutive adult patients admitted to the Royal London Hospital with traumatic injuries, with 219 participants at baseline. Follow-up survey was 8 months later (n=109). Standardised measures assessed post-traumatic stress symptoms (PTSS) (Acute Stress Disorder Scale and PTSD Checklist) and depressive symptoms (Hospital Anxiety and Depression Scale). Results PTSS and depressive symptoms affected 27% and 33%, respectively, at baseline. At 8 months, 27% and 31% reported these symptoms for PTSS and depressive symptoms, respectively. The repeated measures were assessed with multilevel models: after adjusting for demographic factors, patients with violent injury showed more PTSS (OR 6.27, 95% CI 1.90 to 20.66) and depressive symptoms (OR 3.12, 95% CI 1.08 to 8.99). Conclusions There were high levels of psychological distress among traumatic injury patients. Violent injuries were associated with an increased risk of both post-traumatic and depressive symptoms. People vulnerable to distress would benefit from psychological support, and hospital admission provides a unique opportunity to engage hard-to-reach groups in interventions.

Background Approximately one third of cancer survivors in the United Kingdom face ongoing and debilitating psychological and physical symptoms related to poor quality of life. Very little is known about current post-cancer treatment services. Methods Oncology healthcare professionals (HCPs) were invited to take part in a survey, which gathered both quantitative and free text data about the content and delivery of cancer aftercare and patient needs. Analysis involved descriptive statistics and content analysis. Results There were 163 complete responses from 278 survey participants; 70% of NHS acute trusts provided data. HCPs views on patient post-cancer treatment needs were most frequently: fear of recurrence (95%), fatigue (94%), changes in physical capabilities (89%), anxiety (89%) and depression (88%). A median number of 2 aftercare sessions were provided (interquartile range: 1,4) lasting between 30 and 60 min. Usually these were provided face-to-face and intermittently by a HCP. However, sessions did not necessarily address the issues HCPs asserted as important. Themes from free-text responses highlighted inconsistencies in care, uncertain funding for services and omission of some evidence based approaches. Conclusion Provision of post-cancer treatment follow-up care is neither universal nor consistent in the NHS, nor does it address needs HCPs identified as most important. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3172-1) contains supplementary material, which is available to authorized users.

Background: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD., Methods: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case–control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity., Results: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P, Conclusions: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity., This study was funded by the Medical Research Council, UK. GlaxoSmithKline (G0701420) funded the DeNT study and were co-funders with the Medical Research Centre for the GWAS of the whole sample. The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT- 2003-503428. This study presents independent research [part-] funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The CoLaus/PsyCoLaus was funded by four grants from the Swiss National Science Foundation (#32003B-105993, #32003B-118308, #33CSC0-122661, and #139468), the Faculty of Biology and Medicine of Lausanne, and two grants from GlaxoSmithKline Clinical Genetics.

Cross-Disorder Working Group of the Psychiatric Genomics Consortium - Vicente A.M. Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25640677/ Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk

Summary Facial injuries are widely assumed to lead to stigma and significant psychosocial burden. Experimental studies of face perception support this idea, but there is very little empirical evidence to guide treatment. This study sought to address the gap. Data were collected from 193 patients admitted to hospital following facial or other trauma. Ninety (90) participants were successfully followed up 8 months later. Participants completed measures of appearance concern and psychological distress (post-traumatic stress symptoms (PTSS), depressive symptoms, anxiety symptoms). Participants were classified by site of injury (facial or non-facial injury). The overall levels of appearance concern were comparable to those of the general population, and there was no evidence of more appearance concern among people with facial injuries. Women and younger people were significantly more likely to experience appearance concern at baseline. Baseline and 8-month psychological distress, although common in the sample, did not differ according to the site of injury. Changes in appearance concern were, however, strongly associated with psychological distress at follow-up. We conclude that although appearance concern is severe among some people with facial injury, it is not especially different to those with non-facial injuries or the general public; changes in appearance concern, however, appear to correlate with psychological distress. We therefore suggest that interventions might focus on those with heightened appearance concern and should target cognitive bias and psychological distress.

PurposeThe aims of this study were to examine quality of life, using the Impact of Cancer version 2 (IOCv2), in British non-Hodgkin lymphoma (NHL) survivors and investigate differences between survivors in the UK and the USA.MethodsNHL survivors (326 UK and 667 US) completed the 37-item IOCv2 and psychological distress, fatigue and social support questionnaires.ResultsThe IOCv2 showed good reliability in the British sample with higher internal consistency (Cronbach alpha 0.7-0.9) and no floor and ceiling effects. UK survivors showed significantly higher negative (p&nbsp

Aims and methodWe used an online questionnaire to investigate medical students' perceptions of the apparent hierarchy between specialties, whether they have witnessed disparaging comments (‘badmouthing’ or ‘bashing’) against other specialists and whether this has had an effect on their career choice.ResultsIn total, 960 students from 13 medical schools completed the questionnaire; they ranked medical specialties according to the level of badmouthing and answered questions on their experience of specialty bashing. Psychiatry and general practice attracted the greatest number of negative comments, which were made by academic staff, doctors and students. Twenty-seven per cent of students had changed their career choice as a direct result of bashing and a further 25.5% stated they were more likely to change their specialty choice. Although 80.5% of students condemned badmouthing as unprofessional, 71.5% believed that it is a routine part of practising medicine.Clinical implicationsBashing of psychiatry represents another form of stigmatisation that needs to be challenged in medical schools. It not only has an impact on recruitment into the specialty, but also has the wider effect of stigmatising people with mental health disorders.

Objective Depression is common in cancer patients and detrimentally affects patients' quality of life. Both depression and stress are associated with raised inflammatory marker levels. This prospective study of cancer patients focuses on childhood trauma, recent life events and inflammatory marker levels as risk factors for high post-surgery depressive symptoms. Methods Ninety cancer patients (56 head and neck, 34 colorectal) completed the Hospital Anxiety and Depression Scale, pre-surgery and six, 12 and 24 weeks post-surgery. Recent life events and childhood trauma were assessed at six and 12 weeks respectively. Blood samples were taken pre- and one and six weeks post-surgery to measure C-reactive protein (CRP) and pro-inflammatory cytokine levels. Results Childhood trauma and recent life events were risk factors for higher depressive symptom levels. In colorectal cancer patients, baseline CRP levels were associated with depressive symptom levels at six (p=0.008) and 12 weeks (p=0.038). Baseline and six week Tumour Necrosis Factor-alpha (TNFα) levels were significantly associated with higher depressive symptoms at later time points after adjusting for cancer-related variables. Childhood trauma was positively associated with TNFα and CRP levels in colorectal cancer patients. The associations between inflammatory markers and depressive symptoms were not significant after adjusting for childhood trauma. Limitations Small sample size. Conclusions Raised inflammatory mediator levels may be risk factors for depressive symptoms in colorectal cancer patients and thus worth considering as a potential therapeutic target. These pilot data support recent findings demonstrating long-term effects of childhood adversity on adult health.

Aims and methodAn online survey was used to examine the attitudes of clinical, academic and trainee psychiatrists on the delivery of undergraduate education and why students are not choosing psychiatry as a career. This paper explores whether attitudes to teaching psychiatry to medical students is a factor in poor recruitment to the specialty.ResultsOverall, 390 psychiatrists completed the survey. All groups were highly committed to psychiatry education, but there were significant differences in attitudes that may have an impact on the delivery of medical student teaching, which in turn may influence recruitment. Five major themes emerged from the survey, the most dominant being stigmatisation of psychiatric patients and professionals by the medical profession. These divergent attitudes to teaching and stigma may be contributing to low levels of recruitment into psychiatry.Clinical implicationsEducation of the next generation of psychiatrists is a high priority and active measures are needed to increase commitment and enthusiasm in undergraduate education.

Objective Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders. Method Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEP] study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Genotypage on the Illumina Human610-Quad BeadChip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry. Results Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungenotyped markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1. Conclusions This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.

Medical and nursing students are often anxious about communicating with patients with mental health problems, even when they have received general communication skills training. Communication is particularly challenging when patients are compulsorily admitted to hospital. The study reported here sought to explore medical and nursing students' attitudes to this challenge, stimulated by watching a DVD illustrating professional‐patient communications in this situation. Facilitated discussions of the DVD were recorded and the transcripts were thematically analysed. A strong commitment to three underlying principles of patient‐centred care emerged.1. A preference for egalitarian over authoritarian relationships between patients and professionals.2. A preference for empathetic over bureaucratic approaches to patients.3. Respect for patients as autonomous beings.Students seemed less aware of the need for clear and effective communication of information, and some appear confused about patient‐professional boundaries.

Udgivelsesdato: 2009-August Migraine is frequently comorbid with depression. There appear to be common aetiological factors for both disorders, but the aetiology of migraine within depressed patients, in particular the significance of aura, has been little studied. A large sample of concordantly depressed sibling pairs [the Depression-Network (DeNT) sample] was assessed as having migraine with aura (MA), migraine without aura (MoA), probable migraine or no migraine according to International Headache Society guidelines. Correlations between siblings' migraine status were used to assess the nature of familial liability to migraine. A multiple threshold isocorrelational model fit best, in which different syndromes are conceptualized as different severities of one underlying dimension rather than as having separate aetiologies. Thus, MA and MoA were found to be different forms of the same disorder, with MA occupying the more extreme end of the spectrum of liability. Implications for our understanding of the relationship between migraine and depression are discussed.

BackgroundAn association between depression and headache is well established, but the specificity to migraine is unclear.AimsTo investigate the specificity of the association of depression and migraine.MethodPeople with recurrent depression (n=1259) were compared with psychiatrically healthy controls (n=851) to investigate headache defined according to International Headache Society criteria in each group.ResultsAll headache types were more prevalent in the case group than in the controls. However, the strongest association was between depression and migraine with aura (OR=5.6). Among participants with recurrent headaches, migraine with aura (but not other forms of headache) was highly significantly associated with depression.ConclusionsThe data suggest that not only is there a general relationship between headache and depression but also that among people with recurrent headache there is a specific association between depression and migraine with aura. The association is likely to be explained by overlapping aetiological risk factors.

BackgroundFew studies have examined the rates of physical disorders in those with recurrent depression.AimsTo examine self-reported physical disorders in people with recurrent depression compared with a psychiatrically healthy control group.MethodAs part of a genetic case-control association study, 1546 participants with recurrent depression and 884 controls were interviewed about lifetime ever treatment for 16 different physical health disorders.ResultsThe cases group had a significantly higher frequency of 14 physical disorders and more obesity than the control group. After controlling for age, gender, body mass index (BMI) and multiple testing, those in the cases group had significantly higher rates of gastric ulcer, rhinitis/hay fever, osteoarthritis, thyroid disease, hypertension and asthma.ConclusionsPeople with recurrent depression show high rates of many common physical disorders. Although this can be partly explained by BMI, shared aetiological pathways such as dysfunction of the hypothalamic–pituitary axis may have a role.

Head and neck cancer patients have been reported to show high rates of depression. However, it is important to differentiate between depressive symptoms and a depressive disorder. This review critically examines the relationship between head and neck cancer and depression. There appears to be little evidence for depression leading to an increased risk of developing cancer and although depressive symptoms in head and neck cancer patients are common, very few studies have investigated depressive disorders. The studies that investigated the incidence of a comorbid depressive disorder report a prevalence very close to that of the general population, implying that major depression is not a normal response to cancer. Finally, the evidence suggests that comorbidity of depression with cancer has a negative impact on morbidity and mortality. Both psychosocial and biological factors could account for this. Dysregulation of the stress hormone axis and increased inflammation are common in depressive disorders and have been suggested as underlying pathological mechanisms and are both markers of poor prognosis in cancer. This evidence suggests that a relatively small number of patients develop a depressive disorder following a diagnosis of cancer, but for those that do it may have a substantial impact on their prognosis.

Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta-analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations. This may parallel a similar reduction in 5-methyltetrahydrofolate in the CNS, leading to a potential reduction in monoamine neurotransmitter function and an elevated risk of depressive disorder. To test the hypothesis that the MTHFR C677T polymorphism is involved in the predisposition to MDD, we conducted an association study of 1,222 patients with recurrent MDD and 835 control subjects. This allows 99% power to detect an effect of the size reported in the study of Bjelland et al. [2003], however no significant differences in genotype or allele frequencies between depressive patients and controls were observed. This was the case in the sample as a whole, and when females and males were considered separately. Our findings suggest that the MTHFR C677T polymorphism is not involved in the etiology of clinically significant recurrent MDD. 2007 Wiley-Liss, Inc.

Acidity of products resulting from the reaction of flue gas components emitted from a coal-fired power plant with water contained in a vapor plume from a wet cooling tower was analyzed in a close vicinity of a power plant (710 m from the stack and 315 m from the cooling tower). Samples of this mixture were collected using a precipitation funnel where components of the mixed plumes were discharged from the atmosphere with the rainfall. To identify situations when the precipitation occurred at the same time as the wind directed the mixed vapor and flue gas plumes above the precipitation funnel, an ultrasound anemometer designed for 3D measurements of the wind field located near the funnel was used. Precipitation samples of extremely high acidity were identified - about 5% of samples collected during 12 months showed the acidity below pH=3 and the lowest recorded pH was 1.4. During the measurement period the value of pH characterizing the background acidity of the precipitation was about 6. The main outcome of this study was to demonstrate a very high, and so far completely underestimated, potential of occurrence of episodes of extremely acid depositions in the immediate vicinity of a coal-fired power plant.

Depression and ischemic heart disease (IHD) are strongly related common disorders. Depression itself is an independent cardiac risk factor and is associated with a two- to threefold increase in IHD mortality. Attention has now shifted to identifying the common underlying mechanisms that could make individuals susceptible to both disorders. Abnormalities that have been implicated in this relationship include abnormal platelet activation, decreased baroreceptor sensitivity and endothelial dysfunction. Depression and IHD both have a high association with environmental stress, and depression is characterized by abnormalities of the stress-hormone axis. This review provides a brief overview of some recent developments in our understanding of the pathophysiological links between stress, depression and IHD.

One year after implementation of a new schedule of summative assessment of professional attitude and conduct (AC) for medical undergraduates at the University of Wales College of Medicine (UWCM), we evaluated its effectiveness and obtained feedback of the perceptions of participating teachers and students. An anonymous questionnaire was administered to all 4th year students and their clinical teachers. Four out of 180 students actually failed to complete the 4th year as a result of unsatisfactory AC. Of these, three students were identified as having a problem which benefited from supportive remediation. One hundred and twenty out of 244 (49%) teachers and 166 out of 195 (85%) students completed the feedback questionnaires. The majority of students and teachers agreed that AC should be an integral part of their assessment. However, several problems were highlighted, in particular, students' perception that marks were sometimes based on assessment of knowledge rather than attitude and conduct and teachers' reluctance to identify unprofessional behaviour in students. The use of longitudinal assessment of professional AC was found to be effective at identifying students with persistent AC problems and also provided an opportunity for formative experience. The reluctance of teachers to identify negative behaviours, compared to deficiencies in skill and knowledge, is an important aspect of developing a reliable method of evaluating professional attitudes.

OBJECTIVES: This study was designed to investigate the role of cortisol in stress-induced endothelial dysfunction and impaired baroreflex sensitivity (BRS) by blocking cortisol production with metyrapone before subjecting healthy volunteers to mental stress. BACKGROUND: Mental stress raises cortisol levels and is associated with increased coronary heart disease (CHD) morbidity and mortality, especially from sudden cardiac death. It also causes endothelial dysfunction and impaired BRS. METHODS: We measured brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and BRS in 36 subjects without CHD risk factors who were then randomized in a double-blind fashion to oral metyrapone 750 mg x 2 or placebo. Five hours later we subjected subjects to mental stress and then remeasured endothelial function and BRS. RESULTS: Prestress cortisol levels were significantly higher in the placebo group at 270.5 (30.9) nmol/l versus 89.1 (11.8) nmol/l (p = 0.01), and the increase with stress was higher at 57.9 (17.9) nmol/l versus 11.2 (2.2) nmol/l (p < 0.001). In the placebo group, compared to baseline, FMD and BRS fell significantly from 4.5% (0.7%) to 1.4% (1.1%) (p = 0.02) and 21.4 (2.3) ms/mmHg to 16.3 (1.5) ms/mmHg (p = 0.04), respectively. In the metyrapone group, FMD and BRS were unchanged from baseline: 4.3% (0.9%) versus 5.1% (0.8%) (p = 0.48) and 26.4 (2.9) ms/mmHg versus 24.9 (2.6) ms/mmHg (p = 0.62), respectively. Analysis of covariation showed a significant effect of metyrapone on change in both FMD (p = 0.009) and BRS (p = 0.024). CONCLUSIONS: Stress-related endothelial dysfunction and BRS impairment can be prevented by blocking cortisol production with metyrapone, demonstrating a direct or facilitative role for cortisol in these phenomena and suggesting mechanisms by which stress contributes to CHD and sudden cardiac death.

OBJECTIVES: Depression is independently associated with increased cardiovascular morbidity and mortality, including sudden cardiac death, and this risk is observed even in patients who have been successfully treated for depression. Recent studies have emphasized the importance of impaired baroreceptor sensitivity (BRS) as a predisposing factor for sudden death in patients with manifest cardiac disease. Our objective was to test the hypothesis that BRS is impaired in subjects with depression in remission and with no other cardiac risk factors. METHODS: We measured BRS by the sequence method in 36 patients with treated recurrent depression, who were euthymic at the time of study and with no manifest cardiac disease or "conventional" cardiac risk factors, compared with 39 healthy controls. Exclusion criteria included manifest heart disease or any risk factor for IHD (smoking, hypertension, diabetes, hypercholesterolemia, or body mass index >30). Nine subjects were not on any medication, and 22 were taking antidepressants. None of the controls was taking any medication. RESULTS: BRS was significantly lower in patients than in controls (19.5 [1.78] versus 25.4 [1.69] ms/mm Hg, p = .017). Analysis of covariance, in which age, sex, cholesterol, and body mass index were included, also showed that depression was a significant (p = .027) predictor of BRS. There was no significant difference in BRS adjusted by age and sex between the subjects taking antidepressants compared with those on no medications (p = .40). CONCLUSIONS: These data indicate that BRS is impaired in otherwise healthy patients with depression and may contribute to their increased cardiac risk.

Background. Umbilical artery Doppler velocimetry is a routine method for fetal surveillance in high-risk pregnancy. Uterine artery Doppler seems to give comparable information, but it can be difficult to interpret as there are two arteries, which might show notching and/or increased pulsatility index (PI) as signs of increased vascular impedance. Combining the information on vascular resistance on both sides in a new score might simplify and improve evaluation of placental circulation. Methods. Uterine and umbilical artery Doppler velocimetry was evaluated in 633 high-risk pregnancies. The managing clinician was informed only about the umbilical artery flow. The umbilical artery flow spectrum was semiquantitatively divided into four blood flow classes (BFC), expressing signs of increasing vascular resistance. The uterine artery Doppler flow spectrum was divided into five uterine artery scores (UAS), taking into account presence/absence of notching and/or increase in PI. By adding UAS to BFC, a new placental score (PLS) was constructed with values ranging from 0 to 7, indicating general placental vascular resistance. The scores were related to three outcome variables: small-for-gestational age (SGA), premature delivery (

Chronic facial pain is associated with depression, stress and other chronic pain disorders such as fibromyalgia. There is growing evidence that all these conditions share underlying pathophysiological processes. This review explores this relationship and examines the role of the main stress hormone axis, the hypothalamic-pituitary-adrenal axis, in the pathogenesis of facial pain including possible future therapeutic approaches.

Aim. The aim of this study was to evaluate umbilical artery (UA) and uterine artery (Ut.A) Doppler velocimetry in a low-risk pregnancy group with decreased fetal movements. Material and methods. Eight hundred and eighty-eight women were examined because of decreased fetal movements. All fetuses were alive on maternal admission. In all cases, UA and Ut.A Doppler velocimetries were performed, as well as a nonstress test (NST). The managing clinician was informed only of the UA Doppler. Results. In the group of 135 women who gave birth within 2 days, UA velocimetry was abnormal in seven fetuses. In 11 cases, Ut.A vascular resistance was abnormal and in 18 cases 'notch' was stated. There were 19 emergency sections in this group. Signs of increased placental vascular resistance were correlated with need for operational delivery because of fetal distress. Among the remaining 753 women who delivered after more than 2 days after examination, UA velocimetry showed abnormality in five fetuses. In 42 cases the Ut.A pulsatility index was abnormal and in 118 cases an early end diastolic 'notch' was present. There was one perinatal death in this group. Conclusions. Decreased fetal movement perception by mothers should be taken seriously. Abnormal placental Doppler was an infrequent finding in these low-risk pregnancies. However, adding UA and Ut.A Doppler velocimetries to conventional NST surveillance might be reassuring for managing clinicians.

ObjectivesOver two million people in the UK are living with and beyond cancer. A third report diminished quality of life.DesignA review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors.Data sourcesDatabases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO.Study selectionPublished systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data.OutcomesThe primary outcome of interest was any measure of global (overall) quality of life.Analytical methodsQuality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components.ResultsOf 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life.ConclusionsExercise-based interventions were effective in the short (less than 3–8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.

BackgroundObesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.AimsTo investigate whether higher BMI increases the risk of major depression.MethodTwo instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case–control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.ResultsLinear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient −0.03, 95% CI −0.18 to 0.13, P = 0.73; GRS: coefficient −0.02, 95% CI −0.11 to 0.07, P = 0.62).ConclusionsOur instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Depression is a common serious disorder that has a high comorbidity with chronic facial pain. This article provides an overview of the clinical presentation, pathophysiology and diagnosis of depression. In particular, it addresses some of the problems associated with identifying depressive symptoms in dental patients who have chronic facial pain.

There is increasing evidence that patients treated for trauma or cancer of the head and neck may go on to experience psychological distress. We aimed to measure the impact of this on their quality of life (QoL) and to explore their willingness to be referred for psychological support. A total of 96 patients with facial injuries and 124 with cancer of the head and neck completed a self-reported questionnaire to identify psychological distress (Hospital Anxiety and Depression Scale (HADS) and the Acute Stress Disorder (ASD) Scale), quality of life (WHOQoL-BREF), satisfaction with treatment, and willingness to accept psychological support. Thirty-nine percent of patients showed high levels of depressive symptoms and 43% reported high levels of anxiety; 43% in the trauma group and 12% in the cancer group had high ASD scores. Patients with high scores on the HADS reported poorer QoL, and 40% of those with high levels of psychological distress were willing to consider psychological support. Despite the fact that patients report high levels of satisfaction with their medical and surgical care, many have psychological problems and have needs that are not being met. A large proportion would use psychological support services.

Stressful life events are an established trigger for depression and may contribute to the heterogeneity within genome-wide association analyses. With depression cases showing an excess of exposure to stressful events compared to controls, there is difficulty in distinguishing between "true" cases and a "normal" response to a stressful environment. This potential contamination of cases, and that from genetically at risk controls that have not yet experienced environmental triggers for onset, may reduce the power of studies to detect causal variants. In the RADIANT sample of 3,690 European individuals, we used propensity score matching to pair cases and controls on exposure to stressful life events. In 805 case-control pairs matched on stressful life event, we tested the influence of 457,670 common genetic variants on the propensity to depression under comparable level of adversity with a sign test. While this analysis produced no significant findings after genome-wide correction for multiple testing, we outline a novel methodology and perspective for providing environmental context in genetic studies. We recommend contextualizing depression by incorporating environmental exposure into genome-wide analyses as a complementary approach to testing gene-environment interactions. Possible explanations for negative findings include a lack of statistical power due to small sample size and conditional effects, resulting from the low rate of adequate matching. Our findings underscore the importance of collecting information on environmental risk factors in studies of depression and other complex phenotypes, so that sufficient sample sizes are available to investigate their effect in genome-wide association analysis. © 2013 Wiley Periodicals, Inc.

To assess the impact of cancer (IOC) on subsequent quality of life (QOL), 718 long-term haematological cancer survivors completed validated psychosocial, functional and QOL scales, including IOC. Fifteen percent reported significant psychological distress, 18% high levels of fatigue and 10% moderate to severe functional impairment. These groups of participants also showed poorer QOL. There were no significant differences in psychological distress (P = 0·76), fatigue (P = 0·23) or functional impairment (P = 0·74) across different cancer subtypes. Two separate hierarchical regression analyses examined the combined association of disease-type, psychosocial and other factors on negative and positive IOC scores respectively. Higher negative IOC scores were significantly associated (P ≤ 0·001) with medical comorbidity, psychological distress, lower social support, high fatigue levels and functional impairment. Paediatric patients (diagnosed at

Problems of sexual function and fertility in long-term survivors (≥5 years) of haematological malignancy are often neglected in clinic. Our centre carried out a questionnaire study in this population addressing patient-perceived fertility and sexual function. 718 patients responded (56% of those invited; 39% Hodgkin, 45% non-Hodgkin lymphoma, 16% acute leukaemia). Respondent women were more likely to remain childless than a normal control population. Self-reported infertility was more likely in men than women [odds ratio (OR) 1·77, P = 0·001]. Myeloablative therapy increased the likelihood of childlessness (OR 2·48, P = 0·004). Few attended fertility support services (12%). 24% of men banked sperm and 29% of these used the sample, of which 46% resulted in successful pregnancy. Fertility clinic attendance and sperm storage was more likely post-1990 (OR 4·05, P < 0·001; OR 5·05, P < 0·001 respectively). Reporting a negative impact of cancer on sexual function was more common in women than men (OR 2·20, P < 0·001), and increased with current age and age at diagnosis (by 3-4% per year, P ≤ 0·001) but decreased with longer follow-up (by 2%/year, P = 0·005). Patients on anti-depressants and those reporting cancer-related body change/appearance concerns more frequently reported a negative impact (P < 0·04 and P < 0·03 respectively). These self-reported outcomes confirm literature findings, suggest improvement over time, but highlight a need for involvement of support services.

Objective. The objective of this study was to examine the comorbidity of depressive disorders in patients with chronic facial pain presenting to a multidisciplinary facial pain clinic. Study Design. Data were collected from 72 consecutive patients with chronic facial pain who had received a multidisciplinary evaluation including a psychiatric examination for the presence of depressive disorders. Results. Twenty-eight percent of patients met criteria of the latest Diagnostic and Statistical Manual of Mental Disorders for major depression, and 25% met the criteria for minor depression. A further 22% reported subsyndromal depressive symptoms. Temporomandibular disorders were demonstrable in 71% of these patients, but the remaining 29% had no objective physical findings. There was no statistical difference in comorbidity of depressive disorders in patients with temporomandibular disorders compared with patients without temporomandibular disorders. Conclusion. Screening for symptoms of depression should be an integral part of the evaluation of all patients with chronic facial pain, even when masticatory muscle or temporomandibular joint disorders are identified.

The term 'phantom bite' is used to describe an uncommon condition in which patients are preoccupied with their dental occlusion, believing that it is abnormal. The condition is remarkable for the nature of the involved explanations and interpretations that the patients give and for their persistence in trying to find a solution to what appears to be a relatively minor problem. Three clinical cases that illustrate the nature of this condition are presented and problems associated with the management of affected patients are discussed. Phantom bite can be a disabling disorder which is difficult to treat. Available evidence suggests that the symptoms cannot be improved by occlusal treatments. It is therefore essential to avoid extensive irreversible restorative treatment. General dental practitioners should refer patients for specialist opinion and management. Psychiatric assessment with recommendations for management should be obtained if possible. The prognosis is poor for symptom elimination but need not necessarily be poor for patients' overall functioning and well-being. It is suggested that emphasis should be placed on building adaptive coping skills. Further research is needed to elucidate the nature of the condition to improve treatment.

Large, rare copy number variants (CNVs) have been implicated in a variety of psychiatric disorders, but the role of CNVs in recurrent depression is unclear. We performed a genome-wide analysis of large, rare CNVs in 3106 cases of recurrent depression, 459 controls screened for lifetime-absence of psychiatric disorder and 5619 unscreened controls from phase 2 of the Wellcome Trust Case Control Consortium (WTCCC2). We compared the frequency of cases with CNVs against the frequency observed in each control group, analysing CNVs over the whole genome, genic, intergenic, intronic and exonic regions. We found that deletion CNVs were associated with recurrent depression, whereas duplications were not. The effect was significant when comparing cases with WTCCC2 controls (P=7.7 × 10(-6), odds ratio (OR) =1.25 (95% confidence interval (CI) 1.13-1.37)) and to screened controls (P=5.6 × 10(-4), OR=1.52 (95% CI 1.20-1.93). Further analysis showed that CNVs deleting protein coding regions were largely responsible for the association. Within an analysis of regions previously implicated in schizophrenia, we found an overall enrichment of CNVs in our cases when compared with screened controls (P=0.019). We observe an ordered increase of samples with deletion CNVs, with the lowest proportion seen in screened controls, the next highest in unscreened controls and the highest in cases. This may suggest that the absence of deletion CNVs, especially in genes, is associated with resilience to recurrent depression.Molecular Psychiatry advance online publication, 1 November 2011; doi:10.1038/mp.2011.144.

Objectives: To determine whether patients with treated depression but no other risk factors for coronary heart disease (CHD) have abnormal arterial endothelial function, an abnormality that is common to other acquired risk factors for CHD. Design: Case–control study. Setting: Secondary care departments of cardiology and psychiatry in a single centre and the surrounding community. Participants: Patients with treated depression and matched healthy controls, aged 18–55 years, without conventional acquired risk factors for CHD. These were recruited from local community mental health clinics, general practices, and patient support groups, and through posters placed in public areas of the hospital. Patients had major depression as defined in the American Psychiatric Association’s Diagnostic and statistical manual of mental disorders , fourth edition. Fifteen patients and 12 controls were recruited, and 12 patients and 10 controls completed the study. Outcomes: Brachial artery flow mediated dilatation and baroreflex sensitivity. Results: Arterial endothelial function measured by flow mediated dilatation was impaired in depression (mean (SEM) −0.7% (1.7%)) compared with controls (5.7% (0.9%), p = 0.005 by non-paired t test). Baroreflex sensitivity did not differ significantly between the groups. Conclusion: Arterial endothelial function is impaired in treated depression. This abnormality may contribute to the increased risk of CHD seen in depression.

Background Migraine is a common disorder that often coexists with depression. While a functional polymorphism in methyleneterahydrofolate reductase gene (MTHFR C677T) has been implicated in depression; the evidence to support an association of MTHFR with migraine has been inconclusive. We aim to investigate the effect of this variant on propensity for migraine and to perform a systematic review and meta-analysis of studies of MTHFR and migraine to date. Methods Individuals with migraine (n = 447) were selected from the Depression Case Control (DeCC) study to investigate the association between migraine and MTHFR C677T single nucleotide polymorphism (SNP) rs1801133 using an additive model compared to non-migraineurs adjusting for depression status. A meta-analysis was performed and included 15 studies of MTHFR and migraine. Results MTHFR C677T polymorphism was associated with migraine with aura (MA) (OR 1.31, 95% CI 1.01-1.70, p = 0.039) that remained significant after adjusting for age, sex and depression status. A meta-analysis of 15 case-control studies showed that T allele homozygosity is significantly associated with MA (OR = 1.42; 95% CI, 1.10-1.82) and total migraine (OR = 1.37; 95% CI, 1.07-1.76), but not migraine without aura (OR = 1.16; 95% CI, 0.36-3.76). In studies of non-Caucasian population, the TT genotype was associated with total migraine (OR= 3.46; 95% CI, 1.22-9.82), whereas in studies of Caucasians this variant was associated with MA only (OR = 1.28; 95% CI, 1.002-1.63). Conclusions MTHFR C677T is associated with MA in individuals selected for depression study. A meta-analysis of 15 studies supports this association and demonstrated effects across ethnic groups.

We thank those who agreed to participate in the studies and the many colleagues who contributed to collection and phenotypic characterisation of the clinical samples, to genotyping and to statistical analyses. This study was funded by the Medical Research Council, UK and GlaxoSmithKline (G0701420). The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. This research was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme. Dr Cohen-Woods and Dr Schosser were both funded by Postdoctoral Fellowships from the National Institute for Health Research (NIHR) specialist Biomedical Research Centre for Mental Health. Dr Rucker is funded by a Research Training Fellowship from the Wellcome Trust. The CoLaus/PsyCoLaus study was supported by grants from the Swiss National Science Foundation (# 3200B0-105993, # 3200B0-118308, 33CSC0122661) and from GlaxoSmithKline. S Bergmann is grateful for financial support from the GiorgiCavaglieri Foundation, the Swiss National Science Foundation (Grant # 3100AO-116323/1), the Swiss Institute of Bioinformatics and the European Framework Project 6 (through the AnEuploidy and EuroDia projects)., There is evidence that obesity related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to Body Mass Index (BMI) in two independent samples of major depressive disorder (MDD) cases and controls. We analysed 88 polymorphisms in the FTO gene in a clinically ascertained sample of 2442 MDD cases and 809 controls (Radiant Study). Eight of the top 10 SNPs showing the strongest associations with BMI were followed-up in a population-based cohort (PsyCoLaus Study) consisting of 1292 depression cases and 1690 controls. Linear regression analyses of the FTO variants and BMI yielded 10 SNPs significantly associated with increased BMI in the depressive group but not the control group in the Radiant sample. The same pattern was found in the PsyCoLaus sample. We found a significant interaction between genotype and affected status in relation to BMI for 7 SNPs in Radiant (p, Medical Research Council UK (MRC), GlaxoSmithKline G0701420, European Commission Joint Research Centre LSHB-CT-2003-503428, European Community (EC), National Institute for Health Research (NIHR), Wellcome Trust, Swiss National Science Foundation (SNSF) 3200B0-105993 3200B0-118308 33CSC0122661 3100AO-116323/1, GiorgiCavaglieri Foundation, Swiss Institute of Bioinformatics, European Framework Project, Medical Research Council UK (MRC) G0801418B G0701003 G0701420 G9817803B

The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case–control association samples for 18 common diseases. Here we present the results of a follow-up case–control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A). Within the current study, we attempted to follow-up these findings in a sample from the UK, the Depression Case Control (DeCC) sample consisting of 1,196 cases and 842 screened controls, phenotyped using exactly the same methods as the MP-GSK sample. Performing Cochran–Mantel–Haenzel statistics to test for genotypic and/or allelic differences between the DeCC and MP-GSK samples, we found no significant differences, thus being able to combine the two samples for association testing. In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis.