Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear. To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade. A study was performed with a nested case–control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression. Incident PCa and subtype by stage and grade. Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02–1.26], ptrend = 0.018, for folate and 1.12 [95% CI, 1.01–1.25], ptrend = 0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity < 0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28–4.12]; ptrend = 0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity > 0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation. The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation. Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.

Abstract Obsessive-compulsive disorder and related disorders (OCRDs) constitute some of the most important conditions in psychiatry. Obsessive-compulsive disorder (OCD) is one of the most prevalent and disabling of the psychiatric disorders and comprises a paradigmatic exemplar of a neuropsychiatric disorder, providing translational research with a unique opportunity to develop an integrated cognitive-affective neuroscience approach to psychiatric disorder. In the recent revision of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), OCD is now grouped within a new chapter on obsessive-compulsive and related disorders, together with body dysmorphic disorder, hoarding disorder, trichotillomania (hair-pulling disorder), and excoriation (skin-picking) disorder. There is a growing database of randomized controlled trials of treatment of OCD and OCRDs, allowing for an evidence-based approach to their management. This volume will summarize the phenomenology, pathogenesis, pharmacotherapy, and psychotherapy of OCD and related disorders.

Symmetry symptoms have some distinct clinical features and may represent a marker of severity in OCD. However, clinical associations, in combination with the association found with the ANKK1 rs1800497 A2 variant, suggest that primary symmetry symptoms may represent a distinctive clinical and psychobiological profile.

Folic acid substitution before and/or during pregnancy does not increase the short-term overall maternal cancer risk.

Although PTSD is a relatively rare outcome of life-threatening MVCs, a substantial minority of PTSD cases occur among the relatively small proportion of people with highest predicted risk. This raises the question whether MVC-related PTSD could be reduced with preventive interventions targeted to high-risk survivors using models based on predictors assessed in the immediate aftermath of the MVCs.

Preschool children often show total expiration times of less than one second in pulmonary function tests. Therefore, FEV1 cannot be used for evaluation of obstructive pulmonary diseases in small children. Aex, the area under the expiratory flow-volume loop, does not depend on the expiration time. The Aex value varies according to the convex or concave shape of the flow volume loop, can be quantified and is a valuable parameter in the diagnosis of obstructive airway diseases.In this study FEV1 und Aex values of 19882 flow-volume loops were measured and compared. The comparison shows a very high correlation coefficient of r = 0.99.The changes of both parameters in an individual after provocation or bronchospasmolysis also demonstrate a strong correlation. A 20 % change of FEV1 equals an Aex change of 36 %.We conclude that measuring Aex is a good alternative to measuring FEV1 especially if the FEV1 cannot be obtained due to short expiration times.

We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.

Abstract Behavioural therapy is effective in both adult and paediatric obsessive–compulsive disorder (OCD). Exposure therapy is a key component of behavioural therapy. Cognitive interventions may also play a role in the treatment of OCD. It is useful to obtain a patient’s explanatory model of their disorder. Both pharmacotherapy and psychotherapy reverse striatal dysfunction in OCD.

This finding corroborates and extends the understanding of anxiety in various forms as a risk factor for IHD. New evidence of negative consequences over time underlines the importance of proper diagnosis and treatment for health anxiety.

Khan and Brown's work 1 on public domain data from the archives of the U.S. Food and Drug Administration (FDA) emphasizes that drug-placebo differences in recent antidepressant trials are smaller than in early investigations, and draws a number of conclusions about the nature of clinical depression and optimal trial design. Several relevant issues in regards to this and related work on drug-placebo differences in psychiatry research may be worth emphasizing. First, it is important for psychiatry to steer an even course between the polar positions of scientism and scepticism. Mental disorders such as depression are not analogous to squares; they are not natural kinds that can simply be defined using necessary and sufficient criteria (2, 3; see also 4 in this issue of the journal). At the same time, mental disorders are not social constructions that are solely determined by socio-political considerations, and that therefore differ wholly from time to time and place to place. While efforts such as the Research Domain Criteria (RDoC), which aim to ground psychiatric constructs in translational neuroscience, may help lead to advances in psychiatric nosology and clinical trials over the long term 5, iterative improvements of diagnostic criteria and guidelines will anchor clinical practice and interventional research for now and for the foreseeable future 6. Second, it is relevant to note that psychiatry's approach to mental disorders has a great deal in common with the rest of medicine's approach to physical disorders. The rest of medicine accepts that many conditions are best conceptualized as syndromes 7. Arguably, psychiatry has led the way in terms of providing valid, reliable and useful approaches to the diagnosis of medical conditions where simple biomarkers are not available or helpful 8. While the introduction of paradigm-shifting innovations and personalized medicine initiatives in clinical trials methodology for interventional research in psychiatry may occur over time, in the shorter term we can more certainly expect iterative improvements (perhaps including ideas emphasized by Khan and Brown, such as limiting the number of sites and treatment arms) to FDA and European Medicines Agency (EMA) guidelines for undertaking pivotal clinical trials. Third, it is crucial to emphasize that a broad range of causal mechanisms are likely involved in the pathogenesis and treatment of mental disorders such as depression 9. Not surprisingly, any specific pharmacological agent, acting on only a limited subset of such mechanisms, may have a relatively low effect size, particularly when inclusion criteria lead to investigation of a heterogeneous phenotype. Antidepressant effect sizes may, however, be higher for some narrower phenotypes (e.g., melancholic depression) that are often excluded from clinical trials (e.g., due to characteristic suicidal ideation). Such effect sizes may also differ in the U.S. and Europe, for a range of reasons 10. Furthermore, effect sizes for psychiatric treatments are as least as high as those in the rest of medicine 11, 12. Steering a course between scientism and scepticism also means finding a balance between over-optimism and over-pessimism with regards to psychiatry in general and antidepressants in particular. We need to acknowledge the enormous advances made in psychopharmacological research over the past several decades, while also emphasizing that there remain significant needs and opportunities for better understanding the relevant proximal and distal psychobiology of mental disorders, for better implementing and scaling-up available treatments, and for more efficacious and effective drugs 13. The level of liquid in our glass is arguably at 50%, and we need to deal with this reality accordingly. Steering a course between scientism and scepticism may also impact our perspective on the placebo response. The reliance of modern clinical research on randomized placebo-controlled trials has led to an ever growing database demonstrating that placebo is a remarkably powerful intervention for a range of psychiatric and medical conditions, including milder cases of depression 14, 15. This should not be cause for embarrassment or despair for psychiatry, but rather an impetus for research on the underlying psychobiology of the placebo response, and on how to better harness such effects in clinical practice 16. Further advances in this direction would arguably help ensure that our glass is more than half-full.