Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex.

Rhesus D incompatibility increases risk for schizophrenia, with some evidence that risk is limited to male offspring. The purpose of this study is to determine whether risk for schizophrenia due to Rhesus D incompatibility differs by offspring sex using a nuclear family-based candidate gene approach and a meta-analysis approach. The genetic study is based on a sample of 277 nuclear families with RHD genotype data on at least one parent and at least one child diagnosed with schizophrenia or related disorder. Meta-analysis inclusion criteria were (1) well-defined sample of schizophrenia patients with majority born before 1970, (2) Rhesus D incompatibility phenotype or genotype data available on mother and offspring, and by offspring sex. Two of ten studies, plus the current genetic study sample, fulfilled these criteria, for a total of 358 affected males and 226 affected females. The genetic study found that schizophrenia risk for incompatible males was significantly greater than for compatible offspring (p=0.03), while risk for incompatible and compatible females was not significantly different (p=.32). Relative risks for incompatible males and females were not significantly different from each other. Meta-analysis using a larger number of affected males and females supports their difference. Taken together, these results provide further support that risk of schizophrenia due to Rhesus D incompatibility is limited to incompatible males, although a weak female incompatibility effect cannot be excluded. Sex differences during fetal neurodevelopment should be investigated to fully elucidate the etiology of schizophrenia

The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

<b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISCI1, NDE1,NDEL1, PDE4B and PDE4D, the 'DISCI network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10 -year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 x 10(-8)), located on a non -coding exon of NDE1. Variants within the NM. locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the IVDET locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.Peer reviewe

Problem solving ability and repetition of deliberate self-harm: a multicentre study.

Background. While recent studies have found problem-solving impairments in individuals who engage in deliberate self-harm (DSH), few studies have examined repeaters and non-repeaters separately. The aim of the present study was to investigate whether specific types of problem-solving are associated with repeated DSH. Method. As part of the WHO/EURO Multicentre Study on Suicidal Behaviour, 836 medically treated DSH patients (59% repeaters) from 12 European regions were interviewed using the European Parasuicide Study Interview Schedule (EPSIS II) approximately 1 year after their index episode. The Utrecht Coping List (UCL) assessed habitual responses to problems. Results. Factor analysis identified five dimensions – Active Handling, Passive-Avoidance, Problem Sharing, Palliative Reactions and Negative Expression. Passive-Avoidance – characterized by a pre-occupation with problems, feeling unable to do anything, worrying about the past and taking a gloomy view of the situation, a greater likelihood of giving in so as to avoid difficult situations, the tendency to resign oneself to the situation, and to try to avoid problems – was the problem-solving dimension most strongly associated with repetition, although this association was attenuated by self-esteem. Conclusions. The outcomes of the study indicate that treatments for DSH patients with repeated episodes should include problem-solving interventions. The observed passivity and avoidance of problems (coupled with low self-esteem) associated with repetition suggests that intensive therapeutic input and follow-up are required for those with repeated DSH

Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Selection Bias in a Study of Implantable Defibrillator Patients: The Role of Type D Personality

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Selection bias constitutes a major issue in research using volunteers as study participants. Purpose We examined whether research in partners may affect participation rates of implantable cardioverterdefibrillator (ICD) patients with a Type D personality (joint presence of negative affectivity and social inhibition). Method Patients who underwent ICD implantation between May 2003 and November 2007, and who had a partner, were included (n=440). In September 2005, a substudy on partners of ICD patients was added (n=276 patients). Results The proportion Type D patients after the start of the partner substudy was significantly lower as compared to the proportion before this substudy (17.5 % versus 28.8%; p= 0.006). Patients who participated following the start of the partner substudy were less likely to have a Type D personality (OR=0.44; p=0.002), adjusting for possible confounders. In the partner substudy, nonparticipation was more prevalent among partners of Type D patients as compared to partners of non-Type D patients (20.4 % versus 10.1%; p=0.044). Partner nonparticipation was marginally significantly associated with Type D personality of the patient (OR=2.13; p=0.083), adjusting for confounders. Conclusions The addition of a partner substudy may be related to a decreased proportion of participants with a Type D personality. Nonparticipation was more prevalent among partners of Type D patients. These observations may influence results of studies, as Type Ds tend to be less healthy

MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability

Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function. Accordingly, fibroblasts of affected individuals from one family demonstrated severe depletion of GANP. GANP has been described to function as an mRNA export factor, and to suppress TDP-43-mediated motor neuron degeneration in flies. Thus our results suggest defective mRNA export from nucleus as a potential pathogenic mechanism of axonal degeneration in these patients. The identification of MCM3AP variants in affected individuals from multiple centres establishes it as a disease gene for childhood-onset recessively inherited Charcot-Marie-Tooth neuropathy with intellectual disability.Peer reviewe

Secondary Prevention of Suicide

Leo Sher and colleagues discuss recent research on interventions to prevent secondary suicide and discuss the additional research that is needed