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

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

Quick assessment of hopelessness: a cross-sectional study

BACKGROUND: Lengthy questionnaires reduce data quality and impose a burden on respondents. Previous researchers proposed that a single item ("My future seems dark to me") and a 4-item component of the Beck's Hopelessness Scale (BHS) can summarise most of the information the BHS provides. There is no clear indication of what BHS cutoff values are useful in identifying people with suicide tendency. METHODS: In a population-based study of Chinese people aged between 15 and 59 in Hong Kong, the Chinese version of the BHS and the Centre for Epidemiologic Studies – Depression scale were administered by trained interviewers and suicidal ideation and suicidal attempts were self-reported. Receiver operating characteristics curve analysis and regression analysis were used to compare the performance of the BHS and its components in identifying people with suicidality and depression. Smoothed level of suicidal tendency was assessed in relation to scores on the BHS and its component to identify thresholds. RESULTS: It is found that the 4-item component and, to a lesser extent, the single item of the BHS perform in ways similar to the BHS. There are non-linear relationship between suicidality and scores on the BHS and the 4-item component; cutoff values identified accordingly have sensitivity and specificity of about 65%. CONCLUSION: The 4-item component is a useful alternative to the BHS. Shortening of psycho-social measurement scales should be considered in order to reduce burden on patients or respondents and to improve response rate

Malaria and obesity: obese mice are resistant to cerebral malaria

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A multicenter study on Leigh syndrome : disease course and predictors of survival

Peer reviewe

Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.Peer reviewe