Kalsi G.,Virginia Commonwealth University |
Kuo P.-H.,National Taiwan University |
Aliev F.,Virginia Commonwealth University |
Aliev F.,Ankara University |
And 14 more authors.
Human Molecular Genetics | Year: 2010
Studies of alcohol dependence (AD) have consistently found evidence of linkage on chromosome 4q21-q32. A genome-wide linkage scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample also provided its strongest evidence of linkage on chromosome 4q22-q32 using an index of AD severity based on the count of DSM-IV AD symptoms (ADSX; LOD 5 4.59). We conducted a systematic, gene-centric association study using 518 LD-tagging single nucleotide polymorphisms (SNPs) in the 65 known and predicted genes within the 1-LOD interval surrounding the linkage peak. Case-only regression analysis with the quantitative variable of ADSX was performed in the 562 genetically independent cases; nominal support for association was demonstrated by 32 tagging SNPs in 14 genes. We did not observe study-wide significance, but gene-wise correction for multiple testing with the Nyholt procedure yielded empirical evidence of association with two genes, DKK2 (dickkopf homolog 2) (P 5 0.007) and EGF (epidermal growth factor) (P 5 0.025) in the IASPSAD sample. Three SNPs in DKK2 (rs427983; rs419558; rs399087) demonstrated empirical significance. Assessment of possible replication in 847 cases of European descent from a large independent sample, the Collaborative Study of the Genetics of Alcoholism, yielded replication for DKK2 but not EGF. We observed genotypic and phenotypic replication for DKK2 with the three SNPs yielding significant association with ADSX in the IASPSAD sample. Haplotype-specific expression measurements in post-mortem tissue samples suggested a functional role for DKK2. This evidence notwithstanding, replication is needed before confidence can be placed in these findings. © The Author 2010. Published by Oxford University Press. All rights reserved.
Aas M.,University of Oslo |
Blokland G.A.M.,Harvard University |
Blokland G.A.M.,The Broad Institute of MIT and Harvard |
Chawner S.J.R.A.,University of Cardiff |
And 26 more authors.
Psychiatric Genetics | Year: 2016
The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Escobedo A.A.,Academic Paediatric Hospital Pedro Borras |
Escobedo A.A.,Aberdeen Group |
Ballesteros J.,University of the Basque Country |
Gonzalez-Fraile E.,Institute of Psychiatric Research |
Almirall P.,Committee on Clinical Parasitology
Acta Tropica | Year: 2016
Metronidazole is frequently used against Giardia infection; however, it has been associated with significant failure rates in clearing parasites from the gut; additionally, as it should be taken for 5 to 10 days, it is associated with poor compliance, probably due to side effects. Other drugs, including tinidazole (TNZ) and albendazole (ABZ) have been included in the antigiardial armamentarium. Our aim was to assess the efficacy of ABZ compared with TNZ in Giardia infections in children. A systematic review and a meta-analysis were carried out. PubMed, Medline, EMBASE, CENTRAL, and LILACS were searched electronically until February 2015. Also relevant journals and references of studies included therein were hand-searched for randomised controlled trials (RCTs). The meta-analysis was limited to RCTs evaluating the use of ABZ compared with TNZ in children with Giardia infection. The assessed outcome was parasitological efficacy. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Five RCTs including 403 children were included. Overall, TNZ significantly outperformed ABZ without differences between subgroups defined by ABZ dosages [relative risk, (RR) 1.61 (95% CI): (1.40-1.85); P<0.0001]. The 95% prediction interval range is 1.28-2.02. There was no significant heterogeneity (I2=0%; Q-test of heterogeneity P=0.4507. The number-needed-to-treat, the average number of patients who need to be treated with TNZ to gain one additional good outcome as compared with ABZ was 4, 95% CI: 3-5. Our results show that TNZ outperforms ABZ in the treatment of Giardia infections in children from developing countries. © 2015 Elsevier B.V.
MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of alzheimer disease subjects
Long J.M.,Institute of Psychiatric Research |
Ray B.,Institute of Psychiatric Research |
Lahiri D.K.,Institute of Psychiatric Research |
Lahiri D.K.,Indiana University
Journal of Biological Chemistry | Year: 2014
Background: BACE1 is the rate-limiting enzyme in the synthesis of Aβ from amyloid precursor protein. Results: Human miR-339-5p negatively regulates BACE1 and Aβ in human brain cultures and is reduced in AD specimens. Conclusion: Human miR-339-5p physiologically regulates human BACE1 protein expression and Aβ and is dysregulated in the AD brain. Significance: miR-339-5p represents a novel drug target in AD. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Martin-Carrasco M.,Institute of Psychiatric Research |
Martin-Carrasco M.,Research Center en Red Salud Mental |
Evans-Lacko S.,Institute of Psychiatry |
Evans-Lacko S.,The London School of Economics and Political Science |
And 9 more authors.
European Archives of Psychiatry and Clinical Neuroscience | Year: 2016
This European Psychiatric Association (EPA) guidance paper is a result of the Working Group on Mental Health Consequences of Economic Crises of the EPA Council of National Psychiatric Associations. Its purpose is to identify the impact on mental health in Europe of the economic downturn and the measures that may be taken to respond to it. We performed a review of the existing literature that yields 350 articles on which our conclusions and recommendations are based. Evidence-based tables and recommendations were developed through an expert consensus process. Literature dealing with the consequences of economic turmoil on the health and health behaviours of the population is heterogeneous, and the results are not completely unequivocal. However, there is a broad consensus about the deleterious consequences of economic crises on mental health, particularly on psychological well-being, depression, anxiety disorders, insomnia, alcohol abuse, and suicidal behaviour. Unemployment, indebtedness, precarious working conditions, inequalities, lack of social connectedness, and housing instability emerge as main risk factors. Men at working age could be particularly at risk, together with previous low SES or stigmatized populations. Generalized austerity measures and poor developed welfare systems trend to increase the harmful effects of economic crises on mental health. Although many articles suggest limitations of existing research and provide suggestions for future research, there is relatively little discussion of policy approaches to address the negative impact of economic crises on mental health. The few studies that addressed policy questions suggested that the development of social protection programs such as active labour programs, social support systems, protection for housing instability, and better access to mental health care, particularly at primary care level, is strongly needed. © 2016, Springer-Verlag Berlin Heidelberg.