Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects.

To identify the genomic regions that confer risk and protection for major depressive disorder (MDD) in humans, large-scale studies are needed. Such studies should collect multiple phenotypes, DNA, and ideally, biological material that allows gene expression analysis, transcriptomic, proteomic, and metabolomic studies. In this paper, we briefly review linkage studies of MDD and then describe the large-scale nationwide biological sample collection in Dutch twin families from the Netherlands Twin Register (NTR) and in participants in the Netherlands Study of Depression and Anxiety (NESDA). Within these studies, 1862 participants with a diagnosis of MDD and 1857 controls at low liability for MDD have been selected for genome-wide genotyping by the US Foundation for the National Institutes of Health Genetic Association Information Network. Stage 1 genome-wide association results are scheduled to be accessible before the end of 2007. Genome-wide association results are open-access and can be viewed at the dbGAP web portal (http://www.ncbi.nlm.nih.gov). Approved users can download the genotype and phenotype data, which have been made available as of 9 October 2007

Modeling the Cost-Effectiveness of Health Care Systems for Alcohol Use Disorders: How Implementation of eHealth Interventions Improves Cost-Effectiveness

Background: Informing policy decisions about the cost-effectiveness of health care systems (ie, packages of clinical interventions) is probably best done using a modeling approach. To this end, an alcohol model (ALCMOD) was developed. Objective: The aim of ALCMOD is to estimate the cost-effectiveness of competing health care systems in curbing alcohol use at the national level. This is illustrated for scenarios where new eHealth technologies for alcohol use disorders are introduced in the Dutch health care system. Method: ALCMOD assesses short-term (12-month) incremental cost-effectiveness in terms of reductions in disease burden, that is, disability adjusted life years (DALYs) and health care budget impacts. Results: Introduction of new eHealth technologies would substantially increase the cost-effectiveness of the Dutch health care system for alcohol use disorders: every euro spent under the current system returns a value of about the same size (€ 1.08, ie, a "surplus" of 8 euro cents) while the new health care system offers much better returns on investment, that is, every euro spent generates € 1.62 in health-related value. Conclusion: Based on the best available evidence, ALCMOD's computations suggest that implementation of new eHealth technologies would make the Dutch health care system more cost-effective. This type of information may help (1) to identify opportunities for system innovation, (2) to set agendas for further research, and (3) to inform policy decisions about resource allocation

The contribution of major depression to the global burden of ischemic heart disease: A comparative risk assessment

Background: Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. Methods: A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010.Results: The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. Conclusions: The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event