Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Childhood and later life stressors and increased inflammatory gene expression at older ages.

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists.

Prevalence of dementia in the United States: the aging, demographics, and memory study.

AIM: To estimate the prevalence of Alzheimer's disease (AD) and other dementias in the USA using a nationally representative sample. METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender. RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71-79 years to 37.4% of those aged 90 and older. CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Cost-effectiveness of the lower treatment goal (of JNC VI) for diabetic hypertensive patients. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

BACKGROUND: The recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) to lower blood pressure (BP) in diabetic patients to less than 130/85 mm Hg may have negative economic consequences. A formal cost-effectiveness analysis was therefore performed, comparing the costs and potential benefits of a BP goal of less than 140/90 mm Hg (as recommended by JNC V) vs less than 130/85 mm Hg (as inJNC VI). METHODS: A 24-cell computer model was populated with costs (1996 dollars), relative risks, and age-specific base-line rates for death and 4 nonfatal adverse events (stroke, myocardial infarction, heart failure, and end-stage renal disease), derived from published data. Costs and benefits were discounted at 3%. RESULTS: For 60-year-old diabetic persons with hypertension, treating to the lower BP goal increases life expectancy by 0.48 (discounted) years and lowers (discounted) lifetime medical costs by $1450 compared with treating BP to less than 140/90 mm Hg. The lower treatment BP goal results in an overall cost savings over a wide range of initial conditions, and for nearly all analyses for patients older than 60 years. CONCLUSIONS: Any incremental treatment for 60-year-olds that costs less than $414 annually and successfully lowers BP from below 140/90 to below 130/85 mm Hg would be cost saving in the long term, due to the reduction in attendant costs of future morbidity. The lower treatment goal recommended for high-risk hypertensive patients compares favorably in cost-effectiveness with many other frequently recommended treatment strategies, and saves money overall for patients aged 60 years and older.

Comparative cost-effectiveness of HMG-CoA reductase inhibitors in secondary prevention of acute myocardial infarction.

The cost-effectiveness of each of the six hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors currently available was studied. For a cohort of patients between the ages of 60 and 85 years with coronary heart disease (CHD) who were taking atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, or simvastatin, the number of survivors, the annual direct cost per survivor, and the annual indirect cost saving per survivor associated with the predicted reduction in the rate of nonfatal myocardial infarction recurrences were projected. Percent reductions in excess mortality due to CHD were derived from the relative risks of cardiac mortality in treatment versus control groups in the Scandinavian Simvastatin Survival Study (4S). Doses necessary to provide a long-term 35.57% reduction in low-density- lipoprotein (LDL) cholesterol, as seen in 4S, were estimated. One-way sensitivity analyses were performed to assess the importance of the baseline assumptions. The cost per year of life saved ranged from $5,421 with atorvastatin to $15,073 with lovastatin. The patient's age at time of diagnosis of CHD had a major impact on the cost-effectiveness of the drugs; cost-effectiveness per year of life saved was higher for older patients than younger patients. The six currently marketed HMG-CoA reductase inhibitors varied widely in cost and effectiveness in producing reductions in the LDL-cholesterol concentrations that have been shown to prevent recurrent MI; there was an approximately threefold difference in the cost per year of life saved between the most cost-effective and least cost-effective agents.

Cohort parity analysis: statistical estimates of the extent of fertility control.

Cohort parity analysis (CPA) is a method for indirect measurement of the extent and timing of the adoption of fertility control within marriage. It uses information on the parity distribution of a cohort of women of specified marriage ages and durations. A multinomial model of parity provides a convenient framework for the computation of distributional parameters describing the extent to which marital fertility control has been accepted and characterizing the way control has been used within specific durations of marriage. This leads to a pair of easily implemented formulas for upper- and lower-bound estimates of the expected proportion of the population ever controlling and the distribution of controllers by parity. The power of CPA is illustrated, using census data for currently married couples in Dublin, Belfast, and other county boroughs of Ireland in 1911.