Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic

glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or halpotypes associated with the particular candidate gene loci in these EPZ004777 concentration illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in CBL0137 SZ and BD as well as their relationships with clinical presentations and treatment progress over time. (C) 2010 Elsevier

Ltd. All rights reserved.”
“Although both obesity and the metabolic syndrome (MetS) are known risk factors for decline in physical function, the joint association of obesity and metabolic alterations with risk of incident mobility limitation is unknown.

Data are from 2,984 women and men aged 70-79 years participating in the Health, Aging, and Body Composition Study

without mobility limitation at baseline. Obesity was defined as body mass index greater than or equal Selleckchem GKT137831 to 30 kg/m(2) and the MetS as meeting greater than or equal to 3 of the ATP III criteria. Mobility limitation was defined as any difficulty walking one-quarter mile or climbing 10 steps during two consecutive semiannual assessments for more than 6.5 years.

Incidence of mobility limitation was 55% in women and 44% in men. In women, adjusted risk of developing mobility limitation was progressively greater in nonobese participants with the MetS (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.24-1.80), obese participants without the MetS (HR = 1.95, 95% CI = 1.51-2.53), and obese participants with the MetS (HR = 2.16, 95% CI = 1.78-2.63) relative to the nonobese without the MetS. In men, the corresponding adjusted HRs (95% CI) were 1.07 (0.87-1.32), 1.64 (1.19-2.25), and 1.41 (1.12-1.78). Elevated inflammatory markers partly explained the association between obesity, the MetS, and mobility limitation, particularly in nonobese and obese participants with the MetS.

Obesity itself, independent of its metabolic consequences, is a risk factor for mobility limitation among obese older adults. In addition, having the MetS increases the risk of functional decline in older nonobese women but not in men.