Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study.

BACKGROUND: Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson's disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. METHODS: We genotyped a prioritized noncoding variant in SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. RESULTS: The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio, 1.40; P = .0032). CONCLUSIONS: This result increases confidence in the notion that in many clinically well-characterized patients, genetic variation in SNCA contributes to "sporadic" disease.

Integrated behavioral health practice facilitation in patient centered medical homes: A promising application.

INTRODUCTION: The purpose of this study was to assess the degree of behavioral health (BH) integration change in patient-centered medical homes (PCMHs) when using a practice facilitator (PF) specially trained in implementing integrated care and how a quasi-experimental design assists in this process. METHOD: Twelve PCMHs, 8 Federally Qualified Health Centers and 4 private practices, with varying degrees of BH services participated in this study. The degree of BH integration was assessed with a quasi-experimental design using the Maine Health Access Foundation's Site Self Assessment (MeHAF SSA) at baseline and after implementing site-specific BH services. The sites tracked completion of unique objectively measured goals being implemented using the Goal Attainment Scale (GAS) score. RESULTS: At the conclusion of the study, sites saw a statistically significant increase in the level of BH integration from a baseline of 2.73 (SD = 0.44) to a postintervention score of 3.49 (SD = 0.22) with improvements from mild-moderate overall integration to moderate-advanced overall integration (p < .001). In addition, 10 out of the 12 sites achieved successful implementation of unique goals with assistance from the PF. DISCUSSION: This study provides the first quasi-experimental/pretest-posttest evidence utilizing real-world data that the practice facilitation method is an effective solution toward increasing the degree of BH integration. This paper describes the real-world efforts to evaluate the degree of BH integration change in PCMHs when using a PF with content expertise in BH integration within primary care. (PsycINFO Database Record

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson's disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson's disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson's disease identifies PGC-1α as a potential therapeutic target for early intervention.