Efficacy of Electrical Stimulation Intervention in Treating Adults with Dysphagia: A Systematic Review

Purpose: Dysphagia is a term used for a swallowing disorder resulting from problems with the oral cavity, pharynx, esophagus, or gastroesophageal junction. Dysphagia can have significant impacts on an individual’s quality of life and statistics suggest that nearly 15 million adults in the United States present with swallowing disorders. Common medical complications associated with dysphagia are malnutrition, dehydration, aspiration pneumonia, and even death. Traditional dysphagia treatment (TDT) for adults currently consists of diet modification, compensatory strategies involving postural adjustments, and swallowing exercises to strengthen musculature. The objective of this systematic review is to determine whether electrical stimulation (ES) improves swallowing function in adults with dysphagia. Methodology: Four indexed databases were searched to obtain studies pertaining to the use of ES in dysphagia treatment and its success. Application of inclusionary and exclusionary criteria narrowed the results and relevant studies were selected for this systematic review. Studies were also hand-selected and appraised for validity to ensure minimal bias. Results: Results of the selected studies revealed varying statistically significant effects of ES as a treatment for adults with dysphagia. However, many studies suggest ES is most effective in producing positive outcomes when coupled with TDT. Conclusion: The results of the systematic review suggest efficacy of ES is highest when it is used in conjunction with TDT. Studies with statistically significant results reported on only a minor improvement with ES. None of the studies reported negative outcomes related to ES. Additional research is needed to determine overall efficacy of ES as an evidence-based intervention for adults with dysphagia resulting from various etiologies.https://scholarworks.uvm.edu/csdms/1005/thumbnail.jp

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Identification of common genetic risk variants for autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation (Molecular Psychiatry, (2018), 10.1038/s41380-018-0112-7)

textabstractFollowing publication, the authors noticed that ‘Laura Cantwell’, ‘Otto Valladares’, and ‘Li-San Wang’ were inadvertently omitted from the author list. These authors have now been added to the author list in 21st, 77th, and 79th position, respectively. This has been corrected in both the PDF and HTML versions of the article

Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation (Molecular Psychiatry, (2018), 10.1038/s41380-018-0112-7)

Following publication, the authors noticed that ‘Laura Cantwell’, ‘Otto Valladares’, and ‘Li-San Wang’ were inadvertently omitted from the author list. These authors have now been added to the author list in 21st, 77th, and 79th position, respectively. This has been corrected in both the PDF and HTML versions of the article

Mol Psychiatry

The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 x 10(-7)), an immunoglobulin gene whose antibodies interact with beta-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 x 10(-7)), and a zinc-finger protein ZNF655 (gene-based p = 5.0 x 10(-6)). The latter two suggest an important role for transcriptional regulation in AD pathogenesis

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

International audienceAutism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways