Severity of Depression Predicts Remission Rates Using Transcranial Magnetic Stimulation

Background: Multiple factors likely impact response and remission rates in the treatment of depression with repetitive transcranial magnetic stimulation (rTMS). Notably the role of symptom severity in outcomes with rTMS is poorly understood.Objective/Hypothesis: This study investigated the predictors of achieving remission in patients suffering from depression who receive ≥3 rTMS treatments per week. Methods: Available data on 41 patients treated at Walter Reed National Military Medical Center from 2009 to 2014 were included for analysis. Patients received a range of pulse sequences from 3,000 to 5,000 with left sided or bilateral coil placement. Primary outcome measures were total score on the Patient Health Questionnaire (PHQ-9) or the Quick Inventory of Depressive Symptomatology—Self Rated (QIDS-SR). Remission was defined as a total score less than five, and response was defined as a 50% decrease in the total score on both outcome metrics. Outcomes in patients diagnosed as suffering from mild or moderate depression were compared to those suffering from severe depression. Results: Of the 41 patients receiving treatment, 16 reached remission by the end of treatment. Remission rate was associated with the initial severity of depression, with patients with mild or moderate depression reaching remission at a significantly higher rate than those with severe depression. Total number of rTMS sessions or length of treatment were not predictors of remission. Conclusion: Patients with a baseline level of depression characterized as mild or moderate had significantly better outcomes following rTMS compared to patients with severe depression

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Iraq War Clinician Guide 50 Traumatized Amputee VI. Treating the Traumatized Amputee

Although injuries resulting from war produce many turbulent and confused emotions, the needs of those who suffer amputations are unique. Amputation or blindness results in a loss of body function and is an insult to the patient&apos;s psychological sense of body integrity and competence. In addition to the loss of body parts, service members often must endure other injuries, as well as psychological traumas. Fear of persistent threats, anxiety related to military career curtailment, and reactions to other past overwhelming experiences may all contribute to the complex turmoil with which they struggle. Any of the above by itself is enough to overwhelm one’s psychological equilibrium. Combined with the loss of a limb, eye, or other body part, additional trauma can be exceptionally devastating. Caring for the amputee patient requires a biopsychosocial approach. The initial clinical focus is rightly on medical stabilization. Follow-on rehabilitation focuses on restoring the individual to the greatest physical, psychological, social and economic functioning possible (Haslam et al., 1960; Mendelson, Burech, Phillips, &amp; Kappel, 1986). A successful team approach to rehabilitation includes the patient, physicians, nurses, therapists, and family members working together to create short and long term goals for the patient’s rehabilitation. As the medical injury stabilizes, attention must shift to ensure the psychological well being of the patient and the support of his/her confident reintegration into society. This chapter focuses on the unique psychological needs of the amputee patient. A brief review of the literature on treatment of amputee patients is provided. As members of the Walter Reed Army Medical Center Psychiatry Consultation Liaison Service (WRAMC PCLS) at the military medical center receiving the majority of amputees from Operation Iraqi Freedom, we provide a description of the amputee population treated and the therapeutic practices that have appeared to be most successfully implemented

Differential Enzymatic Activity of Common Haplotypic Versions of the Human Acidic Mammalian Chitinase Protein*

Mouse models have shown the importance of acidic mammalian chitinase activity in settings of chitin exposure and allergic inflammation. However, little is known regarding genetic regulation of AMCase enzymatic activity in human allergic diseases. Resequencing the AMCase gene exons we identified 8 non-synonymous single nucleotide polymorphisms including three novel variants (A290G, G296A, G339T) near the gene area coding for the enzyme active site, all in linkage disequilibrium. AMCase protein isoforms, encoded by two gene-wide haplotypes, and differentiated by these three single nucleotide polymorphisms, were recombinantly expressed and purified. Biochemical analysis revealed the isoform encoded by the variant haplotype displayed a distinct pH profile exhibiting greater retention of chitinase activity at acidic and basic pH values. Determination of absolute kinetic activity found the variant isoform encoded by the variant haplotype was 4-, 2.5-, and 10-fold more active than the wild type AMCase isoform at pH 2.2, 4.6, and 7.0, respectively. Modeling of the AMCase isoforms revealed positional changes in amino acids critical for both pH specificity and substrate binding. Genetic association analyses of AMCase haplotypes for asthma revealed significant protective associations between the variant haplotype in several asthma cohorts. The structural, kinetic, and genetic data regarding the AMCase isoforms are consistent with the Th2-priming effects of environmental chitin and a role for AMCase in negatively regulating this stimulus

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways