Lakshika Tennakoon

HPA axis genetic variation, cortisol and psychosis in major depression.

Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h (r2=0.288) and from 0100 to 0900 h (r2=0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.

Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol

The neuropeptide oxytocin (OT) promotes social behavior and attenuates stress responsivity in mammals. Recent clinical evidence suggests OT concentrations may be dysregulated in major depression. This study extends previous research by testing whether: 1) OT concentrations vary systematically in depressive disorders with and without hypercortisolemia, 2) gender differences in OT concentrations are observed in depressed vs. healthy control participants, and 3) OT concentrations are predictive of clinical phenotypes. Plasma OT concentrations of psychotic major depressive (PMD; n = 14: 10 female, 4 male), non-psychotic major depressive (NPMD; n = 17: 12 female, 5 male), and non-depressed, healthy control (n = 19: 11 female, 8 male) participants were assayed at 2000, 2400, 0400, and 0800 h. Plasma cortisol concentrations were quantified at 2300 h, and clinical phenotypes were determined. As expected, PMD participants, compared to NPMD and healthy control participants, showed higher plasma cortisol concentrations. Although both depressed groups showed similar OT concentrations, a significant interaction effect between group and gender was observed. Specifically, depressed females exhibited lower mean OT concentrations than depressed males. Further, depressed vs. healthy control female participants exhibited lower mean OT concentrations, whereas depressed vs. healthy control male participants showed a trend in the opposite direction. OT concentrations were also predictive of desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III. All findings were independent of cortisol. These data suggest that OT signaling may provide a mechanism by which to better understand female-biased risk to develop depressive disorders and that plasma OT concentrations may be a useful biomarker of certain clinical phenotypes.

Ontology driven data integration for autism research

Autism Spectrum Disorder is an inherently complex phenomenon requiring large studies of many different types to further understanding of its causes. The National Database for Autism Research (NDAR) is being constructed to aid in this effort by providing a means for researchers to share and integrate data. An autism ontology drafted by a group at Stanford is being incorporated for use by NDAR to allow semantic data integration. The architecture upon which NDAR is built — the UCSD Developed Data Integration Environment — supports the use of this autism ontology, including annotation of data with ontological concepts and ontology enhanced queries on databases, both central and federated.

ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression

The hypothesis that allelic variation in the multidrug resistance-1 (MDR1 or ABCB1) gene encoding the P-glycoprotein (P-gp) blood–brain barrier efflux pump is associated with remission and side effects was tested in chronic major depression patients treated with P-gp substrates. In 83 patients from the REVAMP trial, frequency of and time to remission as well as side effects was tested among genotype groups at 6 ABCB1 single nucleotide polymorphisms (SNPs). These six SNPs are significantly associated with remission and time to remission, with minor allele carriers on rs2235040 and rs9282564 attaining statistical significance after controlling for the other ABCB1 SNPs. The six ABCB1 SNPs are also significantly associated with the average side effects. However, here common homozygotes on rs2235040 and rs9282564 demonstrated significantly higher side effects after controlling for the effects of the other ABCB1 SNPs. These findings confirm and extend previous observations that minor alleles of two ABCB1 SNPs predict remission to treatment with substrates and demonstrate that common homozygotes on these SNPs experience greater side effects. Results point to the potential importance of ABCB1 variation for personalized medicine approaches to treating depression.

Costs and Financial Burden of Initial Hospitalizations for Firearm Injuries in the United States, 2006–2014

Objectives To quantify the inflation-adjusted costs associated with initial hospitalizations for firearm-related injuries in the United States. Methods We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify patients admitted for firearm-related injuries from 2006 to 2014. We converted charges from hospitalization to costs, which we inflation-adjusted to 2014 dollars. We used survey weights to create national estimates. Results Costs for the initial inpatient hospitalization totaled

Decreased hypothalamic functional connectivity with subgenual cortex in psychotic major depression.

6.61 billion. The largest proportion was for patients with governmental insurance coverage, totaling

Hospitalized Patients with Heart Failure and Common Bacterial Infections: A Nationwide Analysis of Concomitant Clostridium Difficile Infection Rates and In-Hospital Mortality

2.70 billion (40.8%) and was divided between Medicaid (

The relationships of positive and negative symptoms with neuropsychological functioning and their ability to predict verbal memory in psychotic major depression

2.30 billion) and Medicare (

Climbing-Related Injury Among Adults in the United States: 5-Year Analysis of the National Emergency Department Sample

0.40 billion). Self-pay individuals accounted for

Using an integrated ontology and information model for querying and reasoning about phenotypes: The case of autism.

1.56 billion (23.6%) in costs. Conclusions From 2006 to 2014, the cost of initial hospitalizations for firearm-related injuries averaged