Major Depressive Disorder and Measures of Cellular Aging: An Integrative Review

Major depressive disorder (MDD) affects millions of individuals and causes significant suffering worldwide. It has been speculated that MDD is associated with accelerated aging-related biological and functional decline. To examine the accelerated aging hypothesis, one of the biomarkers under study is leukocyte telomeres, and specifically the measure of telomere length and telomerase activity. This review integrates findings from eleven human studies which evaluated telomere length and telomerase activity, in order to synthesize the state of the current science and to inform the development of new knowledge and enhance nursing research of depression using appropriate biobehavioral measures. Although preliminary, the findings from this integrated review suggest that there is evidence to support a conceptualization of depression as a stress-related condition in which telomeres shorten over time in relation to cumulative exposure to the chronic stress of depression. For the purposes of testing in future nursing research, visual representations of the theoretical connection between stress vulnerabilities, depression, and health outcomes and key moderators and mediators involved in this conceptualization are provided. The findings from this review and the conceptual framework provided may be a useful step towards advancing therapeutic nursing interventions for this debilitating chronic condition

Recruiting for Epigenetic Research: Facilitating the Informed Consent Process

Because the effects of epigenetic (gene-environment interaction) changes have been associated with numerous adverse health states, the study of epigenetic measures provides exciting research opportunities for biobehavioral scientists. However, recruitment for studies focusing on any aspect of genetics poses challenges. Multiple factors, including lack of knowledge regarding a research study, have been identified as barriers to recruitment. Strengthening the informed consent process through extended discussion has been found to be effective in recruiting for research studies in general, yet there is a paucity of information that focused on such a recruitment strategy for epigenetic studies. In this paper, we share our experiences with strategies to strengthen the informed consent process as well as provide samples of materials developed to heighten potential participants’ understanding of epigenetics, in 4 epigenetic research studies with women from diverse backgrounds experiencing a range of health issues. The combined enrollment success rate for epigenetic studies using the process was 89% with participants representing a diverse population. We posit that carefully developed recruitment scripts provided a foundation for improving potential participants’ understanding of the research project. Easy to understand illustrations of the epigenetic process provided a basis for active engagement and encouraged individual questions

Penalized Ordinal Regression Methods for Predicting Stage of Cancer in High-Dimensional Covariate Spaces

The pathological description of the stage of a tumor is an important clinical designation and is considered, like many other forms of biomedical data, an ordinal outcome. Currently, statistical methods for predicting an ordinal outcome using clinical, demographic, and high-dimensional correlated features are lacking. In this paper, we propose a method that fits an ordinal response model to predict an ordinal outcome for high-dimensional covariate spaces. Our method penalizes some covariates (high-throughput genomic features) without penalizing others (such as demographic and/or clinical covariates). We demonstrate the application of our method to predict the stage of breast cancer. In our model, breast cancer subtype is a nonpenalized predictor, and CpG site methylation values from the Illumina Human Methylation 450K assay are penalized predictors. The method has been made available in the ordinalgmifs package in the R programming environment

Perceived Stress Levels, Chemotherapy, Radiation Treatment and Tumor Characteristics Are Associated with a Persistent Increased Frequency of Somatic Chromosomal Instability in Women Diagnosed with Breast Cancer: A One Year Longitudinal Study

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage breast cancer and quantified their somatic chromosomal instability levels using a cytokinesis-blocked micronuclear/cytome assay at 4 timepoints: before chemotherapy (baseline); four weeks after chemotherapy initiation; six months after chemotherapy (at which time some women received radiotherapy); and one year following chemotherapy initiation. Overall, a significant change in instability frequencies was observed over time, with this change differing based on whether the women received radiotherapy (p=0.0052). Also, significantly higher instability values were observed one year after treatment initiation compared to baseline for the women who received: sequential taxotere/doxorubicin/cyclophosphamide (pp=0.014). Significant predictive associations for acquired micronuclear/cytome abnormality frequencies were also observed for race (p=0.0052), tumor type [luminal B tumors] (p=0.0053), and perceived stress levels (p=0.0129). The impact of perceived stress on micronuclear/cytome frequencies was detected across all visits, with the highest levels of stress being reported at baseline (p =0.0024). These findings suggest that the cancer-related exposome has an impact on both healthy somatic cells and tumor cells, and may lead to persistent chromosomal instability. In addition, stress was a significant predictor of chromosomal instability; thus, interventions that aim to reduce stress may reduce acquired soma-wide chromosomal instability for cancer survivors

Epigenetics in Research and Practice

This special issue focused on the intersection of epigenetics with nursing research and practice. The first paper in this series addresses the role of epigenetic modifications in pain and analgesia response, highlighting the need for future research on epigenomic modification in the development of chronic pain, and summarizes the therapeutic potential to alter epigenetic processes to improve health outcomes. The second studies the epigenetic alterations and an increased frequency of micronuclei in women with fibromyalgia, highlighting a difference in an epigenetic biomarker in participants versus controls. The third paper explored the role of epigenetics in critical illness and the need for clinicians to understand and navigate the novel therapies of the future based on advances in epigenetic science. The fourth paper described the complexity of recruiting participants for epigenetic research and highlighted strategies, including scripts for facilitating the informed consent process. The fifth paper was an insightful review of the epigenetic mechanisms that may contribute to the biological response to trauma and risk for posttraumatic stress disorder. The sixth paper discussed the state of the science in understanding measures of cellular aging in depression

Tryptophan Degradation in Women with Breast Cancer: A Pilot Study

Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy

Educating Future Nursing Scientists: Recommendations for Integrating Omics Content in PhD Programs

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science\u27s Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals

Epigenetic Alterations and an Increased Frequency of Micronuclei in Women with Fibromyalgia

Fibromyalgia (FM), characterized by chronic widespread pain, fatigue, and cognitive/mood disturbances, leads to reduced workplace productivity and increased healthcare expenses. To determine if acquired epigenetic/genetic changes are associated with FM, we compared the frequency of spontaneously occurring micronuclei (MN) and genome-wide methylation patterns in women with FM () to those seen in comparably aged healthy controls ( (MN); (methylation)). The mean (sd) MN frequency of women with FM (51.4 (21.9)) was significantly higher than that of controls (15.8 (8.5)) (; df = 1; ). Significant differences ( sites) in methylation patterns were observed between cases and controls considering a 5% false discovery rate. The majority of differentially methylated (DM) sites (91%) were attributable to increased values in the women with FM. The DM sites included significant biological clusters involved in neuron differentiation/nervous system development, skeletal/organ system development, and chromatin compaction. Genes associated with DM sites whose function has particular relevance to FM included BDNF, NAT15, HDAC4, PRKCA, RTN1, and PRKG1. Results support the need for future research to further examine the potential role of epigenetic and acquired chromosomal alterations as a possible biological mechanism underlying FM

The 1% Campaign

The purpose of The1% Campaign is to raise scholarship funds for first year VCU students who are dependents of VCU/VCUHS employees. Honoring Dr. Grace E. Harris, this fund will eventually provide tuition and fees for new students for need-based and/or merit-based scholarships. The ultimate goal of The 1% Campaign is to entirely fund one percent of the entering first year class which is approximately thirty to thirty-five students. The recipients will be named Grace E. Harris Scholars

Tryptophan degradation in women with breast cancer: a pilot study

<p>Abstract</p> <p>Background</p> <p>Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy.</p> <p>Findings</p> <p>Blood samples were collected from women with a recent diagnosis of breast cancer (<it>n </it>= 33) before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (<it>n </it>= 24) provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP) was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (<it>p </it>= 0.036), which remained elevated in women with breast cancer throughout the treatment trajectory.</p> <p>Conclusions</p> <p>The findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.</p