Doctor of Philosophy

dissertationDepressive disorders (DD) are a leading cause of disability worldwide and display diverse symptoms including anhedonia, melancholia, decreased concentration, sleep and appetite disturbances, and suicidal thoughts and acts. Current available medications are still ineffective for more than 30% of patients, suggesting DD are multi-faceted heterogeneous disorders. Despite intense research, as yet there are no widely used biological diagnostic tests for DD. Since DD are likely a manifestation of both genetic and environmental factors, gene expression of peripheral blood leukocyte allows for a non-invasive means to evaluate trait- and state-dependent neurophysiological dysregulation. In this dissertation, we employed real-time quantitative polymerase chain reaction (qPCR) to evaluate differences between healthy controls and patients with medication-refractory depression, for a panel of candidate genes previously implicated in depression as well as novel genes implicated in related neurological disorders. Chapter 1 begins with an overview of the multiple domains involved in depression and of previous literature findings evaluating protein and gene expression. Chapter 2 describes one of our studies of gene expression of a small panel of 14 genes involved in the immune and stress response in 19 patients with medication-refractory depression, before and following symptom improvement, compared to 20 healthy controls. We found that patients displayed trait- and state-dependent dysregulation in immune cytokines IL-10 and IL-6, transcription factor NFkB1, the serotonin receptor HTR1D, GABAA modulator DBI, and the adrenergic receptors ADR2A and ADRB1. Furthermore, the dopamine receptor DRD4, the glucocorticoid receptor NR3C1, and SULT1A1 displayed acute changes following treatment, though no differences were observed Pretreatment. In Chapter 3, we describe another gene expression study with results using a larger sample size (42 patients and 38 controls) and an expanded gene panel (46 genes) that includes candidate genes from diverse biological pathways. In this study, we found upregulation of IL-10 and IL-6 as well as dysregulation in the amyloid precursor protein, neuregulin-1, and several ion channels that have roles in anxiety, pain, and fatigue. Finally, Chapter 4 summarizes results from both studies and discusses future research into promising biomarkers and novel mechanisms of depression

Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed

Mixed method approach to understanding participation barriers in a perinatal depression group telehealth intervention trial

Group telehealth interventions (GTI) may reduce perinatal depressive and anxiety (PDA) symptom burden among peripartum individuals. However, study participation for this population may be challenging. The objective of this study was to use a mixed methods approach to understand themes associated with completion of planned interventions in randomized controlled trial (RCT) assessing GTI efficacy on PDA

A Group Telehealth Intervention for Rural Perinatal Depression and Anxiety: A Pilot Study

More than one in five rural childbearing women experience perinatal depression (PD). Major barriers to mental health services in rural areas include lack of mental health resources. Telehealth is an approach to improving access to services but has not been well studied in rural childbearing populations. We explored the feasibility, acceptability, and preliminary assessment of effectiveness of a group telehealth intervention for PD in rural women. Pregnant and postpartum women seeking services at rural public health clinics were screened for PD. Those who screened positive were invited to participate in eight weekly group videoconference sessions facilitated by a mental health professional. Recruitment, enrollment, participation, and follow-up were documented. Measures of depression (Edinburgh Postnatal Depression Scale [EPDS]) and anxiety (Generalized Anxiety Disorder scale [GAD-7]) were administered at four time points. One thousand eight hundred one women were screened for depression and 37% (671) screened positive. Only 25% (168) of those who screened positive agreed to be contacted; 42 women consented and 64.3% attended at least five telehealth sessions. Scores on the EPDS and GAD-7 were significantly decreased preintervention to postintervention, and at 3- and 6-month follow-up (p \u3c .01). Results suggest that group videoconferencing holds promise for increasing access to mental health services, but significant barriers to participation exist for most rural women seeking services at rural public health clinics. To increase feasibility and acceptability, further research is needed to address mental health stigma, establish a network for universal screening beyond public health clinics, and build trusted relationships for the identification and treatment of women with perinatal mood disorders

Cancer caregivers at the end-of-life: How much me vs. how much we?

Objective: This study explored cancer caregivers' individual and communal coping through their use of personal and communal pronouns during naturally occurring conversations. Methods: Nurse-home hospice visits involving cancer patients and their partner caregivers were audio recorded and then transcribed. Pronoun use was analyzed using Linguistic Inquiry Word Count (LIWC) software and descriptive statistics compared patient and partner caregivers' pronoun use. Personal and communal pronoun use was examined within six identified topics of caregiver speech: patient medical care, daily life, emotion, criticism/disagreement, relationships with family/friends, and asserting needs. Results: Dyads (N = 76) had an average of 35.8 years in their relationship. Caregivers used proportionately more first-person singular (I-talk) than first-person plural (we-talk). However, they used significantly less I-talk than patients and less I-talk than LIWC measures in naturally occurring speech. Caregivers were most likely to discuss patient medical care (41.9%) and least likely to discuss their own needs (3.8%). Conclusion: Partner caregivers may find it easier to express emotions related to communal stressors, rather than their individual ability to cope with end-of-life caregiving. Innovation: Examining personal and communal pronoun use by partner caregivers during nurse-home hospice visits may provide a more objective measure of caregiver coping than standard self-report measures

GoFundMe as a Medical Plan: Ecological Study of Crowdfunding Insulin Success

BackgroundIndividuals in need of medical care turn to crowdfunding websites to engage a “crowd” or group for financial support. In the last decade, access to insulin has decreased considerably for several reasons, including the rising cost of insulin, increasing popularity of high-deductible insurance plans, and increasing insurance premiums. Many people with diabetes are forced to ration or go without insulin, and they turn to crowdfunding websites to seek financial donations to purchase insulin needed to reduce health risks and mortality, and sustain quality of life.  ObjectiveThis study aimed to explore crowdfunding campaign requests to purchase insulin in the United States. MethodsIn this retrospective, quantitative, and qualitative study, we coded the text of GoFundMe online crowdfunding campaigns and viral measures (shares, hearts, and comments) from February 25 to April 15, 2019. We described campaigns (N=205) and explored the factors associated with campaign success using correlations and qualitative thematic analysis. ResultsThe majority of campaigns were initiated by middle-aged adults (age 26-64 years; 77/205, 37.6%), those with type 1 diabetes (94/205, 45.9%), and those needing funds owing to insurance coverage issues (125/205, 61.0%). The factors associated with campaign success included requests for ≤US $500 (P=.007) and higher viral measures (shares, P=.007; hearts, P<.001; comments, P=.002). The following 4 themes emerged from the campaign text: (1) desire for self-management and survival, (2) diabetes management untenable given insulin access, (3) aftermath of insulin unaffordability, and (4) privacy issues with crowdfunding. Campaign comments were both supportive (tangible, informational, and emotional) and unsupportive (questioned the need for the campaign and deemed crowdfunding inappropriate). ConclusionsDespite crowdfunding websites being used to support the purchase of insulin, campaigns raised only a fraction of the money requested. Therefore, GoFundMe campaigns are not a reliable solution to obtain funds for insulin in the United States. Applying quantitative and qualitative methods is adequate to analyze online crowdfunding for costs of medications such as insulin. However, it is critical for people with diabetes to use resources other than online crowdfunding to access and obtain insulin owing to low success rates. Clinicians should routinely assess difficulty accessing or affording insulin, and federal health care policies should support lowering the cost of insulin

A Telehealth Diabetes Intervention for Rural Populations: Protocol for a Randomized Controlled Trial

BackgroundDiabetes self-management education and support (DSMES) is a crucial component of diabetes care associated with improved clinical, psychosocial, and behavioral outcomes. The American Association of Diabetes Care and Education Specialists, the American Diabetes Association, and the American Academy of Family Physicians all recommend DSMES yet accessing linguistically and culturally appropriate DSMES is challenging in rural areas. The Diabetes One-Day (D1D) program is an established DSMES group intervention that has not been adapted or evaluated in rural communities. ObjectiveThe specific aims of this paper are (1) to adapt the existing D1D program for use in rural communities, called rural D1D (R-D1D); and (2) to conduct a patient-level randomized controlled trial to examine the effects of R-D1D and standard patient education, guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. MethodsThis is a protocol for a pilot type II hybrid implementation-effectiveness trial of a culturally adapted virtual DSMES program for rural populations, R-D1D. We will use Boot Camp Translation, a process grounded in the principles of community-based participatory research, to adapt an existing DSMES program for rural populations, in both English and Spanish. Participants at 2 rural primary care clinics (4 cohorts of N=16 plus care partners, 2 in English and 2 in Spanish) will be randomized to the intervention or standard education control. The evaluation is guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Patient-level effectiveness outcomes (hemoglobin A1c, diabetes distress, and diabetes self-care behaviors) will be assessed using patient-reported outcomes measures and a home A1c test kit. Practice-level and patient-level acceptability and feasibility will be assessed using surveys and interviews. ResultsThis study is supported by the National Institute of Nursing. The study procedures were approved, and the adaptation processes have been completed. Recruitment and enrollment started in July 2021. ConclusionsTo our knowledge, this will be the first study to evaluate both effectiveness and implementation outcomes for virtually delivered DSMES, culturally adapted for rural populations. This research has implications for delivery to other rural locations where access to specialty diabetes care is limited. Trial RegistrationClinicalTrials.gov NCT04600622; https://clinicaltrials.gov/ct2/show/NCT04600622 International Registered Report Identifier (IRRID)DERR1-10.2196/3425