Integration of Biomarkers to Advance Family Nursing Research Across the Lifespan Elizabeth Corwin,...

Integration of Biomarkers to Advance Family

Nursing Research Across the Lifespan

Elizabeth Corwin, PhD, RN, FAAN, Emory University

School of Nursing

Funding Acknowledgement • Psychoneuroimmune Contributions to Postpartum Depression

(R01NR011278, National Institute of Nursing Research)

• Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women (R01NR014800, National Institute of Nursing

Research)

I have no conflicts of interest to report

Family Caregiving• >30 million individuals in U.S. provide care annually for

chronically ill, disabled or aged family member • Care is often:• longitudinal • with worsening trajectories for loved ones

• physically demanding• isolating, lonely, & sad• frightening (financially & physically)

• Example: • Caregivers of family members with dementia

provide an average of 16.6 hours/week–for years.

(National Alliance for Caregiving, in collaboration with AARP, 2009)(Schultz and Martire, 2004)

Health Outcomes of Caregivers of Spouses with Alzheimer’s Disease• Multiple adverse outcomes compared to non-

caregivers of same age

• 63% higher mortality rate • Increased risk of infectious disease• Increased risk of chronic illness• Cardiovascular disease (hypertension, MI)• Diabetes• Depression

• This limits their ability to provide care

• (Kiecolt-Glaser, et al., 2008; Gouin, et al., 2008)

Family Caregiving • Caregiving crosses generations

• As does its impact – on caregiver and recipient

Adverse Health Outcomes of FamilyCaregivers Across the Lifespan

• Spouses of patients with cancer (Li &Like, 2013; Haley, et al., 2003; Jassem, Haley, et al., 2015)

• Parents of autistic children (Lovell et al., 2012; 2015)

• Parents of children with TBI (Wharewere-Mika, et al., 2015)

• Mothers of children and adolescents with pediatric cancer (Miller et al., 2008; Rohleder, et al, 2009; Palma et al., 2015)

• Mothers of children who die(Jiong et al., 2003; Espinosa,Evans, 2013)

Common Denominator: Chronic Stress

Normally… with acute stress

Pro-inflammatory cytokines Cortisol

* Limits exaggerated inflammation

* Limits exaggerated production of cortisol

However…With exposure to chronic stress

Cells may develop glucocorticoid resistance (GR)• Cortisol cannot limit cytokine production

• Leads to dysregulation of inflammatory response• Cortisol partially escapes negative feedback

• Leads to increased cortisol BOTH OF WHICH ADVERSELY IMPACT MOOD and HEALTH

Pro-inflammatory cytokines cortisol

WHY INCLUDE BIOMARKERS?

How do they advance Family Nursing Research?

Biomarkers• What they are:• Measurable indicators of health, a state, or a disease• Human chorionic gonadotropin (hCG)• Prostate specific antigen (PSA)• Cholesterol• HbgA1c• Atrial or brain natiuretic peptide (ANP/BNP)• C-reactive protein (CRP)• Diurnal salivary cortisol• Pro- and anti-inflammatory cytokines• Reactive oxygen species• Brain-derived neurotrophic factor (BDNF)• Telomeres & telomerase

What about the Care Recipient?

•What are the health outcomes?

Telomere Length: A Marker of Cellular Aging – An Indicator of

Chronic StressReduced telomere length in mothers with

chronically ill children (Epel, et al., Proceedings of the Natl Acad Sci, 2004)

Reduced telomere length in long-term caregivers of Alzheimer’s patients (Gamjanovic, et al., J of Immunology, 2007)

Reduced telomere length in children of depressed mothers (Gotlib, et al., Molecular Psychiatry, 2015)

Shorter telomere length in newborns related to maternal prenatal depression (Entringer, et al., Am J Obstet Gynecol, 2013)

What the Inclusion of Biomarkers Adds To Family Nursing Research

• The potential to uncover the underlying biological mechanism responsible for a particular symptom or an adverse health outcome

• The potential for precision nursing interventions

• If you know the mechanism, you can target it

• If you target it, you can measure your success

•Over time

•In real time

An Exemplar:Spontaneous Preterm Birth

• Most common type of preterm birth• Associated with significant adverse outcomes for

families• Risk factors include • Previous preterm birth• Infection/Inflammation• Chronic Stress & elevated HPA axis hormones

• Mechanisms remain unclear • Interventions to predict or prevent PTB of limited

success

Step 1Uncover the Mechanism

Minority and low-income pregnant women experience > risk of PTB than Caucasian and/or higher income women

Minority and low-income pregnantwomen report increased chronic stress compared to Caucasian andhigher income women (Geronimous, 2008)

A Biological Fingerprint of Disadvantage

• In our longitudinal study of 201 healthy, pregnant women, followed from the 3rd trimester through 6-months postpartum• We identified PNI dysregulation and loss of the

bidirectional cytokine-cortisol feedback in pregnant low income and minority women compared to higher income Caucasian women.

(Corwin, et al., Psychoneuroendocrinology, 2013)

• PNI dysregulation and loss of feedback continued through 6-months postpartum

Average daily cortisol concentration (mean+SE) (AUC) in Caucasian higher income women compared to

minority and low income pregnant and postpartum women

Pro-Inflammatory cytokine levels in Caucasian/higher income women vs

minority/low income pregnant and postpartum women

All slopes significant for Caucasian/higher income pregnant women (blue) but not lower income/minority pregnant women(red) (*p<0.05, **p<.001, ***p<.0001)

Cytokine-glucocorticoid feedback in Caucasian/higher income women vs minority/low income pregnant

women

Month 3 postpartum cytokine-glucorticoid feedback in Caucasian/higher income women (blue) vs minority/low

income (green) postpartum women

All slopes significant for Caucasian/higher income pregnant women (blue) but not lower income/minority pregnant women (green)

AFRICAN-AMERICAN FAMILY CARETAKERS

OUR CURRENT STUDY: Focusing on the Population Most at Risk

Effects of Chronic Stress on the Microbiome and PTB in Black Women

(R01NR014800)

• Gut microbiome mirrors our stress

• Elevated cortisol “leaky gut”

• increases inflammation

• Oral microbiome

• A source blood borne infection or systemic inflammation

• Vaginal microbiomeA route to PTB

Step 2: Precision - Tailor the Intervention

• Go back to the mechanismChronic stress Inflammation and cortisol

• Design an intervention to Chronic Stressor

• Design an intervention to change a women’s response to chronic stress

MindfulnessYogaExerciseSingingSpirituality

Step 3: Test the Intervention

• Go back to the mechanism - Chronic stress inflammation and increased cortisol

• Target the patient - Does this person show the phenotype predictive of PNI dysregulation?• If so…

• Test the intervention- Did it work?• Did it return normal cytokine-glucocorticoid

feedback?• Did it reduce inflammation? Cortisol?• Did it return the microbiome to more protective

state?

Family CaregivingIntegrating biomarkers can help predict and guide

precision family nursing research & care

across generations

QUESTIONS?

Thank You