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