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Caring for women for life

Hormones, birth, breastfeeding, and their

impact on perinatal mood disorders

Alison Stuebe, MD, MSc

astuebe@med.unc.edu

Case CC/ID: 29 yo G2P1011 at 4 weeks postpartum presents for lactation consultation for sore nipples

HPI: Presented to LC for evaluation of sore nipples, and infant found to be at birth weight, with 4 oz gain in last 2

weeks. The LC asks her to complete an EPDS.

The EPDS Case On further discussion, she reports that immediately after the baby’s birth, the patient remembers feeling euphoric and

being unable to sleep. Now, she reports worsening

sleeplessness, tearfulness, anxiety and depression, waking

frequently to check on the baby.

She denies any personal history of anxiety or depression, but

her mother has frequent paranoid thoughts and episodes of manic behavior, to the extent that she no longer has contact

with her mother. Her maternal grandmother had similar

psychiatric symptoms, and the patient says, "I don't want to be that kind of mother for my baby.”

Today’s objectives

•�Understand the relationship

between breastfeeding and

postpartum depression

•�Discuss mechanisms linking

these two disorders

•�Apply strategies for integrated management of mood

disorders and breastfeeding

problems

Postpartum Support International / http://www.postpartum.net/ Caring for women for life

Understand the relationship between breastfeeding and

postpartum depression

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Conventional Wisdom: Breastfeeding prevents postpartum depression

“The many health benefits of breastfeeding include

less risk of postpartum depression for you.”

- The Joint Commission

Does not breastfeeding cause depression?

“At the level of a mother’s basic biology, the decision to bottle feed unwittingly mimics conditions associated with the death of

an infant. Child loss is a well documented trigger for depression particularly in mothers, and growing evidence shows that bottle

feeding is a risk factor for postpartum depression.”

1.96 2.13 2.24

0.1

1

10

First Day First Week Second Week

OR postpartum depression at 2 months, severe pain vs. no pain

Watkins, Zolnoun, Meltzer-Brody and Stuebe. Obstet Gynecol August 2011

Prospective data from 2586 women

who initiated breastfeeding in the

Infant Feeding Practices Survey II.

Or does bad breastfeeding cause depression?

Paul et al (2013) Pediatrics 131(4): e1218-24.

Higher state anxiety

during the postpartum stay was

associated with

shorter breastfeeding duration in a

prospective cohort

study.

Dennis C-L and McQueen K (2009). Pediatrics 123(4): e736-751.

Stuebe et al (2014). J Womens Health

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Stuebe, A. M., K. Grewen, et al. (2012). "Failed lactation and perinatal depression: common problems with shared neuroendocrine mechanisms?" Journal of Women's Health 21(3): 264-272. Caring for women for life

Discuss mechanisms linking these two disorders

Breastfeeding is a two-person organ system

Milk synthesis

Dopamine (-)

Prolactin

Milk secretion

Oxytocin

Anterior pituitary

Posterior pituitary

Paraventricular nucleus

(+)

Milk ejection

reflex

Placenta

Progesterone (-)

Hypothalamus

(+)

Cortisol T3, T4

Insulin Growth hormone

Breastfeeding

Success

Let Down

Latch

Moving Milk

Ejection moves milk to the areola

CNS mechanisms allow the baby to access mothers’ milk

Speroff et al. Reproductive Endocrinology and Infertility.

167

69

114 114

139

163 159

Control Ice water Math + shock Toe Pull

Distraction and Milk Volume (g)

saline oxytocin

Newton & Newton. J. Pediatr 1948; 33:698-704.

Stress and Milk Volume Latch ‘milks’ the milk

Rhythmic suckling transfers milk from breast to baby.

INCORRECT

CORRECT

Photos © Jane Morton, MD, FAAP

AAP Breastfeeding Residency Curriculum

Breastfeeding

Success

Let Down

Latch

Moving Milk

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Demand drives supply

Emptying lobules drives ongoing milk production.

Breastfeeding

Success

Let Down

Latch

Moving Milk

Mother

Baby

Breast

Communication in a two-person

organ system

Quiet, alert baby with strong suck can latch

and moves milk

Engagement triggers

oxytocin

Breast stimulation triggers oxytocin

and prolactin

Breastfeeding

Success

Let Down

Latch

Moving Milk

Depression and infant behavior

•�Exposure to depression in utero associated with differences in infant

»�Neonatal neuromuscular maturity

»�Early suckling behavior

»�Infant temperament

•�Does exposure to depression in utero affect latch, feeding

cues, and temperament, thereby latch and milk removal?

Reviewed in Stuebe, A. M., K. Grewen, et al. (2012). "Failed lactation and perinatal depression: common problems with shared neuroendocrine mechanisms?" Journal of Women's Health 21(3): 264-272.

Maternal mood affects behavior

Sensitivity Intrusiveness Withdrawal Child Engagement

Depression Anxiety Control

Feldman et al (2009) " J Am Acad Child Adolesc Psychiatry 48(9): 919-27.

Mother

Baby

Breast

Depression interferes with

breastfeeding physiology

Exposure to depression may affect

oromotor function

Mother-infant interaction

dysregulated

Stress suppresses oxytocin

Breastfeeding

Success

Let Down

Latch

Moving Milk

Stuebe, A. M., K. Grewen, et al. (2012). Journal of Women's Health 21(3): 264-272.

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Caring for women for life

What’s the underlying physiology?

Neurosteroids and perinatal depression

Milk synthesis

Dopamine (-)

Prolactin

Milk secretion

Oxytocin

Anterior pituitary

Posterior pituitary

Paraventricular nucleus

(+)

Milk ejection

reflex

Placenta

Progesterone (-)

Hypothalamus

(+)

Cortisol T3, T4

Insulin Growth hormone

Mean plasma concentrations of estrone (E1), estradiol (E2), estriol (E3), and progesterone (P)

during pregnancy.

Fetal and maternal neuroendocrine changes around partuition.

Peripartum neuroendocrinology

Neuropsychopharmacology (2006) 31, 1249–1263.

GABA receptors are downregulated during pregnancy, and must return to

normal levels after partuition to maintain steady level of inhibition

In a knockout mouse model, loss of the GABA(R)delta gene prevents

postpartum recruitment of GABA(R), and results in aberrant mothering

behavior and decreased pup survival.

Maguire J, & Mody I (2008). GABA(A)R plasticity during pregnancy: relevance to postpartum

depression. Neuron, 59(2), 207-213. PubmedCID

2875248

‘About two days after delivery some women become excited, sleepless, and

incoherent; they have a flushed face, a rather full

pulse and slight elevation of temperature; this is called ‘milk fever,’ and coincides

with the beginning of the flow of milk.’

- George Savage, 1875

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Caring for women for life

What’s the underlying physiology?

Oxytocin and the autonomic nervous system

Vagus

III. Myelinated vagus: Social communication,

self-soothing, calming, inhibits “a

I. Unmyelinated vagus: Immobilization (death

feigning, passive avoidance)

II. Sympathetadrenal syste

Mobilization (active avoida

Porges SW. Biol Psychol 74:116-143, 2007

•�What happens to lactation when you interfere with oxytocin-vagal pathways?

»�The cPAG is a brain region implicated in maternal response

to nursing in rats

»�Researchers studied the effect of lesion in cPAG region on

maternal behavior

»�Damaging this region of the brain interfered with feeding

behavior

Brain Research 804:21-35, 1998

Effect on weight gain Effect on attack behavior

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Increased vagal tone, maternal

behavior

Reduced stress reactivity, decreased depression and anxiety

Stressor

SNS PNS

Central oxytocin

pathways

-

+

CRH

ACTH

Modulation of cortisol

Hypothalamus

Pituitary

Adrenal

-

Maternal oxytocin response

to feeding at 8 weeks among women with

depression/anxiety symptoms (dashed line) or

without mood symptoms (solid line).

Stuebe, Grewen & Meltzer-Brody (2013) Journal of Women's Health 22(4): 352-361.

Oxytocin AUC during feeding and maternal mood.

Stuebe, Grewen & Meltzer-Brody, In press

Does the relationship between oxytocin and cortisol vary among individuals?

Meinlschmidt, G. and C. Heim (2007). "Sensitivity to intranasal oxytocin in adult men with early parental separation." Biological Psychiatry 61(9): 1109-1111

0

4

8

12

16

Post

feed

Res

t

0

4

8

12

16

0 100 200 300

Spee

ch

OT AUC during feeding

PA

SAT

0 100 200 300

Rec

ove

ry

OT AUC during Feeding

w/ symptoms w/o symptoms

OT AUC during feeding

and cortisol during TSST among women with and

without mood symptoms at 8 weeks postpartum.

Do postpartum mood symptoms modify the association between oxytocin and cortisol?

Oxytocin receptor polymorphisms, social support and stress response

Chen, F. S., R. Kumsta, et al. (2011). "Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans." Proceedings of the National Academy

of Sciences of the United States of America 108(50): 19937-19942.

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Oxytocin receptor polymorphisms and postpartum mood

0.9%

7.6%

GG AG/AA

rs53576

EPDS �13 at 3 months

Carriage of the A allele was associated with an

increased risk of depression symptoms

among 260 participants in the Pregnancy, Infection

and Nutrition Postpartum

Study (p=.01).

Mood, mother and infant: The psychobiology of impaired dyadic development

R01 HD073220-A1A, Stuebe (PI)

Specific Aim 1: Use lactation as a physiologic challenge to quantify the extent to which PPD reduces oxytocin, dysregulates stress

reactivity, and diminishes maternal sensitivity.

Specific Aim 2: Use standardized mother-infant interactions

to determine the extent to which PPD & reduced maternal sensitivity impair development of infant emotional regulation

and increase risk for insecure attachment.

�Specific Aim 3: Determine the extent to which diminished

maternal oxytocin and reduced sensitivity mediate associations between PPD, impaired infant emotional regulation, and

insecure attachment.

Caring for women for life

Discuss treatment plans for characteristic mood disorders

associated with the perinatal period

Case

•�CC/ID: 35 yo G2P2 at 5.5 months postpartum seen in consultation for breastfeeding associated pain.

•�She describes the pain as “consistent burning with deeper

pain on and off throughout the day. Sometimes, it feels that I cannot completely “empty” my breast� pain radiates

to my arm / armpit.”

•�EPDS: 15

Clinical Pearl: Screen early and often for postpartum depression/anxiety

•� PPD affects up to 15% of mother-infant dyads

•� Edinburgh Postnatal Depression Survey is a validated screening tool that takes <5 minutes to complete

•� Like all screening tools, interpret the EPDS in the context of the

clinical situation

»�Score �13 sensitivity 75%, specificity 84% for MDD

»�Review responses, not just the total score

•� Key questions:

»�Are you sleeping?

»�Are you having any scary thoughts?

•� Close follow-up to distinguish situational vs mood disorder

Clinical Pearl: Start with non-medical therapy

•�Are you sleeping?

»�Must balance importance of on-demand feeding with

maternal medical need for sleep

•�Are you eating?

»�Protein, regular meals

•�Are you engaged in life outside your home?

•�Offer or refer for psychotherapy

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Clinical Pearl: Sleep & breastfeeding are not mutually exclusive

•�Optimizing sleep

»�The goal for sleep is 6 hours of continuous sleep

»�Use sleep aids as needed

»�Enlist help of partner to bring baby to mom just for feeding during her 6 hours of sleep

Clinical Pearl: Sleep & breastfeeding are not mutually exclusive

•�Optimizing feeding

»�Limit feedings to 30-40 minutes total time/ feeding

»�Intense feeding plans generally only can be sustained for 3-4

days by anyone

»�Focus on what is most productive & find other ways to

accomplish the rest

»�Milk making hormones are highest level between 2-5 AM

•�Consider longer sleep interval from evening till middle of this

range, rather than across this range

•�Maximize breast emptying following this time frame

•�Mother must have time to enjoy her baby, not just feed

Clinical Pearl: Include sleep aid when starting medication

•� Trazodone

»�Start at 25mg and increase up to 200mg if needed for sleep (50mg is

usual dose)

»�Addressing sleep can vastly improve mood symptoms

•� Benzodiazepines

»�Klonopin 0.5mg at bedtime and � tab BID as needed until SSRI “kicks” in

»�Used because of its longer half life, can use smaller amounts less often

•� Sertraline

»�Best safety profile of currently available SSRIs

»�Start at 25mg QAM x 6 days, then increase to 50 mg

»�Onset of effects 2-3 weeks

•� Collaborate with pediatric provider

Maternal sertraline and infant serotonin

Epperson N et al. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry 2001 Oct;158(10):1631-7.

Case 3

•�Presenting concern

»�Pain with breastfeeding during let-down, thus pumping and

bottle-feeding

•�History of postpartum depression

»�1st and 3rd children, hospitalization for major depressive

episode in 5 years ago

»�EPDS today 4, seen by psychiatrist this morning

•�Observed feeding

»�Infant established good latch, but pulled away and clicked

tongue during let down at time of increased maternal pain.

»�On/off latch after the let down, milk frequently spilling from

sides of mouth. Choking with second let down.

Clinical Pearl: Depression affects both mood and maternal sensitivity

•�When seeing a mom with a history of depression / anxiety, evaluate maternal symptoms and mother-infant interaction

»�This mother was unaware of infant’s response to overactive

let-down, including coughing, writhing, and clamping to control flow

»�Depression / anxiety associated with impaired maternal sensitivity and intrusive behaviors

•�Treatment requires both addressing mood symptoms and helping mom respond to infant cues while addressing

presenting symptoms

»�Review cues, work with mother to understand baby’s needs and desires

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Bunik et al (2014). "Trifecta Approach to Breastfeeding:

Clinical Care in the Integrated Mental Health Model." J Hum Lact.

To learn more

Academy of Breastfeeding Medicine Protocols

http://www.bfmed.org/

UNC Breastfeeding Management Algorithms

http://mombaby.org/breastfeeding

Postpartum Support International

http://www.postpartum.net/

UNC Center for Women’s Mood Disorders

http://www.med.unc.edu/psych/wmd/mood-disorders/perinatal

Today’s agenda

•�Understand the relationship between breastfeeding and postpartum depression

»�There is considerable overlap between breastfeeding difficulties

and depressive symptoms – we need to screen for and treat both

»�The evidence suggests that breastfeeding does not prevent PPD

•�Discuss mechanisms linking these two disorders

»�Shared mechanisms affect lactation and maternal mood,

suggesting that breastfeeding problems and depression may be

biologically linked

•�Apply strategies for integrated management of mood disorders and breastfeeding problems

»�Screen early and often, start with non-medical therapy, address

both sleep and feeding, and teach mothers to recognize and

respond to baby’s cues

Kim Andringa Diane Asbill

Betsy Bledsoe Martha Cox

Mala Elam Barbara Fredrickson

Susan Gaylord

Susan Girdler Karen Grewen

Karen Hardy

Samantha Meltzer-Brody Kim Newton

Chris Raines David Rubinow

Brenda Pearson

Cort Pederson Cathi Propper

Ashley Soh John Thorp

University of North Carolina

Division of Maternal-Fetal Medicine

Department of Psychiatry Center for Developmental Science

Frank Porter Graham Institute

National Institutes of Health