LAURA J. MILLER MDDIRECTOR, WOMEN’S MENTAL HEALTH DIVISION

BRIGHAM AND WOMEN’S HOSPITALHARVARD MEDICAL SCHOOL

Perinatal Depression Update

What we’ll cover

“Perinatal” depression is major (clinical) depression occurring during pregnancy and/or postpartum

We’ll review findings from recent research about Causes of perinatal depression Risks of untreated perinatal depression for offspring Treatments for perinatal depression Models of delivering care for perinatal depression

Perinatal perturbations

Hormonal flux

Neurotransmitter alterations

Inflammatory responseSocial role transitions

Sleep & circadian changes

Physical activity changesSocial rhythm changes

Stressors and genetic susceptibility

Pain

Genetic susceptibility to stress

“Orchid” alleles more susceptible to stress

“Cactus” alleles more resilient in the face of stress

The 5-HTTLPR-ss allele predicts postpartum depressive symptoms only in the presence of negative life events.

Mehta D et al: J Affect Disord 136(3):1192-7, 2012

Hormonal flux affects stress response

In this study, rats were given estrogen and progesterone to simulate the hormonal state of pregnancy.

In half of the rats, these hormones were abruptly discontinued.

In the other half, the hormones were gradually tapered.

Abrupt withdrawal had a greater effect on stress reactivity, as measured by startle response to noises.

Doornbos B et al: Life Sci 84(3-4):69-74, 2009

Bloch M et al: J Clin Endocrinol Metab 90(2):695-9, 2005

• Estrogen and progesterone were given to healthy women with and without history of postpartum depression, and then abruptly withdrawn to simulate birth.

• The women were then given corticotropin releasing hormone (CRH) and their cortisol levels were measured. This is a test for the physiologic reactivity of their stress response systems.

• PPD- women had no “perinatal” change in stress reactivity.

• PPD+ women had greater “perinatal” stress reactivity.

Hormonal flux and stress reactivity in women

Postpartum depressed (  ) relative to postpartum control subjects (○): left lateral orbitofrontal cortex (LLO), mesiotemporal cortex (MTC) and subgenual anterior cingulate (SUB)

Serotonin (5HT-1A) receptor binding is reduced in women with postpartum depression compared to controls.1

Estrogen regulates serotonergic function.2

Tryptophan3

Trytophan, found in food, is a “building block” for serotonin.

In pregnancy, serum tryptophan is reduced, especially relative to competing amino acids (t/caa).

Postpartum, tryptophan rises but t/caa is even lower.

1. Moses-Kolko EL et al: Fertil Steril 88(3):685-92, 2008; 2. Donner N, Handa RJ: Neurosci 163(2):705-18, 2009; 3. Maes M et al: Psychol Med 31:847-58, 2001; 2004

Perinatal changes in serotonin

Perinatal inflammation

A woman’s body “gets ready” for birth by increasing inflammation (pro-inflammatory cytokines).

Levels of inflammation are further increased by stress, sleep deprivation and pain.

Levels of inflammation correlate with increase in postpartum depressive symptoms.

Kendall-Tackett K: Int Breastfeed J 2:6-19, 2007; Maes M et al: Psychoneuroendocrinol 25(2):121-37, 2000

Mean serum concentrations of pro-inflammatory cytokines in pregnant women who are ZDS reactors (– – –) versus nonreactors (—), at the end of term (PRE) and 1 (DAY1) and 3 (DAY3) days postpartum.

Perinatal social role transitions

Changing from a known to an unknown realityTaking on a new maternal identity, with

associated feelings, behaviors and skillsRenegotiating prior social roles, such as

employment status, relationship with partner, and roles within the extended family

Balancing multiple demands and disruptionsExperiencing losses, such as loss of control,

freedom, and sense of selfStrongly influenced by sociocultural context

Emmanuel E, St. John W: J Advanced Nurs 66(9):2104-15, 2010

Risk factors for perinatal depression

Stressful negative life eventsLack of social supportIntimate partner violenceUnintended pregnancyLow socioeconomic statusLancaster CA et al: Am J Obstet Gynecol 5-14, Jan 2010

Protective transition rituals

CeremoniesCleansing ritualsSeclusionRest SolicitudeReturn to home of

originEberhard-Gran M et al: Arch Womens Ment Health 13(6):459-66, 2010

Circadian and social rhythm changes

Sleep quality declines throughout pregnancy and postpartum1

Reduced sleep efficiency Reduced restorative sleep Disrupted sleep architecture and circadian rhythm even

when naps allow for normal total sleep timePhysical activity declines throughout pregnancy

and only partially rebounds postpartum2

Daily routines and social zeitgebers can be far less predictable3

1. Ross LE et al: J Psychiatry Neurosci 30(4):247-56, 2005; 2. Pereira MA et al: Am J Prev Med 32(4):312-9, 2007; 3. Grandin LD et al: Clin Psychol Rev 26(6):679-94, 2006

Obstetric risks of antenatal depression

1. Marcus SM: Can J Clin Pharmacol 16:15-22, 2009. 2. Li D et al: Hum Reprod 24:146-53, 2009; 3. Bansil P et al: J Womens Health 19:329-34, 2010; 4. Henrichs J et al: Psychol Med 40:633-43, 2010

Reduced prenatal care and health maintenance1

Preterm birth2,3

Reduced birth weight4

Effects of intrauterine problems on offspring development

Vrekoussis T et al: Ann N Y Acad Sci 1205:69-75, 2010

Fetal programming

“Epigenetic” means something that influences whether a gene is expressed

A woman’s mood and stress while pregnant can have epigenetic effects on fetal development, leading to enduring effects on emotions, behavior or cognitive abilities

This is posited to be a way of “reading” and adapting to the outside world

Severe, prolonged stress or depression can elevate cortisol, which binds to promoter regions of fetal genes

Studies show that maternal depression is associated with increased methylation at promoter regions of genes that affecting glucocorticoid receptors (part of the stress response system)

Denslow SA, Wade PA: Oncogene 26:5433-8, 2007

Glover V et al. Psychoneuroendocrinology. 2009;34(3):430-435

Effects of antenatal depression on offspring

Newborns: excessive crying; more inconsolable1

Babies: poorer growth; increased risk of infection2-3

Children: more difficult temperaments - more distress, sadness, fear, shyness, frustration4

1. Zuckerman et al: J Dev Behav Pediatr 11:190-4,1990; 2. Rahman et al: Arch Gen Psychiatry 61:941-52, 2004; 3. Traviss GD et al: PLoS One 7(2): e30707,2012; 4. Huot RL et al: Ann N Y Acad Sci 1032:234-6, 2004

Postpartum depression and parenting

Parenting may be intact despite depression

Risks can include Reduced ability to read baby’s cues1

Reduced responsiveness to infant distress2

Reduced ability to communicate range of emotions1

Reduced enrichment1 Less healthy feeding and sleeping practices1

Postpartum stressors can compound antenatal biological vulnerability3

1. Paulson JF et al: Pediatrics 118:659-68, 2006; 2. Pearson RM et al: Psychol Med 40:621-31, 2010; 3. Rice F et al: Psychol med 40:335-45, 2010

Infanticide due to postpartum depression

Rare; greater risk with psychotic symptomsRarely has a history of abusing childrenMost often part of a suicide attemptNo anger toward baby; wish not to abandon

baby and/or not to burden others with babyRarely attempt to conceal; often self-report

D’Orban PT: Br J Psychiatry 134:560-71, 1979; Silverman RA, Kennedy LW: Violence Vict 3:113-27, 1988; Haapasalo J, Petaja S: Violence Vict 14:219-39, 1999; Kauppi A et al: Arch Womens Ment Health 11(3):201-6, 2008

Ego-dystonic thoughts of harming babies

“These fears always started with the words “what if” and left me questioning my sanity as well as the safety of my family. “What if I accidentally dropped my baby out of a second story window?” What if I dropped her on purpose?” “What if I grabbed a hammer and smashed it against my husbands skull as he slept?” “What if I tossed my infant into the swimming pool and walked away?” And countless other unnerving what if questions.” 

“I need to pause and make a very clear distinction. I never wanted to do those things. I knew they were wrong. I desperately loved my babies.  This added to my shame and confusion.”

http://www.incourage.me/2010/03/battles.html

“She turned up in so many of my dreams – watching me, following me, but never saying anything. In my dreams, she never helped. She just stared at me, as if to say, ‘Well?’ During the various stages of my life, I often wondered if I was responsible for her illness and incarceration. After all, she was taken away at my birth, so who else could be blamed?

Buchwald A: Leaving Home: A Memoir. New York: Putnam, 1993

Postpartum depression: long-term risks for offspring

Poorer health-related quality of life1

Higher rates of depression Maternal PPD predicts childhood HPA abnormalities,

which in turn predict offspring depressive symptoms in adolescence2

Higher rates of behavioral disturbance3

Lower cognitive abilities PPD affects adolescent IQ4

Postpartum maternal mood predicts performance on high school entrance exams5

1. Darcy JM et al: J Am Board Fam Med 24(3):249-57, 2011; 2. Halligan SL et al: Biol Psychiatry 62:40-6, 2007; 3. Brennan PA et al: Dev Psychol 36:759-66,l 2000; 4. Hay DF et al: J Child Psychol Psychiatry 49:1079-88, 2008; 5. Galler et al: J Child Psychol Psychiatry 45:1064-75, 2004

Established treatments

Antidepressant medication Studies show risks are same or less than

risks of untreated major depression Electroconvulsive therapy

Used for severe episodes Psychotherapy

Interpersonal Psychotherapy and Cognitive-Behavioral Therapy both work

Treatment burden reduces access Technology-enabled versions are being

developed and studiedMiller LJ et al: Perinatal depression screening and treatment. In Handler A, Kennelly J,Peacock N, eds.: Women's Reproductive and Perinatal Health: Interventions and Evidencefor Reducing Racial and Ethnic Disparities. Springer 2010

Emerging treatments

Estrogen therapy Phototherapy (light therapy) Transcranial magnetic stimulation Omega-3 essential fatty acids Family and couples therapy Support groups; warm lines; doula

support

Miller LJ et al: Perinatal depression screening and treatment. In Handler A, Kennelly J,Peacock N, eds.: Women's Reproductive and Perinatal Health: Interventions and Evidencefor Reducing Racial and Ethnic Disparities. Springer 2010

Models of delivering care

Screening all perinatal women for depression with validated tools can greatly improve detection

Unfortunately, screening alone does not improve outcomes

Integrating mental health assessment and care directly into perinatal care settings can improve entry into treatment Treatment entry went from 0% - 90% in

recently studied model in a community health center

Miller LJ et al, J Womens Health 20(10):1046-52, 2012