Förlossningsdepression- Studier på mammor och barn i

Uppsala

Alkistis SkalkidouDocent, Överläkare

Institutionen förKvinnors och Barns Hälsa

INCIDENCE OF DEPRESSION • 15%-20% of adults experience a major

depressive episode each year• The incidence among women is twice that of

men and peaks between 18 to 44 years of age - the childbearing years

DEPRESSION IN WOMEN

Women are at increased risk of mood disorders during periods of hormonal fluctuation

premenstrualpostpartumperimenopausal

Kendell et al, Br J Psychiatry, 1987

Admission of women to PSYCHIATRIC CLINICS perinatally

SPECTRUM OF POSTPARTUM MOOD DISORDERS

POSTPARTUM DEPRESSION

• As high as 19.2% of women experience depression (PPD) over the first year postpartum

• Onset can be as early as 24 hours or as late as several months following delivery

• Higher incidence by lower socioeconomic status

Gavin et al, Obstet Gynecol, 2005

SYMPTOMS OF POSTPARTUM DEPRESSION

Hopelessness Loss of pleasure in activities

Helplessness Mood changes

Persistent sadness Inability to adjust to role ofmotherhood

Irritability Inability to concentrate

Low self-esteem Sleep /appetite disturbances

Not different from non-postpartum depression

Williamson et al, Assessment, 2012

Mild Severe

• Severe Symptoms:– Thoughts of death– Thoughts of suicide– Wanting to flee or get away– Being unable to feel love for the baby– Thoughts of harming the baby– Thoughts of not being able to protect the

infant– Hopelessness

THE ETIOLOGY OF POSTPARTUM DEPRESSION

Hormonal factors

Psychosocial factors

Genetic vulnerability

POSTPARTUM DEPRESSION

THE hormonal hypothesis

Chroussos et al, Ann Intern Med, 1998

THE hormonal basis

After childbirth: Dramatic decreases in estradiol, progesterone, cortisol, thyroid hormones

HPA axis hyporesponsiveness for the first week postpartum

Vulnerability of with previous history of PPD

FROM HORMONES TO DEPRESSION…

– Serotoninergic system

– Dopaminergic system

– Inflammatory response

– BDNF system

– Brain plasticity d

Role of psychiatric background

O’Hara et al, j Abnorm Psychol, 1984

established risk factors

• history of depression• depression and anxiety during pregnancy • neuroticism • low self-esteem • postpartum blues • stressful life events (including childcare-related stressors) • poor marital relationship• poor social support• low socioeconomic status (SES)• being single• unwanted pregnancy• obstetrical stressors• difficult infant temperament

O’Hara & McCabe, Annu Rev Clin Psychol, 2013

Delivery factors-central role of delivery experience

Eckerdal et al, 2016 (Submitted)

GENETICS

Associations of PPD risk with the following genetic polymorphisms in 5-HTTPLR (serotonin receptor)MAO-ACOMT

Associations only with early-onset PPD (8 weeks)Figuiredo et al, J Affect Disord, 2015

CONSEQUENCES OF PPD

Maternal impact

Recurrent depressive episodes

Negative emotionality

Increased risk of subsequent somatic morbidity

Negative effects on parenting

CONSEQUENCES OF PPD

Impact on breastfeeding

Negative feeding outcomes

Decreased breastfeeding duration

Increased difficulties during breastfeeding

Decreased levels of breastfeeding self-efficacyDennis & McQueen, Pediatrics,

2009

CHILD CONSEQUENCES

• Cognitive development

• Poor development of language and IQ

• More profound the effect on boys

• Linear associations with chronicity of depression

Child CONSEQUENCES• Behavior

• higher levels of internalizing

• externalizing • general

psychopathology • negative

affect/behavior • lower levels of positive

affect/behavior

Goodman et al, Clin Child Fam Psychol Rev, 2013

Brand & Brennan, Clin Obstet Gynecol, 2009

Important is the role of epigenetic modifications!!!

• Physical health• Primarily infections• Maladaptive parenting of

depressed mothers

SCREENING FOR POSTPARTUM DEPRESSION

The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.

SCREEN ALL POSTPARTUM WOMEN FOR PPD BECAUSE A WOMAN MAY:

• Be unable to recognize she is depressed• Believe her symptoms are “normal” for new

moms• Fear being labeled a “bad mother” if she admits

her maternal experience does not meet society’s picture of bliss

• Feel she is going crazy and fears her baby will be taken from her

Who Could Screen?

• Clinicians & service providers who work with pregnant & postpartum women– Advance Practice Nurses–CNMs, and NPs– Physicians–OB/GYN, Family Practice, Pediatrics– NICU staff– Public health, hospital, and parish nurses– Prenatal care coordinators– WIC dietitians– Lactation consultants & home visitors (PH nurse, etc.)– Social workers– Midwives at delivery ward– Others?

WHEN TO SCREEN FOR PMD

• At preconception visit• During prenatal intake & subsequent visits• During postpartum exams• During infant’s WCC & WIC visits• When infant is seen for sick care or in ER• At early intervention home visits• At family planning visits during the first year

postpartum• At mother’s visits for routine episodic care

Identification of women at risk-Stratification of risk

SCREENING TOOLS

• There are several tools available:– Edinburgh Postnatal Depression Scale

(EPDS)– The Mills Depression & Anxiety

Checklist– The Center for Epidemiological

Studies Depression Scale (CES-D)– Others, often on various websites for

mental health

EDINBURGH POSTNATAL DEPRESSION SCALE (EPDS)

• Designed for home or outpatient use• Consists of 10 questions• Can be completed in approx. 5 minutes• Reviews feelings the previous 7 days• Scored 0-3 depending on symptom severity • Depending on study, cut off is 13 - 9 points

EPDS

treatment

• Pharmacological intervention

• Counseling, individual and/or group

• Support groups

PSYCHOTHERAPY

O’ Hara et al, Arch Gen Psych, 2000Studart et al, Psychother Pract Res, 1995

Appleby et al, BMJ, 1997Wickberg & Hwang, J Affect Dosord, 1996

IPT: Interpersonal Psychotherapy, CBT: Cognitive Behavioral Therapy, RCT: Randomized Controlled Trial

Antidepressants• Fluoxetine: only drug proven as effective as

cognitive-behavioral counseling and more effective than placebo; transmits through breast milk

• Nortriptyline• Sertraline *• Paroxetine

-use for >6 months, data lacking in regards to optimal duration

-use in combination with adjunctive anxiolytics (lorazepam, clonazepam)

Wisner et al, J Clin Psychopharmacol, 2006Misrir al, J Clin Psych, 2004

Appleby et al, BMJ, 1997

Other Considerations

• If the woman chooses to breastfeed while on antidepressants, she should work collaboratively with a psychiatrist and her pediatrician

• If the infant experiences insomnia or other behavior changes, his serum should be assayed for the presence of medication

• In sufficient data for potential neurodevelopmental deficits of the baby

Hormonal Therapy

• Transdermal estrogen: effective in severe postpartum depression - women treated for 6 months

- estrogen patch more effective than placebo for treating postpartum depression, effect occurred by 1st

month and remained statistically significant- for last 3 months, women given progesterone

12days/month to reduce risks of unopposed estrogen• Sublingual 17-beta estradiol

- effective in 2 case reports and uncontrolled series of 23 cases

• Monotherapy or adjunctive to antidepressants• BREASTFEEDING

Gregoire et al, Lancet, 1996Ahokas er al, J Clin Psych, 2001

Alternative options• Enhanced professional and social

support

• Massage therapy (reduced anxiety)

• Behavioral sleep intervention

• Electroconvulsive therapy

Mother-baby units

När mamman drabbas av:

• Psykos• Bipolär sjukdom• Svår ångest eller depression• Annan sjukdom som kräver

inläggning

Och har en bebis upp till 12 månader gammal

Treatment and activities

PPD studier in Uppsala

UPPSAT-studien

UPPSAT – resultat

Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: a nested case-control study within the UPPSAT cohort(Skalkidou et al., Psychoneuroendocrinology 2009)

• Negative association between Leptin levels and depressive symptoms 6 weeks and 6 months postpartum

• Leptin – possible biomarker for postpartum depression?

UPPSAT – resultat

Seasonality patterns in postpartum depression (Sylvén et al., American Journal of Obstetrics and Gynecology, 2010)

• Seasons vary greatly in Sweden…

• Women giving birth during autumn/winter higher risk for postpartum depression

Seasonality

UPPSAT – resultat

Thyroid function tests at delivery and risk for postpartum depressive symptoms (Sylvén et al., Psychoneuroendocrinology 2012)

• Postpartum depression and thyroid disturbances common complications after delivery

• TSH taken at delivery could predict depressive symptoms at 6 months postpartum

Pappan- partner

Pappan- partner

BASIC

Biology, Affect, Stress, Imaging and Cognition in Pregnancy and the

Puerperium

BASIC

• Autumn 2009• Longitudinal study• Web-based questionnaires• BIOLOGICAL focus

www.basicstudie.se

BASIC

• 22 % of pregnant women in Uppsala

• Goal: inclusion of 5000 women

4200

270

Förlossning

BlodprovNavelsträngsblodNavelsträngsbiopsi

Bioimpedans

Vid ES:Ryggmärgsvätska

(Placentabiopsi)(Fostervatten)

FormulärMUS

3800

148

6v. pp

6v.pp enkätAllmänna frågorAmningLiv just nuSömnTobakAlkoholEPDSBeckLivshändelserDSRS IBQPartner

6m. pp

12m. pp

6m.pp enkätAllmänna frågorAmningLiv just nuSömnTobakAlkoholEPDSBeckLivshändelserBondingPTSD Partner

12m.pp enkätJust nuLITESLEIBQVPSQ

8v.pp

BesökSTAI-SSTAI-TMADRS-SIUSMUSWDEQEPDS

Blodprov

HjärtvariabilitetBioimpedans

Vilka är med?

Not participatingn = 3097

Participatingn = 661

Age 30,6 ±5,2*** 31,9 ±4,6

Nulliparous 42,6% 43,1%

Any pregnancycomplication

20,6%* 16,8%

Gestational length, days

276** 278

Premature birth 6,9% 5,4%

AURORA 2,2% 1,7%

SSRI use ?? 4,0%

All Uppsala women giving birth 2011

Current PhD projects• Do women with prior depression have an altered cortisol awakening

response during pregnancy?– Charlotte Hellgren

• Endocrinology of antenatal depression– Anna-Karin Hannefors

• The HPA axis system in PPD– Stavros Iliadis

• Attachment styles and perinatal depression– Cathrine Axfors

• Perinatal complications and depressive symptoms– Patricia Eckerdal

• Placental mRNA expression in depressed mothers– Åsa Edvinsson, Helena Kaihola

• In search of protein-level biomarkers in perinatal depression

• Epigenetic studies within the U-BIRTH cohort

Current PhD projects• Do women with prior depression have an altered cortisol awakening

response during pregnancy?– Charlotte Hellgren

• Endocrinology of antenatal depression– Anna-Karin Hannefors

• The stress response system in PPD– Stavros Iliadis

• Attachment styles and perinatal depression– Cathrine Axfors

• Perinatal complications and depressive symptoms– Patricia Eckerdal

• Placental mRNA expression in depressed mothers– Åsa Edvinsson, Helena Kaihola

• In search of protein-level biomarkers in perinatal depression

• Epigenetic studies within the U-BIRTH cohort

CortisolLevels,nmol/L

Iliadis et al, submitted

Iliadis et al, submitted

CSF vs serum/plasma

Exploratory metabolomics

MedverkandeUPPSALA UNIVERSITY

Dept of Women’s and Children’s Health/Obstetrics and Gynecology• Alkistis Skalkidou, Inger Sundström-Poromaa, Birgitta BirgisdottirDept of Neuroscience, Psychiatry• Lisa Ekselius, Fotios Papadopoulos Dept Physical and Analytical Chemistry • Jonas BergquistDept of Immunology, Genetics and Pathology• Masood Kamali-Moghaddam

Prof. Hasse Karlsson, Turku University, FinlandProf. Georgios Chrousos, Athens University, GreeceProf. Maria Klapa, Patras University, Greece

U-BIRTH studien

BASIC-child studien

Esscher et al., accepted

Esscher et al., accepted

” I decided to be happy because this improves my health”

Voltaire

Tack !