. there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do

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2 . there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns - the ones we don't know we don't know."

3 Psychiatric disorder and childbirth - concept with a long history A young woman in child-bed not well purged after birth and delivery, fell into a great delirium suddenly without any disease afore going. She was angry most with her best friends, husband and mother, but she spoke many things religiously.. Felix Plater 1602 The beautiful wife of Carcinator, who always enjoyed the best of health, was many times attacked by melancholia after childbirth and remained insane for a month, but recovered with treatment Jao Rodrigues de Castelo Branco 1551

4 Affective disorders and childbirth - important today

5 Nosology n Wide variety of disorders occur in relationship to parturition not just postnatal depression n Psychiatric illness can be precipitated by pregnancy and childbirth - new onsets or recurrence n Pregnancy can influence existing psychiatric illness n Psychiatric disorders can influence obstetric course n Will focus here on postpartum mood disorders - Pose some questions not so many answers!

6 What affective syndromes occur postnataly? n Blues Onset: days 2-5 Duration: a few days Symptoms: mood lability Treatment: self limiting n Postnatal depression Onset: few days 6 months Duration: weeks months years Symptoms: typical symptoms of depression Treatment: antidepressants psychotherapy (CBT)

7 Puerperal Psychosis n Onset: first two weeks typical n Duration: weeks months n Symptoms: severe affective psychosis, mixed, kaleidoscopic delusions fleeting not fixed hallucinations (auditory, visual) negative symptoms not prominent erplexity and confusion n Treatment: medication admission

8 Problems with the concept of postnatal affective episodes Are rates of illness increased? Are there differences in symptomatology? Are there differences in the illness course? Are the risk factors similar? Are there differences in management?

9 Classification systems (DSM, ICD) Puerperal episodes are just episodes of illness that happen to occur following childbirth which is acting as a non-specific trigger The concept of postnatal depression does not emerge from 30 years of research with much scientific credit Professor Ian Brockington Motherhood and Mental Health

10 The importance of the concept of Postpartum Episodes n Cause great personal suffering for women n Wide ranging influences including on relationships with partner and children n Possible long term consequences for the social and cognitive development of the child n Reduce stigma n Important in the political fight for services for women at this time n May help us understand the aetiology of mood disorders

11 What differentiates PND? n Risk factors similar to depression in general n No differences in the symptom pattern Although initially thought that Atypical symptoms more common (neurotic symptoms, anxiety, irritability, phobias), probably no difference in symptomatology (Cooper et al, 2007) n Is depression more common? Selection into parenthood (Munk-Olsen 2007) When other risk factors are controlled for there is an increased risk (Eberhand-Gran et al, 2002)

12 Are hormonal factors important? n Many studies no consistent results n Methodological problems n Study simulated the hormonal changes of pregnancy and the puerperium (Bloch et al, 2000) Women with a history of PND are differentially sensitive to mood-destabilizing effects of gonadal steroids n Abnormal sensitivity to normal physiology

13 Familiality of Postnatal episodes in women with major depression Relative with PND No relative with PND (N= 31) (N= 59) PND No PND Chi-square = p < Forty et al, Am J Psych 2006

14 Evidence of specific trigger in PND Forty et al, Am J Psych, 2006

15 Emerging evidence of a specific link n Vulnerability to PND familial n Different genetic factors n Pure PND has different course n Rates increased if other risk factors controlled for n Women with PND have different sensitivity to hormonal manipulation

16 Puerperal / Postpartum Psychosis

17 Is childbirth associated with increased risk? Number of admissions Weeks prior to delivery Weeks following delivery Onset of major functional disorders in the puerperium Kendell et al 1987

18 What women are particularly at risk? Pop BP previous PP Episodes of PP per 1000 deliveries Jones and Craddock, AJPsych 2001 Robertson et al, BJPsych 2005

19 Is the risk across the psychosis spectrum? Relative Risk of admission in first postpartum month 5 0 UP BP Schiz Munk-Olsen et al 2006

20 Is the risk across the psychosis spectrum? Munk-Olsen et al 2009

21 Is this due to stopping medication? % Remaining Stable Pregnancy (Weeks 1 40) (n=59) Nonpregnant Pregnant (n=42) Nonpregnant Postpartum Weeks at Risk Off Lithium Postpartum (Weeks 41 64) (n=20) Viguera AC. Am J Psychiatry. 2000;157: (n=25)

22 Close relationship to delivery Percent st week 2nd week 3rd week 4th week 6th week Percent Onset of pp by week Onset of pp in days Heron, et al 2007

23 How should all this impact on management? The dilemma n Reproductive safety of many medications a problem n but women with bipolar disorder are at very high risk of an episode in relationship to childbirth n and. stopping medication may precipitate an episode

24 Always consider pregnancy n 50% pregnancies are unplanned n women of reproductive potential n Rediscover the interest in the sex lives of our patients that psychiatry had for most of the last century

25 Effects of stopping medication Viguera et al. Am J Psychiatry. 2007

26 Risks to mother & baby Benefits to mother & baby Risks of Drugs n Risk of teratogenicity n Risk of neonatal toxicity and withdrawal n Risk of longer term neurobehavioural / cognitive problems Risks of illness n Untreated illness may affect birth weight and gestational age at delivery n Possible detrimental effect of stress in pregnancy on the foetus n May impact on mother-infant attachment and later infant development

27 Drug X n Passes freely across the placenta and is secreted into breast milk n Studies have shown: doses of > 300 mg /day decrease chances of conception effects on sperm motility increased risk of miscarriage with doses > 300 mg / day a link between drug X and teratogenesis, fetal resorption, and low fetal weight studies in rodents have found an increase in the rate of malformations, specifically cleft palate and ectrodactyly, with doses of 100 mg/kg/d or more. children born to mothers who consumed >500mg/day were more likely to have faster heart rates, tremors, increased breathing rate, and spend more time awake in the days following birth association reported of high doses in pregnancy and subsequent SIDS

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29 Identify women are at risk n History of SEVERE postnatal illness Puerperal Psychosis n History of BP spectum disorder / other psychosis n Family history of Puerperal Psychosis or Bipolar Disorder n At antenatal booking.. Any woman who has had a psychiatric admission / been treated by psychiatric services?

30 Managing women at high risk n Full risk assessment - individualise risk n General advice n Relapse signature n Close monitoring from late pregnancy and early intervention n Written management plan in hand held notes n Liaise with Obstetrician / midwife / GP / social worker / Psychiatric team..and whoever else may be involved

31 What is the trigger? n Stress - life event n Psychological issues in transition to parenthood - CSA n Hormonal changes sex steroids Thyroid HPA axis

32 What is the trigger?

33 Are genetic factors involved? My family has a grand tradition, after a woman gives birth, she goes mad."

34 Do genetic factors influence vulnerability to PP? n Episodes of PP represent a marker for a more familial form of BP disorder Jones and Craddock, Psych Genet 2002 n Evidence for familiality of the puerperal trigger in BP families Jones and Craddock, Am J Psych 2001

35 Results: rates of PP following first delivery Relative with PP No relative with PP (N= 27) (N= 125) PP episode No PP episode Chi-square = p = Jones and Craddock, Am J Psych 2001

36 Recent findings on the Y chromosome Testis Determining Factor (TDF) Gadgetry (MAC-locus) Channel Flipping (FLP) Catching and Throwing (BLZ-1) Self-confidence (note: unlinked to ability) Ability to remember and tell jokes (GOT-1) Addiction to death and destruction movies (T-2) Air Guitar (RIF) Ability to identify aircraft (DC10) Spitting Sitting on the toilet reading (SIT) Inability to express affection on the phone (ME-2) Selective hearing loss (HuH?) Total lack of recall for dates (OOPS)

37 Specific genetic factors influencing puerperal triggering Jones et al Am J Psych 2007

38 WTCCC WTCCC. Nature 2007; 447: Bipolar disorder 200 women with PP Coronary heart disease Hypertension Rheumatoid arthritis Crohn s disease Type 1 diabetes Type 2 diabetes

39 Pathway analysis of PP women n Implicates pathway implicated in preeclampsia vascular endothelial growth factor receptor activity n 6 of 8 genes positively associated n Further work needed

40 Summary and Conclusions n Known knowns: Concept of postpartum depression controversial emerging evidence of specific relationship to childbirth in some women Women with bipolar disorder at very high risk Genetic factors implicated n Known unknowns: Understanding puerperal trigger will lead to improvements for women with postpartum episodes and increase our understanding of affective disorders more generally

41 Unknown unknowns "I would not say that the future is necessarily less predictable than the past. I think the past was not predictable when it started.