Postpartum bipolar disorder

## Contents

* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Onset groups
* 5 Course
* 6 Managementand prevention
* 6.1 Pre-conception counseling
* 6.2 Home treatment and hospitalization
* 6.3 Acute episode
* 6.4 Prevention
* 6.5 Research directions
* 7 References

## Signs and symptoms[edit | edit source]

About 40% of patients experiencing postpartum bipolar disorder have puerperal mania,[1][2]: 217 with increased energy or activity and sociability, reduced need for sleep, rapid thinking and pressured speech, euphoria and irritability, loss of inhibition, violence, recklessness and grandiosity (including religious and expansive delusions); puerperal mania is considered to be particularly severe, with highly disorganized speech, extreme excitement and eroticism.[2]: 212–213

Delusions have been associated with this disorder (including delusional parasitosis,[3] delusional misidentification syndrome,[4] and denial of pregnancy or birth[5]), as well as hallucinations,[6] disorders of the will and self,[7] catalepsy and other symptoms of catatonia,[8] self-mutilation[9] and other severe disturbances of mood.[10] Historically, literature from the 18th century also describes symptoms not typically documented today, such as rhyming speech,[11] enhanced intellect,[12] and enhanced perception.[13]

Another 25% have an acute polymorphic (cycloid) syndrome, which is a changing clinical state, with transient delusions, fragments of other syndromes, extreme fear or ecstasy, perplexity, confusion, and motility disturbances.[citation needed] In the past, some experts regarded this as pathognomonic (specific) for puerperal psychosis, but this syndrome is found in other settings, not just the reproductive process, and in men.[citation needed] These psychoses are placed in the World Health Organization's ICD-10 under the rubric of acute and transient psychotic disorders.[14] In general psychiatry, manic and cycloid syndromes are regarded as distinct, but, studied long-term among childbearing women, the bipolar and cycloid variants are intermingled in a wide variety of combinations; in this context, it seems best to regard them as members of the same 'bipolar/cycloid' group.[citation needed] Together, the manic and cycloid variants make up about two thirds of childbearing psychoses.[15]: 177

## Causes[edit | edit source]

The cause of postpartum bipolar disorder breaks down into two parts – the nature of the brain anomalies that predispose to manic and depressive symptoms, and the triggers that provoke these symptoms in those with the bipolar diathesis. The genetic, anatomical and neurochemical basis of bipolar disorder is at present unknown, and is one of the most important projects in psychiatry; but is not the main concern here. The challenge and opportunity presented by the childbearing psychoses is to identify the triggers of early postpartum onset and other onset groups.

Considering that these psychoses have been known for centuries, little effort has so far been made to understand the underlying biology.[16] Research has lagged far behind other areas of medicine and psychiatry.[17] There is a dearth of knowledge and of theories. There is evidence of heritability, both from family studies[18][19][20] and molecular genetics.[21] Early onset cases occur more frequently in first time mothers,[22] but this is not true of late postpartum or pregnancy onset. There are not many other predictors. Sleep deprivation has been suggested.[23] Inhibition of steroid sulphatase caused behavioural abnormalities in mice.[24] A recent hypothesis,[25]: 75–82 supported by collateral studies, invokes the re-awakening of auto-immunity after its suppression during pregnancy, on the model of multiple sclerosis or autoimmune thyroiditis; a related hypothesis has proposed that abnormal immune system processes (regulatory T cell biology) and consequent changes in myelinogenesis may increase postpartum psychosis risk.[26] Aberrant steroid hormone–dependent regulation of neuronal calcium influx via extracellular matrix proteins and membrane receptors involved in responding to the cell's microenvironment might be important in conferring biological risk.[27] Another promising lead is based on the similarity of bipolar-cycloid puerperal and menstrual psychosis; many women have had both. Late-onset puerperal psychoses, and relapses may be linked to menstruation. Since almost all reproductive onsets occur when the menstrual cycle is released from a long period of inhibition, this may be a common factor, but it can hardly explain episodes starting in the 2nd and 3rd trimesters of pregnancy.[15]: 320–330

## Diagnosis[edit | edit source]

Postpartum bipolar disorders must be distinguished from a long list of organic psychoses that can present in the puerperium, and from other non-organic psychoses; both of these groups are described below. It is also necessary to distinguish them from other psychiatric disorders associated with childbirth, such as anxiety disorders, depression, post-traumatic stress disorder, complaining disorders and bonding disorders (emotional rejection of the infant), which occasionally cause diagnostic difficulties.

Clinical assessment requires obtaining the history from the mother herself and, because she is often severely ill, lacking in insight and unable to give a clear account of events, from at least one close relative. A social work report and, in mothers admitted to hospital, nursing observations are information sources of great value. A physical examination and laboratory investigations may disclose somatic illness complicating the obstetric events, which sometimes provokes psychosis. It is important to obtain the case records of previous episodes of mental illness, and, in patients with multiple episodes, to construct a summary of the whole course of her psychiatric history in relation to her life.

In the 10th edition of the International Classification of Diseases, published in 1992, the recommendation is to classify these cases by the form of the illness, without highlighting the postpartum state. There is, however, a category F53.1, entitled 'severe mental and behavioural disorders associated with the puerperium', which can be used when it is not possible to diagnose some variety of affective disorder or schizophrenia. The American Psychiatric Association's Diagnostic and Statistical Manual, whose 5th edition was published in May 2013, allows the use of a 'peripartum onset specifier' in episodes of mania, hypomania or major depression if the symptoms occur during pregnancy or the first four weeks of the puerperium. The failure to recognize postpartum psychosis, and its complexity, is unhelpful to clinicians, epidemiologists, and other researchers.[15]: 166

## Onset groups[edit | edit source]

Postpartum bipolar disease belongs to the bipolar spectrum, whose disorders exist in two contrasting forms – mania and depression. They are highly heritable,[28] and affected individuals (less than 1% of the population[29]) have a lifelong tendency (diathesis) to develop psychotic episodes in certain circumstances. The 'triggers' include a number of pharmaceutical agents, surgical operations, adrenal corticosteroids, seasonal changes, menstruation and childbearing. Research into puerperal mania is, therefore, not the study of a 'disease-in-its-own right', but an investigation into the childbearing triggers of bipolar disorder.

Psychoses triggered in the first two weeks after the birth – between the first postpartum day (or even during parturition[15]: 115–116 until about the 15th day – complicate approximately 1/1,000 pregnancies.[22] The impression is sometimes given that this is the only trigger associated with childbearing. But there is evidence of four other triggers – late postpartum,[15]: 200–204 prepartum,[15]: 190–195 post-abortion[15]: 184–190 and weaning.[15]: 204–206 Marcé, widely considered an authority on puerperal psychoses,[30] claimed that they could be divided into early and late forms; the late form begins about six weeks after childbirth, associated with the return of the menses.[31] His view is supported by the large number of cases in the literature with onset 4–13 weeks after the birth, mothers with serial 4-13 week onsets and some survey evidence.[32] The evidence for a trigger acting in pregnancy is also based on the large number of reported cases, and particularly on the frequency of mothers experiencing two or more prepartum episodes. There is evidence, especially from surveys,[33] of bipolar episodes triggered by abortion (miscarriage or termination). The evidence for a weaning trigger rests on 32 cases in the literature, of which 14 were recurrent. The relative frequency of these five triggers is given by the number of cases in the literature – just over half early postpartum onset, 20% each late postpartum and prepartum onset, and the rest post-abortion and weaning onset.

In addition, episodes starting after childbirth may be triggered by adrenal corticosteroids, surgical operations (such as Caesarean section) or bromocriptine as an alternative to, or in addition to, the postpartum trigger.[34]

## Course[edit | edit source]

With modern treatment, a full recovery can be expected within 6–10 weeks.[25]: 38 [15]: 214 After recovery from the psychosis, some mothers have depression, which can last for weeks or months. About one third have a relapse, with a return of psychotic symptoms a few weeks after recovery; these relapses are not due to a failure to comply with medication, because they were often described [35] before pharmaceutical treatment was discovered.[36] A minority have a series of periodic relapses related to the menstrual cycle.[15]: 214 Complete recovery, with a resumption of normal life and a normal mother-infant relationship is the rule.[25]: 23

Many of these mothers experience other bipolar episodes, on the average about one every six years. Although suicide is almost unknown in an acute puerperal manic or cycloid episode, depressive episodes later in life carry an increased risk,[19][37] and it is wise for mothers to maintain contact with psychiatric services in the long term.

In the event of a further pregnancy, the recurrence rate is high – in the largest series, about three quarters had a recurrence, but not always in the early puerperium; the recurrence could occur during pregnancy, or later in the postpartum period.[15]: 214–215

## Managementand prevention[edit | edit source]

### Pre-conception counseling[edit | edit source]

Women with a personal or family history of puerperal psychosis or bipolar disorder are at higher risk of a puerperal episode.[20][38][39] The highest risk of all (82%) is a combination of a previous postpartum episode and at least one earlier non-puerperal episode.[15]: 274 Counseling regarding risks of recurrence should be discussed with patients who have these risk factors, and may include the potential side effects to the fetus associated with certain psychiatric medications, the frequency of episode recurrence, and the risks and benefits of various treatments during pregnancy and breast-feeding.[40] The teratogenic risks of antipsychotic agents are small,[41] but are higher with lithium[15]: 231–232 and anti-convulsant agents.[42] Carbamazepine, an anticonvulsant, when taken in early pregnancy, has some teratogenic effects,[43] but valproate, a different member of the anticonvulsant class, is associated with spina bifida and other major malformations, and a foetal valproate syndrome;[44] it is not usually recommended in women who may become pregnant.[45] More recent reviews demonstrate varying effects of different anticonvulsants (or antiepileptic medications) when given during pregnancy: the type of medication, dosage, and timing of the medication during pregnancy has different levels of safety for the fetus.[42] Given late in pregnancy, antipsychotic agents and lithium[15]: 230–232 can have adverse effects on the infant. Stopping mood-stabilisers carries a higher risk for bipolar episode recurrence during pregnancy.[46]

### Home treatment and hospitalization[edit | edit source]

It has been recognized since the 19th century[47] that it is optimal for a woman with puerperal psychosis to be treated at home, where she can maintain her role as homemaker and mother to her other children, and develop her relationship with the new-born. But there are many risks,[48] and it is essential that she is monitored by a competent adult round the clock, and visited frequently by professional staff. Home treatment is a counsel of perfection and most women will be admitted to a psychiatric hospital, many as an emergency, and usually without their babies. In a few countries, especially Australia, Belgium, France, India, the Netherlands, Switzerland and the United Kingdom, special units allow the admission of both woman and infant. Conjoint admission has many advantages, but the risks to the infant of admission to a ward full of severely ill mothers should not be understated,[49][2]: 556–558 and the high ratio of nursing staff, required to safeguard the infants, make these among the most expensive psychiatric units.

### Acute episode[edit | edit source]

These mothers require sedation with anti-psychotic (neuroleptic) agents, but are liable to extrapyramidal symptoms,[15]: 228 including neuroleptic malignant syndrome.[50] Since the link with bipolar disorder was recognized (about 1970), treatment with mood-stabilizing agents, such as lithium[25]: 20–23 and anti-convulsant drugs, has been employed with success. Electroconvulsive therapy has the reputation of efficacy in this disorder,[18] and it can be given during pregnancy (avoiding the risk of pharmaceutical treatment), with due precautions.[51] But there have been no trials, and Dutch experience has shown that almost all mothers recover quickly without it.[25]: 22 After recovery the mother may need antidepressant treatment and/or prophylactic mood stabilizers; she will need counselling about the risk of recurrence and will often appreciate psychotherapeutic support.[40]

### Prevention[edit | edit source]

There is much evidence that lithium can at least partly prevent episodes in mothers at high risk.[25]: 45–59 It is dangerous during parturition, when pressure in the pelvis can obstruct the ureters and raise blood levels.[15]: 233–234 Started after the birth its adverse effects are minimal, even in breast-fed infants.[52]

### Research directions[edit | edit source]

The lack of a formal diagnosis in the DSM and ICD has hindered research.[40] Research is needed to improve the care and treatment of affected mothers, but it is of paramount importance to investigate the causes, because this can lead to long term control and elimination of the disease. The opportunities come under the heading of clinical observation, the study of the acute episode, long-term studies, epidemiology, genetics and neuroscience.[15]: 369–371 In a disorder with a strong genetic element and links to the reproductive process, costly imaging, molecular-genetic and neuroendocrinological investigations will be decisive. These depend on expert laboratory methods. It is important that the clinical study is also 'state-of-the-art'– that scientists understand the complexity of these psychoses, and the need for multiple and reliable information sources to establish the diagnosis.

## References[edit | edit source]

1. ↑ Meltzer E S, Kumar R (1985) Puerperal mental illness, clinical features and classification: a study of 142 mother-and-baby admissions. British Journal of Psychiatry 147: 647-654.
2. ↑ 2.0 2.1 2.2 Brockington IF (1996). Motherhood and Mental Health. Oxford: Oxford University Press.
3. ↑ Ahokas A, Aito M, Turiainen S (February 2000). "Association between oestradiol and puerperal psychosis". Acta Psychiatrica Scandinavica. 101 (2): 167–9, discussion 169–70. doi:10.1034/j.1600-0447.2000.96005.x. PMID 10706019. S2CID 42278657.
4. ↑ Silva JA, Leong GB, Longhitano M, Botello TE (February 1991). "Delusion of fetal duplication in a Capgras patient". Canadian Journal of Psychiatry. 36 (1): 46–7. doi:10.1177/070674379103600109. PMID 2029683. S2CID 39442045.
5. ↑ Martin MG (1980). Étude sur la folie puerpérale (Ph.D. thesis). Lille. case 20.
6. ↑ Weill M (1851) Considération générales sur la folie puerpérale. Thèse, Strasbourg, case 10.
7. ↑ Capelle J (1929) Puerpéralité et psychoses. Thèse, Bordeaux,case 13.
8. ↑ Scherer M (1905) Über die Geistesstörungen beim Zeugungs- und Fortplanzungs-geschäft des Weibes. Inaugural-Dissertation, Kiel, case 6.
9. ↑ Rocher G (1877) Étude sur la folie puerpérale. Thèse, Paris, case 5.
10. ↑ Jones I, Chandra PS, Dazzan P, Howard LM (November 2014). "Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period". Lancet. 384 (9956): 1789–1799. doi:10.1016/S0140-6736(14)61278-2. PMID 25455249. S2CID 44481055.
11. ↑ Hoffmann F (1721) De primipara ex terrore facta maniaca et feliciter restituta. Dec. III, casus III, pages 125-127.
12. ↑ Reichard (1787) Eine heftige Raseren von zurückgetretener Milch, vorzüglich durch den Hurhamschen Spiessglas-Wein geheilt. Stark's Neues Archiv für die Geburtshülfe, Frauenzimmer und neugebohrner Kinder-Krankheiten 1: 78-89.
13. ↑ Osiander F B (1797). Neue Denkwürdigkeiten für Ärzte und Geburtshelfer. Göttingen, Rosenbusch, volume 1, pages 90-128.
14. ↑ World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines, Geneva, World Health Organization, pages 101-102.
15. ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 Brockington IF (2017). The Psychoses of Menstruation and Childbearing. Cambridge: Cambridge University Press. pp. 1–278.
16. ↑ Davies W. (2017) Understanding the pathophysiology of postpartum psychosis: challenges and new approaches. World Journal of Psychiatry 7(2):77-88 doi:10.5498/wjp.v7.i2.77
17. ↑ Brockington I F (2018) Publications on 'puerperal psychosis', 2013-2017. Annals of Women's Health 2: 1-8.
18. ↑ 18.0 18.1 Prothero C (1969) Puerperal psychoses: a long-term study 1927-1961. British Journal of Psychiatry 115: 9-30.
19. ↑ 19.0 19.1 Schöpf J (1992) Postpartum-Psychosen: Beitrag zur Nosologie. Thesis, Zürich.
20. ↑ 20.0 20.1 Jones I, Craddock N (2001) Familiarity of the puerperal trigger in bipolar disorder: results of a family study. American Journal of Psychiatry 158: 913-917.
21. ↑ Jones I, Hamshere M, Nangle J M, Bennett P, Green E, Heron J, Segurado R, Lambert D, Holmans P, Corvin A, Owen M, Jones L, Gill M, Craddock N (2007) Bipolar affective puerperal psychosis: genome-wide significant evidence for linkage to chromosome 16. American Journal of Psychiatry 164: 1099-1104.
22. ↑ 22.0 22.1 Kendell RE, Chalmers JC, Platz C (May 1987). "Epidemiology of puerperal psychoses". The British Journal of Psychiatry. 150 (5): 662–73. doi:10.1192/bjp.150.5.662. PMID 3651704. S2CID 4613996.
23. ↑ Lewis K J S, Foster R G, Jones I R (2016) Is sleep disruption a trigger for postpartum psychosis? British Journal of Psychiatry 208: 409-411.
24. ↑ Humby T, Cross E S, Messer L, Guerrero S, Davies W (2016) A pharmacological mouse model suggests a novel risk pathway for postpartum psychosis. Psychoneuroendocrinology 74: 363-370.
25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 Bergink V (2013). First-onset postpartum psychosis (Ph.D. thesis). Rotterdam.
26. ↑ Dazzan P, Fuste M, Davies W. (2018) Do defective immune system-mediated myelination processes increase postpartum psychosis risk? Trends in Molecular Medicine 24(11): 942-949 doi:10.1016/j.molmed.2018.09.002
27. ↑ Thippeswamy H, Davies W (June 2021). "A new molecular risk pathway for postpartum mood disorders: clues from steroid sulfatase-deficient individuals". Archives of Women's Mental Health. 24 (3): 391–401. doi:10.1007/s00737-020-01093-1. PMC 8116278. PMID 33219387. S2CID 227076500.
28. ↑ Bertelsen A, Harvald B, Hauge M (April 1977). "A Danish twin study of manic-depressive disorders". The British Journal of Psychiatry: The Journal of Mental Science. 130 (4): 330–51. doi:10.1192/bjp.130.4.330. PMID 558030. S2CID 23050201.
29. ↑ Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, Whiteford HA (August 2016). "The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013". Bipolar Disorders. 18 (5): 440–50. doi:10.1111/bdi.12423. hdl:11343/291577. PMID 27566286. S2CID 46097223.
30. ↑ Marcé LV (1858). Traité de la Folie des Femmes Enceintes, des Nouvelles Accouchées et des Nourrices, et Considérations Médico-légales qui se rattachent à ce sujet. Paris: Baillière.
31. ↑ Marcé LV (1862). Traité Pratique des Maladies Mentales. Paris: Baillière. pp. 143–147.
32. ↑ Munk-Olsen T, Laursen TM, Pedersen CB, Mors O, Mortensen PB (December 2006). "New parents and mental disorders: a population-based register study". JAMA. 296 (21): 2582–9. doi:10.1001/jama.296.21.2582. PMID 17148723. S2CID 22927772.
33. ↑ Reardon DC, Cougle JR, Rue VM, Shuping MW, Coleman PK, Ney PG (May 2003). "Psychiatric admissions of low-income women following abortion and childbirth". Canadian Medical Association Journal. 168 (10): 1253–6. PMC 154179. PMID 12743066.
34. ↑ Brockington I (February 2017). "Non-reproductive triggers of postpartum psychosis". Archives of Women's Mental Health. 20 (1): 55–59. doi:10.1007/s00737-016-0674-9. PMC 5237449. PMID 27722949.
35. ↑ Delay J, Boitelle G, Corteel A (1948). Les psychoses du postpartum: étude cyto-hormonale. Semaines d'Hôpitaux de Paris 24: 2891-2901.
36. ↑ Delay J, Deniker P (1952) Les traitements de psychose par une méthode neurolytique dérivée de l'hibernothérapie; le 4560 RP utilisée seul en cure prolongée et continue. Comptes Rendus de la Congrès des Médecins Aliénists et Neurolologists de France 50: 497-502.
37. ↑ Klompenhouwer J L (1992) Puerperal psychosis. Thesis, Rotterdam.
38. ↑ Wesseloo R, Kamperman A M, Munk-Olsen T, Pop V J M, Kushner S A, Bergink V (2016) Risk of postpartum relapse in bipolar disorder and postpartum psychosis: a systematic review and meta-analysis. American Journal of Psychiatry 173: 117-127.
39. ↑ Blackmore E R, Rubinow D R, O'Conner T G, Liu X, Tang W, Craddock N, Jones I (2013) Reproductive outcomes and risk of subsequent illness in women diagnosed with postpartum psychosis. Bipolar Disorders 15: 394-404.
40. ↑ 40.0 40.1 40.2 Jones I, Chandra P S, Dazzan P, Howard L M (2014) Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet 384: 1789-1799.
41. ↑ Habermann F, Fritzsche J, Fuhlbrück F, Wacker E, Allignol A, Weber-Schöndorfer C, Meister R, Schäfer C (2013) Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study. Journal of Clinical Psychopharmacology 33: 453-462.
42. ↑ 42.0 42.1 Tomson, Torbjörn; Battino, Dina; Perucca, Emilio (April 2019). "Teratogenicity of antiepileptic drugs". Current Opinion in Neurology. 32 (2): 246–252. doi:10.1097/WCO.0000000000000659. ISSN 1473-6551. PMID 30664067. S2CID 58608931. Archived from the original on 2023-10-19. Retrieved 2024-01-07.
43. ↑ Matolon S, Schechtman S, Goldzweig G, Ornoy A (2002) The teratogenic effect of carbamezepine: a meta-analysis of 1255 exposures. Reproductive Toxicology 16: 9-17.
44. ↑ Clayton-Smith J, Donnai D (1995) Fetal valproate syndrome. Journal of Medical Genetics 32: 724-727.
45. ↑ Stahl, Stephen M., ed. (2020), "Valproate", Prescriber's Guide: Stahl's Essential Psychopharmacology (7 ed.), Cambridge: Cambridge University Press, pp. 829–836, doi:10.1017/9781108921275.142, ISBN 978-1-108-92601-0, archived from the original on 2024-01-11, retrieved 2023-01-26
46. ↑ Viguera A C, Whitfield T, Baldessarini R J, Newport D J, Stowe Z, Reminick A, Zurick A, Cohen L S (2007) Risk of recurrence of women with bipolar disorder during pregnancy: a prospective study of mood stabilizer discontinuation. American Journal of Psychiatry 164: 1817-1824.
47. ↑ Godding W W (1874) Puerperal insanity. Boston Medical & Surgical Journal 10: 317-319.
48. ↑ Conolly J (1864) Clinical features of the principle forms of insanity. Lecture 13. Description and treatment of puerperal insanity. Lancet i: 349-354.
49. ↑ Margison F R (1981) Assessing the use of a psychiatric unit for mothers and their babies: risks to the babies. M Sc thesis, Manchester.
50. ↑ Price D K, Turnbull G J, Gregory R P, Stevens D R (1989). Neuroleptic malignant syndrome in a case of postpartum psychosis. British Journal of Psychiatry 155: 849-852.
51. ↑ Anderson E L, Reti I M (2009) ECT in pregnancy: a review of the literature from 1941 to 2007. Psychosomatic Medicine 71: 235-242.
52. ↑ Viguera A C, Newport D J, Ritchie J, Stowe Z, Whitfield T, Mogielnicki J, Baldessarini R J, Zurick A, Cohen L S (2007) Lithium in breast milk and nursing infants: clinical implications. American Journal of Psychiatry 164: 342-345.