One Potential Cause of Postpartum Psychosis

Autoimmune disorders may result in postpartum psychosis.

Posted Oct 08, 2015

Postpartum psychosis is a severe psychiatric condition that can affect women following childbirth. It is relatively uncommon, occurring after about 0.1% of deliveries (one in a thousand). A few days to a few weeks following the birth of a child, women who develop this condition exhibit a mixture of psychotic, manic, and cognitive symptoms (including a confusional state). This condition is very different from the much more common postpartum depressive disorders that may occur in the weeks or months following delivery.

Postpartum psychosis is more common in women who have had a previous episode of postpartum psychosis. In fact, women with an earlier episode of postpartum psychosis are at high risk (30%) for developing another psychotic episode following a subsequent pregnancy.

It has been known for some time that there is a relationship between postpartum psychosis and bipolar disorder. Some women who develop postpartum psychosis have a prior history of bipolar disorder, and others have a family history of bipolar disorder.

Treatment of postpartum psychosis usually involves the use of antipsychotic medications, lithium, and benzodiazepines (Valium-like drugs). Women often recover fully with proper treatment. Those who have no prior history of bipolar disorder or other psychotic illness unrelated to pregnancy can usually be tapered off medications after several months of treatment without recurrence of symptoms.

A paper recently published in the American Journal of Psychiatry by Veerle Bergink and colleagues adds to our knowledge about this fascinating and frightening condition. These investigators report the possibility of a specific cause of postpartum psychosis that may be responsible for about 4% of cases.

The Bergink group studied 96 women with postpartum psychosis. Twenty-one of these individuals had a history of bipolar disorder or another psychotic disorder unrelated to previous pregnancies. Thirteen had a prior history of postpartum psychosis, and 62 had no prior psychiatric history. 

In this study, the researchers were interested in investigating whether any of the women showed signs of having an autoimmune encephalopathy. This group of disorders occurs when the body produces antibodies to constituents of its own brain cells. These encephalopathies can cause a number of neurologic and psychiatric symptoms, including psychosis and confusion. One type of autoimmune encephalitis involves antibodies to a brain cell receptor known as the NMDA receptor. Susannah Cahalan has written about this recently discovered brain disorder in her bestselling memoir “Brain on Fire.”

Blood samples from the 96 women with postpartum psychosis were screened for evidence of autoimmune encephalitis, and samples from 4 of the 96 patients tested positive. Two of these 4 women had antibodies to the NMDA receptor and, therefore, may have had a disorder similar to that experienced by Susannah Cahalan. The other two women had antibodies against different components of brain cells, but the exact target of the antibodies could not be identified. 

The clinical histories for these 4 individuals were no different than the clinical picture for the other 92 women with postpartum psychosis. Three of the 4 had no prior psychiatric history, while one had a prior episode of postpartum psychosis. These 4 women responded to the standard psychiatric treatment mentioned above. Interestingly, the 2 patients with NMDA receptor antibody encephalitis were highly sensitive to the movement disorder side effects of antipsychotic medications. About 70% of persons with psychosis associated with NMDA receptor antibody encephalitis unrelated to postpartum psychosis have movement disorder symptoms.

One remarkable aspect of this study is that all 4 women responded to psychiatric medications. Persons with more typical cases of autoimmune encephalitis usually require aggressive anti-immunologic therapies, including high dose steroids and other immunosuppressive treatments. 

Many questions arise from this study. Were the antibodies identified in the 4 women causally related to their psychiatric illnesses or were they incidental findings? Why did these 4 patients improve without the use of immunosuppressive approaches? Why didn’t the 2 women with NMDA receptor antibody encephalitis have other symptoms that are common to this disorder, such as seizures or symptoms of movement disorder? Would persons with “typical” NMDA receptor antibody encephalitis respond to lithium and benzodiazepines? 

Over time, it is likely that more “causes” of illnesses like postpartum psychosis, bipolar disorder, and schizophrenia will be elucidated. These various “causes” will likely share the ability to disrupt specific brain systems. The pattern of brain system disruption then leads to symptoms that result in descriptive diagnoses such as postpartum psychosis, bipolar disorder, or schizophrenia. As more specific causes are elucidated, possibilities for more targeted and mechanistic treatments could follow.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD