Innovative preventive intervention research to predict and treat Postpartum Depression and Post Traumatic Stress

Disorder Prof. Ronen H. Segman, M.D. Department of Psychiatry.

While some of us remain resilient at the face of the stressful challenges of life, a vulnerable minority develops reactive depression and post traumatic stress disorder following delivery or traumatic events. Post-Partum Depression (PPD) is a psychiatric disorder that occurs in 10-20% of pregnancies and can lead to physical and psychological damage to the developing infant, causing maternal morbidity and mortality. The mechanism(s) of PPD is unknown. As written in Genesis 3:16, “In sorrow thou shalt bring forth children” seems as relevant today as then, with one in seven mothers afflicted with depression. Unfortunately, currently most postpartum depression cases remain undiagnosed, with suicide constituting the leading cause of maternal death following delivery. In fact, postpartum psychosis occurs in 1 to 3 mothers per 1,000 births, and has a 5% suicide and a 4% infanticide rate. PPD develops early following delivery. Despite an increasing number of studies dealing with the biological mechanisms of depression in general, little is known about the molecular mechanisms unique to the triggering of PPD. The cellular and molecular changes in the brain of these women have not been investigated in detail; most studies have focused on the investigation of the fetus and its postnatal development. In fact, 80% of women are undiagnosed, since the illness is often undetected and is usually concealed by the woman, causing her to suffer in silence.

Following exposure to life threatening trauma, a substantial subgroup of individuals develop long term maladaptive Posttraumatic Stress Disorder (PTSD). PTSD consists of recurring intrusive memories of the stressful events, avoidance of places reminiscent of the trauma, constantly increased vigilance and arousal, a sense of foreshortened future and depression. We currently do not know how to identify those prone to develop a chronic course, nor do we possess effective treatments to prevent it from becoming chronic. Once chronic, PTSD runs a belligerent course, and we have no available treatment to effectively relief symptoms. Beyond subjective suffering and functional impairment, subjects with PTSD and depression develop a lifelong stress- induced inflammatory state, leading to premature cardiovascular illness, significantly shorter life span, and increased risk for dementia. Hadassah serves as a community hospital for Jerusalem and its vicinity and as a tertiary referral center specializing in the treatment of civilian and military trauma victims suffering from PTSD. Prof. Segman is also studying women suffering from postpartum posttraumatic stress disorder, a mental illness which affects a disproportionately high number of women in childbearing age, with a lifetime prevalence of 10.4–13.8 %. He is looking for immune biomarkers involved in this disorder before the mental illness becomes noticeable.

Prof. Ronen H. Segman, Senior Physician in the Department of Psychiatry, and his research team at Hadassah have investigated this phenomenon and have discovered a distinct gene expression signature in blood cells immediately after life threatening trauma or delivery, which predicts the development of PTSD or depression, respectively, among susceptible subjects. These initial findings were reported in the prestigious peer-reviewed journal Molecular Psychiatry, receiving an accompanying editorial; this journal is currently ranked third among 497 psychiatry and mental health journals worldwide. Looking further into this interesting finding, Prof. Segman found among depressed mothers altered hormonal sensitivity, which suppresses immune cell gene expression; in other words, he discovered a gene signature which leads to a preliminary model that can be used to predict response to immune therapy by evaluating gene expression in immune cells. These discoveries form the basis for diagnostic kits for predicting the onset of depression or PTSD using just a simple blood test and for directing a range of novel treatments aimed at harnessing a patient’s immune system to achieve a cure. This intervention will be individually tailored for focused use among a subset of vulnerable subjects who express early signs heralding triggering of persisting psychiatric reactivity.

This investigation is of the utmost importance as it deals with a disease that affects 10 to 20% of women who give birth each year and as such can be qualified as reaching epidemic proportions. In the United States alone, 15% of four million live births annually, approximately 600,000 women, suffer each year from PPD . Moreover, maternal depression during the first formative year of life impairs maternal-infant attachment, and affects socioemotional and neurocognitive development in infants, resulting in long-term behavioral and emotional problems, including increased vulnerability to mental illness. Thus, Dr. Segman’s molecular findings can potentially revolutionize the diagnosis and treatment of this highly prevalent and neglected ailment.

Prof. Segman is Director of the National Institute for Psychobiology in Israel (NIPI), a pioneering institute that supports Israel’s finest scientific minds conducting cutting edge psychobiological research. He is also Academic Chair of the Department of Psychiatry at the Hebrew University and Director of the Psychiatric Ambulatory Services and Molecular Psychiatry Laboratory at Hadassah. He has received several awards for his research and teaching at the medical school. He has published widely on the molecular genetics of psychiatric disorders and treatments. The Post partum depression study is done in collaboration with Prof. Drorith Hochner Celnikier, head, OB/GYN Department, Hadassah Mt. Scopus Hospital.