The New Biology of PMDD

In the late 1990s, we were able to demonstrate that PMDD was not a hormone deficiency disorder but rather a hormone sensitivity disorder; i.e., normal levels or changes in reproductive steroids (estrogen and progesterone) triggered the symptoms of PMDD but did so only in a subgroup of women who, for unknown reasons, were sensitive to these hormonal changes. We subsequently demonstrated the same phenomenon in women with a history of postpartum depression. We showed, therefore, in two mood disorders – PMDD and PPD – that changes in hormone levels that had no effect at all on mood in most women were capable of triggering substantial mood changes in a subgroup of women. But what was responsible for this differential sensitivity? We now have at least a partial answer.

In the January issue of Molecular Psychiatry, Neelima Dubey, Jessica Hoffman and colleagues demonstrated that the cells of women with PMDD differ from those without PMDD in both their baseline functioning and in their response to estrogen and progesterone. These findings show that an important family of genes that regulate the response to both the internal and external environments are more active in women with PMDD and, of greater interest, respond differently when the cells are exposed to estrogen or progesterone. In other words, the cells themselves were differentially sensitive to reproductive steroids, just as women with PMDD show differential behavioral response to changes in reproductive steroids. These findings are important for three reasons: 1) they demonstrate a biological basis for PMDD; and 2) they may help us identify targets for developing effective therapies; and 3) they provide clues to help us understand how a biological signal may be transformed into a change in mood and behavior.

David R. Rubinow, MD

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The Role of Sexual Abuse in PMDD

David R. Rubinow, M.D.

No one needs to be told that abuse is not good for your health.  Recent studies, however, have revealed a new possible consequence of abuse, namely premenstrual dysphoria [1-4].  Further, it looks like PMDD  not only represents an enduring lesson that the body has learned from the stress surrounding abuse, but PMDD also “rewires” the effects of  abuse from those seen in the absence of PMDD [5].

These conclusions emerge from several lines of evidence.  First, decades old studies identified a link between abuse and PMDD, with a greater proportion of PMDD reporting a history of physical or sexual abuse compared with women without PMDD [4].  Second, women with a history of PMDD and abuse have higher pain sensitivities and a significantly increased prevalence of migraine with aura, but women with an abuse history lacking PMDD fail to show these increased rates of pain sensitivity [5].  Third, women with a history of PMDD and abuse have multiple measures of disturbed cardiovascular function both at baseline and after challenge tests, but abuse does not predict these enduring physiological differences in women without a history of PMDD [6].

How can we make sense of the special physiological state that appears to accompany the combination of PMDD and history of abuse?  As inferred from studies showing persistent hormonal consequences of combat in men and abuse in women, genetic vulnerability coupled with severe stress may contribute to these disorders [7].  According to this model,  genetic factors that may influence resilience or stress maladaptation are likely separate from those that cause hormone sensitivity (the source of PMDD), but these genetic “systems” are nonetheless capable of interacting with each other to generate very specific (albeit distributed) biological effects. Thus the enduring biological effects of women with PMDD and a history of abuse are different from those seen in women with solely a history of one condition or the other.  Another possibility would suggest that the recurrent experience of symptoms in PMDD (rather than the genetic predisposition to PMDD) might interact with either the physiological consequences of abuse or the absence of protective, resilience factors to yield the abnormalities observed.

In either case, there are several important take-home messages. First, it is likely that the recurrent symptoms of PMDD are not without enduring, physiological impact, much as has been demonstrated for abuse histories.  And second, understanding the means by which different stress-linked disorders interact – either at the level of susceptibility or recurrent symptom expression – will be critical to our ability to identify and prevent the risks to health that women with abuse and PMDD experience.

  1. Paddison, P. L., Gise, L. H., Lebovits, A., Strain, J. J., Cirasole, D. M., & Levine, J. P. (1990). Sexual abuse and premenstrual syndrome: comparison between a lower and higher socioeconomic group. Psychosomatics31(3), 265-272.
  2. Golding, J. M., Taylor, D. L., Menard, L., & King, M. J. (2000). Prevalence of sexual abuse history in a sample of women seeking treatment for premenstrual syndrome. Journal of Psychosomatic Obstetrics & Gynecology21(2), 69-80.
  3. Koci, A., & Strickland, O. (2007). Relationship of adolescent physical and sexual abuse to perimenstrual symptoms (PMS) in adulthood. Issues in mental health nursing28(1), 75-87.
  4. Perkonigg, A., Yonkers, K. A., Pfister, H., Lieb, R., & Wittchen, H. U. (2004). Risk factors for premenstrual dysphoric disorder in a community sample of young women: the role of traumatic events and posttraumatic stress disorder.The Journal of clinical psychiatry65(10), 1314-1322.
  5. Fleischman, D. S., Bunevicius, A., Leserman, J., & Girdler, S. S. (2013). Menstrually Related Mood Disorders and a History of Abuse: Moderators of Pain Sensitivity.
  6. Girdler, S. S., Leserman, J., Bunevicius, R., Klatzkin, R., Pedersen, C. A., & Light, K. C. (2007). Persistent alterations in biological profiles in women with abuse histories: influence of premenstrual dysphoric disorder. Health psychology: official journal of the Division of Health Psychology, American Psychological Association26(2), 201.
  7. Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2003). Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. FOCUS: The Journal of Lifelong Learning in Psychiatry1(3), 282-289.
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Interview with Dr. Samantha Meltzer-Brody

Check out this interview with Dr. Samantha Meltzer-Brody on postpartum anxiety and depression!

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UNC Perinatal Psychiatry Inpatient Unit Celebrates One-Year Anniversary


Highlights of Past Year

After the dust settled we admitted our first patient on Aug. 15th, 2011.  Since then have admitted over 115 patients, including  treating patients from Iowa, Washington, DC, Florida and South Carolina and fielding    referrals from many other states.

Average length of stay is 9.73 days with a mean of 7 during the last 3 months.  This is consistent with overall year’s data.

Experienced 3 weeks at steady census of 5 patients in May 2012

Data collection has evidence of improved outcome measures in patient’s report in areas of depression and anxiety.

Continuing Education of Staff

Currently have 5 core staff – 1 RN certified in advanced fetal monitoring;  6 RN’s certified in basic fetal monitoring.
5 RN’s have completed 40 hours of advanced clinical shadowing and monitoring


July 2011 – NPR spot that put our name on the map

August 2011 – Daily Tar Heel, News and Observer, Huffington Post, CNN

September 2011 –Documentary about the unit.  Producer received an Emmy nomination – link

October 2011 – Time Healthland Magazine

November 2011- Nurse Magazine


October 2011 – Nurse Manager received award from Nurse Director group for  opening of perinatal unit

April 2012- Dr. Samantha Meltzer-Brody – named one of the Triangle’s top Ten women in Medicine and also named Sanders Clinical Scholar.

Summer 2012 – DeeDee Fryer – recognized as a UNC Plus Person in the Growth Pillar for achievements on the perinatal unit.

September 2012- Facebook program page goes live on Sept. 7th.   By Sept. 15th, over 125 likes – link

September 18th 2012 – Facebook Chat with Dr. Meltzer -Brody

October 2012 – ANCC Magnet presentation by Lynne Burns, Nurse manager

October 2012 – Marce Society presentation by Dr. Meltzer-Brody

November 2012- APNA presentation by DeeDee Fryer & Chris Raines

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Dr. Samantha Meltzer-Brody Interviewed in Huffington Post

Samantha Meltzer-Brody, UNC Chapel Hill Associate Professor and Director of the Perinatal Psychiatry Program, was interviewed in Huffington Post on the cyclical nature of depression and poverty.

Meltzer-Brody explains, “There is a huge economic effect, because if Mom is miserable she is not going to be able to hold a job. Mothers suffer, so kids suffer, and then the next generation repeats the process over again.”

Be sure to check out the full article at the link.

Also, to learn more about Dr. Meltzer-Brody’s research, visit

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2011 Women’s Mental Health Conference

The UNC Center for Women’s Mood Disorders and UNC Eating Disorders Program are partnering to host the 7th annual Women’s Mental Health Conference on November 5, 2011. The theme of this year’s conference is Women’s Mental Health Across the Lifespan: Puberty, Pregnancy and Perimenopause.

We are thrilled that many of our wonderful UNC faculty members will be here to share their clinical experience and discuss new treatment strategies. Our special guest speakers are Rebecka Peebles, MD, Assistant Professor of Pediatrics at Children’s Hospital of Philadelphia and Katherine Wisner, MD, MS, Professor of Psychiatry, OBGYN, and Epidemiology at the University of Pittsburgh.

Our conference will provide tools to empower health care providers to ask the critical questions to detect eating and women’s reproductive mood disorders across the
lifespan, to effectively manage these disorders when appropriate in their practices, and to
appraise when specialty referral is required.

Please join us! Registration is now open.

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Tackling Postpartum Depression

“Women during pregnancy and postpartum have very unique needs. Pregnancy and delivery and the time in the first few months postpartum is a very special time, and it’s also a very vulnerable time for women … The story of our inpatient unit occurring is really a story about the collaborative spirit at UNC and our focus on innovation and really doing the right thing to help patients.”-Dr. Samantha Meltzer-Brody, Director of the Perinatal Psychiatry Program at the University of North Carolina

Learn more about our new Perinatal Psychiatry Inpatient Unit in this segment from WUNC’s The State of Things. Dr. Meltzer-Brody talks about how our new unit came to be and former UNC patient Amy Martin talks about her experience with postpartum depression.

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Estrogen Receptor Beta and Cancer

Last week, a symposium held in Stockholm reviewed the biological effects of estrogen receptor beta. Striking among the presentations was a dual role of this receptor isoform in the regulation of cell growth: decreasing proliferation in the prostate, breast and colon (and hence a potential anti-cancer effect); and increasing proliferation in the hippocampus (and hence potentially improving certain types of cognitive function).  The role in physiology of this receptor subtype, discovered in 1996, is likely to continue to evolve and will potentially yield new, improved, and specific forms of treatment for an array of disorders.

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Mental Health Minute

Dr. Susan Killenberg shares a new approach to treating depression that is now available at UNC Mental Health Specialists.

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Real Doctors, Real People

Professor of  Obstetrics and Gynecology. 


Meet Dr. John Steege, a UNC physician and an investigator on several research studies ongoing at the UNC Center for Women’s Mood Disorders.

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