Posts Tagged Massachusetts General Hospital

Low Estrogen Linked to PTSD


Low Estrogen Linked to PTSDHigh levels of estrogen may help protect a woman from mood disorders, while low levels of the hormone can make a woman more susceptible to trauma at certain times in her menstrual cycle, according to new research by Harvard and Emory University neuroscientists.

Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference has remained unclear.  The new research, however, suggests that women are most at risk for symptoms of post-traumatic stress disorder (PTSD) when their estrogen is low during the menstrual cycle.

“PTSD is a disorder of recovery,” said author Mohammed Milad, associate professor of psychiatry at Harvard Medical School (HMS) and director of the Behavioral Neuroscience Laboratory at Massachusetts General Hospital (MGH).

Men may be less susceptible to mood disorders since testosterone is regularly converted into estrogen in the male brain, resulting in a more steady flow of estrogen.

In healthy women and female rats, estrogen calms the fear response, according to the Harvard researchers, who were led by Kelimer Lebron-Milad, an HMS instructor of psychiatry.

The Emory researchers, led by postdoctoral researcher Ebony Glover, proved that the same is true for women suffering from PTSD. The higher their blood levels of estrogen were when they completed a fear-extinction task, the less likely women were to act startled.

Both studies used “fear-conditioning” experiments, in which the participant is trained to fear a safe “conditioned stimulus” such as a colored shape, paired with a frightening or painful “unconditioned stimulus” like a shock to the finger or a puff of air to the neck or eye.

Overall, women or female rats showed less fear to the neutral stimulus when their estrogen levels were high rather than low.

PTSD is common in women after a trauma such as rape or sexual assault, which studies say are experienced by 25 to 30 percent of women in their lifetimes, and the symptoms last on average four times as long in women as in men after trauma.

This new research suggests the reason for this vulnerability may be the monthly menstrual change in estrogen.

“People are afraid to look into the influence of sex hormones on ‘fear learning’ and extinction,” said Mohammed Milad, “because it’s such a complex system.”

When Milad studied fear as a Ph.D. student, his lab used only male rats. But when he began to study fear in humans as a postdoctoral researcher, he saw that female data were much more variable.

“The data led me there,” to sex differences, Milad said. “Since females add variance, scientists have tended to avoid studying them” in rodent research, he said. Studies of the human brain would tend to combine men and women, assuming that neurological gender differences were minimal. But this attitude is changing.

In addition, since birth control pills affect estrogen levels, they may be used as a future treatment against post-traumatic stress.

The research is published in Biological Psychiatry.

Source:  Biological Psychiatry

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Do ovaries continue to produce eggs during adulthood?


ScienceDaily (July 26, 2012) — A compelling new genetic study tracing the origins of immature egg cells, or ‘oocytes’, from the embryonic period throughout adulthood adds new information to a growing controversy. The notion of a “biological clock” in women arises from the fact that oocytes progressively decline in number as females get older, along with a decades-old dogmatic view that oocytes cannot be renewed in mammals after birth.

After careful assessment of data from a recent study published in PLoS Genetics, scientists from Massachusetts General Hospital and the University of Edinburgh argue that the findings support formation of new eggs during adult life; a topic that has been historically controversial and has sparked considerable debate in recent years.

Eggs are formed from progenitor germ cells that exit the mitotic cycle, thereby ending their ability to proliferate through cell division, and subsequently enter meiosis, a process unique to the formation of eggs and sperm which removes one half of the genetic material from each type of cell prior to fertilization.

While traditional thinking has held that female mammals are born with all of the eggs they will ever have, newer research has demonstrated that adult mouse and human ovaries contain a rare population of progenitor germ cells called oogonial stem cells capable of dividing and generating new oocytes. Using a powerful new genetic tool that traces the number of divisions a cell has undergone with age (its ‘depth’) Shapiro and colleagues counted the number of times progenitor germ cells divided before becoming oocytes; their study was published in PLoS Genetics in February this year.

If traditional thinking held true, all divisions would have occurred prior to birth, and thus all oocytes would exhibit the same depth regardless of age. However, the opposite was found — eggs showed a progressive increase in depth as the female mice grew older.

In their assessment of the work by Shapiro and colleagues — published recently in a PLoS Genetics Perspective article — reproductive biologists Dori Woods, Evelyn Telfer and Jonathan Tilly conclude that the most plausible explanation for these findings is that progenitor germ cells in ovaries continue to divide throughout reproductive life, resulting in production of new oocytes with greater depth as animals age.

Although these investigations were performed in mice, there is emerging evidence that oogonial stem cells are also present in the ovaries of reproductive-age women, and these cells possess the capacity, like their mouse counterparts, to generate new oocytes under certain experimental conditions. While more work is needed to settle the debate over the significance of oocyte renewal in adult mammals, Woods and colleagues emphasize that “the recent work of Shapiro and colleagues is one of the first reports to offer experimental data consistent with a role for postnatal oocyte renewal in contributing to the reserve of ovarian follicles available for use in adult females as they age.”

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The above story is reprinted from materials provided by Public Library of Science.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Woods DC, Telfer EE, Tilly JL. Oocyte Family Trees: Old Branches or New Stems? PLOS Genet, 2012 DOI: 10.1371/journal.pgen.1002848

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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CT angiography speeds emergency diagnosis of heart disease in low-risk patients


ScienceDaily (July 25, 2012) — Incorporating coronary CT angiography (CCTA) into the initial evaluation of low-risk patients coming to hospital emergency departments (EDs) with chest pain appears to reduce the time patients spend in the hospital without incurring additional costs or exposing patients to significant risks. The report of a study conducted at nine U.S. hospitals appears in the July 26 New England Journal of Medicine.

“We found that the use of CCTA in emergency department evaluation of acute chest pain very effectively identified which patients did or did not have coronary artery obstruction, allowing clinicians to focus the use of resources on patients with heart disease,” says Udo Hoffmann, MD, MPH, director of the Cardiac MR PET CT program at Massachusetts General Hospital (MGH) and corresponding author of the NEJM article. “Although the use of CCTA added to the amount of diagnostic testing used in the evaluation process, compared with current standard protocols it significantly reduced length of stay without increasing costs.”

CCTA combines advanced CT scanning with the use of intravenous contrast material to produce detailed images of blood vessels supplying the heart without the need for cardiac catheterization. Several previous studies, including an immediate predecessor to the current one, have indicated that CCTA can effectively distinguish chest pain patients that do not have coronary artery disease, but those studies all had such limitations as lack of a control group or limited analysis of factors like costs and radiation exposure. The current study — ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography)-II — was designed to determine whether a CCTA-based evaluation strategy could improve clinical decision making at different hospitals across the country.

From April 2010 to January 2012, patients arriving at the participating hospitals’ EDs for evaluation of chest pain who had no history of cardiovascular disease and whose initial tests — ECG and measurement of the biomarker troponin — did not clearly indicate a heart attack were invited to participate in the trial. Those who agreed to participate were randomly assigned to one of two groups. The control group proceeded with standard evaluation, with all diagnostic and treatment decisions being made by hospital physicians not part of the study group. The other group had CCTA as part of their ED evaluation, with the results being shared with attending physicians who, again, made all clinical decisions. Participants who were discharged from the hospital within 24 hours of arrival were called within 72 hours to assess their status, and all participants were called 28 days after hospital discharge and asked whether any return ED visits or rehospitalizations had taken place. Participant responses were verified by checking their medical records. About 1,000 patients completed the study, including the 28-day followup.

The investigators found that participants in the CCTA group had significant reductions in the amount of time from ED arrival until discharge either from the ED or after a hospital stay, with half of the CCTA group being discharged within 8.6 hours but only 10 percent of the control group being released so quickly. The amount of time until a diagnosis of heart disease was either ruled out or confirmed was also shorter for the CCTA group than for the controls, and more patients receiving CCTA were discharged directly from the ED rather than being admitted to an observation unit. The percentage of patients actually diagnosed with heart disease was similar in both groups at around 8 percent, and there were no missed diagnoses in either group.

Analysis of total clinical resources used from arrival to discharge indicated that CCTA participants had more diagnostic procedures than control group members, but the difference was not statistically significant. Neither were there any significant differences between groups in total costs through the 28-day followup in those participants for whom cost information was available. CCTA group participants were exposed to higher cumulative doses of radiation, but the authors note that recent studies have indicated that CCTA can often be successfully performed using lower doses and suggest that future studies test the utility of low-dose CCTA examination.

“It’s very important to strive for the greatest efficiency in diagnostic testing, and in this study, additional testing was primarily carried out in patients found to have coronary artery disease,” Hoffmann says. “There also were fewer adverse clinical events in those receiving CCTA, although the study group was too small to conclude that CCTA reduced those risks.

“Showing at a variety of clinical sites that CCTA is at least as good as standard ED evaluation without increasing costs elevates the procedure from one appropriate only for specialized settings to one that can be applied in many centers,” he adds. “I’d really like to commend the commitment and teamwork of all the participating sites and departments, which was essential to the successful completion of this study.” Hoffmann is an associate professor of Radiology at Harvard Medical School.

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Story Source:

The above story is reprinted from materials provided by Massachusetts General Hospital.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Udo Hoffmann, Quynh A. Truong, David A. Schoenfeld, Eric T. Chou, Pamela K. Woodard, John T. Nagurney, J. Hector Pope, Thomas H. Hauser, Charles S. White, Scott G. Weiner, Shant Kalanjian, Michael E. Mullins, Issam Mikati, W. Frank Peacock, Pearl Zakroysky, Douglas Hayden, Alexander Goehler, Hang Lee, G. Scott Gazelle, Stephen D. Wiviott, Jerome L. Fleg, James E. Udelson. Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain. New England Journal of Medicine, 2012; 367 (4): 299 DOI: 10.1056/NEJMoa1201161

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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