Skin disease studies go deep: depression/inflammation insight

A recent paper from Miller and psychiatry chair Mark Rapaport looks at clinical trials testing an anti-inflammatory drug against psoriasis, to see whether participants’ depressive symptoms improved. Read more

New insight into how brain cells die in Alzheimer's and FTD

(Epi)genetic hallucinations induced by loss of LSD1 resemble Alzheimer's. Another surprise: LSD1 aggregates in Alzheimer's brain, looking like Tau Read more

2B4: potential immune target for sepsis survival

Emory immunologists have identified a potential target for treatments aimed at reducing mortality in sepsis, an often deadly reaction to Read more

PTSD

Big data with heart, for psychiatric disorders

Imagine someone undergoing treatment by a psychiatrist. How do we know the treatment is really working or should be modified?

To assess whether the patient’s condition is objectively improving, the doctor could ask him or her to take home a heart rate monitor and wear it continuously for 24 hours. An app connected to the monitor could then track how much the patient’s heart rate varies over time and how much the patient moves.

Heart rate variability can be used to monitor psychiatric disorders

MD/PhD student Erik Reinertsen is the first author on two papers in Physiological Measurement advancing this approach, working under the supervision of Gari Clifford, interim chair of Emory’s Department of Biomedical Informatics.

Clifford’s team has been evaluating heart rate variability and activity as a tool for monitoring both PTSD (post-traumatic stress disorder) and schizophrenia. Clifford says his team’s research is expanding to look at treatment-resistant depression and other mental health issues.

For clinical applications, Clifford emphasizes that his plans focus on tracking disease severity for patients who are already diagnosed, rather than screening for new diagnoses. His team is involved in much larger studies in which heart rate data is being combined with physical activity data from smart watches, body patches, and clinical questionnaires, as well as other behavioral and exposure data collected through smartphone usage patterns.

Intuitively, heart rate variability makes sense for monitoring PTSD, because one of the core symptoms is hyperarousal, along with flashbacks and avoidance or numbness. However, it turns out that the time that provides the most information is when heart rate is lowest and study participants are most likely asleep, or at their lowest ebb during the night.

Home sleep tests generate a ton of information, which can be mined. This approach also fits into a trend for wearable medical technology, recently highlighted in STAT by Max Blau (subscription needed).

The research on PTSD monitoring grows out of work by cardiologists Amit Shah and Viola Vaccarino on heart rate variability in PTSD-discordant twin veterans (2013 Biological Psychiatry paper). Shah and Vaccarino had found that low frequency heart rate variability is much less (49 percent less) in the twin with PTSD. Genetics influences heart rate variability quite a bit, so studying twins allows those factors to be accounted for. Read more

Posted on by Quinn Eastman in Heart, Neuro Leave a comment

How estrogen modulates fear learning — molecular insight into PTSD in women

Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD) at some points in their menstrual cycles or lifetimes, while high estrogen levels may be protective.

New research from Emory University School of Medicine and Harvard Medical School provides insight into how estrogen changes gene activity in the brain to achieve its protective effects.

The findings, published in Molecular Psychiatry, could inform the design of preventive treatments aimed at reducing the risk of PTSD after someone is traumatized.

The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification to the shape of DNA that is usually a sign of genes that are turned off.

The group included adult women of child-bearing age, in which estrogen rises and falls with the menstrual cycle, and women that had gone through menopause and had much lower estrogen levels.

“We knew that estrogen affects the activity of many genes throughout the genome,” says Alicia Smith, PhD, associate professor and vice chair of research in the Department of Gynecology and Obstetrics at Emory University School of Medicine. “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”

That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning. Read more

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Neuroscientists show hippocampus also has important role in emotional regulation

A region of the brain called the hippocampus is known for its role in memory formation. Scientists at Yerkes National Primate Research Center, Emory University are learning more about another facet of hippocampal function: its importance in the regulation and expression of emotions, particularly during early development.

Using a nonhuman primate model, their findings provide insight into the mechanisms of human psychiatric disorders associated with emotion dysregulation, such as PTSD (post-traumatic stress disorder) and schizophrenia. The results were published online recently by the journal Psychoneuroendocrinology.

“Our findings demonstrate that damage to the hippocampus early in life leads to increased anxiety-like behaviors in response to an unfamiliar human,” says research associate Jessica Raper, PhD, first author of the paper. “However, despite heightened anxious behavior, cortisol responses to the social stress were dampened in adulthood.”

The hormone cortisol modulates metabolism, the immune system and brain function in response to stress. Reduced hippocampal volume and lower cortisol response to stressors have been demonstrated as features of and risk factors for PTSD, Raper says. Also, the dampened daily rhythms of cortisol seen in the nonhuman primates with hippocampal damage resemble those reported in first-episode schizophrenia patients.

Follow-up studies could involve temporary interference with hippocampus function using targeted genetic techniques, she says. Read more

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Trio with Emory roots probing PTSD-hypertension links

This grant announcement from the American Heart Association caught Lab Land’s eye. All three of the scientists involved in this project, examining the connections between hypertension, inflammation and the sympathetic nervous system in PTSD, have Emory connections:

*Kerry Ressler, previously Emory Psychiatry/HHMI-supported/Yerkes-based lab/Grady Trauma Project, who moved this summer to Harvard’s McLean Hospital

Related finding that emerged from the Grady Trauma Project: Blood pressure drugs linked with lower PTSD symptoms

*Paul Marvar, who worked with both David Harrison and Kerry Ressler at Emory, and is now at George Washington University

Related item on Marvar’s work: Immune cells required for stress-induced rise in blood pressure in animals

*Jeanie Park, kidney specialist who is here now! The grant is exploring the relationship between the sympathetic nervous system, regulation of blood pressure and PTSD.

2015 TV interview with Park on her chronic kidney disease research

Posted on by Quinn Eastman in Heart, Neuro Leave a comment

Striking graph showing gene-stress interactions in PTSD

This graph, from a recent paper in Nature Neuroscience, describes how variations in the gene FKBP5 make individuals more susceptible to physical and sexual abuse, and thus more likely to develop PTSD (post-traumatic stress disorder).nn.3275-F1

The paper is the result of a collaboration between Elisabeth Binder and her colleagues at the Max Planck Institute of Psychiatry in Munich, and Emory psychiatrists Kerry Ressler and Bekh Bradley. The population under study is made up of inner-city Atlanta residents, part of the Grady Trauma Project overseen by Ressler and Bradley. This paper analyzes samples from a group of individuals that is more than twice as large as the original 2008 paper defining the effect of FKBP5, and adds mechanistic understanding: how regulation of the FKBP5 gene is perturbed.

Back to the graph — in addition to the effects of the different forms of the gene, it is striking how high the rate of PTSD is for both individuals with the protective and risk forms of FKBP5. Also, for individuals who did not experience abuse, the PTSD rate is actually higher for the “protective” form of the gene. On this point, the authors write:

It is, however, possible that the described polymorphisms Gafas Ray Ban outlet define not only risk versus resilience, but possibly environmentally reactive versus less reactive individuals. This would imply that the so-called risk-allele carriers may also profit more from positive environmental change.

The FKBP5 gene encodes a protein that regulates responses to the stress hormone cortisol. Thus, it acts in blood and immune system cells, not only the brain, and is involved in terminating the stress response after the end of a threat. In the paper’s discussion, the authors propose that FKBP5 may have a role in sensitivity to other immune and metabolic diseases, in addition to PTSD and depression.

Max Planck press release on Binder paper

Recent post on Shannon Gourley’s related work (how stress hormone exposure leads to depression)

 

 

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Neurosurgery via genetics to modulate anxiety

If you hear someone talking about a stress hormone, they’re probably talking about cortisol. It’s released by the adrenal glands in stressful situations, whether you have to escape a bear or just give a speech. Cortisol is supposed to prepare the body for “fight or flight.”

Kerry Ressler, MD, PhD

Let’s step back a bit, and look at how the brain triggers cortisol production: through a peptide produced in the brain called CRF (corticotropin-releasing factor). CRF is elevated in several disorders such as depression and PTSD, and is also thought to be involved in drug and alcohol dependency.

Neurons that make CRF are found in locations all over the brain, so studying them can be tricky. Kerry Ressler and his colleagues have developed an intriguing tool for studying CRF. In the places where CRF is produced in a mouse’s brain, they can take out the gene of their choice.

Green spots (above) and blue staining (below) indicate where CRF is produced in the mouse brain.
PVN = hypothalamus, paraventricular nucleus
CeA = central amygdala

In a new paper in PNAS, postdoc Georgette Gafford and Ressler use this tool in a subtle way. They have mice where a gene for a GABA receptor, one of the main inhibitory receptors (brakes) in the nervous system, is deleted, but only in the CRF neurons. This basically has the effect of turning up the volume on CRF production in several parts of the brain. It appears that modulating GABA receptors is something that normally happens to regulate CRF production, but in this case, a restraint on these stress-sensitive cells has been taken off.

“These mice are normal in many ways – normal locomotor and pain responses and no difference in depressive-like behavior or Pavlovian fear conditioning. However, these mutants have increased anxiety-like behavior,” Gafford and Ressler write.

They also have “impaired extinction of conditioned fear,” meaning that they have trouble becoming NOT afraid of something, like a buzzing sound, to which they have been sensitized by shocks. This is analogous to PTSD in which patients remain afraid and aren’t able to successfully inhibit their prior fear learning, even after the context is now safe.  [A 2011 paper goes into more detail on this biological aspect of PTSD in a civilian population.]

“These data indicate that disturbance of this specific population of neurons causes increased anxiety and impaired fear extinction, and helps us to further understand mechanisms of fear- and anxiety-related disorders such as PTSD,” Ressler and Gafford write.

In the mutant mice, a drug that blocks CRF rescued their behavioral impairments. Some other recent investigations of mice with CRF overproduction in the brain revealed “surprising paradoxical effects.”

Drugs that block CRF have been in clinical trials, some with mixed results.  A trial now proceeding at Emory is evaluating a CRF antagonist in women with PTSD.

Ressler, associate professor of psychiatry and behavioral sciences, is a Howard Hughes Medical Investigator, with a laboratory at the Yerkes National Primate Research Center. He is also co-director of the Grady Trauma Project.

 

 

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Theater Emory Event Provides Platform for Awareness and Discussion about the Challenges of Military Life

Theater Emory is partnering with Theater of War Productions to present a free public performance of “Theater of War” on March 26, 7 p.m. in Cannon Chapel on the Emory University campus.

Actors Elizabeth Marvel and Bill Camp in Theater of War (Credit: Howard Korn)

Actors Elizabeth Marvel and Bill Camp in Theater of War (Credit: Howard Korn)

“Theater of War” is an interactive program intended to increase awareness of post-deployment psychological health issues, disseminate information regarding available resources and foster greater family, community, and troop resilience. The presentation uses dramatic readings of ancient Greek plays as a catalyst for town hall discussions about the challenges faced by service members, veterans and their families.

Panelists who will lead the discussion following the readings include:

Timothy (Tim) Puetz, PhD, MPHc
Tim Puetz separated from the US Army in 2010 after 8 years of service split between the Medical Service Corps and Infantry branches. He has consulted on Veteran’s Affairs research grants related to PTSD and mental health. He is currently a graduate student at Emory University, Rollins School of Public Health.

Christiane (Christi) O’Hara, PhD
Christiane O’Hara, PhD is a clinical psychologist and the mother of an active duty soldier presently serving in Iraq. As Co-Chairmain for a local non-profit, The ArtReach Foundation: Project America, she serves our active duty military personnel, veterans, and families as a Trainer and Training Coordinator. She is also a Red Cross Consulting Psychologist with the Traumatic Brain Injury Clinic at Eisenhower Army Medical Center, Fort Gordon, and a USO Georgia volunteer at the Atlanta airport.

CSM Phillip Stringfield, USA NGGA HHC 560th BFSB
Command Sergeant Major Stringfield is the highest ranking active duty enlisted person with the Army National Guard’s 560th Battlefield Surveillance Brigade out of Ft. Gillem, GA.

Theater of War Productions, supported by a generous grant from the Stavros Niarchos Foundation in collaboration with the United Service Organizations (USO), is partnering with ten prominent theaters and universities across the United States to present “Theater of War” for mixed audiences comprised of military service members and civilians.

Cannon Chapel is located at 515 Kilgo Circle, NE, Atlanta, GA 30322. Advance tickets not required, but seating is limited. For parking, directions and details, visit www.theater.emory.edu.

The Emory presentation of “Theater of War” is supported by the Stavros Niarchos Foundation, the USO, the Emory Rollins School of Public Health, the Emory Center for Ethics, the Michael C. Carlos Museum, Creativity: Art & Innovation, and the Center for Creativity & Arts.

Posted on by Wendy Darling in Uncategorized Leave a comment

New Biological Pathway Identified for PTSD

Emory MedicalHorizon

High blood levels of a hormone produced in response to stress are linked to post-traumatic stress disorder in women but not men, a study from researchers at Emory University and the University of Vermont has found.

The results were published in the Feb. 24 issue of Nature.

The hormone, called PACAP (pituitary adenylate cyclase-activating polypeptide), is known to act throughout the body and the brain, modulating central nervous system activity, metabolism, blood pressure, pain sensitivity and immune function. The identification of PACAP as an indicator of PTSD may lead to new diagnostic tools and eventually, to new treatments for anxiety disorders.


Video on YouTube

“Few biological markers have been available for PTSD or for psychiatric diseases in general,” says first author Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center. “These results give us a new window into the biology of PTSD.”

Read more @ emoryhealthsciences.org.

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When veterans face emotional trauma

Emory researcher Barbara Rothbaum, PhD, professor of psychiatry and behavioral sciences, Emory School of Medicine,  and director of the Trauma and Anxiety Recovery Program, has been treating military personnel with posttraumatic stress disorder (PTSD) for more than a decade, helping them to learn how to deal with troubling memories. Through therapy, the service members are taught that by re-living the traumatic event, they can begin to learn how to control the effect those memories have when they surface.

Barbara Rothbaum, PhD, demonstrating virtual reality exposure therapy used to help veterans with PTSD.

PTSD is treatable and treatments vary from exposure therapy to medication to meditation techniques. Symptoms include reliving the event; avoiding situations that stir up memories of the event; discomfort expressing feelings; being constantly on the lookout for danger; irritability; drinking or drug problems; and employment, social and relationship problems.

Many times it’s the family members, friends or co-workers who are first to identify a change in the veteran or service member. Symptoms can arise abruptly and begin to interfere with every day activities. When those symptoms last for more than four weeks, it is likely that individual has posttraumatic stress disorder (PTSD).

Rothbaum emphasizes that treatment for PTSD is very effective.  She encourages active duty military personnel, veterans and others who have been exposed to trauma to seek diagnosis and treatment for problems that persist.  Symptoms can worsen with time, or cause social and employment problems that complicate recovery, but treatment can help.

More information on PTSD is available from the U.S. Department of Veterans Affairs. A clinical trial taking place at Emory uses virtual reality therapy for military personnel who have served in Iraq and Afghanistan and have been diagnosed with PTSD.

Emory PTSD research by Dr. Rothbaum and her colleagues is featured on GE’s Healthymagination website.

Posted on by Kathi Baker in Uncategorized Leave a comment

Posttraumatic stress disorder fed by avoidance

Service members returning from war historically have been haunted by traumatic memories related to combat. Problems can arise when these troublesome memories are suppressed instead of being confronted.

The military trains its service members well for combat, but teaching each individual how to deal emotionally with the trauma that comes with it is a challenge that has yet to be resolved. Unfortunately, many of those brave men and women have trouble admitting or recognizing an emotional problem. They tend to believe that avoiding troublesome memories is the best solution and do not come forward for help.

Once a service member returns home from a war zone, symptoms caused by haunting memories can arise and begin to interfere with every day activities. When those symptoms last for more than four weeks, it is likely that individual has posttraumatic stress disorder (PTSD).

Emory researcher Barbara Rothbaum, PhD, professor of psychiatry and behavioral sciences, Emory School of Medicine, and director of the Trauma and Anxiety Recovery Program, has been treating military personnel with posttraumatic stress for more than a decade, helping them to learn how to deal with the troubling memories. Through exposure therapy, the service members are taught that by re-living the traumatic event, they can begin to handle those memories when they surface.

Rothbaum is also a pioneer in exposure therapy using virtual reality software that was developed for both Vietnam veterans and service members returning from the war in Iraq.

Military commanders recognize that symptoms of PTSD are not as obvious as a physical injury, but nonetheless just as important, and they are ready to develop programs to quickly identify and treat active duty service members and veterans who are showing symptoms of PTSD before they worsen, says Rothbaum.

PTSD is treatable and treatments vary from exposure therapy to medication to meditation techniques. Symptoms include reliving the event; avoiding situations that stir up memories of the event; discomfort expressing feelings; being constantly on the lookout for danger; irritability; drinking or drug problems and employment, social and relationship problems.

More information on PTSD is available from the U.S. Department of Veterans Affairs. A clinical trial taking place at Emory uses virtual reality therapy for military personnel from Iraq who have PTSD.

Posted on by Kathi Baker in Uncategorized Leave a comment