Doxycycline May Mute Painful Memories Associated With PTSD

MedicalResearch.com Interview with:
Dominik R Bach, PhD, MD

University of Zurich

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Posttraumatic stress disorder (PTSD) can occur after a psychological trauma such as physical violence, abuse, or natural disaster. It is characterised by increased arousal, flashbacks, and nightmares that reflect memories of the trauma. Current therapies include talking therapy, but it is costly and does not work in everybody. This is why we were looking for ways of reducing aversive memories with a drug. In the current study, we found that the antibiotic doxycycline impairs the formation of negative memories in healthy volunteers.

To form memories, the brain needs to strengthen connections between neurons. It has recently emerged that for strengthening such connections particular proteins are required that sit between nerve cells, so-called MMPs. They are involved in many disorders outside the brain, such as certain cancers and heart disease. This is how we already know that doxycycline suppresses the activity of MMPs. Since doxycycline is relatively safe and readily accessible, our research was relatively straightforward.

76 healthy volunteers – half women, half men – came to the laboratory and received either placebo (a sugar pill) or 200 mg doxycycline. They then took part in a computer test in which one screen color was often followed by a mildly painful electric shock and another color was not.

A week later, volunteers came back to the lab. They were shown the colors again , this time followed by a loud sound but never by shocks. The loud sounds made people blink their eyes – a reflexive response to sudden threat. This eye blink response was measured. Volunteers who had initially been under placebo had stronger eye blink after the color that predicted electric shock than after the other color. This “fear response” is a sensitive measure for memory of negative associations. Strikingly, the fear response was 60% lower in participants who had initially taken doxycycline.

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Female Career Vietnam War Veterans Report Leading Happy, Productive Lives

MedicalResearch.com Interview with:

Jeanne Mager Stellman, PhD Professor Emerita & Special Lecturer Department of Health Policy & Management Mailman School of Public Health Columbia University York NY 10032

Dr. Jeanne Stellman

Jeanne Mager Stellman, PhD
Professor Emerita & Special Lecturer
Department of Health Policy & Management Mailman
School of Public Health Columbia University
York NY 10032

MedicalResearch.com: What is the background for this study?

Response: We examined the experiences of 1285 American women, military and civilian, who served in Vietnam during the war and responded to a mail survey conducted approximately 25 years later in which they were asked to report and reflect upon their experiences and social and health histories.

The data were collected as part of a much larger study that centered about methodological approaches to studying health effects of the military herbicides used in Vietnam. To our knowledge, this is the first study

(a) to describe the experiences of civilian women deployed to a war zone and to compare them to those of military women;

(b) to differentiate the experiences and outcomes among military women by the length of their military career service;

(c) to contextualize the general health and happiness, marital characteristics, and childbearing patterns of women deployed to Vietnam and those of their peers by comparing them to a contemporaneous nationally representative age-matched cohort, the General Social Survey (GSS).

Overall, this paper provides insight into the experiences of the understudied women who served in Vietnam, and sheds light on subgroup differences within the sample.

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Ketamine Before Stressful Event May Reduce Risk of PTSD

MedicalResearch.com Interview with:

Christine Ann Denny, Ph.D. Assistant Professor Department of Psychiatry Columbia University Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. New York, NY 10032-2695

Dr. Christine Ann Denny

Christine Ann Denny, Ph.D.
Assistant Professor
Department of Psychiatry
Columbia University
Division of Integrative Neuroscience
Research Foundation for Mental Hygiene, Inc.
New York, NY 10032-2695

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Post-traumatic stress disorder (PTSD) is one of the most common psychiatric illnesses, affecting about 8 million adult Americans, and an annual prevalence of about 3.5% worldwide. At-risk populations such as soldiers and veterans are at a higher risk to develop PTSD. Stress exposure is one of the major risk factors for PTSD and major depressive disorder (MDD), a disorder which is often co-morbid with PTSD.

There are currently very limited treatments for PTSD and MDD. In addition, these disorders are treated in a symptom-suppression approach, which only mitigate symptoms and work in only a small fraction of patients. Prevention is rarely an approach considered except in the form of behavioral intervention. However, pharmacological approaches to preventing psychiatric diseases has not yet been developed.

Our laboratory has previously found that ketamine, a general anesthetic and rapid-acting antidepressant, administered sub-anesthetically prior to stress can prevent against stress-induced depressive-like behaviors. We decided to delve into the literature to determine whether ketamine has any effects on PTSD in the clinic. We found numerous reports linking ketamine to PTSD, but the results were varied. We realized that the main difference in all of these studies was the timing of administration. We decided to systematically test the efficacy of ketamine in mice at various time points relative to a stressor to determine when would be the most effective window to buffer against heightened fear expression.

We found that ketamine administered 1 week, but not 1 month or 1 day, prior to a stressor was the most effective time point to administer the drug to buffer fear. This is critical, as it suggests that a pharmacological approach to enhance resilience can be more effective at protecting against PTSD symptoms than attempting to mitigate symptoms after it has already affected an individual.

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Cognitive Behavior Therapy Most Effective Treatment for OCD, Anxiety and PTSD

David Mataix-Cols

Prof. Mataix-Cols

MedicalResearch.com Interview with:
David Mataix-Cols PhD
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council
Stockholm, Sweden

MedicalResearch.com: What is the background for this study?

Response: Exposure-based Cognitive Behavior Therapy (CBT) is the treatment of choice for patients with anxiety, obsessive compulsive disorder (OCD) and post-traumatic stress disorders. Some patients do not respond sufficiently to such treatment. This has led researchers to find ways to augment (enhance) CBT with pharmacological agents, such as D-cycloserine (DCS).

Because CBT is such a powerful treatment for most patients, we suspected that the effects of DCS would probably be small. This means that very large samples of patients are needed to show statistically significant differences between groups. Previous studies and meta-analyses were underpowered to detect such small effects. Combining the raw data from all available studies to date gave us the power we needed to address the question of whether DCS is an efficacious augmenting strategy, over and above CBT.

We also had a second research question. Previous research from our group had suggested that there may be undesirable interactions between DCS and antidepressants, whereby patients taking both types of drugs would have significantly worse outcomes (see Andersson et al JAMA Psychiatry. 2015 Jul;72(7):659-67.
doi: 10.1001/jamapsychiatry.2015.0546).

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Veterans with PTSD Have High Prevalence of Sleep Disorders

MedicalResearch.com Interview with:

Jim Burch, MS, PhD Associate Professor Dept. of Epidemiology & Biostatistics Cancer Prevention & Control Program Arnold School of Public Health University of South Carolina, Columbia, SC and Health Science Specialist WJB Dorn Department of Veterans Affairs Medical Center Columbia, SC

Dr. Jim Burch

Jim Burch, MS, PhD
Associate Professor
Dept. of Epidemiology & Biostatistics
Cancer Prevention & Control Program
Arnold School of Public Health
University of South Carolina, Columbia, SC and
Health Science Specialist
WJB Dorn Department of Veterans Affairs Medical Center
Columbia, SC

MedicalResearch.com: What is the background for this study?

Response: Over 21 million Veterans live in the U.S., and nearly 9 million of them receive healthcare through the Veterans Health Administration, which is the largest integrated healthcare system in the U.S. The military population is particularly vulnerable to sleep disturbances due to their work schedules, living conditions, and other physical and psychological factors that accompany their jobs. However, previous studies have not comprehensively described the scope and characteristics of sleep disorders among Veterans. Sleep is considered a physiological necessity. Inadequate sleep has been associated with a wide range of adverse health outcomes, including an increased risk of chronic diseases such as heart disease and cancer, psychiatric disorders, reduced quality of life, and increased mortality.

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Telehealth System Improved Mental Health and Depression in Army Study

MedicalResearch.com Interview with:

Bradley E. Belsher, Ph.D. Chief of Research Translation and Integration, Deployment Health Clinical Center, Defense Center of Excellence for PH and TBI Research Assistant Professor, Department of Psychiatry Uniformed Services University of the Health Sciences

Dr. Bradley Belsher

Bradley E. Belsher, Ph.D.
Chief of Research Translation and Integration,
Deployment Health Clinical Center,
Defense Center of Excellence for PH
and TBI
Research Assistant Professor, Department of Psychiatry
Uniformed Services University of the Health Sciences


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One out of five U.S. military service members returning from overseas military conflicts meets screening criteria for at least one mental health condition, yet fewer than half of service members will receive help from a mental health professional. The consequences of inadequate mental health treatment are considerable and can lead to significant social and functional problems for service members and their families. In response to these mounting concerns, the Military Health System (MHS) has increased efforts to expand and improve the identification and treatment of mental health disorders. Given that the average service member visits primary care three times each year, the MHS has invested considerable resources into the integration of mental health services into the primary care setting. Collaborative care is an effective model for integrating mental health services into primary care and has demonstrated effectiveness in treating different mental health conditions to include depression and anxiety disorders. However, no previous studies have examined whether the concept can work in the MHS.

Recently, the first large-scale, randomized effectiveness trial evaluating an integrated health care model in primary care for PTSD and depression in the DoD was conducted. This trial randomized 666 military members treated across six large Army bases to a centrally-assisted collaborative telecare (CACT) approach for PTSD and depression or to the existing standard of care (usual collaborative care). This effectiveness trial targeted a large population of service members as they came into primary care and minimized exclusion criteria to improve the generalizability of the findings and broaden the applicable reach of the intervention.

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Nightmares Linked to Increased Suicide Risk in PTSD

MedicalResearch.com Interview with:
Donna L. Littlewood PhD Student
School of Psychological Sciences
University of Manchester, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Every year over 800,000 people die by suicide, and for every individual’s death, it is estimated that another 20 people will make a suicide attempt. Therefore, to be able to prevent suicide, we need to understand the different factors that can combine to make an individual think about ending their own life.

Recent research indicates that nightmares are associated with suicidal thoughts and behaviours, and that this association is independent of other related suicide risk factors, such as, depression and PTSD. However, it is now important for research to examine the mechanisms that underpin this association, as this information will support the development of clinical interventions to prevent subsequent suicide attempts and deaths

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10% of ICU Patients At Risk of Developing PTSD

Mayur Patel, MD, MPH, FACS Assistant Professor of Surgery & Neurosurgery Vanderbilt University Medical Center Staff Surgeon and Surgical Intensivist Nashville VA Medical Center

Dr. Mayur Patel

MedicalResearch.com Interview with:
Mayur Patel, MD, MPH, FACS
Assistant Professor of Surgery & Neurosurgery
Vanderbilt University Medical Center
Staff Surgeon and Surgical Intensivist
Nashville VA Medical Center

Medical Research: What is the background for this study?

Dr. Patel: Post-traumatic stress disorder (PTSD) can occur in patients after the traumatizing events of critical illness. Survivors of critical illness have reported PTSD symptoms months to even years after critical illness, possibly related to nightmare-like experiences, safety restraints creating communication barriers, and protective mechanical ventilation causing feelings of breathlessness and fear of imminent death. But, the epidemiology of PTSD after critical illness is unclear with wide ranging estimates (0-64%) and largely fails to distinguish past PTSD from new PTSD specifically resulting from the critical care experience.

Our study provides estimates on new cases of PTSD stemming specifically from the ICU experience. Pre-existing PTSD has rarely been systematically assessed in prior cohorts, and our work took extra effort to distinguish pre-existing PTSD from new PTSD cases. Civilian populations have dominated the literature of PTSD after critical illness, and this research is the first to also include the expanding and aging Veteran population.  Continue reading

Veterans with PTSD Require More Sedatives in Critical Care Units

Jad Kebbe, MD Jacobs School of Medicine and Biomedical Sciences Department of Medicine University of Buffalo

Dr. Jad Kebbe

MedicalResearch.com Interview with:
Jad Kebbe, MD
Jacobs School of Medicine and Biomedical Sciences
Department of Medicine
University of Buffalo

Medical Research: What is the background for this study? What are the main findings?

Dr. Kebbe: This study proceeded after sensing that post-traumatic stress disorder (PTSD) was a major contributor to ill outcomes in Veterans who are hospitalized in general, and mechanically ventilated in the intensive care unit (ICU) in particular. There is plenty of data depicting the comorbid roles PTSD plays in other medical conditions, leading to an increase in the use of medical services. Furthermore, PTSD affects a Veteran’s adherence to both medical and psychiatric therapies. Having said this, the ICU course could itself negatively affect a pre-existing PTSD, or even lead to the inception of such a condition de novo. However, to date, there has been no study looking at the effect a pre-existing PTSD diagnosis may have on the ICU hospitalization and thereafter.

Our study confirmed that PTSD led to an increase in sedative requirements (opiates and benzodiazepines) for Veterans who were mechanically ventilated for more than 24h between 2003 and 2013, and revealed a trend towards an increase in mortality when compared to Veterans not suffering from PTSD.

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Female Vietnam War Vets Have High Prevalence of PTSD

Kathryn Magruder, Ph.D., M.P.H. Johnson Veterans Affairs Medical Center Charleston, S.C.MedicalResearch.com Interview with:
Kathryn Magruder, Ph.D., M.P.H.
Johnson Veterans Affairs Medical Center
Charleston, S.C.

Medical Research: What is the background for this study? What are the main findings?

Dr. Magruder: There has been lots of attention and concern over PTSD in your younger veterans — both male and female — and in male Vietnam veterans.  Too often the women who served during the Vietnam Era have been largely overlooked.  We felt like we owed it to them to understand better their responses to their wartime experiences — even if 40 years later.  It’s never too late to do the right thing!

Our main finding is that the women who served in Vietnam had high prevalence of PTSD (20% lifetime, 16% current) and this was not attributable to cases that had developed prior to entering the military.  This was higher than the women who served near Vietnam or in the United States.  When we looked at their reported experiences during the Vietnam Era, the women who were in Vietnam reported higher levels of exposure to all of the items on our scale.  It was these experiences — especially sexual harassment, performance pressures, and experiences with triage and death — that explained their higher levels of PTSD.

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Overreaction of Brain’s Alarm Clock May Be Involved in PTSD

Robert C. Froemke, PhD, Assistant professor NYU Langone and Skirball Institute of Biomolecular Medicine New York

MedicalResearch.com Interview with:
Robert C. Froemke, PhD, Assistant professor
NYU Langone and Skirball Institute of Biomolecular Medicine
New York

Medical Research: What is the background for this study? What are the main findings?

Dr. Froemke: We studied how a brain area called the ‘locus coeruleus’ is involved in hearing. The locus coeruleus is the brain’s alarm clock, it’s a small region deep in the brainstem that is responsible for arousal and wakefulness, activated by surprising or potentially dangerous events. The locus coeruleus releases the neurochemical noradrenalin (similar to adrenalin) throughout the brain to greatly increase brain activity, and so might convey the significance of sounds related to past events that were very important or startling in some way (like the sound of an alarm, a baby crying, or other sounds that require immediate attention).

We found that sounds related to surprising events can come to directly activate the locus coeruleus, meaning that this brain area can learn from past experience. This learning happens quickly (within seconds to minutes) and can be incredibly long-lasting, up to weeks as measured in our study, and we suspect indefinitely or all life-long. We studied this by training lab rats to respond to sounds, poking their nose in a hole to get a food reward whenever they heard a certain sound. We activated the locus coeruleus briefly in some of these animals, and observed that they were much more sensitive to this sound and learned much faster than other unstimulated animals. We made recordings of electrical activity in the locus coeruleus and the auditory cortex, one of the major ‘hearing’ parts of the brain. In stimulated animals, sounds activated the locus coeruleus within tens of milliseconds, releasing noradrenalin into the auditory cortex to greatly boost the audio processing there- making almost every neuron respond very vigorously to that special sound.

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Mindfulness-Based Stress Therapy May Reduce PTSD Symptoms in Veterans

Melissa A. Polusny, PhD, LP Staff Psychologist/Clinician Investigator Core Investigator, Center for Chronic Disease Outcomes Research Associate Professor, University of Minnesota Medical School Minneapolis VA Health Care System (B68-2) One Veterans Drive Minneapolis, MN 5541MedicalResearch.com Interview with:
Melissa A. Polusny, PhD, LP
Staff Psychologist/Clinician Investigator
Core Investigator, Center for Chronic Disease Outcomes Research
Associate Professor, University of Minnesota Medical School
Minneapolis VA Health Care System
One Veterans Drive Minneapolis, MN 5541

Medical Research: What is the background for this study? What are the main findings?

Dr. Polusny: VA has invested heavily in the dissemination of prolonged exposure therapy and cognitive processing therapy as first-line treatments for PTSD; however, 30% to 50% of Veterans do not show clinically significant improvements and dropout rates are high. Evidence suggests that mindfulness-based stress reduction – an intervention that teaches individuals to attend to the present moment in a non-judgmental, accepting manner – can reduce symptoms of anxiety and depression. This randomized clinical trial compared mindfulness-based stress reduction with present-centered group therapy – sessions focused on current life problems. We randomly assigned 116 Veterans with PTSD to receive nine sessions of mindfulness-based stress reduction therapy (n=58) or nine sessions of present-centered group therapy (n=58). Outcomes were assessed before, during and after treatment, and at two-month follow-up. Exclusion criteria included: substance dependence (except nicotine), psychotic disorder, suicidal or homicidal ideation, and/or cognitive impairment or medical illness that could interfere with treatment. The primary outcome was a change in self-reported PTSD symptom severity over time. Secondary outcomes included interview-rated PTSD severity scores, self-reported depression symptoms, quality of life, and mindfulness skills.

Mindfulness-based stress reduction therapy – compared with present-centered group therapy – resulted in a greater decrease in self-reported PTSD symptom severity. Veterans in the mindfulness-based stress reduction group were more likely to show clinically significant improvement in self-reported PTSD symptom severity (49% vs. 28%) at two-month follow-up, but they were no more likely to have loss of PTSD diagnosis (53% vs. 47%). Veterans participating in mindfulness-based stress reduction therapy reported greater improvement in quality of life and depressive symptoms than those in present-centered group therapy; however improvement in depressive symptoms scores did not reach the level of significance. Improvements in quality of life made during treatment were maintained at 2-month follow-up for Veterans in the mindfulness-based stress reduction group, but reports of quality of life returned to baseline levels for those in present-centered group therapy. The dropout rate observed for mindfulness-based stress reduction therapy (22%) in this study was lower than dropout rates reported in previous studies for PE (28.1% to 44%) and CPT (26.8% to 35%).

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