Weakening Neural Connections Can Eliminate Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho MD PhD Department of Molecular, Cell and Systems Biology University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho MD PhD
Department of Molecular, Cell and Systems Biology
University of California, Riverside
Riverside, CA 92521

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

Response: To survive in a dynamic environment, animals develop fear responses to dangerous situations. For these adaptive fear responses to be developed, the brain must discriminate between different sensory cues and associate only relevant stimuli with aversive events.

In our current study, we investigated the neural mechanism how the brain does this, using a mouse model of fear learning and memory. Our study demonstrates that the formation of fear memory associated with an auditory cue requires selective synaptic strengthening in neural pathways that convey the auditory signals to the amygdala, an essential brain area for fear learning and memory.

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Functional Brain Markers Can Suggest Susceptibility to PTSD

MedicalResearch.com Interview with:

Jennifer Stevens, PhD Director, Neuroscience of Memory, Emotion, and Stress Laboratory Instructor, Dept of Psychiatry & Behavioral Sciences Emory University School of Medicine

Dr. Stevens

Jennifer Stevens, PhD
Director, Neuroscience of Memory, Emotion, and Stress Laboratory
Instructor, Dept of Psychiatry & Behavioral Sciences
Emory University School of Medicine

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

Response: Post-traumatic stress disorder (PTSD) was once thought to be a disorder of combat veterans, however, we now know that more than 60% of Americans experience a traumatic event during their lifetimes, and that this can have negative consequences for mental and physical health. Many people recover from the psychological effects of trauma without any intervention, but a significant proportion have long-lasting debilitating symptoms.

Supported by the NIH, the cutting edge of PTSD research includes new strategies for preventing the disease, rather than treating PTSD after patients have been living with symptoms for months to years. In order to prevent the disease, it is critical that we are able to quickly identify people who will be at risk for the disease following a trauma, so that preventive strategies can be deployed bedside in the emergency room or in the battlefield. In the current study, we used functional MRI to predict which individuals would recover from trauma, and which individuals would have long-lasting symptoms of PTSD.

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How and Where Does the Brain Encode Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho, M.D., Ph.D. Assistant Professor Department of Cell Biology & Neuroscience University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho, M.D., Ph.D.
Assistant Professor
Department of Cell Biology & Neuroscience
University of California, Riverside
Riverside, CA 92521

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

Response: In order to survive in a dynamic environment, animals develop adaptive fear responses to dangerous situations, which requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. Dysregulation of this process leads to maladaptive generalized fear in post-traumatic stress disorder (PTSD), which affects 7 percent of the U.S. population.

In this study, we found that a population of hippocampal neurons project to both amygdala and medical prefrontal cortex (mPFC). We also found neural mechanisms how these double-projecting neurons efficiently convey contextual information to the amygdala and mPFC to encode and retrieve fear memory for a context associated with an aversive event.

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Genetic Factors Raise Risk of PTSD After Trauma, Especially in Women

MedicalResearch.com Interview with:

Laramie E Duncan, PhD</strong> Stanford University

Dr. Duncan

Laramie E Duncan, PhD
Stanford University

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

Response: Posttraumatic stress disorder (PTSD) is a mental health condition that some people experience after a traumatic event, like a terrorist attack, military conflict, or violence in the home. When people have PTSD, they may experience flashbacks to the traumatic event, nightmares, and other recollections of the event that can interfere with their day-to-day lives.

Before this study, not everyone was convinced that genetic factors make some people more prone to developing PTSD than others. Using a study of over 20,000 people and analyzing over two hundred billion (200,000,000,000) pieces of genetic information, we demonstrated that developing PTSD is partly genetic. We also found that genetic factors seem to play a stronger role for women than men, though for everyone, experiencing trauma is still the most important factor.

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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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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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Psychiatric Research Focuses On Major Hubs of Complex Brain Systems

MedicalResearch.com Interview with:

Glenn Saxe, MD Arnold Simon Professor of Child and Adolescent Psychiatry and Chair, Department of Child and Adolescent Psychiatry NYU Langone’s Child Study Center

Dr. Glenn Saxe

Glenn Saxe, MD
Arnold Simon Professor of Child and Adolescent Psychiatry and
Chair, Department of Child and Adolescent Psychiatry
NYU Langone’s Child Study Center
Dr. Saxe’s bio page

 

MedicalResearch.com: What is the background for this approach? What are the main advantages and drawbacks to the CS-CN method in psychiatry research?

Dr. Saxe: Psychiatric disorders are complex and, in all likelihood, emerge and are sustained over time because they form what is called a complex system, involving the interaction between a great many variables of different types (e.g. molecules, neurons, brain circuits, developmental, social variables). There is a strong literature on complex systems in other fields that show remarkably similar properties between vastly different types of systems. Unfortunately, data methods used in research in psychiatry are not designed to ‘see’ the possible complex systems nature of a psychiatric disorder. Our method is designed to identify networks of variables related to psychiatric disorders that, together, have properties of complex systems. If such a system is identified, it may reveal new ways to treat these disorders.

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