An Evaluation of Neurobiological Similarities of Tinnitus and PTSD

Jul 26, 2021

Although tinnitus and PTSD often occur together, they are distinct disorders. Tinnitus is an auditory disorder in which a person “hears” noise—usually as ringing, buzzing, or whooshing sounds— despite no external objective noise source. PTSD is a trauma-related disorder identified by intrusions of the traumatic event via unwanted, recurring memories, avoidance of reminders, negative thoughts and mood, and excessive vigilance for danger.

Similarities between tinnitus and PTSD

Previous studies have documented similarities between tinnitus and PTSD among Cambodian refugees, as well as U.S. veterans. Neuroimaging data from a recent clinical trial indicated that the brain’s auditory-vigilance network was the most dysregulated among active duty service members with PTSD, compared to combat controls and civilian controls. Due to similar symptoms between tinnitus-related distress and PTSD and similar dysregulated resting-state brain networks, it remains important to improve understanding of how these two distinct disorders may be related.

This STRONG STAR-affiliated study led by John Moring, PhD, of The University of Texas Health Science Center at Health San Antonio, is the first to prospectively examine the overt emotional, behavioral, and cognitive symptoms of tinnitus-related distress and PTSD, as well as the overlapping functional connectivity between tinnitus and PTSD within the brain. To do this, investigators will conduct audiometric and psychological assessments and resting-state functional magnetic resonance imaging (fMRI) with 120 active duty military and veteran participants. The study will include 30 participants with tinnitus and PTSD, 30 with PTSD only, 30 with tinnitus only, and 30 with neither condition.

Participants will be recruited from the Hearing Center of Excellence and clinics within Wilford Hall Ambulatory Surgical Center, which is located at Joint Base San Antonio-Lackland.

Identifying areas of the brain associated with the two conditions

The research team will analyze the symptom overlap between tinnitus and PTSD and will use fMRI to examine the neurobiological factors related to the two conditions, both separately and conjointly. Investigators also will use psychological assessments and data derived from the neuroimaging to identify specific regions of the auditory-vigilance network associated with distress related to tinnitus and PTSD.

Analysis of the shared cognitive, emotional, and behavioral symptoms and neurobiology associated with tinnitus and PTSD will help clinicians and researchers fully understand tinnitus and PTSD independently and conjointly. Results will lead to the identification of neurobiological markers for tinnitus and PTSD, identification of observable characteristics of individuals with both conditions, and development of therapies to reduce distress and impairment.

Neurobiological Predictors and Mechanisms in Exposure Therapy for PTSD

Apr 11, 2018

Prolonged Exposure, or PE, is one of the most effective treatments for posttraumatic stress disorder. The therapy has helped many PTSD patients face thoughts, feelings and situations that they have avoided due to distress. Even with this effective therapy, however, many patients continue to suffer with PTSD symptoms following treatment.

In this study for the Consortium to Alleviate PTSD, a research team led by Sheila A.M. Rauch, PhD, of the Emory University School of Medicine and Atlanta VA Medical Center, will use neuroscience methods in an effort to learn how effective therapy for PTSD works on a biological level in order to learn how to make it work even better.

Neurobiological studies have found links between PTSD severity and the levels of certain compounds produced by the body. Dr. Rauch and her fellow CAP investigators want to know if changes in the levels of those substances can serve as biomarkers of response to therapy.

To help answer such questions, this study will work with active duty military personnel and veterans who enrolled in either of two studies utilizing PE that are part of the clinical trials network of the STRONG STAR Consortium and the Consortium to Alleviate PTSD.

Dr. Rauch and her colleagues will measure various neuroendocrine and neurosteroid substances before, during, and after the patients’ treatment periods to see how those substances change in response to therapy, potentially shedding light on components of PE that are most effective. They also will compare differences in biomarkers resulting from different ways of delivering PE. Substances to be measured include cortisol, allopregnanolone and related metabolites, and dehydroepiandrosterone.

Potential benefits

The ability to measure neurobiological processes in response to PTSD treatment will provide a guide for making improvements to treatment so that more patients will benefit. This study will inform our understanding of how therapy works (or does not work) and how we might improve treatments based on these biological responses.

Genetic and Epigenetic Alterations as Biomarkers for PTSD Diagnosis and Prognosis

Nov 20, 2016

Although some studies have shown that genetics play a role in one’s susceptibility to develop posttraumatic stress disorder, we are at the very early stages of discovering the specific role of various genetic factors underlying this debilitating condition. Key questions that need to be addressed include: Why do some people get PTSD while others do not? Why do some people recover faster than others from treatment? And importantly, are there measurable genetic biomarkers – physical indicators – that can identify the presence of the disorder, reflect whether a patient is improving, and reveal who may be at risk to develop PTSD?

Douglas E. Williamson, PhD, of Duke University and the Durham VA Medical Center along with his outstanding team of collaborators have developed a study for the Consortium to Alleviate PTSD that will evaluate potential diagnostic and prognostic genetic biomarkers to detect PTSD, indicate who has responded to treatment, and identify individuals at risk to develop PTSD if they are exposed to a traumatic event.

Multidisciplinary team

The collaborative team of scientists includes a genetic epidemiologist, a psychiatric geneticist, a geneticist, a neuroanatomist, human postmortem experts, biostatisticians, and a clinical psychologist.

Investigators will analyze samples available in a repository from studies conducted under the auspices of the STRONG STAR Multidisciplinary Research Consortium that includes epidemiologic studies and clinical trials, as well as from a separate human brain bank to screen the entire genome in an effort to identify genetic and epigenetic markers linked with PTSD.

Resources that they will analyze include postmortem brain tissue from people with and without PTSD; blood samples collected from patients prior to and after treatment for PTSD; and data from blood collections and PTSD assessments of service members before and after deployment.

Potential benefits

It is expected that this project will be an important first step in identifying diagnostic and prognostic biomarkers of PTSD as well as filling gaps in our understanding of new genetic mechanisms underlying PTSD. That improved understanding could guide medical science in the quest to improve detection, treatment, and prevention of this disorder and related conditions.

Cognitive and Neuronal Markers in Posttraumatic Stress Disorder

Jun 02, 2015

Researchers have found increasing evidence that a dysfunction in the prefrontal cortex of some individuals’ brains plays a role in the development of posttraumatic stress disorder (PTSD). The dysfunction affects cognitive flexibility (CF), or the capacity to shift thought and action according to changing demands in the environment. That can include the ability to inhibit incorrect response.

Cognitive flexibility and higher order thinking are influenced by a protein, brain-derived neurotrophic factor (BDNF). A genetic variation, or single nucleotide polymorphism (SNP), on the BDNF gene has been shown to influence BDNF function and cognition. Previous research also has associated that genetic variation, known as BDNF Val66Met SNP, with risk for PTSD.

But little is known about the nature of the relationship between those factors and how they influence speed of response to therapy for PTSD.

In this STRONG STAR-affiliated study, Principal Investigator M. Danet Lapiz-Bluhm, PhD, RN, and her research team will measure CF and BDNF function in military members with PTSD prior to treatment with Cognitive Processing Therapy (CPT) and then following therapy. The study piggybacks on a Department of Defense-funded clinical trial led by Patricia Resick, PhD, providing CPT therapy to active-duty military members with PTSD after service in Iraq and Afghanistan. That study features an individualized approach to therapy by providing it at variable lengths until symptoms are resolved, rather than the standard regimen of 12 one-hour CPT sessions.

CPT was designed by STRONG STAR investigator Patricia Resick, PhD, of Duke University Medical Center. CPT is a cognitive-behavioral therapy that gives patients an understanding of how their thoughts about a traumatic event influence their feelings and reactions to it, then helps them develop a new way of thinking that alleviates their distress and allows them to regain control of their lives

Dr. Lapiz-Bluhm’s team will recruit participants from Dr. Resick’s parent CPT study, who will provide saliva and blood samples. Saliva and plasma will be analyzed for BDNF. Whole blood will undergo genetic analysis to identify which of the patients have the Val66Met SNP variation.

Study aims

With a goal of improving understanding of various factors influencing PTSD treatment outcome, this study will:

Test active-duty military members with PTSD for cognitive flexibility performance and determine whether speed of response to CPT treatment is related to presence of the Val66Met SNP and the amount of BDNF detected in plasma and saliva. The researchers hypothesize that poor performance in tests for CF, presence of Val66Met SNP, and abnormal peripheral BDNF levels will be associated with delayed treatment response to CPT.
Determine the relationship between change in performance in tests for CF and peripheral BDNF levels with the change in symptom severity following CPT. The researchers hypothesize that the amount of PTSD symptom reduction will be associated with changes in CF performance and BDNF levels.

Expected benefits

Understanding of cognitive and neurotrophic mechanisms in PTSD and following treatment with CPT will potentially contribute to the development of improved strategies to treat or prevent PTSD.

Neuroimaging Studies of PTSD and PTSD Treatment among Combat Veterans

Aug 18, 2010

Many of us have imagined the possibility of reading someone’s mind, but in the successful treatment of PTSD and other mental health problems, so much untapped potential lies in the ability to read someone’s brain. For example, what alterations in the intricate circuitry and function of the brain contribute to the nightmares, flashbacks, depression, anxiety, social withdrawal, and numerous other symptoms associated with PTSD? Likewise, how do our brains influence our response to trauma, and how do physical and emotional trauma impact the brain? When someone receives successful treatment for PTSD, what, if any, changes in brain structure and function occur as a result? Is it possible that new interventions could be designed to stimulate those same changes and enhance treatment?

STRONG STAR investigators are in a unique position to help answer these questions, thanks to the size and variety of the Consortium’s clinical PTSD treatment trials and the world-class resources and faculty expertise at the University of Texas Health Science Center at San Antonio’s Research Imaging Institute. Peter Fox, MD, director of the imaging institute and of the STRONG STAR Neuroimaging Core, has designed a STRONG STAR investigation that will apply advanced neuroimaging methods to study PTSD in the context of ongoing treatment trials to address

the underlying neuroanatomical pathology (changes in the anatomy of the nervous system or nervous tissue that accompany the development of PTSD);
the underlying pathophysiology (functional changes in the brain that are associated with the disorder); and
neurobiological changes corresponding with PTSD treatment.

The ultimate goal is to shed light on the underlying neurobiology of PTSD in hopes of developing more effective, targeted treatment interventions.

Previous obstacles yield new opportunities for discovery

Dr. Fox’s study will utilize the strength’s of STRONG STAR to overcome previous obstacles in neuroimaging research on PTSD, enabling his research team to realize the full potential of this state-of-the-art research technique.

Opportunity #1: A large number of similar patients. Previous neuroimaging studies on PTSD have generally employed small, diverse samples of PTSD patients, typically including some individuals with childhood onset of PTSD, often resulting from abuse, and some individuals with adult onset of PTSD, often resulting from various causes, including accidents, assaults, and combat exposure. With so much variability among a small group of study participants, it has been difficult for researchers to discern the subtle consequences of PTSD, including how PTSD affects neural circuitry regulating emotional processing and general cognitive function. Unlike these previous studies, Dr. Fox’s STRONG STAR trial will include a large number of more homogeneous participants; all will be military personnel or veterans whose PTSD is related to combat exposure.

Opportunity #2: Consideration of resting brain activity and TBI. Other neuroimaging studies on PTSD have not examined resting state brain activity, which has shown significant promise as a marker for other neurological and psychiatric conditions. Another shortfall has been the inability of previous PTSD studies to examine the impact of co-occurring traumatic brain injury, which is a significant problem among veterans of the wars in Iraq and Afghanistan. Both of these are key components of Dr. Fox’s investigation.

Opportunity #3: Ability to see the effects of treatment. PTSD treatment studies have largely not been used to examine the underlying neural changes associated with successful treatment – an area of research that holds vast potential for radical treatment advances. This is a primary focus of this STRONG STAR trial led by Dr. Fox.

STRONG STAR participants, STRONG STAR results

Study participants will be recruited from various STRONG STAR clinical trials, including one trial using cognitive-behavioral therapy to treat PTSD and a second trial looking at the influence of alcohol dependence and alcoholic subtype on response to drug therapy for PTSD. Researchers also will recruit a control group of soldiers who returned from deployment to Iraq or Afghanistan without PTSD. Using a combination of state-of-the-art brain imaging methods and various cognitive and emotional tests and physical challenges, researchers will look for PTSD-specific patterns of brain activity in PTSD patients compared to the control group. Because study participants will undergo the same tests and assessments before and after treatment, researchers also expect to identify changes in patterns of brain activity associated with successful PTSD treatment.

STRONG STAR researchers expect these investigations to improve understanding of the neurobiology of PTSD and the underlying mechanisms of successful treatment, which in turn should lead to improved PTSD prevention and treatment for veterans and civilians alike.

Genetic and Environmental Predictors of Combat-Related PTSD

Aug 18, 2010

The more you know about your enemy, the better equipped you are to fight. That’s true in war, and it holds true in our battle against physical and mental ailments.

As researchers have learned more about the root causes of heart disease and other physical afflictions, the medical field has responded with a wide array of new prevention, diagnostic, and treatment methods. STRONG STAR hopes to help achieve equally valuable advances in the fight against posttraumatic stress disorder (PTSD) as it strives to understand how we respond to and are affected by trauma at the most basic biological level – our DNA.

What do we know about the causes of PTSD?

Currently, there is not a good understanding of how PTSD develops after exposure to a trauma, particularly combat-related stress, and what factors lead to increased vulnerability or resilience. Although every person with PTSD has been exposed to a traumatic event, research shows that the majority of people who experience a trauma do not develop PTSD. Why is it that some people remain resilient after trauma; some experience difficulties in the short term but heal from their psychological wounds fairly quickly; and others develop a chronic problem with PTSD?

We have some clues. Multiple environmental factors have been shown to affect PTSD risk, including the nature of the trauma itself, how many traumas a person has faced, age at the time of trauma, early life adversity, as well as an individual’s level of social support.

On the other hand, studies with families and twins provide evidence that susceptibility to-or resilience against-PTSD is at least partially inherited. For example, Sack and colleagues published a study in 1995 showing that Cambodian refugee children of parents with PTSD had a 5-fold greater risk than refugee children of parents without PTSD. A twin study published by K.C. Koenen in 2007 concluded that genes account for approximately 30% of the variance in PTSD risk.

As with other complex diseases and mental health disorders, the root causes of PTSD are likely to be varied and intertwined, with contributions by genetics, environmental factors, and the interplay between the two.

How does STRONG STAR plan to get to the root of the problem?

Douglas E. Williamson, PhD, with the University of Texas Health Science Center at San Antonio is working to untangle this complicated web with a study he has developed for STRONG STAR. In the first large-scale prospective study of its kind, Dr. Williamson and his colleagues are looking at changes in the expression of genes as a result of combat-related stress associated with the development of PTSD. The study is enlisting the help of approximately 4,000 Army Soldiers who volunteer to provide blood samples and answer a variety of questions before and after deployment to Afghanistan. Through their study participation, these service members will allow researchers to collect the necessary data and perform the analyses needed to identify genetic risk factors that influence the development of combat-related PTSD.

All study participants will be screened prior to deployment. Then, upon their return to the U.S., those who are identified through routine military screening to have symptoms of PTSD will be invited to participate in a second study assessment. An equal number of those who do not show symptoms of PTSD-matched for combated-related stress, gender, military unit, and rank-likewise will be invited to participate in this second round of assessments.

With the data gathered, Dr. Williamson and his colleagues aim to do three things:

Determine whether there are changes in gene expression-that is, the activity or output of particular genes-associated with the onset of PTSD after exposure to combat-related stress. In other words, can exposure to combat-related stress affect the way our genes behave, the RNA they make, ultimately resulting in the alteration of the body’s production of various proteins and hormones? Do those changes contribute to the development of PTSD?
Identify specific variants in the genetic architecture involved in deployment-related changes in gene expression and associated with PTSD. Here researchers want to see which genes are sensitive to combat-related stress and how changes in their expression are linked with the development of PTSD.
Identify significant interactions between noncombat-related stressors and genes that are linked with the onset of PTSD. For example, were there genetic variations even before deployment in individuals who were exposed to early childhood trauma that potentially increased sensitivity to combat-related stress? Are genetic variations seen in individuals who have been experiencing other ongoing stressful life events? Are there associations with these genetic changes and increased PTSD risk after exposure to combat-related stress or as combat-related stress levels increase?

Answers to these questions will help researchers understand what happens with our genes and related basic biology as we are exposed to trauma. This, in turn, could enlighten new intervention efforts, including medication treatments that offset biological factors that lead to PTSD’s development.

Study participants who exhibit symptoms of PTSD following deployment will be offered the opportunity to enroll in ongoing STRONG STAR treatment trials or referred to other clinical resources that can help them recover now. And thanks to these service members’ study participation, STRONG STAR researchers expect to find ways to improve future PTSD prevention and treatment efforts, with the potential to help countless service members, veterans, and civilians for years to come.