Challenges for implementing a PTSD preventive genomic sequencing program in the U.S. military.

• Author: Lazaro-Munoz, Gabriel
• Position: Post-traumatic stress disorder - Frederick K. Cox International Law Center Symposium: International Regulation of Emerging Military Technologies

There is growing interest in using the quickly developing field of genomics to contribute to military readiness and effectiveness. Specifically, influential military advisory panels have recommended that the U.S. military apply genomics to help treat, prevent, or minimize the risk for post-traumatic stress disorder (PTSD) among service members. This article highlights some important scientific, legal, and ethical challenges regarding the development and deployment of a preventive genomic sequencing (PGS) program to predict the risk of PTSD among military service members.

Contents I. Introduction II. PTSD as Problem for Service Members and the Military III. Scientific Challenges for PTSD Preventive Genomic Sequencing A. Psychiatric Genomics B. How are Psychiatric Genomics Addressing these Challenges? C. What about PTSD Genomics? IV. Legal Challenges for implementing a PTSD-PGS Program in the Military A. Equal Protection B. Invasion of Privacy: Lessons from DoD DNA Registry C. Unreasonable Seizure of Genomic Information D. Unreasonable Search of Genomic Information V. Ethical Challenges A. Unit Cohesion and Fair Distribution of Combat Risk B. During Active Duty, Training, or Recruitment? C. Genetic Essentialism and Post-Service Stigmatization D. Research Ethics Issues VI. Conclusions I. INTRODUCTION

Technological superiority is an essential aspect of military readiness and effectiveness. To achieve this, the United States Department of Defense (DoD) invests approximately $70 billion each year in research, development, test, and evaluation programs. (4) These investments advance technologies that range from precision strike weapons and unmanned vehicles to environmental quality and medical technologies. (5) There is growing interest in using the quickly developing field of genomics to contribute to military readiness and effectiveness. (6) Specifically, influential military advisory panels have recommended that the U.S. military apply genomics to help treat, prevent, or minimize the risk for post-traumatic stress disorder (PTSD) among service members. (7) This article highlights some important scientific, legal, and ethical challenges regarding the development and deployment of a preventive genomic sequencing (PGS) program to predict the risk of PTSD among military service members.

The field of genomics examines the informational content and functional dynamics of the genes that make up the human genome. An important endeavor in genomics is the identification of genetic variants indicating that an individual is at an increased risk of developing a poor health outcome, such as different types of cancer, heart disease, diabetes, and mental health disorders. Recently, the development of massively parallel DNA-sequencing technologies (MPS) has fueled progress in genomics by allowing the sequencing of numerous genes at a time and decreasing the cost of sequencing an individual's genome. (8) MPS has made whole genome- and whole exome-sequencing (WGS/WES) more accessible to researchers and clinicians, which is quickly expanding the medical community's understanding of the genetics of certain diseases and the potential applications of genomic technologies to both the civilian and military contexts.

DoD has long demonstrated an interest in implementing genetic technologies in the military. To date, DoD has implemented a successful DNA registry for identifying human remains, and routinely screens service men and women for genetic conditions such as sickle cell anemia and Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. (9) The recent surge in WGS/WES research has further increased DoD's interest in applying genomic technologies to the military context. In 2010, the JASON Defense Advisory Panel released a report on the opportunities and challenges of WGS/WES technologies for the military. (10) The JASON report's major recommendation was a call to action:

The DoD should establish policies that result in the collection of genotype and phenotype data, the application of bioinformatics tools to support the health and effectiveness of military personnel, and the resolution of ethical and social issues that arise from these activities. The DoD and the VA should affiliate with or stand up a genotype/phenotype analysis program that addresses their respective needs. Waiting even two years to initiate this process may place them unrecoverably behind in the race for personal genomics information and applications. (11) PTSD was one of the few phenotypes specifically identified by the JASON report, which could be of benefit to DoD because it "might reasonably be expected to have a genetic component [and] have special relevance to military performance and medical cost containment." (12) Nevertheless, the use of PTSD genomics in the military raises a number of questions that must be addressed to avoid extemporaneous applications of genomic technologies that do not sufficiently maximize the benefits and minimize the harms of using these technologies. (13)

An examination of the challenges of implementing a PTSD-PGS program in the military was beyond the scope of the JASON report. This article aims to examine some of the important issues to consider when evaluating the potential use of genomics to identify risk for PTSD in the military and making decisions based on this information. Part II of this article provides a clinical overview of PTSD and examines PTSD as a problem for service members and the military, Part III examines some of the scientific challenges of establishing a PTSD-PGS program and presents the current state of psychiatric and PTSD genomics. Part IV considers some of the legal challenges regarding the potential implementation of a PTSD-PGS in the military, and Part V considers some of the important ethical questions involved.

2. PTSD AS PROBLEM FOR SERVICE MEMBERS AND THE MILITARY

   PTSD can be triggered by exposure to actual or threatened death, serious injury, or sexual violation. (14) However, PTSD is not just any stress or aversive memory related to an actual or threatened traumatic event. PTSD is a trauma- or stress-related disorder with specific symptoms that must be present for at least one month. (15) A PTSD diagnosis requires the presence of one or two symptoms from each of the following symptom groups: Re-experiencing (e.g. flashbacks, spontaneous memories or recurrent dreams of the traumatic event); Avoidance (e.g. when an individual tries to avoid trauma-related thoughts, feelings or external reminders of the event); Negative cognitions and mood (e.g. persistent and distorted sense of blame of self or others, persistent inability to experience positive emotions, inability to remember key aspects of the traumatic event); and Arousal (e.g. aggressive, self-destructive or reckless behavior, exaggerated startle response, hypervigilance, problems with concentration, and sleep disturbances). (16)

   The lifetime prevalence of PTSD in the U.S. general population is estimated at 6.8%. (17) However, the prevalence among service members is generally higher; for example, researchers estimate that 10% of Gulf War veterans (18) and 13.8% of Operation Enduring Freedom and Operation Iraqi Freedom veterans experience PTSD. (19) As one might expect, the incidence of PTSD among service members is closely associated to traumatic events experienced during combat exposure. (20) Therefore, due to the nature of their jobs, service members are particularly at risk of being impacted by PTSD. In fact, PTSD was the third-most common disability for veterans receiving compensation in fiscal year (2012), after tinnitus and hearing loss. (21)

   The economic cost of mental health services is another aspect of the burden of PTSD and other mental health disorders. The estimated two-year cost of PTSD and major depression for 1.6 million service members returning home from Afghanistan and Iraq is between $4.0 billion and $6.2 billion, depending on whether that statistic includes the value of lives lost to suicide mortality. (22) Furthermore, the number of veterans needing mental health services increased from 927,052 to 1.46 million over the last eight years, which led the Department of Veterans Affairs (VA) to increase its mental health care budget 39% from 2009 to 2013. (23)

   PTSD symptoms not only lead to a large degree of suffering for service members, but it also leads to suffering and difficulty for their families. (24) In particular, PTSD often leads to impairments in occupational functioning, which can limit service members' effectiveness on the job and force them to take time off work for treatment. (25) One concern among some military leaders is that PTSD can affect military readiness and effectiveness by decreasing available manpower and military duty performance. (26) These issues, combined with the economic cost of PTSD, make PTSD prevention an important undertaking for DoD. A potential way to prevent or minimize the economic and biopsychosocial burden of PTSD in the military is to identify those service members who are at high genomic risk for developing PTSD and assign them to missions that will minimize their combat exposure or develop interventions that may help to decrease their chances of developing PTSD. When considering this possibility, one of the first steps should be to examine whether genome-based PTSD risk prediction is currently possible, and if not, to identify the scientific questions that remain to be answered before that goal can be realized.

3. SCIENTIFIC CHALLENGES FOR PTSD PREVENTIVE GENOMIC SEQUENCING

   PTSD is a significant problem for the military, and in theory, genomics holds much promise for improving PTSD risk prediction. (27) However, in order to use genomics for PTSD risk prediction and make important personnel decisions based on this information, the military needs a solid scientific foundation that will allow it to reliably predict these risks. Recent developments in genomic technologies and...