Psychiatric Annals

Guest Editorial Free

Understanding Posttraumatic Stress Disorder: From Diagnosis and Neurobiology to Treatment

Charles B. Nemeroff, MD, PhD

This issue of Psychiatric Annals focuses on posttraumatic stress disorder (PTSD), a severe psychiatric disorder that is increasing in prevalence. Compared to other psychiatric disorders, such as major depressive disorder and bipolar disorder, PTSD is poorly understood both in terms of pathophysiology and choice of appropriate treatment. Consequently, many patients continue to suffer with the devastating symptoms of PTSD. The contributors for this issue are leaders in the psychiatry field, and they contribute articles that provide in-depth insight into diagnosis and neurobiology, as well as therapeutic options for PTSD.

Dr. Eric Vermetten and colleagues discuss the major controversies concerning the nosology of PTSD with an emphasis on the changes in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)1 and the forthcoming (in 2018) 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11)2 and their differences. The authors thoughtfully discuss the recent relocation of PTSD from the anxiety disorders section to a “trauma and stressor” disorder group in DSM-51 and ICD-11.2 In spite of the increasing data3 supporting a biological basis for disease vulnerability and the repeated brain alterations demonstrated in PTSD patients, there remains those who continue to claim that PTSD is not a validated psychiatric diagnosis. What is undeniable is the fact that up to 30% to 40%4 of people exposed to severe trauma develop a set of disabling symptoms including avoidance, re-experiencing the trauma, and numbing as well as mood disturbances and cognitive impairment that markedly alter social and occupational functioning. The high rate of comorbid major depression and other Axis I disorders is not fundamentally different than other conditions documented in DSM-51 such as obsessive-compulsive disorder and in no way invalidates the PTSD diagnosis.

Drs. Julius C. Pape and Elisabeth B. Binder provide a comprehensive view of the state-of-the-art genetic and epigenetic contributions for the development of PTSD. Early twin and family studies revealed an important role for genetics in the diathesis for PTSD and more recent studies of gene X environment interactions have provided much needed novel information that has led to a better molecular understanding of how these interactions, mediated by epigenetic mechanisms, regulate gene transcription. A number of candidate genes, particularly those, not surprisingly, associated with the hypothalamic-pituitary-adrenal axis, appear to play a major role in regulating risk for PTSD after trauma exposure. These include polymorphisms of the corticotropin-releasing hormone type 1 receptor, glucocorticoid receptor, NCR3R1 and FKBP5, a glucocorticoid receptor co-chaperone protein, as well as the pituitary adenylate cyclase-activating polypeptide receptor 1, and the opioid-receptor-like 1. Although genome-wide association studies (GWAS) have proven to be a useful strategy to uncover common genetic variations associated with various other medical and psychiatric disorders, the relatively small sample size of the early studies has hampered progress. The newly formed PTSD GWAS consortium may rectify these problems and provide novel findings, although neither the much larger major depression nor schizophrenia GWAS have, arguably, resulted in startling new findings. The emerging role of epigenetic mechanisms in concert with specific genetic polymorphisms (eg, FKBP5) in PTSD vulnerability is described, as is the burgeoning field of noncoding ribonucleic acid (RNAs), including microRNAs.

Drs. Daniel W. Grupe and Aaron S. Heller critically review the structural and functional brain imaging findings in PTSD. They make the extraordinarily important point of the need to distinguish between the neural consequences of trauma and the neurobiology of PTSD, a variable not well-controlled in most studies. Taken together, the extant literature does indicate alterations in the medial prefrontal cortex-amygdalahippocampal circuitry in PTSD. They highlight a substantial number of deficiencies in the current database, most notably the importance of trauma subtype, the age at the time of trauma, the magnitude and chronicity of the trauma, and the interactive effects of early life trauma and adult trauma.

Drs. Erika J. Wolf and Paula P. Schnurr focus on a too long-ignored area—the relationship of PTSD and cardiometabolic health. It is now clear, according to their article, that PTSD is associated with an increased risk for metabolic syndrome and coronary artery disease, including myocardial infarction and stroke. They provide evidence that this relationship is mediated, in part, by accelerated cellular aging facilitated by epigenetic mechanisms.

Finally, Dr. Nils C. Westfall and I review PTSD treatment modalities in literature. There is general and widespread agreement that trauma-focused psychotherapies including exposure therapy and cognitive-processing therapy are evidence-based efficacious first-line treatments. Eye movement desensitization and reprocessing has some low-strength evidence for efficacy. There is insufficient evidence to recommend psychodynamic psychotherapy for PTSD. There are some limited data suggesting the utility of interpersonal psychotherapy and mindfulness-based therapy as well as hypnotherapy for PTSD. In terms of pharmacotherapy, both sertraline and paroxetine are US Food and Drug Administration-approved for the treatment of PTSD, and there is evidence for the efficacy of venlafaxine. Antipsychotic drug augmentation of antidepressants in PTSD does not appear to be effective. Prazosin clearly is effective in reducing PTSD-associated nightmares. Unfortunately, neither psychotherapy nor pharmacotherapy nor their combination frequently result in remission of symptoms in patients with PTSD (see the Westfall and Nemeroff article, this issue).

Clearly, a better understanding of the pathophysiology of PTSD will be necessary before novel and more effective treatments can be developed.

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
  2. ICD-11 beta draft. http://apps.who.int/classifications/icd11/browse/l-m/en. Accessed August 5, 2016.
  3. Heim C, Nemeroff CB. Neurological pathways involved in fear, stress, and PTSD. In: Liberzon I, Ressler K, eds. Neurobiology of PTSD: From Brain to Mind. New York, NY: Oxford University Press; 2015.
  4. Galea S, Nandi A, Vlahov D. The epidemiology of post-traumatic stress disorder after disasters. Epidemiol Rev. 2005;27:78–91 doi:10.1093/epirev/mxi003 [CrossRef]
Authors

About the Guest Editor

Charles B. Nemeroff, MD, PhD

Charles B. Nemeroff, MD, PhD, is the Leonard M. Miller Professor and Chairman of the Department of Psychiatry and Behavioral Sciences and Director of the Center on Aging at the University of Miami Miller School of Medicine in Miami, FL. He received his medical and doctoral degrees (Neurobiology) from the University of North Carolina (UNC) School of Medicine in Chapel Hill, NC. After psychiatry residency training at UNC and Duke University, he held faculty positions at Duke and at Emory University before relocating to the University of Miami in 2009. He has served as President of the American College of Psychiatrists (ACP) and the American College of Neuropsychopharmacology and sits on the Scientific Advisory Board and Board of Directors of the American Foundation for Suicide Prevention and the Anxiety and Depression Association of America.

He has received a number of research and education awards including the Kempf Award in Psychobiology, the Samuel Hibbs Award, Research Mentoring Award, Judson Marmor Award, the Vestermark Award from the American Psychiatric Association (APA), the Mood Disorders Award, Bowis Award, and Dean Award from the ACP. He was elected to the Institute of Medicine of the National Academy of Sciences in 2002.

His research has focused on the pathophysiology of mood and anxiety disorders with a focus on the role of child abuse and neglect as a major risk factor. He has also focused on the role of mood disorders as a risk factor for major medical disorders including heart disease, diabetes, and cancer. He has served on the Mental Health Advisory Council of the National Institute of Mental Health and the Biomedical Research Council for NASA. He is the co-editor-in-chief of the Textbook of Psychopharmacology, published by the APA. His research is currently supported by grants from the National Institutes of Health.

Address correspondence to Charles B. Nemeroff, MD, PhD, Department of Psychiatry and Behavioral Sciences, University of Miami, 1120 Northwest 14 Street, Suite 1455, Miami, FL 33136; email: cnemeroff@med.miami.edu.

Disclosure: Charles B. Nemeroff discloses consultations with Xhale, Takeda, SK Pharma, Clintara/Bracket, Lilly, Skyland Trail, Mitsubishi Tanabe Pharma Development America, Taisho Pharmaceutical Inc, and Sunovion; he is a stockholder in Opko, Antares, Xhale, Celgene, Seattle Genetics, and Abbvie; he serves on the scientific advisory boards of Riverbend, the American Foundation for Suicide Prevention (AFSP), the Brain and Behavior Research Foundation, Xhale, the Anxiety and Depression Association of America (ADAA), and Skyland Trail; he serves on the board of directors of AFSP, Gratitude America, and ADAA; he receives income in excess of $10,000 from Clintara/Bracket, American Psychiatric Publishing, and Xhale; he holds two patents, one for a method and devices for transdermal delivery of lithium (US 6,375,990B1) and the other for a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2). The remaining author has no relevant financial relationships to disclose.

10.3928/00485713-20160808-02

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