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Post-traumatic stress disorder


Post-traumatic stress disorder (PTSD) occurs in 5–10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.

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Figure 1: The prevalence of PTSD.
Figure 2: The function of the HPA axis in PTSD and controls.
Figure 3: Emotional undermodulation and overmodulation in PTSD.
Figure 4: The default mode, salience and central executive networks in PTSD.
Figure 5: Consequences of reduced cortisol signalling in acute aftermath of trauma.
Figure 6: The timing of treatment of PTSD.
Figure 7: Timing of quality of life issues with PTSD.
Figure 8: Systems biology approach to biomarker discovery and validation.


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R.Y. is supported by grants from the US Department of Defense (DOD W81XWH-10-2-0072 and DOD W81XWH-13-1-0071) and a grant from the Lightfighter Trust Foundation (LFT2009-02-1). A.C.M. is supported in part by National Health and Medical Research Council Program Grant number 568970. C.M.N. is supported in part by US National Institutes of Health (NIH) grant R01MH093500. S.E. Hobfoll is partly supported by a grant from the National Institute of Mental Health (RO1MH073687) and the Rush Center for Urban Health Equity (NIH-NHLBI 1P50HL105189). K.C.K. is supported by grants NIH MH078928 and MH093612. T.C.N. is supported in part by a research grant that was awarded and administered by the U.S. Army Medical Research & Materiel Command (USAMRMC; TCN: W81XWH-11-2-0189) and the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration. The authors would like to thank L. M. Bierer for her careful final review of the manuscript, M. E. Bowers for assistance with the development of the graphics and review of references, and H. Bader for administrative coordination and integration of multiple versions of the document.

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Introduction (R.Y.); Epidemiology (K.C.K. and C.W.H.); Mechanisms/pathophysiology (T.C.N., R.Y., C.M.N. and R.A.L.); Diagnosis, screening and prevention (A.C.M.); Management (E.V.); Quality of life (S. E. Hobfoll); Outlook (S. E. Hyman and R.Y.); overview of Primer (R.Y.). All authors contributed to the review and to the editing of the final manuscript.

The views expressed in this article are those of the authors and do not represent an official position of the US Army, US Department of Defense or any of the affiliated institutions listed.

Corresponding author

Correspondence to Rachel Yehuda.

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Competing interests

R.Y. has a patent entitled Genes Associated with Posttraumatic Stress Disorder (2012/0039,812). A.C.M. receives research funding from the Australian Department of Defense and the Australian Department of Veterans Affairs. He is a Group Captain in the RAAF specialist reserves and is an advisor to the Department of Veterans Affairs. K.C.K. has consulted for Synchroneuron Inc. and Accellient Partners. T.C.N. has consulted for Genentech and has received study medication from Actelion for a study funded by the US Department of Defense, and from Glaxo-Smith-Kline for a study funded by the US Department of Veterans Affairs. S. E. Hyman has consulted on early stage drug discovery for Novartis and Sunovion. C.W.H., E.V., R.A.L., C.M.N. and S. E. Hobfoll declare no competing interests.

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Yehuda, R., Hoge, C., McFarlane, A. et al. Post-traumatic stress disorder. Nat Rev Dis Primers 1, 15057 (2015).

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