Abstract
The search for endophenotypes that stand between genetics and disease has been applied to the diagnostic entity of Posttraumatic Stress Disorder (PTSD). Advances are being made in understanding the pathway to disorder in PTSD in terms of brain regions, neuronal networks, stress-related systems (e.g., the hypothalamic–pituitary–adrenal (HPA) axis), and their underlying genetic and neurogenetic bases. The latter are affected by gene–environmental interactions and epigenetic effects, and the environment and context reciprocally interrelate with them, as well. Therefore, a primary focus on (neuro)pathophysiological intermediates in the disease pathway, as appears emphasized in the research domain criteria (RDoC) approach to etiology of psychiatric disorder, and to which the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) subscribes, might detract from a more inclusive biopsychosocial approach that would be more applicable in the case of PTSD. The paper undertakes a comprehensive review of the recent literature in the areas of endophenotypes, neurogenetics, epigenetics, neural networks, HPA axis, neuronal networks, pathways, the PTSD five-factor model, allostasis, and the RDoC criteria for psychiatric diagnosis, and then returns to the topic of endophenotypes. Neuronal networks constitute one integrating area that could help in arriving at an appropriate model of PTSD endophenotype. Pathway analysis provides a rich field for discerning individual differences in PTSD development, more so than the static approach of using DSM-5 symptom criteria. A model of endophenotypes is presented, which considers these factors in relation to PTSD. The paper concludes with implications for the DSM-5, for practice and for court, especially that it would be premature to seek individual biomarkers of PTSD given the current state of knowledge, even if it is burgeoning.
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References
American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR (4th ed., text rev.). Washington: American Psychiatric Association.
American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-V (5th ed.). Washington: American Psychiatric Association.
Amstadter, A. B., Koenen, K. C., Ruggiero, K. J., Acierno, R., Galea, S., Kilpatrick, D. G., & Gelernter, J. (2009). Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. Journal of Anxiety Disorders, 23, 369–373.
Beauchaine, T. P., & McNulty, T. (2013). Comorbidities and continuities as ontogentic processes: Toward a developmental spectrum model of externalizing psychopathology. Development and Psychopathology, 25, 1505–1528.
Beevers, C. G., Wells, T. T., Ellis, A. J., & McGeary, J. E. (2009). Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli. Journal of Abnormal Psychology, 118, 670–681.
Ben-Porath, Y. S., & Tellegen, A. (2012). The Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF): manual for administration, scoring, and interpretation. Minnesota, MN: University of Minnesota Press.
Berenbaum, H. (2013). Classification and psychopathology research. Journal of Abnormal Psychology, 122, 894–901.
Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C., Mercer, K. B., … Ressler, K. J. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA: The Journal of the American Medical Association, 299, 1291–1305.
Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical Pharmacology & Therapeutics, 69, 89–95.
Blaze, J., & Roth, T. L. (2013). Epigenetic mechanisms in learning and memory. Wiley Interdisciplinary Reviews: Cognitive Science, 4, 105–115.
Bloomfield, F. H. (2011). Epigenetic modifications may play a role in the developmental consequences of early life events. Journal of Neurodevelopmental Disorders, 3, 348–355.
Blum, K., Giordano, J., Oscar-Berman, M., Bowirrat, A., Simpatico, T., & Barh, D. (2012). Diagnosis and healing in veterans suspected of suffering from post-traumatic stress disorder (PTSD) using reward gene testing and reward circuitry natural dopaminergic activation. Journal of Genetic Syndrome & Gene Therapy, 3, 1000116. doi:10.4172/2157-7412.1000116
Bonanno, G. A., Mancini, A. D., Horton, J. L., Powell, T. M., Leardmann, C. A., Boyko, E. J., … Smith, T. C. (2012). Trajectories of trauma symptoms and resilience in deployed U. S. military service members: Perspective cohort study. British Journal of Psychiatry, 200, 317–323.
Bowler, R. M., Han, H., Gocheva, V., Nakagawa, S., Alper, H., DiGrande, L., & Cone, J. E. (2010). Gender differences in probable posttraumatic stress disorder among police responders to the 2001 World Trade Center terrorist attack. American Journal of Industrial Medicine, 53, 1186–1196.
Cicchetti, D., & Toth, S. L. (2009). The past achievements and future promises of developmental psychopathology: the coming of age of a discipline. Journal of Child Psychology and Psychiatry, 50, 16–25.
Curley, J. P., Jensen, C. L., Mashoodh, R., & Champagne, F. A. (2011). Social influences on neurobiology and behavior: epigenetic effects during development. Psychoneuroendocrinology, 36, 352–371.
Cuthbert, B. N., & Kozak, M. J. (2013). Constructing constructs for psychopathology: the NIMH research domain criteria. Journal of Abnormal Psychology, 122, 928–937.
Daniels, J. K., Bluhm, R. L., & Lanius, R. A. (2013). Intrinsic network abnormalities in posttraumatic stress disorder: research directions for the next decade. Psychological Trauma: Theory, Research, Practice, and Policy, 5, 142–148.
Day, J. J., & Sweatt, J. D. (2011). Cognitive neuroepigenetics: a role for epigenetic mechanisms in learning and memory. Neurobiology of Learning & Memory, 96, 2–12.
Elhai, J. D., Biehn, T. L., Armour, C., Klopper, J. J., Frueh, B. C., & Palmieri, P. A. (2011). Evidence for a unique PTSD construct represented by PTSD’s D1-D3 symptoms. Journal of Anxiety Disorders, 25, 340–345.
Feil, R. (2008). Epigenetics, and emerging discipline with broad implications. Comptes Rendus Biologies, 331, 837–843.
Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L., & Raichle, M. E. (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. The Natuional Academy of Sciences, 103, 10046–10051.
Ganzel, B. L., & Morris, P. A. (2011). Allostasis and the developing human brain: explicit consideration of implicit models. Development and Psychopathology, 23, 955–974.
Ganzel, B. L., Morris, P., & Wethington, E. (2010). Allostasis and the human brain: Integrating models of stress from the social and life sciences. Psychological Review, 117, 134–174.
Gerson, R., & Rappaport, N. (2013). Traumatic stress and posttraumatic stress disorders in youth: recent research findings on clinical impact, assessment, and treatment. Journal of Adolescent Health, 52, 137–143.
Gong, Q., Li, L., Tognin, S., Wu, Q., Pettersson-Yeo, W., Lui, S., … Mechelli, A. (2014). Using structural neuroanatomy to identify trauma survivors with and without post-traumatic stress disorder at the individual level. Psychological Medicine, 44, 195–203.
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry, 160, 636–645.
Gottesman, I. I., & McGue, M. (2014). Endophenotype. In R. L. Cautin & S. O. Lilienfeld (Eds.), Wiley-Blackwell encyclopedia of clinical psychology. Hoboken, NJ: Wiley.
Gottesman, I. I., & Shields, J. (1972). Schizophrenia and genetics: a twin study vantage point. New York: Academic Press.
Gottesman, I. I., & Shields, J. (1973). Genetic theorizing and schizophrenia. The British Journal of Psychiatry, 122, 15–30.
Gould, T. D., & Gottesman, I. I. (2006). Psychiatric endophenotypes and the development of valid animal models. Genes, Brain and Behavior, 5, 113–119.
Grabe, H. J., Spitzer, C., Schwahn, C., Marcinek, A., Frahnow, A., Barnow, S., … Rosskopf, D. (2009). Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in general population. American Journal of Psychiatry, 166, 926–933.
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., … Weinberger, D. R. (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science, 297, 400–403.
Heim, C., Shugart, M., Craighead, W. E., & Nemeroff, C. B. (2010). Neurobiological and psychiatric consequences of child abuse and neglect. Developmental Psychobiology, 52, 671--690.
Higgins, E. S. (2008). The new genetics of mental illness. Scientific American Mind, 41--47.
Hobfoll, S. E., Mancini, A. D., Hall, B. J., Canetti, D., & Bonanno, G. A. (2011). The limits of resilience: distress following chronic political violence among Palestinians. Social Science and Medicine, 72, 1400–1408.
Insel, T. R., Cuthbert, B. N., Garvey, M. A., Heinssen, R. K., Pine, D. S., Quinn, K. J., Sanislow, C. A., & Wang, P. S. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167, 748--751.
Insel, T. R., & Lieberman, J. A. (2013). DSM-5 and RDoC: Shared interests. The National Institute of Mental Health, www.nimh.nih.gov
Jovanovic, T., & Ressler, K. J. (2010). How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. American Journal of Psychiatry, 167, 648–662.
Juster, R-P., Bizik, G., Picard, M., Arsenault-Lapierre, G., Sindi, S., Trepanier, L., … Lupien, S. J. (2011). A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development. Development and Psychopathology, 23, 725–776.
Kane, A. W., & Dvoskin, J. A. (2011). Evaluation for personal injury claims. New York: Oxford University Press.
Kasai, K., Yamasue, H., Gilbertson, M. W., Shenton, M. E., Rauch, S. L., & Pitman, R. K. (2008). Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder. Biological Psychiatry, 63, 550–556.
Kello, C. T. (2013). Critical branching neural networks. Psychological Review, 120, 230–254.
Kheirbek, M. A., Klemenhagen, C., Sahay, A., & Hen, R. (2012). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nature Neuroscience, 15, 1613–1620.
Kilpatrick, D. G., Koenen, K. C., Ruggiero, K. J., Acierno, R., Galea, S., Resnick, H. S., … Gelernter, J. (2007). The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. American Journal of Psychiatry, 164, 1693–1699.
Knopik, V. S., Maccani, M. A., Francazio, S., & McGeary, J. E. (2012). The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Development and Psychopathology, 24, 1377–1390.
Koenen, K. C., Aiello, A. E., Bakshis, E., Amstadter, A. B., Ruggiero, K. J., Acierno, R., … Galea, S. (2009). Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. American Journal of Epidemiology, 169, 704–711.
Kolassa, I.-T., Ertl, V., Eckart, C., Glöckner, F., Kolassa, S., Pappassotiropoulos, A., … Elbert, T. (2010a). Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: Evidence from survivors of the Rwandan genocide. Journal of Clinical Psychiatry, 71, 543–547.
Kolassa, I.-T., Kolassa, S., Ertl, V., Papassotiropoulos, A., & de Quervain, D. J. (2010b). The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. Biological Psychiatry, 67, 304–308.
Lareau, C. R. (2011). Posttraumatic stress disorder and acute stress disorder. In D. Faust (Ed.), Coping with psychiatric and psychological testimony (6th ed., pp. 610–635). New York: Oxford University Press.
Larrabee, G. J. (2012). Forensic neuropsychology: a scientific approach (2nd ed.). New York: Oxford University Press.
Lenzenweger, M. F. (2013). Thinking clearly about the endophenotype-intermediate phenotype-biomarker distinctions in developmental psychopathology research. Development and Psychopathology, 25, 1347–1357.
Lonsdorf, T. B., Weike, A. I., Nikamo, P., Schalling, M., Hamm, A. O., & Ohman, A. (2009). Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder. Psychological Science, 20, 198–206.
Maercker, A., Brewin, C. R., Bryant, R, A., Cloitre, M., Reed, G. M., van Ommeren, M., … Saxena, S. (2013). Proposals for mental disorders specifically associated with stress in the international classification of diseases-11. The Lancet, 381, 1683–1685.
Masterpasqua, F. (2009). Psychology and epigenetics. Review of General Psychology, 13, 194–201.
McEwen, B. S. (2006). Protective and damaging effects of stress mediators: central role of the brain. Dialogues in Clinical Neuroscience, 8, 367–381.
McEwen, B. S., & Stellar, E. (1993). Stress and the individual. Mechanisms leading to disease. Archives of Internal Medicine, 153, 2093–2010.
McEwen, B. S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338, 171--179.
McNally, R. J. (2003). Progress and controversy in the study of posttraumatic stress disorder. Annual Review of Psychology, 54, 229--252.
McEwen, B. S., & Wingfield, J. C. (2003). The concept of allostasis in biology and biomedicine. Hormones and Behavior, 43, 2–15.
Meaney, M. J. (2010). Epigenetics and the biological definition of gene x environment interactions. Child Development, 81, 41–79.
Meaney, M. J., & Szyf, M. (2005). Maternal care as a model for experience-dependent chromatin plasticity? Trends in Neurosciences, 28, 456–463.
Mehta, D., & Binder, E. B. (2012). Gene x environment vulnerability factors for PTSD: the HPA-axis. Neuropharmacology, 62, 654–662.
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., Rex-haffner, M., Loeschner, A., Gonik, M., Mercer, K. B., Bradley, B., Müller-Myhsok, B., Ressler, K. J., & Binder, E. B. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. PNAS Early Edition, 1–6.
Mercer, K. B., Orchutt, H. K., Quinn, J. F., Fitzgerald, C. A., Conneely, K. N., Barfield, R. T., … Ressler, K. J. (2012). Acute and posttraumatic stress symptoms in a prospective gene x environment study of a university campus shooting. Archives of General Psychiatry, 69, 89–97.
Morris, S. E., & Cuthbert, B. N. (2013). Research domain criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues in Clinical Neuroscience, 14, 29–37.
Morris, S. E., Rumsey, J. M., & Cuthbert, B. N. (2013). Rethinking mental disorders: the role of learning and brain plasticity. Restorative Neurology and Neuroscience. doi:10.3233/RNN-139015
Owen, M. J. (2012). Implications of genetic findings for understanding schizophrenia. Schizophrenia Bulletin, 38, 904--907.
Pergamin-Hight, L., Bakermans-Kranenburg, M. J., van Ijzendoorn, M. H., & Bar-Haim, Y. (2012). Variations in the promoter region of the serotonin transporter gene and biased attention for emotional information: a meta-analysis. Biological Psychiatry, 71, 373–379.
Pezawas, L., Meyer-Lidenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., … Weinberger, D. R. (2005). 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: A genetic susceptibility mechanism for depression. Natural Neuroscience, 8, 828–834.
Pietrzak, R. H., Feder, A., Singh, R., Schechter, C. B., Bromet, E. J., Katz, C. L., … Southwick, S. M. (2014). Trajectories of PTSD risk and resilience in World Trade Center responders: An 8-year prospective cohort study. Psychological Medicine, 44, 205–219.
Pietrzak, R. H., Galea, S., Southwick, S. M., & Gelernter, J. (2013a). Examining the relation between the serotonin transporter 5-HTTPLR genotype x trauma exposure interaction on a contemporary phenotypic model of posttraumatic stress symptomatology: a pilot study. Journal of Affective Disorders, 148, 123–128.
Pietrzak, R. H, Gallezot, J-D., Ding, Y-S., Henry, S., Potenza, M. N., Southwick, S. M., … Neumeister, A. (2013c). Association of posttraumatic stress disorder with reduced in vivo norepinephrine transporter availability in the locus coeruleus. JAMA Psychiatry, 70, 1199–1205.
Pietrzak, R. H., Henry, S., Southwick, S. M., Krystal, J. H., & Neumeister, A. (2013c). Linking in vivo brain serotonin type 1B receptor density to phenotypic heterogeneity of posttraumatic stress symptomatology. Molecular Psychiatry, 18, 399–401.
Pitman, R. K., Sanders, K. M., Zusman, R. M., Healy, A. R., Cheema, F., Lasko, N. B., … Orr, S. P. (2002). Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biological Psychiatry, 51, 189–192.
Ptak, C., & Petronis, A. (2010). Epigenetic approaches to psychiatric disorders. Dialogues in Clinical Neuroscience, 12, 25–35.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences, USA, 98, 676–682.
Rasetti, R., & Weinberger, D. R. (2011). Intermediate phenotypes in psychiatric disorders. Current Opinions in Genetics & Development, 21, 340–348.
Rauch, S. L., Shin, L. M., & Phelps, E. A. (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research—past, present, and future. Biological Psychiatry, 60, 376–382.
Rosen, G. M., & Grunert, B. K. (2012). Posttraumatic stress disorder in the workplace. In S. S. Bush & G. L. Iverson (Eds.), Neuropsychological assessment of work-related injuries (pp. 163–186). New York: Guilford Press.
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry, 65, 760–769.
Roth, T. L., Zoladz, P. R., Sweatt, J. D., & Diamond, D. M. (2011). Epigenetic modifications of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder. Journal of Psychiatric Research, 45, 919–926.
Seckl, J. R., & Meaney, M. J. (2006). Glucocorticoid “programming” and PTSD risk. Annals of the New York Academy of Sciences, 1071, 351–378.
Seeman, E., Singer, B. H., Rowe, J., Horwitz, R. I., & McEwen, B. (1997). Price of adaptation—allostatic load and its health consequences. Archives of Internal Medicine, 157, 2259–2268.
Segman, R., Shalev, A. Y., & Gelernter, J. (2007). Gene-environment interactions: twin studies and gene research in the context of PTSD. In M. J. Friedman, T. M. Keane, & P. A. Resick (Eds.), Handbook of PTSD: science and practice (pp. 190–206). New York: Guilford Press.
Sherin, J. E., & Nemeroff, C. B. (2011). Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues in Clinical Neuroscience, 13, 263–278.
Shields, J., & Gottesman, I. I. (1973). Genetic studies of schizophrenia as signposts to biochemistry. In L. L. Iverson & S. Rose (Eds.), Biochemistry and mental illness (Biochemistry Society Special Publication (Vol. 1, pp. 165–174). London: Biochemical Society.
Simmons, J. M., & Quinn, K. J. (2013). The NIMH Research Domain Criteria (RDoC) project: implications for genetics research. Mammalian Genome. doi:10.1007/s00335-013-9476-9
Skelton, K., Ressler, K. J., Norrholm, S. D., Jovanovic, T., & Bradley-Davino, B. (2012). PTSD and gene variants: new pathways and new thinking. Neuropharmacology, 62, 628–637.
Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., … Casey, B. J. (2010). A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science, 327, 863–866.
Sporns, O. (2010). Networks of the brain. Cambridge, MA: MIT Press.
Sporns, O. (2012). Discovering the human connectome. Cambridge, MA: MIT Press.
Spreng, R. N., Mar, R. A., & Kim, A. S. (2009). The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: a quantitative meta-analysis. Journal of Cognitive Neuroscience, 21, 489–510.
Sterling, P. (2004). Principles of allostasis: optimal design, predictive regulation, pathophysiology and rational therapeutics. In J. Schulkin (Ed.), Allostasis, homeostasis, and the costs of adaptation (p. 17). Cambridge: Cambridge University Press.
Sterling, P., & Eyer, J. (1988). Allostasis: a new paradigm to explain arousal pathology. In S. Fisher & J. Reason (Eds.), Handbook of life stress, cognition and health (pp. 629–649). New York: Wiley.
Stolzenberg, D. S., Stevens, J. S., & Rissman, E. F. (2012). Experience-facilitated improvements in pup retrieval; evidence for an epigenetic effect. Hormones and Behavior, 62, 128–135.
Szyf, M. (2013). How do environments talk to genes? Nature Neuroscience, 16, 2–4.
Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de Los Santos, R., … Galea, S. (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America, 107, 9470–9475.
Vincent, J. L., Kahn, I., Snyder, A. Z., Raichle, M. E., & Buckner, R. L. (2008). Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. Journal of Neurophysiology, 100, 3328–3342.
Weathers, F., Litz, B., Herman, D., Huska, J., & Keane, T. (1993). The PTSD checklist (PLC): reliability, validity, and diagnostic utility. San Antonio, TX: Meeting of the International Society of Traumatic Stress Studies.
Weaver, I. C. (2007). Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let’s call the whole thing off. Epigenetics, 2, 22–28.
Wiecki, T. V., & Frank, M. J. (2013). A computational model of inhibitory control in frontal cortex and basal ganglia. Psychological Review, 120, 329–355.
Wilker, S., & Kolassa, I.-T. (2013). The formation of a neural fear network in posttraumatic stress disorder: insights from molecular genetics. Clinical Psychological Science. doi:10.1177/2167702613479583
Wilkinson, L. S., Davies, W., & Iseles, A. R. (2007). Genomic imprinting effects on brain development and function. Nature Reviews of Neuroscience, 8, 832–843.
Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Brady, K., … Gelernter, J. (2009). Interactive effect of stressful life events and the serotonin trasporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. Archives of General Psychiatry, 66, 1201–1209.
Yehuda, R. (2002). Post-traumatic stress disorder. The New England Journal of Medicine, 346, 108–114.
Yehuda, R. (2009). Status of glucocorticoid alterations in post-traumatic stress disorder. Annals of the New York Academy of Sciences, 1179, 56–69.
Yehuda, R., Bell, A., Bierer, L. M., & Schmeidler, J. (2008). Maternal, not parental, PTSD is related to increased risk for PTSD. Journal of Psychiatric Research, 42, 1104–1111.
Yehuda, R., Engel, S. M., Brand, S. R., Seckl, J., Marcus, S. M., & Berkowitz, G. S. (2005). Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. Journal of Clinical Endocrinology & Metabolism, 90, 4115–4118.
Yehuda, R., Flory, J. D., Pratchell, L. C., Buxbaum, J., Ising, M., & Holsboer, F. (2010). Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology, 212, 405–417.
Yehuda, R., McFarlane, A. C., & Shalev, A. Y. (1998). Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event. Biological Psychiatry, 44, 1305–1313.
Yehuda, R., Teicher, M. H., Seckl, J. R., Grossman, R. A., Morris, A., & Bierer, L. M. (2007). Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of holocaust survivors. Archives of General Psychiatry, 64, 1040–1048.
Young, G. (2008a). Causality and causation in law, medicine, psychiatry, and psychology: progression or regression? Psychological Injury and Law, 1, 161–181.
Young, G. (2008b). Psychological injury and law: an integrative model. Psychological Injury and Law, 1, 150–160.
Young, G. (2011). Development and causality: neo-Piagetian perspectives. New York: Springer Science+Business Media.
Young, G. (2013). DSM-5: Overview, critique, recommendations. Workshop presented at the Canadian Academy of Psychologists in Disability Assessment. Toronto, June 21, 2013.
Young, G. (2014). Malingering, feigning, and response bias in psychiatric/psychological injury: implications for practice and court. International Library of Ethics, Law, and New Medicine, 56. Dordrecht, Netherland: Springer SBM.
Young, G., & Haynes, S. (2014). Embodied causation: unification of causality and etiology in psychology and psychopathology. New York: Springer Science+Business Media.
Young, G., Lareau, C., & Pierre, B. (2014). One quintillion ways to have PTSD comorbidity: recommendations for the disordered DSM-5. Psychological Injury and Law.
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Jon Elhai and Patrick Palmieri served as the action editors. The author is grateful for reviewer comments and corrections.
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Young, G. PTSD, Endophenotypes, the RDoC, and the DSM-5. Psychol. Inj. and Law 7, 75–91 (2014). https://doi.org/10.1007/s12207-014-9187-x
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DOI: https://doi.org/10.1007/s12207-014-9187-x