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Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma


In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients' trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs—both the trauma-exposed and unexposed members—had significantly smaller hippocampi than non-PTSD pairs.

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Figure 1: Discordant monozygotic twin paradigm for assessing MRI differences in PTSD.
Figure 2: Hippocampal volume correlations with post-trauma symptoms.
Figure 3: Total hippocampal volumes for four subject groups.


  1. 1

    Sapolsky, R.M., Uno, H., Rebert, C.S. & Finch, C.E. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J. Neurosci. 10, 2897–2902 (1990).

    CAS  Article  Google Scholar 

  2. 2

    McEwen, B.S. in The Cognitive Neurosciences (ed. Gazzaniga, M.S.) 1117–1135 (MIT Press, Cambridge, Massachusetts, 1995).

    Google Scholar 

  3. 3

    Squire, L.R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195–231 (1992).

    CAS  Article  Google Scholar 

  4. 4

    Zola-Morgan, S. & Squire, L.R. Neuroanatomy of memory. Annu. Rev. Neurosci. 16, 547–563 (1993).

    CAS  Article  Google Scholar 

  5. 5

    Bremner, J.D. et al. MRI-based measurements of hippocampal volume in combat-related posttraumatic stress disorder. Am. J. Psychiatry 152, 973–978 (1995).

    CAS  Article  Google Scholar 

  6. 6

    Gurvits, T.V. et al. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol. Psychiatry 40, 1091–1099 (1996).

    CAS  Article  Google Scholar 

  7. 7

    Bremner, J.D. et al. Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse: a preliminary report. Biol. Psychiatry 41, 23–32 (1997).

    CAS  Article  Google Scholar 

  8. 8

    Stein, M.B., Koverola, C., Hanna, C., Torchia, M.G. & McClarty, B. Hippocampal volume in women victimized by childhood sexual abuse. Psychol. Med. 27, 951–959 (1997).

    CAS  Article  Google Scholar 

  9. 9

    Pitman, R.K. Hippocampal diminution in PTSD: more (or less?) than meets the eye. Hippocampus 11, 73–74 (2001).

    CAS  Article  Google Scholar 

  10. 10

    Bremner, J.D. Hypotheses and controversies related to effects of stress on the hippocampus: an argument for stress-induced damage to the hippocampus in patients with Posttraumatic Stress Disorder. Hippocampus 11, 75–81 (2001).

    CAS  Article  Google Scholar 

  11. 11

    McEwen, B.S. Commentary on PTSD discussion. Hippocampus 11, 82–84 (2001).

    Article  Google Scholar 

  12. 12

    Yehuda, R. Are glucocortoids responsible for putative hippocampal damage in PTSD? How and when to decide. Hippocampus 11, 85–89 (2001).

    CAS  Article  Google Scholar 

  13. 13

    Kulka, R.A. et al. Trauma and the Vietnam War Generation: Report of Findings from the National Vietnam Veterans Readjustment Study (Brunner/Mazel, New York, 1990).

    Google Scholar 

  14. 14

    Kessler, R.C., Sonnega, A., Bromet, E., Huges, M. & Nelson, C.B. Posttraumatic stress disorder in the National Comorbidity Survey. Arch. Gen. Psychiatry 52, 1048–1060 (1995).

    CAS  Article  Google Scholar 

  15. 15

    Crusio, W.E., Schwegler, H. & & van Abeelen, J.H.F. Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis. Behav. Brain Res. 32, 81–88 (1989).

    CAS  Article  Google Scholar 

  16. 16

    Wimer, C.C., Wimer, R.E. & Roderick, T.H. Some behavioral differences associated with relative size of hippocampus in the mouse. J. Comp. Physiol. Psychol. 76, 57–65 (1971).

    CAS  Article  Google Scholar 

  17. 17

    Schwegler, H. & Lipp, H.P. Hereditary covariations of neuronal circuitry and behavior: correlations between the proportions of hippocampal synaptic fields in the regio inferior and two-way avoidance in mice and rats. Behav. Brain Res. 7, 1–38 (1983).

    CAS  Article  Google Scholar 

  18. 18

    Lyons, D.M., Yang, C., Sawyer-Glover, A.M., Moseley, M.E. & Schatzberg, A.F. Early life stress and inherited variation in monkey hippocampal volumes. Arch. Gen. Psychiatry 58, 1145–1151 (2001).

    CAS  Article  Google Scholar 

  19. 19

    Freeman, T.W., Cardwell, D., Karson, C.N. & Komoroski, R.A. In vivo proton magnetic resonance spectroscopy of the medial temporal lobes of subjects with combat-related posttraumatic stress disorder. Magn. Reson. Med. 40, 66–71 (1998).

    CAS  Article  Google Scholar 

  20. 20

    Schuff, N. et al. Reduced hippocampal volume and n-acetyl aspartate in posttraumatic stress disorder. Ann. NY Acad. Sci. 821, 516–520 (1997).

    CAS  Article  Google Scholar 

  21. 21

    Keane, T.M. & Kaloupek, D.G. Comorbid psychiatric disorders in PTSD: implications for research. Ann. NY Acad. Sci. 821, 24–34 (1997).

    CAS  Article  Google Scholar 

  22. 22

    Bremner, J. et al. Hippocampal volume reduction in major depression. Am. J. Psychiatry 157, 115–127 (2000).

    CAS  Article  Google Scholar 

  23. 23

    Laakso, M.P. et al. A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism. Behav. Brain Res. 109, 177–186 (2000).

    CAS  Article  Google Scholar 

  24. 24

    Sheline, Y., Sanghavi, M., Mintin, M. & Gado, M. Depression duration but not age predicts hippocampal volume loss in medical healthy women with recurrent major depression. J. Neurosci. 19, 5034–5041 (1999).

    CAS  Article  Google Scholar 

  25. 25

    De Bellis, M.D. et al. Hippocampal volume in adolescent-onset alcohol use disorders. Am. J. Psychiatry 157, 737–744 (2000).

    CAS  Article  Google Scholar 

  26. 26

    Miller, G.A. & Chapman, J.P. Misunderstanding analysis of covariance. J. Abnorm. Psychol. 110, 40–48 (2001).

    CAS  Article  Google Scholar 

  27. 27

    De Bellis, M.D. et al. Developmental traumatology part II: brain development. Biol. Psychiatry 45, 1271–1284 (1999).

    CAS  Article  Google Scholar 

  28. 28

    Schuff, N. et al. Decreased hippocampal n-acetylaspartate in the absence of atrophy in Posttraumatic Stress Disorder. Biol. Psychiatry 50, 952–959 (2001).

    CAS  Article  Google Scholar 

  29. 29

    Bonne, O. et al. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am. J. Psychiatry 158, 1248–1251 (2001).

    CAS  Article  Google Scholar 

  30. 30

    Breslau, N. & Davis, G.C. Posttraumatic Stress Disorder in an urban population of young adults: risk factors for chronicity. Am. J. Psychiatry 149, 671–675 (1992).

    CAS  Article  Google Scholar 

  31. 31

    Mellman, T.A., Randolph, C.A., Brawman-Mintzer, O., Flores, L.P. & Milanes, F.J. Phenomenology and course of psychiatric disorders associated with combat-related posttraumatic stress disorder. Am. J. Psychiatry 149, 1568–1574 (1992).

    CAS  Article  Google Scholar 

  32. 32

    Selden, N.R.W., Everitt, B.J., Jarrard, L.E. & Robbins, T.W. Complementary roles for amygdala and hippocampus in aversive conditioning to explicit and contextual cues. Neuroscience 42, 335–350 (1991).

    CAS  Article  Google Scholar 

  33. 33

    Phillips, R.G. & LeDoux, J.E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav. Neurosci. 106, 274–285 (1992).

    CAS  Article  Google Scholar 

  34. 34

    Falls, W.A. & Davis, M. in Neurobiological and Clinical Consequences of Stress: from Normal Adaptation to Post-Traumatic Stress Disorder (eds. Friedman, D.J., Charney, D.S. & Deutch, A.Y.) 177–202 (Lippincott-Raven, Philadelphia, 1995).

    Google Scholar 

  35. 35

    Antelman, S.M. & Brown, T.S. Hippocampal lesions and shuttlebox avoidance behavior: a fear hypothesis. Physiol. Behav. 9, 15–20 (1972).

    CAS  Article  Google Scholar 

  36. 36

    Orr, S.P. et al. De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J. Abnorm. Psychol. 109, 290–298 (2000).

    CAS  Article  Google Scholar 

  37. 37

    Wimer, R.E. & Wimer, C.C. A biometrical-genetic analysis of granule cell number in the area dentata of house mice. Brain Res. 254, 129–140 (1981).

    CAS  Article  Google Scholar 

  38. 38

    Beck, K.D., Powell-Braxton, L., Widmer, H.R., Vlaverde, J. & Hefti, F. Igfl gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14, 717–730 (1995).

    CAS  Article  Google Scholar 

  39. 39

    Pennington, B.F. et al. A twin MRI study of size variations in the human brain. J. Cogn. Neurosci. 12, 223–232 (2000).

    CAS  Article  Google Scholar 

  40. 40

    Thompson, P.M. et al. Genetic influences on brain structure. Nat. Neurosci. 4, 1253–1258 (2001).

    CAS  Article  Google Scholar 

  41. 41

    Eisen, S., Neuman, R., Goldberg, J., Rice, J. & True, W. Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires. Clin. Genet. 35, 423–432 (1989).

    CAS  Article  Google Scholar 

  42. 42

    Janes, G.R., Goldberg, J., Eisen, S.A. & True, W.R. Reliability and validity of a combat exposure index for Vietnam era veterans. J. Clin. Psychol. 47, 80–86 (1991).

    CAS  Article  Google Scholar 

  43. 43

    Eisen, S.A., True, W.R., Goldberg, J., Henderson, W. & Robinette, C.D. The Vietnam Era Twin (VET) Registry: method of construction. Acta Geneticae Medicae et Gemellologiae (Roma) 36, 61–66 (1987).

    CAS  Article  Google Scholar 

  44. 44

    Henderson, W.G. et al. The Vietnam Era Twin Registry: a resource for medical research. Public Health Rep. 105, 368–373 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Orr, S.P. et al. Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure: association with PTSD. Arch. Gen. Psychiatry (in press).

  46. 46

    Blake, D.D. et al. The development of a clinician-administered PTSD scale. J. Trauma. Stress 8, 75–90 (1995).

    CAS  Article  Google Scholar 

  47. 47

    First, M.B., Spitzer, R.L., Gibbon, M. & Williams, J.B.W. Structured Clinical Interview for Axis I DSM-IV Disorders, Version 2.0 (Biometrics Research Department, New York, 1994).

    Google Scholar 

  48. 48

    Selzer, M.L. The Michigan Alcoholism Screening Test: the quest for a new diagnostic instrument. Am. J. Psychiatry 127, 1653–1658 (1971).

    CAS  Article  Google Scholar 

  49. 49

    Shenton, M.A. et al. Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imagery study. N. Engl. J. Med. 327, 604–612 (1992).

    CAS  Article  Google Scholar 

  50. 50

    Weathers, F.W., Ruscio, A.M. & Keane, T.M. Psychometric properties of nine scoring rules for the Clinican-Administered Posttraumatic Stress Disorder Scale. Psychol. Assess. 11, 124–133 (1999).

    Article  Google Scholar 

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This work was supported by Department of Veterans Affairs Merit Review Grants (to M.W.G. and S.P.O.), USPHS Grant R01-MH54636 (to R.K.P.) and USPHS Grant K02-MH01110 (to M.E.S.). The authors would like to thank M. Macklin, K. Sheldon, S. Williston, L. Paulus, H. Croteau and the VA Cooperative Studies VET Registry (M.E. Vitek, K. Bukowski, R. Havlicek, T. Colton, W.E. Nance, R.S. Paffenbarger, Jr., M.M. Weissman and R.R. Williams) for their assistance. We gratefully acknowledge the participation of the veterans of the VET Registry and the non-Registry twin participants.

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Correspondence to Mark W. Gilbertson.

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Gilbertson, M., Shenton, M., Ciszewski, A. et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci 5, 1242–1247 (2002).

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