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Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder

Published online by Cambridge University Press:  04 May 2015

S. J. H. van Rooij ,
M. Kennis ,
R. Sjouwerman ,
M. P. van den Heuvel ,
R. S. Kahn  and
E. Geuze
S. J. H. van Rooij*
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Research Centre, Military Mental Healthcare, Ministry of Defence, The Netherlands
M. Kennis
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Research Centre, Military Mental Healthcare, Ministry of Defence, The Netherlands
R. Sjouwerman
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Research Centre, Military Mental Healthcare, Ministry of Defence, The Netherlands
M. P. van den Heuvel
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
R. S. Kahn
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
E. Geuze
Affiliation:
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Research Centre, Military Mental Healthcare, Ministry of Defence, The Netherlands
*
* Address for correspondence: S. J. H. van Rooij, Ph.D., Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan 100 (HPN A01.1.46), 3584 CX Utrecht, The Netherlands. (Email: [email protected])
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Abstract

Background

Smaller hippocampal volume has often been observed in patients with post-traumatic stress disorder (PTSD). However, there is no consensus whether this is a result of stress/trauma exposure, or constitutes a vulnerability factor for the development of PTSD. Second, it is unclear whether hippocampal volume normalizes with successful treatment of PTSD, or whether a smaller hippocampus is a risk factor for the persistence of PTSD.

Method

Magnetic resonance imaging (MRI) scans and clinical interviews were collected from 47 war veterans with PTSD, 25 healthy war veterans (combat controls) and 25 healthy non-military controls. All veterans were scanned a second time with a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. Based on post-treatment PTSD symptoms, patients were divided into a PTSD group who was in remission (n = 22) and a group in whom PTSD symptoms persisted (n = 22). MRI data were analysed with Freesurfer.

Results

Smaller left hippocampal volume was observed in PTSD patients compared with both control groups. Hippocampal volume of the combat controls did not differ from healthy controls. Second, pre- and post-treatment analyses of the PTSD patients and combat controls revealed reduced (left) hippocampal volume only in the persistent patients at both time points. Importantly, hippocampal volume did not change with treatment.

Conclusions

Our findings suggest that a smaller (left) hippocampus is not the result of stress/trauma exposure. Furthermore, hippocampal volume does not increase with successful treatment. Instead, we demonstrate for the first time that a smaller (left) hippocampus constitutes a risk factor for the persistence of PTSD.

Keywords

Hippocampal volumemagnetic resonance imagingpost-traumatic stress disordertrauma-focused therapywar veterans
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 13 , October 2015 , pp. 2737 - 2746
Copyright
Copyright © Cambridge University Press 2015 

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References

Apfel, BA, Ross, J, Hlavin, J, Meyerhoff, DJ, Metzler, TJ, Marmar, CR, Weiner, MW, Schuff, N, Neylan, TC (2011). Hippocampal volume differences in gulf war veterans with current versus lifetime posttraumatic stress disorder symptoms. Biological Psychiatry 69, 541–548.Google Scholar
Bisson, JI, Ehlers, A, Matthews, R, Pilling, S, Richards, D, Turner, S (2007). Psychological treatments for chronic post-traumatic stress disorder: systematic review and meta-analysis. British Journal of Psychiatry 190, 97–104.CrossRefGoogle ScholarPubMed
Blake, D, Weathers, F, Nagy, L, Kaloupek, D, Klauminzer, G, Charney, DA (1990). Clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behavioral Therapy 13, 187–188.Google Scholar
Bonne, O, Brandes, D, Gilboa, A, Gomori, JM, Shenton, ME, Pitman, RK, Shalev, AY (2001). Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. American Journal of Psychiatry 158, 1248–1251.CrossRefGoogle ScholarPubMed
Bossini, L, Tavanti, M, Lombardelli, A, Calossi, S, Polizzotto, NR, Galli, R, Vatti, G, Pieraccini, F, Castrogiovanni, P (2007). Changes in hippocampal volume in patients with post-traumatic stress disorder after sertraline treatment. Journal of Clinical Psychopharmacology 27, 233–235.Google Scholar
Bradley, R, Greene, J, Russ, E, Dutra, L, Westen, D (2005). A multidimensional meta-analysis of psychotherapy for PTSD. American Journal of Psychiatry 162, 214–227.Google Scholar
Bremner, JD, Bolus, R, Mayer, EA (2007). Psychometric properties of the early trauma inventory – self report. Journal of Nervous and Mental Disease 195, 211–218.Google Scholar
Bremner, JD, Mletzko, T, Welter, S, Quinn, S, Williams, C, Brummer, M, Siddiq, S, Reed, L, Heim, CM, Nemeroff, CB (2005). Effects of phenytoin on memory, cognition and brain structure in post-traumatic stress disorder: a pilot study. Journal of Psychopharmacology 19, 159–165.Google Scholar
Bremner, JD, Vythilingam, M, Vermetten, E, Southwick, SM, McGlashan, T, Nazeer, A, Khan, S, Vaccarino, LV, Soufer, R, Garg, PK, Ng, CK, Staib, LH, Duncan, JS, Charney, DS (2003). MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. American Journal of Psychiatry 160, 924–932.CrossRefGoogle ScholarPubMed
Dale, AM, Fischl, B, Sereno, MI (1999). Cortical surface-based analysis: I. Segmentation and surface reconstruction. NeuroImage 9, 179–194.Google Scholar
Duman, RS, Nakagawa, S, Malberg, J (2001). Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 25, 836–844.Google Scholar
Engvig, A, Fjell, AM, Westlye, LT, Skaane, NV, Sundseth, T, Walhovd, KB (2012). Hippocampal subfield volumes correlate with memory training benefit in subjective memory impairment. NeuroImage 61, 188–194.CrossRefGoogle ScholarPubMed
Fendt, M, Fanselow, MS (1999). The neuroanatomical and neurochemical basis of conditioned fear. Neuroscience and Biobehavioral Reviews 23, 743–760.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (2002). Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Patient Edition (SCID-I/P). Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, Van Der Kouwe, A, Killiany, R, Kennedy, D, Klaveness, S, Montillo, A, Makris, N, Rosen, B, Dale, AM (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341–355.Google Scholar
Fischl, B, Sereno, MI, Dale, AM (1999). Cortical surface-based analysis: II. Inflation, flattening, and a surface-based coordinate system. NeuroImage 9, 195–207.Google Scholar
Foa, EB, Keane, TM, Friedman, MJ, Cohen, JA (2009). Effective Treatments for PTSD: Practice Guidelines from the International Society of Traumatic Stress Studies. Guilford Press: New York.Google Scholar
Gilbertson, MW, Shenton, ME, Ciszewski, A, Kasai, K, Lasko, NB, Orr, SP, Pitman, RK (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience 5, 1242–1247.Google Scholar
Gould, E, Tanapat, P, McEwen, BS, Flugge, G, Fuchs, E (1998). Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proceedings of the National Academy of Sciences 95, 3168–3171.Google Scholar
Gould, E, Tanapat, P, Rydel, T, Hastings, N (2000). Regulation of hippocampal neurogenesis in adulthood. Biological Psychiatry 48, 715–720.CrossRefGoogle ScholarPubMed
Hedges, DW, Woon, FL (2010). Alcohol use and hippocampal volume deficits in adults with posttraumatic stress disorder: a meta-analysis. Biological Psychology 84, 163–168.Google Scholar
Izquierdo, I, Cammarota, M, Vianna, MRM, Bevilaqua, LRM (2004). The inhibition of acquired fear. Neurotoxicity Research 6, 175–188.CrossRefGoogle ScholarPubMed
Karl, A, Schaefer, M, Malta, LS, Dorfel, D, Rohleder, N, Werner, A (2006). A meta-analysis of structural brain abnormalities in PTSD. Neuroscience and Biobehavioral Reviews 30, 1004–1031.CrossRefGoogle ScholarPubMed
Kitayama, N, Vaccarino, V, Kutner, M, Weiss, P, Bremner, JD (2005). Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. Journal of Affective Disorders 88, 79–86.Google Scholar
Kuhn, S, Gallinat, J (2013). Gray matter correlates of posttraumatic stress disorder: a quantitative meta-analysis. Biological Psychiatry 73, 70–74.Google Scholar
Levy-Gigi, E, Szabo, C, Kelemen, O, Keri, S (2013). Association among clinical response, hippocampal volume, and fkbp5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biological Psychiatry 74, 793–800.CrossRefGoogle ScholarPubMed
Lindauer, RJ, Vlieger, EJ, Jalink, M, Olff, M, Carlier, IV, Majoie, CB, Den Heeten, GJ, Gersons, BP (2005). Effects of psychotherapy on hippocampal volume in out-patients with post-traumatic stress disorder: a MRI investigation. Psychological Medicine 35, 1421–1431.CrossRefGoogle ScholarPubMed
Malenka, RC, Nicoll, RA (1999). Long-term potentiation – a decade of progress? Science 285, 1870–1874.Google Scholar
Nordanskog, P, Dahlstrand, U, Larsson, MR, Larsson, EM, Knutsson, L, Johanson, A (2010). Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. Journal of ECT 26, 62–67.Google Scholar
Pohlack, ST, Meyer, P, Cacciaglia, R, Liebscher, C, Ridder, S, Flor, H (2014). Bigger is better! Hippocampal volume and declarative memory performance in healthy young men. Brain Structure and Function 219, 255–267.CrossRefGoogle ScholarPubMed
Sapolsky, RM, Uno, H, Rebert, CS, Finch, CE (1990). Hippocampal damage associated with prolonged glucocorticoid exposure in primates. Journal of Neuroscience 10, 2897–2902.CrossRefGoogle ScholarPubMed
Schneider, SL (2013). The International Standard Classification of Education 2011. Comparative Social Research 30, 365–379.CrossRefGoogle Scholar
Smith, ME (2005). Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies. Hippocampus 15, 798–807.Google Scholar
Teicher, MH, Andersen, SL, Polcari, A, Anderson, CM, Navalta, CP, Kim, DM (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience and Biobehavioral Reviews 27, 33–44.Google Scholar
Tendolkar, I, Van Beek, M, Van Oostrom, I, Mulder, M, Janzing, J, Voshaar, RO, Van Eijndhoven, P (2013). Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: a longitudinal pilot study. Psychiatry Research – Neuroimaging 214, 197–203.Google Scholar
Tischler, L, Brand, SR, Stavitsky, K, Labinsky, E, Newmark, R, Grossman, R, Buchsbaum, MS, Yehuda, R (2006). The relationship between hippocampal volume and declarative memory in a population of combat veterans with and without PTSD. Annals of the New York Academy of Sciences 1071, 405–409.Google Scholar
Vermetten, E, Vythilingam, M, Southwick, SM, Charney, DS, Bremner, JD (2003). Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biological Psychiatry 54, 693–702.Google Scholar
Vythilingam, M, Heim, C, Newport, J, Miller, AH, Anderson, E, Bronen, R, Brummer, M, Staib, L, Vermetten, E, Charney, DS, Nemeroff, CB, Bremner, JD (2002). Childhood trauma associated with smaller hippocampal volume in women with major depression. American Journal of Psychiatry 159, 2072–2080.CrossRefGoogle ScholarPubMed
Vythilingam, M, Luckenbaugh, DA, Lam, T, Morgan, CA III, Lipschitz, D, Charney, DS, Bremner, JD, Southwick, SM (2005). Smaller head of the hippocampus in gulf war-related posttraumatic stress disorder. Psychiatry Research: Neuroimaging 139, 89–99.CrossRefGoogle ScholarPubMed
Weathers, F, Ruscio, AM, Keane, TM (1999). Psychometric properties of nine scoring rules for the Clinician-Administered Posttraumatic Stress Disorder Scale. Psychological Assessment 11, 124–133.Google Scholar
Winter, H, Irle, E (2004). Hippocampal volume in adult burn patients with and without posttraumatic stress disorder. American Journal of Psychiatry 161, 2194–2200.Google Scholar
Woon, FL, Sood, S, Hedges, DW (2010). Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 1181–1188.Google Scholar
Yucel, K, McKinnon, MC, Taylor, VH, Macdonald, K, Alda, M, Young, LT, MacQueen, GM (2007). Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology (Berlin) 195, 357–367.Google Scholar
Yucel, K, Taylor, VH, McKinnon, MC, Macdonald, K, Alda, M, Young, LT, MacQueen, GM (2008). Bilateral hippocampal volume increase in patients with bipolar disorder and short-term lithium treatment. Neuropsychopharmacology 33, 361–367.CrossRefGoogle ScholarPubMed