CoChat
Sign Up
Cited by 139Posttraumatic Stress Disorder ResearchTraumatic Brain Injury ResearchMigration, Health and Trauma

Hippocampal volume differences in gulf war veterans with current versus lifetime posttraumatic stress disorder symptoms

Open access
Apfel, Brigitte A., Ross, Jessica, Hlavin, Jennifer, Meyerhoff, Dieter J., Metzler, Thomas J., Marmar, Charles R., Weiner, Michael W., Schuff, Norbert +1 more·2011·Biological Psychiatry
DOI 10.1016/j.biopsych.2010.09.044PMC PMC3259803
Open this paper in CoChat — free account

Abstract

Background Decreased hippocampal volume is described in posttraumatic stress disorder (PTSD) and depression. However, it is not known whether it is a risk factor for the development of PTSD or a consequence of PTSD. We sought to determine the effects of PTSD and depressive symptoms on hippocampal volume. Methods Clinical and magnetic resonance imaging data were collected in a cross sectional study of 244 Gulf War veterans. Measures included lifetime and current Clinician Administered PTSD Scale, Hamilton Depression Scale, Life Stressor Checklist, and Lifetime Drinking History. Magnetic resonance imaging data were acquired with a 1.5-T scanner and analyzed with automated and semiautomated image processing techniques. Results Eighty-two veterans had lifetime PTSD, 44 had current PTSD, and 38 had current depression. In the linear regression analysis, current PTSD symptoms (standardized coefficient β = -.25, p = .03) but neither lifetime PTSD symptoms nor current depression were associated with smaller hippocampal volume. Gender, age, history of early life trauma, education, lifetime and current alcohol use, current marijuana use, and treatment with antidepressants did not have independent effects. Participants with chronic PTSD had, on average, a smaller hippocampus compared with those with remitted PTSD. Conclusions The finding that current but not lifetime PTSD symptom severity explains hippocampal size raises two possibilities: either a small hippocampus is a risk factor for lack of recovery from PTSD (trait) or PTSD effects on hippocampal volume are reversible once PTSD symptoms remit and the patient recovers (state).

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2010.09.044

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Apfel et al. (2011) identified, on average, smaller hippocampal volumes among subjects with chronic PTSD compared to acute PTSD and acute depression subgroups.

    “Apfel et al. (2011) identified, on average, smaller hippocampal volumes among the subjects with chronic PTSD, as opposed to other two subgroups.”

    From Neuroimaging research in posttraumatic stress disorder – Focus on amygdala, hippocampus and prefrontal cortex (2019) · cites this paper as Apfel et al. (2011)

    The Results report that participants with chronic PTSD had smaller mean hippocampal volumes than two other groups. Those groups were participants who had recovered from PTSD and participants who had never developed PTSD—not acute PTSD and acute depression subgroups. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 78 · Cited by 139

Research works printed but not linked: 64

  1. [1]Karl A Schaefer M Malta LS Dorfel D Rohleder N Werner A 2006 A meta-analysis of structural brain abnormalities in PTSD Neurosci Biobehav Rev 30 1004 1031 16730374
  2. [3]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 15988763
  3. [4]Sala M Perez J Soloff P Ucelli di Nemi S Caverzasi E Soares JC Brambilla P 2004 Stress and hippocampal abnormalities in psychiatric disorders Eur Neuropsychopharmacol 14 393 405 15336301
  4. [5]De Kloet ER Vreugdenhil E Oitzl MS Joels M 1998 Brain corticosteroid receptor balance in health and disease Endocr Rev 19 269 301 9626555
  5. [6]McEwen BS Gould EA Sakai RR 1992 The vulnerability of the hippocampus to protective and destructive effects of glucocorticoids in relation to stress Br J Psychiatry Suppl 18 23 1389022
  6. [7]Dickerson BC Eichenbaum H 2010 The episodic memory system: Neurocircuitry and disorders Neuropsychopharmacology 35 86 104 19776728 PMC2882963
  7. [8]Pitman R Shalev A Orr S Corbetta M Gazzaniga M 2000 Posttraumatic stress disorder: Emotion, conditioning, and memory The New Cognitive Neurosciences 2 New York Plenum Press 687 700
  8. [9]Magarinos AM McEwen BS 1995 Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Involvement of glucocorticoid secretion and excitatory amino acid receptors Neuroscience 69 89 98 8637636
  9. [10]Abrous DN Koehl M Le Moal M 2005 Adult neurogenesis: from precursors to network and physiology Physiol Rev 85 523 569 15788705
  10. [11]Sapolsky RM 2000 Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders Arch Gen Psychiatry 57 925 935 11015810
  11. [12]McEwen BS Angulo J Cameron H Chao HM Daniels D Gannon MN 1992 Paradoxical effects of adrenal steroids on the brain: Protection versus degeneration Biol Psychiatry 31 177 199 1737079
  12. [13]Moghaddam B 2002 Stress activation of glutamate neurotransmission in the prefrontal cortex: Implications for dopamine-associated psychiatric disorders Biol Psychiatry 51 775 787 12007451
  13. [14]Smith MA Makino S Kvetnansky R Post RM 1995 Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus J Neurosci 15 1768 1777 7891134 PMC6578156
  14. [15]Sunanda Rao MS Raju TR 1995 Effect of chronic restraint stress on dendritic spines and excrescences of hippocampal CA3 pyramidal neurons—a quantitative study Brain Res 694 312 317 8974660
  15. [16]Magarinos AM McEwen BS Flugge G Fuchs E 1996 Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews J Neurosci 16 3534 3540 8627386 PMC6579123
  16. [17]Stewart MG Davies HA Sandi C Kraev IV Rogachevsky VV Peddie CJ 2005 Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: A three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities Neuroscience 131 43 54 15680690
  17. [18]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 Proc Natl Acad Sci U S A 95 3168 3171 9501234 PMC19713
  18. [19]Sapolsky RM Uno H Rebert CS Finch CE 1990 Hippocampal damage associated with prolonged glucocorticoid exposure in primates J Neurosci 10 2897 2902 2398367 PMC6570248
  19. [20]Felmingham K Williams LM Whitford TJ Falconer E Kemp AH Peduto A Bryant RA 2009 Duration of posttraumatic stress disorder predicts hippocampal grey matter loss Neuroreport 20 1402 1406 19794316
  20. [21]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 Biol Psychiatry 54 693 702 14512209 PMC3233762
  21. [22]Gilbertson MW Shenton ME Ciszewski A Kasai K Lasko NB Orr SP Pitman RK 2002 Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma Nat Neurosci 5 1242 1247 12379862 PMC2819093
  22. [24]Kessler RC Sonnega A Bromet E Hughes M Nelson CB 1995 Posttraumatic stress disorder in the National Comorbidity Survey Arch Gen Psychiatry 52 1048 1060 7492257
  23. [26]McKinnon MC Yucel K Nazarov A MacQueen GM 2009 A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder J Psychiatry Neurosci 34 41 54 19125212 PMC2612082
  24. [29]Weiner MW Meyerhoff DJ Neylan TC Hlavin J Ramage ER McCoy D in press The relationship between gulf war illness, brain N-acetyl aspartate and post-traumatic stress disorder Mil Med PMC3279571 21882779
  25. [30]First M Spitzer R Gibbon M Williams J 1996 Structured Clinical Interview for DSM-IV Axis 1 Disorders—Non-Patient Edition (SCID-I/NP, Version 2.0) New York Biometrics Research Department, New York State Psychiatric Institute
  26. [31]Blake DD Weathers FW Nagy LM Kaloupek DG Gusman FD Charney DS Keane TM 1995 The development of a Clinician-Administered PTSD Scale J Trauma Stress 8 75 90 7712061
  27. [32]Weathers FW Keane TM Davidson JR 2001 Clinician-administered PTSD scale: A review of the first ten years of research Depress Anxiety 13 132 156 11387733
  28. [33]Hamilton M 1960 A rating scale for depression J Neurol Neurosurg Psychiatry 23 56 62 14399272 PMC495331
  29. [34]Wolfe J Kimerling R Brown PJ Chresman KR Levin K 1996 Psychometric Review of the Life Stressor Checklist-Revised Lutherville, Maryland Sidran Publishing Group
  30. [36]Skinner HA Sheu WJ 1982 Reliability of alcohol use indices. The Lifetime Drinking History and the MAST J Stud Alcohol 43 1157 1170 7182675
  31. [37]Hsu YY Schuff N Du AT Mark K Zhu X Hardin D Weiner MW 2002 Comparison of automated and manual MRI volumetry of hippocampus in normal aging and dementia J Magn Reson Imaging 16 305 310 12205587 PMC1851676
  32. [38]Christensen GE Joshi SC Miller MI 1997 Volumetric transformation of brain anatomy IEEE Trans Med Imaging 16 864 877 9533586
  33. [39]Gazdzinski S Durazzo TC Yeh PH Hardin D Banys P Meyerhoff DJ 2008 Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics Psychiatry Res 162 133 145 18178068 PMC2270338
  34. [40]Buckner RL Head D Parker J Fotenos AF Marcus D Morris JC Snyder AZ 2004 A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: Reliability and validation against manual measurement of total intracranial volume Neuroimage 23 724 738 15488422
  35. [41]Dale AM Fischl B Sereno MI 1999 Cortical surface-based analysis. I. Segmentation and surface reconstruction Neuroimage 9 179 194 9931268
  36. [43]Pajonk FG Wobrock T Gruber O Scherk H Berner D Kaizl I 2010 Hippocampal plasticity in response to exercise in schizophrenia Arch Gen Psychiatry 67 133 143 20124113
  37. [44]Boldrini M Underwood MD Hen R Rosoklija GB Dwork AJ John Mann J Arango V 2009 Antidepressants increase neural progenitor cells in the human hippocampus Neuropsychopharmacology 34 2376 2389 19606083 PMC2743790
  38. [45]Chen F Madsen TM Wegener G Nyengaard JR 2009 Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression [published online ahead of print November 17] Hippocampus 19921703
  39. [46]Dranovsky A Hen R 2006 Hippocampal neurogenesis: Regulation by stress and antidepressants Biol Psychiatry 59 1136 1143 16797263 PMC7537828
  40. [47]Warner-Schmidt JL Duman RS 2006 Hippocampal neurogenesis: Opposing effects of stress and antidepressant treatment Hippocampus 16 239 249 16425236
  41. [48]Lucassen PJ Meerlo P Naylor AS van Dam AM Dayer AG Fuchs E 2010 Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action Eur Neuropsychopharmacol 20 1 17 19748235
  42. [49]Duman RS Nakagawa S Malberg J 2001 Regulation of adult neurogenesis by antidepressant treatment Neuropsychopharmacology 25 836 844 11750177
  43. [50]Koolschijn PC van Haren NE Cahn W Schnack HG Janssen J Klumpers F 2010 Hippocampal volume change in schizophrenia J Clin Psychiatry 71 737 744 20492835
  44. [51]Wang Z Neylan TC Mueller SG Lenoci M Truran D Marmar CR 2010 Magnetic resonance imaging of hippocampal subfields in post-traumatic stress disorder Arch Gen Psychiatry 67 296 303 20194830 PMC2848481
  45. [52]Neylan TC Mueller SG Wang Z Metzler TJ Lenoci M Truran D 2010 Insomnia severity is associated with a decreased volume of the CA3/dentate gyrus hippocampal subfield Biol Psychiatry 68 494 496 20598672 PMC2921477
  46. [53]Duan X Kang E Liu CY Ming GL Song H 2008 Development of neural stem cell in the adult brain Curr Opin Neurobiol 18 108 115 18514504 PMC2464621
  47. [54]Ehninger D Kempermann G 2008 Neurogenesis in the adult hippocampus Cell Tissue Res 331 243 250 17938969
  48. [55]Pitman RK Gilbertson MW Gurvits TV May FS Lasko NB Metzger LJ 2006 Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure Ann N Y Acad Sci 1071 242 254 16891575 PMC2770249
  49. [56]Macklin ML Metzger LJ Litz BT McNally RJ Lasko NB Orr SP Pitman RK 1998 Lower precombat intelligence is a risk factor for posttraumatic stress disorder J Consult Clin Psychol 66 323 326 9583335
  50. [57]Pitman RK 2010 Posttraumatic stress disorder and dementia: What is the origin of the association? JAMA 303 2287 2288 20540170
  51. [58]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 Am J Psychiatry 158 1248 1251 11481158 PMC2819102
  52. [59]Lindauer RJ Vlieger EJ Jalink M Olff M Carlier IV Majoie CB 2005 Effects of psychotherapy on hippocampal volume in out-patients with post-traumatic stress disorder: A MRI investigation Psychol Med 35 1421 1431 16164766
  53. [60]De Bellis MD Hall J Boring AM Frustaci K Moritz G 2001 A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder Biol Psychiatry 50 305 309 11522266
  54. [61]Tottenham N Sheridan MA 2009 A review of adversity, the amygdala and the hippocampus: A consideration of developmental timing Front Hum Neurosci 3 68 20161700 PMC2813726
  55. [63]Cardenas V Samuelson K Lenoci M Studholme C Neylan T Marmar C in press Changes in brain anatomy during the course of PTSD Psychiatry Res PMC3175765 21683556
  56. [64]Agartz I Momenan R Rawlings RR Kerich MJ Hommer DW 1999 Hippocampal volume in patients with alcohol dependence Arch Gen Psychiatry 56 356 363 10197833
  57. [65]Laakso MP Vaurio O Savolainen L Repo E Soininen H Aronen HJ Tiihonen J 2000 A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism Behav Brain Res 109 177 186 10762687
  58. [66]Richardson HN Chan SH Crawford EF Lee YK Funk CK Koob GF Man-dyam CD 2009 Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence Neurobiol Dis 36 1 10 19501165 PMC2742572
  59. [68]Bremner JD Randall P Vermetten E Staib L Bronen RA Mazure C 1997 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 8988792 PMC3229101
  60. [70]Rao U Chen LA Bidesi AS Shad MU Thomas MA Hammen CL 2010 Hippocampal changes associated with early-life adversity and vulnerability to depression Biol Psychiatry 67 357 364 20015483 PMC2821020
  61. [71]Frodl T Reinhold E Koutsouleris N Reiser M Meisenzahl EM 2010 Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression J Psychiatr Res 44 799 807 20122698
  62. [72]Teicher MH Tomoda A Andersen SL 2006 Neurobiological consequences of early stress and childhood maltreatment: Are results from human and animal studies comparable? Ann N Y Acad Sci 1071 313 323 16891580
  63. [73]Malberg JE Eisch AJ Nestler EJ Duman RS 2000 Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus J Neurosci 20 9104 9110 11124987 PMC6773038
  64. [74]Balu DT Lucki I 2009 Adult hippocampal neurogenesis: Regulation, functional implications, and contribution to disease pathology Neurosci Biobehav Rev 33 232 252 18786562 PMC2671071

Authors
Apfel, B. A., Ross, J., Hlavin, J., Meyerhoff, D. J., Metzler, T. J., Marmar, C. R., Weiner, M. W., Schuff, N., & Neylan, T. C.
Affiliations
  • San Francisco VA Medical Center (US)
  • New York University (US)
Corresponding author
Apfel, Brigitte A.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2011-03
Volume
69
Issue
6
Pages
541-548
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2010.09.044
PMC
PMC3259803
OpenAlex
W2053453668
Cited by
139
References
78
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 14 · 2020: 12 · 2019: 6 · 2018: 15 · 2017: 8 · 2016: 8 · 2015: 15 · 2014: 17 · 2013: 11 · 2012: 9
FWCI
8.51
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Lincoln (University of Nebraska) (submittedVersion)
Funders
  • Department of Defense (DAMD17-01-1-0764)
  • National Institutes of Health/National Institute of Environmental Health Sciences (ES09883)
  • Mental Illness Research, Education, and Clinical Center of the Department of Veterans Affairs
  • Office of Academic Affiliations
  • Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs (R01 AA10788)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Social Sciences › Psychology › Clinical Psychology › Migration, Health and Trauma
Keywords
post-traumatic stress disorder, hippocampal volume, Gulf War veterans, depression, chronic PTSD, hippocampal atrophy, brain structure, alcohol consumption, cannabis use, antidepressant treatment, early trauma
MeSH terms
Adult, Aged, Analysis of Variance, Cross-Sectional Studies, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Regression Analysis, Stress Disorders, Post-Traumatic, Veterans, Gulf War

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review