Background: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. Methods: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. Results: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. Conclusion: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.

1.
Elzinga BM, Bremner JD: Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)? J Affect Disord 2002;70:1–17.
2.
Pitman RK: Post-traumatic stress disorder, hormones, and memory. Biol Psychiatry 1989;26:221–223.
3.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994.
4.
Bremner JD, Southwick SM, Charney DS: The neurobiology of posttraumatic stress disorder: An integration of animal and human research; in Saigh P, Bremner JD (eds): Posttraumatic Stress Disorder: A Comprehensive Text. New York, Allyn and Bacon, 1999, pp 103–143.
5.
Nadel L, Jacobs WJ: The role of the hippocampus in PTSD, panic and phobia; in Kato N (ed): Hippocampus: Functions and Clinical Relevance. Amsterdam, Elsevier, 2003.
6.
Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP, Pitman RK: Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci 2002;5:1242–1247.
7.
Bremner JD, Randall P, Scott TM: Deficits in short-term memory in adult survivors of childhood abuse. Psychiatry Res 1995;59:97–107.
8.
Bremner JD, Randall P, Vermetten E: Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse – a preliminary report. Biol Psychiatry 1997;41:23–32.
9.
Gurvits TV, Shenton ME, Hokama H, Ohta H, Lasko NB, Gilbertson MW: Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry 1996;40:1091–1099.
10.
Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B: Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med 1997;27:951–959.
11.
Villarreal G, Hamilton DA, Petropoulos H, Driscoll I, Rowland LM, Griego JA, Kodituwakku PW, Hart BL, Escalona R, Brooks WM: Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder. Biol Psychiatry 2002;52:119–125.
12.
Beckham JC, Crawford AL, Feldman ME: Trail making test performance in Vietnam combat veterans with and without posttraumatic stress disorder. J Trauma Stress 1998:11:811–819.
13.
Jenkins MA, Langlais PJ, Delis DA, Cohen RA: Attentional dysfunction associated with posttraumatic stress disorder among rape survivors. Clin Neuropsychol 2000;14:7–12.
14.
Sutker PB Winstead DK, Galina ZH, Allain AN: Cognitive deficits and psychopathology among former prisoners of war and combat veterans of the Korean conflict. Am J Psychiatry 1991;148:67–72.
15.
Sutker PB, Vasterling JJ, Brailey K, Allain AN: Memory, attention, and executive deficits in POW survivors: contributing biological and psychological factors. Neuropsychology 1995;9:118–125.
16.
Bonne O, Brandes D, Gilboa A, Gomori JM, Shenton ME, Pitman RK, Shalev AY: Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am J Psychiatry 2001;158: 1248–1251.
17.
Driessen M, Herrmann J, Stahl K, Zwaan M, Meier S, Hill A, Osterheider M, Petersen D: Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 2000;57:1115–1122.
18.
Collins DL, Zijdenbos AP, Baare WFC, Evans AC: ANIMAL + INSECT: improved cortical structure segmentation. Proc Inform Process Med Imaging IPMI, Visegrád, June/July 1999, pp 210–223.
19.
Wright IC, McGuire PK, Poline JB, Travere JM, Murray RM, Frith CD, Frackowiak RSJ, Friston KJ: A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia. Neuroimage 1995;2:244–252.
20.
Wright IC, Ellison ZR, Sharma T, Friston KJ, Murray RM, Mcguire PK: Mapping of grey matter changes in schizophrenia. Schizophrenia Res 1999;35:1–14.
21.
Vargha-Khadem F, Watkins KE, Price CJ, Ashburner J, Alcock KJ, Connelly A, Frackowiak RSJ, Friston KJ, Pembrey, ME, Mishkin M, Gadian DG, Passingham RE: Neural basis of an inherited speech and language disorder. Proc Natl Acad Sci USA 1998;95:12695–12700.
22.
Shah PJ, Ebmeier KP, Glabus MF, Goodwin G: Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Br J Psychiatry 1998;172:527–532.
23.
Krams M, Quinton R, Ashburner J, Friston KJ, Frackowiak RS, Bouloux PM, Passingham RE: Kallmann’s syndrome: Mirror movements associated with bilateral corticospinal tract hypertrophy. Neurology 1999;52:816–822.
24.
Abell F, Krams M, Ashburner J, Passingham RE, Friston KJ, Frackowiak RSJ, Happe F, Frith CD, Frith U: The neuroanatomy of autism: a voxel based whole brain analysis of structural scans. Neuroreport 1999;10:1647–1651.
25.
Woermann FG, Free SL, Koepp MJ, Ashburner J, Duncan JD: Voxel-by-voxel comparison of automatically segmented cerebral grey matter – a rater-independent comparison of structural MRI in patients with epilepsy. Neuroimage 1999;10:373–384.
26.
Sowell ER, Thompson PM, Holmes CJ, Batth R, Jernigan TL, Toga AW: Localizing age-related changes in brain structure between childhood and adolescence using statistical parametric mapping. Neuroimage 1999;9:587– 597.
27.
May A, Ashburner J, Büchel C, McGonigle DJ, Friston KJ, Frackowiak RSJ, Goadsby PJ: Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med 1999;5:836–838.
28.
Ashburner J, Friston KJ: Voxel-based morphometry – the methods. Neuroimage 2000;11:805–821.
29.
Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RSA: Voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;14:21–36.
30.
Keane TM, Kaloupek DG, Weathers FW: Ethnocultural considerations in the assessment of PTSD; in Marsella AJ, Friedman MJ, Gerrity ET, Scurfield RM (eds): Ethnocultural Aspects of Posttraumatic Stress Disorder: Issues, Research, and Clinical Applications. Washington, American Psychological Association, 1996.
31.
Mollica RF, Caspi-Yavin Y, Bollini P, Truong T, Tor S, Lavelle J: The Harvard Trauma Questionnaire. Validating a cross-cultural instrument for measuring torture, trauma, and posttraumatic stress disorder in Indochinese refugees. J Nerv Ment Dis 1992;180:111–116.
32.
Goldberg D, Hillier VA: Scaled version of the General Health Questionnaire. Psychol Med 1979;9:139–145.
33.
Raven J, Raven JC, Court JH: Coloured Progressive Matrices. Oxford, Oxford Psychologists Press, 1998.
34.
Dureman I, Kebbon L, Osterberg E: Manual till DS-Batteriet Psykologi Förlaget. Stockholm, Psykologiförlaget ab, 1971.
35.
Poline JB, Frith CD, Heather JD, Frackowiak RSJ, Friston KJ, Ashburner J: Spatial registration and normalisation of images. Hum Brain Mapp 1995;2:165–189.
36.
Andreasen NC, Magnotta VA, Harris G, Heckel D, O’Leary DS, Yuh WTC: Structural MR image processing using the BRAINS2 toolbox. Comput Med Imaging Graph 2002;26:251–264.
37.
Mayo Clinic: Analyze software. 1995–2004 Technical Report; http://www.mayo.edu/bir/Software/Analyze/Analyze.html.
38.
Holmes CJ, Cherry SR, Mazziotta JC, Woods RP, Grafton ST: Automated image registration. I. General methods and intrasubject, intramodality validation. J Comput Assist Tomogr 1998; 22:139–152.
39.
Holmes CJ, Cherry SR, Mazziotta JC, Woods RP, Grafton ST: Automated image registration: intersubject validation of linear and nonlinear models. J Comput Assist Tomogr 1998; 22:153–165.
40.
Tournoux P, Talairach J: Co-Planar Stereotaxic Atlas of the Human Brain. New York, Thieme, 1998.
41.
Nordstrom M, Greitz D, Magnotta V, Sedvall G, Agartz I, Okuguwa G: Reliability and reproducibility of brain tissue volumetry from segmented mr scans. Eur Arch Psychiatry Clin Neurosci 2001;251:255–261.
42.
Worsley KJ, Poline JP, Frith CD, Frackowiak RSJ, Friston KJ, Holmes AP: Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 1995;2:189–210.
43.
Buchel C, Wise RJ, Mummery CJ, Poline JB, Friston KJ: Nonlinear regression in parametric activation studies. Neuroimage 1996;4:60–66.
44.
Agartz I, Sääf J, Wahlund LO, Wetterberg L: T1 and T2 relaxation time estimates and brain measures during withdrawal in alcoholic men. Drug Alcohol Depend 1992;29:157–169.
45.
Agartz I, Momenan R, Rawlings RR, Kerich MJ, Hommer DW: Hippocampal volumes in alcohol dependence. Arch Gen Psychiatry 1999;56:356–363.
46.
Laakso MP, Vaurio O, Savolainen L, Repo E, Soininen H, Aronen HJ, Tiihonen J: A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism. Behav Brain Res 2000;109:177–186.
47.
Sullivan EV, Marsh L, Mathalon DH, Lim KO, Pfefferbaum A: Relationship between alcohol withdrawal seizures and temporal lobe white matter volume deficits. Alcohol Clin Exp Res 1996;20:348–354.
48.
Bradley R, Greene J, Russ E, Dutra L, Westen D: A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatry 2005;162:214–227.
49.
Bonne O, Brandes D, Gilboa A: Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am J Psychiatry 2001;158:1248–1251.
50.
Semple WE, Goyer PF, McCormick R: Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories. Psychiatr Res Neuroimaging 1996;67:17–28.
51.
Liberzon I, Taylor SF, Amdur R, Jung TD, Chamberlain KR, Minoshima S: Brain activation in PTSD in response to trauma-related stimuli. Biol Psychiatry 1999;45:817–826.
52.
Rauch SL, van der Kolk BA, Fisler RE, Alpert NM, Orr SP, Savage CR: A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch Gen Psychiatry 1996;53:380–387.
53.
Shin LM, McNally RJ, Kosslyn SM, Thompson WL, Rauch SL, Alpert NM: Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related posttraumatic stress disorder: a PET investigation. Am J Psychiatry 1999;156:575–584.
54.
Shin LM, Whalen PJ, Pitman RK, Bush G: An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatr 2001;50:932–942.
55.
Rauch SL, Whalen PJ, Shin LM, McInerney S, Macklin ML, Lasko NB, Orr SP, Pitman RK: Exaggerated amygdala responses to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biol Psychiatry 2000;47:769–776.
56.
Rauch SL, Shin LM, Wright CI: Neuroimaging studies of amygdala function in anxiety disorders. Ann NY Acad Sci 2003;985:389–410.
57.
Shin LM, Kosslyn SM, McNally RJ, Alpert NM, Thompson WL, Rauch SL: Visual imagery and perception in posttraumatic stress disorder: a positron emission tomographic investigation. Arch Gen Psychiatry 1997;54:233–241.
58.
Pitman RK, Shin LM, Rauch SL: Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging. J Clin Psychiatry 2001;62(suppl 17):47–54.
59.
Villarreal G, King CY: Brain imaging in PTSD. Semin Clin Neuropsychiatry 2001;6:131–145.
60.
Carrion VG, Weems CF, Eliez S, Patwardhan A, Brown W, Ray RD, Reiss AL: Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder. Biol Psychiatry 2001;50:943–951.
61.
Sigmundsson T, Suckling J, Maier M, Williams SCR, Bullmore ET, Greenwood KE, Fukuda R, Ron M, Toone BK: Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. Am J Psychiatry 2001;158, 234–243.
62.
Suzuki M, Nohara S, Hagino H, Kurokawa K, Yotsutsuji T, Kawasaki Y, Takahashi T, Matsui M, Watanabe N, Seto H: Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI. Schizophr Res 2002;55, 41–54.
63.
Brewer JB, Zhao Z, Desmond JE, Glover GH, Gabrieli JDE: Making memories: brain activity that predicts how well visual experience will be remembered. Science 1998;281:1185–1187.
64.
Wagner AD, Schacter DL, Rotte M, Koutstaal W, Maril A, Dale AM, Rosen BR, Buckner RL: Building memories: remembering and forgetting of verbal experiences as predicted by brain activity. Science 1998;281:1188–1191.
65.
Fernández G, Weyerts H, Schrader-Bölsche M, Tendolkar I, Smid HGOM, Tempelmann C, Hinrichs H, Scheich H, Elger CE, Mangun GR, Heinze HJ: Successful verbal encoding into episodic memory engages the posterior hippocampus: a parametrically analysed functional magnetic resonance imaging study. J Neurosci 1998;18:1841–1847.
66.
Fernández G, Brewer JB, Zhao Z, Glover GH, Gabrieli JDE: The level of sustained entorhinal activity at study correlates with subsequent cued recall performance: a functional magnetic resonance imaging study with high acquisition rate. Hippocampus 1999; 9:35–44.
67.
Fernández G, Effern A, Grunwald T, Pezer N, Lehnertz K, Dümpelmann M, Van Roost D, Elger CE: Real-time tracking of memory formation in the human rhinal cortex and hippocampus. Science 1999; 285:1582–1585.
68.
Otten LJ, Henson RN, Rugg MD: Depth of processing effects on neural correlates of memory encoding: relationship between findings from across- and within-task comparisons. Brain 2001;124:399–412.
69.
Fell J, Klaver P, Lehnertz K, Grunwald T, Schaller C, Elger CE, Fernández G: Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nature Neurosci 2001;4:1259–1264.
70.
Strange BA, Otten LJ, Josephs O, Rugg MD, Dolan RJ: Dissociable human perirhinal, hippocampal, and parahippocampal roles during verbal encoding. J Neurosci 2002;22:523–528.
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