Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-02T20:12:08.090Z Has data issue: false hasContentIssue false
  • English
  • Français

Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: a meta-analytic study

Published online by Cambridge University Press:  19 December 2016

Michael D. Nelson  and
Alecia M. Tumpap
Michael D. Nelson*
Affiliation:
Department of Psychology, Gonzaga University, Spokane, Washington, USA
Alecia M. Tumpap
Affiliation:
Department of Psychology, Gonzaga University, Spokane, Washington, USA
*
*Address for correspondence: Michael D. Nelson, Assistant Professor, Department of Psychology, Gonzaga University, 502 East Boone Avenue, AD Box 54, Spokane, WA 99258, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Many studies have reported hippocampal volume reductions associated with posttraumatic stress disorder (PTSD), while others have not. Here we provide an updated meta-analysis of such reductions associated with PTSD and evaluate the association between symptom severity and hippocampal volume.

Methods

A total of 37 studies met the criteria for inclusion in the meta-analysis. Mean effect sizes (Hedges’ g) and 95% confidence intervals (CI95%) were computed for each study and then averaged to obtain an overall mean effect size across studies. Meta-regression was employed to examine the relationship between PTSD symptom severity and hippocampal volume.

Results

Results showed that PTSD is associated with significant bilateral reduction of the hippocampus (left hippocampus effect size=–0.400, p<0.001, 5.24% reduction; right hippocampus effect size=–0.462, p<0.001, 5.23% reduction). Symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS), was significantly associated with decreased left, but not right, hippocampal volume.

Conclusions

PTSD was associated with significant bilateral volume reduction of the hippocampus. Increased symptom severity was significantly associated with reduced left hippocampal volume. This finding is consistent with the hypothesis that PTSD is more neurotoxic to the left hippocampus than to the right. However, whether the association between PTSD and lower hippocampal volume reflects a consequence of or a predisposition to PTSD remains unclear. More prospective studies are needed in this area.

Keywords

Posttraumatic stress disorderhippocampusmagnetic resonance imagingmeta-analysissymptom severity
Type
Original Research
Information
CNS Spectrums , Volume 22 , Issue 4 , August 2017 , pp. 363 - 372
Copyright
© Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
2. Villarreal, G, Hamilton, DA, Petropoulus, H, et al. Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder. Biol Psychiatry. 2002; 52(2): 119–125.CrossRefGoogle ScholarPubMed
3. Kessler, RC, Berglund, P, Delmer, O, Jin, R, Merikangas, KR, Walters, EE. Lifetime prevalence and age-of-onset distributions of DSM–IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6): 593–602. http://jamanetwork.com/journals/jamapsychiatry/fullarticle/208678.Google Scholar
4. Kessler, RC, Chiu, WT, Demler, O, Merikangas, KR, Walters, EE. Prevalence, severity, and comorbidity of 12-month DSM–IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6): 617–627. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847357/pdf/nihms176704.pdf.CrossRefGoogle ScholarPubMed
5. Squire, LR, Zola-Morgan, S. The medial temporal lobe memory system. Science. 1991; 253(5026): 1380–1386.Google Scholar
6. Treves, A, Rolls, ET. Computational analysis of the role of the hippocampus in memory. Hippocampus. 1994; 4(3): 374–391.Google Scholar
7. van Strien, NM, Cappaert, NLM, Witter, MP. The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci. 2009; 10(4): 273–282.CrossRefGoogle ScholarPubMed
8. Vermetten, E, Bremner, JD. Circuits and systems in stress: applications to neurobiology and treatment in posttraumatic stress disorder. Depress Anxiety. 2002; 16(1): 14–38.Google Scholar
9. Brewin, CR, Kleiner, JS, Vasterling, JJ, Field, AP. Memory for emotionally neutral information in posttraumatic stress disorder: a meta-analytic investigation. J Abnorm Psychol. 2007; 116(3): 448–463.Google Scholar
10. Johnsen, GE, Asbjørnsen, AE. Consistent impaired verbal memory in PTSD: a meta-analysis. J Affect Disord. 2008; 111(1): 74–82. Epub ahead of print Apr 2.CrossRefGoogle ScholarPubMed
11. Burgess, N, Maguire, EA, O’Keefe, J. The human hippocampus and spatial and episodic memory. Neuron. 2002; 35(4): 625–641. http://www.cell.com/neuron/fulltext/S0896-6273(02)00830-9.Google Scholar
12. Giap, BT, Jong, CN, Ricker, JH, Cullen, NK, Zafonte, RD. The hippocampus: anatomy, pathophysiology, and regenerative capacity. J Head Trauma Rehabil. 2000; 15(3): 875–894.CrossRefGoogle ScholarPubMed
13. Squire, LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992; 99(2): 195–231. Erratum in Psychol Rev. 1992; 99(3): 582.Google Scholar
14. Weiss, SJ. Neurobiological alterations associated with traumatic stress. Perspect Psychiatr Care. 2007; 43(3): 114–122.CrossRefGoogle ScholarPubMed
15. Bremner, JD, Randall, P, Scott, TM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995; 152(7): 973–981. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233767/pdf/nihms-340189.pdf.Google ScholarPubMed
16. Bremner, JD. Neuroimaging of posttraumatic stress disorder. Psychiatr Ann. 1998; 28(8): 445–450.Google Scholar
17. Tischler, L, Brand, SR, Stavitsky, K, et al. The relationship between hippocampal volume and declarative memory in a population of combat veterans with and without PTSD. Ann N Y Acad Sci. 2006; 1071(1): 405–409.Google Scholar
18. Levy-Gigi, E, Szabo, C, Richter-Levin, G, Kéri, S. Reduced hippocampal volume is associated with overgeneralization of negative context in individuals with PTSD. Neuropsychology. 2015; 29(1): 151–161. Epub ahead of print Jul 28, 2014.Google Scholar
19. Milad, MR, Wright, CI, Orr, SP, Pitman, RK, Quirk, GJ, Rauch, SL. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry. 2007; 62(5): 446–454. Epub ahead of print Jan 9.CrossRefGoogle ScholarPubMed
20. Milad, MR, Orr, SP, Lasko, NP, Chang, Y, Rauch, SL, Pitman, RK. Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. J Psychiatr Res. 2008; 42(7): 515–520; Epub ahead of print Feb 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377011/pdf/nihms46966.pdf.Google Scholar
21. Höschl, C, Hajek, T. Hippocampal damage mediated by corticosteroids: a neuropsychiatric research challenge. Eur Arch Psychiatry Clin Neurosci. 2001; 251(Suppl 2): II81–II88.Google Scholar
22. Vermetten, E, Bremner, JD. Circuits and systems in stress, I: preclinical studies. Depress Anxiety. 2002; 15(3): 126–147.CrossRefGoogle ScholarPubMed
23. Teicher, M, Tomoda, A, Andersen, S. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann N Y Acad Sci. 2006; 1071(1): 313–323.CrossRefGoogle ScholarPubMed
24. Duman, RS, Malberg, J, Nakagawa, S. Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther. 2001; 299(2): 401–407. http://jpet.aspetjournals.org/content/299/2/401.long.Google Scholar
25. Li, L, Chen, S, Liu, J, Zhang, J, He, Z, Lin, X. Magnetic resonance imaging and magnetic resonance spectroscopy study of deficits in hippocampal structure in fire victims with recent-onset posttraumatic stress disorder. Can J Psychiatry. 2006; 51(7): 431–437.Google Scholar
26. Schuff, N, Marmar, CR, Weiss, DS, et al. Reduced hippocampal volume and N-acetyl aspartate in posttraumatic stress disorder. Ann N Y Acad Sci. 1997; 821(1): 516–520.Google Scholar
27. Schuff, N, Neylan, TC, Lenoci, MA, et al. Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder. Biol Psychiatry. 2001; 50(12): 952–959. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733624/pdf/nihms125448.pdf.CrossRefGoogle ScholarPubMed
28. Shu, XJ, Xue, L, Liu, W, et al. More vulnerability of left than right hippocampal damage in right-handed patients with post-traumatic stress disorder. Psychiatry Res. 2013; 212(3): 237–244. Epub ahead of print Nov 11, 2012.CrossRefGoogle ScholarPubMed
29. Bossini, L, Tavanti, M, Calossi, S, et al. Magnetic resonance imaging volumes of the hippocampus in drug-naïve patients with post-traumatic stress disorder without comorbidity conditions. J Psychiatr Res. 2008; 42(9). 752–762. Epub ahead of print Sep 24, 2007.Google Scholar
30. Bremner, JD, Randall, P, Vermetten, E, 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. 1997; 41(1): 23–32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229101/pdf/nihms-340184.pdf.Google Scholar
31. Bremner, JD, Vythilingam, M, Vermetten, E, et al. MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry. 2003; 160(5): 924–932. http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.160.5.924.Google Scholar
32. Chalavi, S, Vissia, EM, Giesen, ME, et al. Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms. Hum Brain Mapp. 2015; 36(5): 1692–1704. Epub ahead of print Dec 29, 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400262/pdf/nihms-673286.pdf.Google Scholar
33. Emdad, R, Bonekamp, D, Sondergaard, HP, et al. Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls. Psychother Psychosom. 2006; 75(2): 122–132.CrossRefGoogle ScholarPubMed
34. Gurvits, TV, Shenton, ME, Hokama, H, et al. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry. 1996; 40(11): 1091–1099. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910907/pdf/nihms170395.pdf.CrossRefGoogle ScholarPubMed
35. Hedges, DW, Allen, S, Tate, DF, et al. Reduced hippocampal volume in alcohol and substance naïve Vietnam combat veterans with posttraumatic stress disorder. Cogn Behav Neurobiol. 2003; 16(4): 219–224.Google Scholar
36. Lindauer, RJL, Vlieger, EJ, Jalink, M, et al. Smaller hippocampal volume in Dutch police officers with posttraumatic stress disorder. Biol Psychiatry. 2004; 56(5): 356–363.CrossRefGoogle ScholarPubMed
37. Morey, RA, Gold, AL, Labar, KS, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiat. 2012; 69(11): 1169–1178. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647246/pdf/nihms452834.pdf.Google Scholar
38. Pavić, L, Gregurek, R, Rados, M, et al. Smaller right hippocampus in war veterans with posttraumatic stress disorder. Psychiatry Res. 2007; 154(2): 191–198; Epub ahead of print Jan 26.Google Scholar
39. Schmahl, C, Berne, K, Krause, A, et al. Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder. J Psychiatry Neurosci. 2009; 34(4): 289–295. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702446/pdf/0340289.pdf.Google Scholar
40. Shin, LM, Shin, PS, Heckers, S, et al. Hippocampal function in posttraumatic stress disorder. Hippocampus. 2004; 14(3): 292–300.CrossRefGoogle ScholarPubMed
41. Starčević, A, Dimitrijević, I, Aksić, M, et al. Brain changes in patients with posttraumatic stress disorder and associated alcoholism: MRI-based study. Psychiatr Danub. 2015; 27(1): 78–83. http://www.hdbp.org/psychiatria_danubina/pdf/dnb_vol27_no1/dnb_vol27_no1_78.pdf.Google Scholar
42. Vythilingam, M, Luckenbaugh, DA, Lam, T, et al. Smaller head of the hippocampus in Gulf War–related posttraumatic stress disorder. Psychiatry Res. 2005; 139(2): 89–99.Google Scholar
43. Weniger, G, Lange, C, Sachsse, U, Irle, E. Amygdala and hippocampal volumes and cognition in adult survivors of childhood abuse with dissociative disorders. Acta Psychiatr Scand. 2008; 118(4): 281–290.CrossRefGoogle ScholarPubMed
44. Wignall, EL, Dickson, JM, Vaughan, P, et al. Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder. Biol Psychiatry. 2004; 56(11): 832–836.Google Scholar
45. Winter, H, Irle, E. Hippocampal volume in adult burn patients with and without posttraumatic stress disorder. Am J Psychiatry. 2004; 161(12): 2194–2200.Google Scholar
46. Bonne, O, Brandes, D, Giboa, A, et al. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. Am J Psychiatry. 2001; 158(8): 1248–1251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819102/pdf/nihms170397.pdf.CrossRefGoogle ScholarPubMed
47. Eckart, C, Kaufmann, J, Kanowski, M, et al. Magnetic resonance volumetry and spectroscopy of hippocampus and insula in relation to severe exposure of traumatic stress. Psychophysiology. 2012; 49(2): 261–270. Epub ahead of print Oct 21, 2011.CrossRefGoogle ScholarPubMed
48. Fennema-Notestine, C, Stein, MB, Kennedy, CM, Archibald, SL, Jernigan, TL. Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder. Biol Psychiatry. 2002; 52(11): 1089–1101.CrossRefGoogle ScholarPubMed
49. Freeman, T, Kimbrell, T, Booe, L, et al. Evidence of resilience: neuroimaging in former prisoners of war. Psychiatry Res. 2006; 146(1): 59–64; Epub ahead of print Dec 19, 2005.Google Scholar
50. Gilbertson, MW, Shenton, ME, Ciszewski, A, et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002; 5(11): 1242–1247. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819093/pdf/nihms170404.pdf.Google Scholar
51. Golier, JA, Yehuda, R, De Santi, S, Segal, S, Dolan, S, de Leon, MJ. Absence of hippocampal volume differences in survivors of the Nazi Holocaust with and without posttraumatic stress disorder. Psychiatry Res. 2005; 139(1): 53–64.Google Scholar
52. Hara, E, Matsuoka, Y, Hakamata, Y, et al. Hippocampal and amygdalar volumes in breast cancer survivors with posttraumatic stress disorder. J Neuropsychiatry Clin Neurosci. 2008; 20(3): 302–308. http://neuro.psychiatryonline.org/doi/full/10.1176/jnp.2008.20.3.302.CrossRefGoogle ScholarPubMed
53. Jatzko, A, Rothenhofer, S, Schmitt, A, et al. Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods. J Affect Disord. 2006; 94(1–3): 121–126. Epub ahead of print May 15.Google Scholar
54. Landré, L, Destrieux, C, Baudry, M, et al. Preserved subcortical volumes and cortical thickness in women with sexual abuse-related PTSD. Psychiatry Res. 2010; 183(3): 181–186; Epub ahead of print Aug 4.CrossRefGoogle ScholarPubMed
55. Pederson, CL, Maurer, SH, Kaminski, PL, et al. Hippocampal volume and memory performance in a community-based sample of women with posttraumatic stress disorder secondary to child abuse. J Trauma Stress. 2004; 17(1): 37–40.CrossRefGoogle Scholar
56. Starčević, A, Srdjan, P, Radojicic, Z, et al. Volumetric analysis of amygdala, hippocampus, and prefrontal cortex in therapy-naïve PTSD participants. BioMed Res Int. 2014; 2014: 1–6. Article ID 968495.CrossRefGoogle ScholarPubMed
57. Wang, Z, Neylan, TC, Mueller, SG, et al. Magnetic resonance imaging of hippocampal subfields in posttraumatic stress disorder. Arch Gen Psychiatry. 2010; 67(3): 296–303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848481/pdf/nihms184801.pdf.Google Scholar
58. Yehuda, R, Golier, JA, Tischler, L, et al. Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: relation to risk and resilience factors. J Psychiatr Res. 2007; 41(5): 435–445; Epub ahead of print Jan 30, 2006.Google Scholar
59. Yehuda, R, Golier, JA, Bierer, LM, et al. Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [18F]FDG uptake on PET. Psychiatry Res. 2010; 184(2). 117–127. Epub ahead of print Oct 8.Google Scholar
60. Kitayama, N, Vaccarino, V, Kutner, M, Weiss, P, Bremner, JD. Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. J Affect Disord. 2005; 88(1): 79–86.Google Scholar
61. Smith, ME. Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: a meta-analysis of structural MRI studies. Hippocampus. 2005; 15(6): 798–807.CrossRefGoogle ScholarPubMed
62. Karl, A, Schaefer, M, Malta, LS, Dorfel, D, Rohleder, N, Werner, A. A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev. 2006; 30(7): 1004–1031. Epub ahead of print May 26.Google Scholar
63. Woon, FL, Sood, S, Hedges, DW. Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(7): 1181–1188. Epub ahead of print Jun 21.Google Scholar
64. Woon, FL, Hedges, DW. Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus. 2008. 18(8): 729–736.Google Scholar
65. Woon, F, Hedges, DW. Gender does not moderate hippocampal volume deficits in adults with posttraumatic stress disorder: a meta-analysis. Hippocampus. 2011; 21(3): 243–252. Epub ahead of print Sep 29, 2010.CrossRefGoogle Scholar
66. O’Doherty, DC, Chitty, KM, Saddiqui, S, Bennett, MR, Lagopoulos, J. A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res. 2015; 232(1): 1–33. Epub ahead of print Jan 30.CrossRefGoogle ScholarPubMed
67. Blake, DD, Weathers, FW, Nagy, LM, et al. The development of a clinician-administered PTSD scale. J Trauma Stress. 1995; 8(1): 75–90.Google Scholar
68. Lindauer, RJ, Olff, M, van Meijel, EP, Carlier, IV, Gersons, BP. Cortisol, learning, memory, and attention in relation to smaller hippocampal volume in police officers with posttraumatic stress disorder. Biol Psychiatry. 2006; 59(2): 171–177.Google Scholar
69. Admon, R, Milad, M R, Hendler, T. A causal model of post-traumatic stress disorder: Disentangling predisposed from acquired neural abnormalities. Trends Cogn Sci. 2013; 17(7): 337–347. Epub ahead of print Jun 12.Google Scholar
70. Apfel, BA, Ross, J, Hlavin, J, et al. Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms. Biol Psychiatry. 2011; 69: 541–548. Epub ahead of print Nov 20, 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259803/pdf/nihms291995.pdf.Google Scholar
71. Cohen, J. Statistical Power Analysis for the Behavioral Sciences, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum; 1988.Google Scholar
72. Weathers, FW, Ruscio, AM, Keane, TM. Psychometric properties of nine scoring rules for the Clinician-Administered Posttraumatic Stress Disorder Scale. Psychol Assess. 1999; 11(2): 124–133.CrossRefGoogle Scholar
73. Borenstein, M, Hedges, LV, Higgins, JPT, Rothstein, HR. Introduction to Meta-Analysis. West Sussex, UK: Wiley; 2009. https://www.meta-analysis-workshops.com/download/bookChapterSample.pdf.Google Scholar
74. Hedges, LV, Olkin, I. Statistical Methods for Meta-Analysis. New York: Academic Press; 1985.Google Scholar
75. Cooper, H, Hedges, LV, Valentine, JC, eds. The Handbook of Research Synthesis and Meta-Analysis, 2nd ed. New York: The Russell Sage Foundation; 2009.Google Scholar
76. Admon, R, Leykin, D, Lubin, G, et al. Stress-induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service. Hum Brain Mapp. 2013; 34(11): 2808–2816. Epub ahead of print Jul 17, 2012.Google Scholar
77. Koenigs, M, Huey, ED, Raymont, V, et al. Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nat Neurosci. 2008; 11(2): 232–237. Epub ahead of print Dec 23, 2007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693133/pdf/nihms-108233.pdf.CrossRefGoogle ScholarPubMed
78. van Rooij, SJ, Kennis, M, Sjouwerman, R, van den Heuvel, MP, Kahn, RS, Geuze, E. Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder. Psychol Med. 2015; 45(13): 2737–2746. Epub ahead of print May 4.CrossRefGoogle ScholarPubMed
79. Zhang, J, Tan, Q, Yin, H, et al. Decreased gray matter volume in the left hippocampus and bilateral calcarine cortex in coal mine flood disaster survivors with recent-onset PTSD. Psychiatry Res. 2011; 192(2): 84–90.Google Scholar