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Diminished medial prefrontal cortex activation during the recollection of stressful events is an acquired characteristic of PTSD

Published online by Cambridge University Press:  12 September 2017

M. K. Dahlgren ,
L. M. Laifer ,
M. B. VanElzakker ,
R. Offringa ,
K. C. Hughes ,
L. K. Staples-Bradley ,
S. J. Dubois ,
N. B. Lasko ,
C. A. Hinojosa  and
S. P. Orr
...Show all authors
M. K. Dahlgren
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
L. M. Laifer
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA
M. B. VanElzakker
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
R. Offringa
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA
K. C. Hughes
Affiliation:
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
L. K. Staples-Bradley
Affiliation:
Psychology Department, University of California Los Angeles, Los Angeles, CA, USA
S. J. Dubois
Affiliation:
University of New England, Portland, ME, USA
N. B. Lasko
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
C. A. Hinojosa
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
S. P. Orr
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
R. K. Pitman
Affiliation:
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
L. M. Shin*
Affiliation:
Department of Psychology, Tufts University, Medford, MA, USA Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
*
Author for correspondence: L. M. Shin, E-mail: [email protected]
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Abstract

Background

Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD.

Methods

In this case–control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement.

Results

Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups.

Conclusions

Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

Keywords

fMRIfunctional neuroimagingpost-traumatic stress disorderscript-driven imageryskin conductancetwin study
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 7 , May 2018 , pp. 1128 - 1138
Copyright
Copyright © Cambridge University Press 2017 

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References

American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th edn. American Psychiatric Association: Washington, DC.Google Scholar
Bauer, MR, Reuf, AM, Pineles, SL, Japuntich, SJ, Macklin, ML, Lasko, NB, Orr, SP (2013) Psychological assessment of PTSD: a potential research domain criteria construct. Psychological Assessment 25, 1037–1034.Google Scholar
Beck, AT, Steer, RA (1987) Manual for the Revised Beck Depression Inventory. Psychological Corp: San Antonio, TX.Google Scholar
Beck, AT, Steer, RA (1993) Beck Anxiety Inventory Manual. Harcourt Brace: San Antonio, TX.Google Scholar
Bernstein, DP, Fink, L, Handelsman, L, Foote, J, Lovejoy, M, Wenzel, K, Sapareto, E, Ruggiero, J (1994) Initial reliability and validity of a new retrospective measure of child abuse and neglect. American Journal of Psychiatry 151, 1132–1136.Google Scholar
Blake, DD, Weathers, FW, Nagy, LM, Kaloupek, DG, Gusman, FD, Charney, DS, Keane, TM (1995) The development of a clinician-administered PTSD scale. Journal of Traumatic Stress 8, 75–90.Google Scholar
Boudewyns, PA, Hyer, L (1990) Physiological response to combat memories and preliminary treatment outcome in Vietnam veteran PTSD patients treated with direct therapeutic exposure. Behavior Therapy 21, 63–87.Google Scholar
Bremner, JD, Narayan, M, Staib, LH, Southwick, SM, McGlashan, T, Charney, DS (1999) Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. American Journal of Psychiatry 156, 1787–1795.Google Scholar
Brett, M, Anton, JL, Valabregue, R, Poline, JB (2002) Region of interest analysis using an SPM toolbox. In Presented at: 8th International Conference on Functional Mapping of the Human Brain; June 2–6, 2002; Sendai, Japan. Available on CD-ROM in NeuroImage 16.Google Scholar
Britton, JC, Phan, KL, Taylor, SF, Fig, LM, Liberzon, I (2005) Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery. Biological Psychiatry 57, 832–840.Google Scholar
Brohawn, KH, Offringa, R, Pfaff, DL, Hughes, KC, Shin, LM (2010) The neural correlates of emotional memory in posttraumatic stress disorder. Biological Psychiatry 68, 1023–1030.Google Scholar
Fani, N, Ashraf, A, Afzal, N, Jawed, F, Kitayama, N, Reed, L, Bremner, JD (2011) Increased neural response to trauma scripts in posttraumatic stress disorder following paroxetine treatment: a pilot study. Neuroscience Letters 491, 196–201.Google Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). Biometrics Research, New York State Psychiatric Institute: New York, NY.Google Scholar
Fowles, DC, Christie, MJ, Edelberg, R, Grings, WW, Lykken, DT, Venables, PH (1981) Publication recommendations for electrodermal measurements. Psychophysiology 18, 232–239.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
Gold, AL, Shin, LM, Orr, SP, Carson, MA, Rauch, SL, Macklin, ML, Lasko, NB, Metzger, LJ, Dougherty, DD, Alpert, NM, Fischman, AJ, Pitman, RK (2011) Decreased regional cerebral blood flow in medial prefrontal cortex during trauma-unrelated stressful imagery in Vietnam veterans with post-traumatic stress disorder. Psychological Medicine 41, 2563–2572.Google Scholar
Hayes, JP, Hayes, SM, Mikedis, AM (2012) Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biology of Mood & Anxiety Disorders 2(9). doi:10.1186/2045-5380-2-9.Google Scholar
Henderson, WG, Eisen, S, Goldberg, J, True, WR, Barnes, JE, Vitek, ME (1990) The Vietnam era twin registry: a resource for medical research. Public Health Reports 105, 368–373.Google Scholar
Isserles, M, Shalev, AY, Roth, Y, Peri, T, Kutz, I, Zlotnick, E, Zangen, A (2013) Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder-a pilot study. Brain Stimulation 6, 377–383.Google Scholar
Janes, GR, Goldberg, J, Eisen, SA, True, WR (1991) Reliability and validity of a combat exposure index for Vietnam era veterans. Journal of Clinical Psychology 47, 80–86.Google Scholar
Kasai, K, Yamasue, H, Gilbertson, MW, Shenton, ME, Rauch, SL, Pitman, RK (2008) Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder. Biological Psychiatry 63, 550–556.Google Scholar
Lanius, RA, Williamson, PC, Boksman, K, Densmore, M, Gupta, M, Neufeld, RW, Gati, JS, Menon, RS (2002) Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation. Biological Psychiatry 52, 305–311.Google Scholar
Lanius, RA, Williamson, PC, Densmore, M, Boksman, K, Gupta, MA, Neufeld, RW, Gati, JS, Menon, RS (2001) Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. American Journal of Psychiatry 158, 1920–1922.Google Scholar
Lanius, RA, Williamson, PC, Hopper, J, Densmore, M, Boksman, K, Gupta, MA, Neufeld, RWJ, Gati, JS, Menon, RS (2003) Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biological Psychiatry 53, 204–210.Google Scholar
Liberzon, I, Britton, JC, Phan, KL (2003) Neural correlates of traumatic recall in posttraumatic stress disorder. Stress: the International Journal on the Biology of Stress 6, 151–156.Google Scholar
Lindauer, RJ, Booij, J, Habreken, JB, Uylings, HB, Olff, M, Carlier, IV, den Heeten, GJ, van Eck-Smit, BLF, Gersons, BPR (2004) Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder. Biological Psychiatry 56, 853–861.Google Scholar
Mai, J, Majtanik, M, Paxinos, G (2015) Atlas of the Human Brain, 4th edn. Elsevier Inc.: London.Google Scholar
Orr, SP, Lasko, NB, Metzger, LJ, Berry, NJ, Ahern, CE, Pitman, RK (1998) Psychophysiologic assessment of women with posttraumatic stress disorder resulting from childhood sexual abuse. Journal of Consulting & Clinical Psychology 66, 906–913.Google Scholar
Orr, SP, McNally, RJ, Rosen, GM, Shalev, A (2004) Psychophysiological reactivity: implications for conceptualizing PTSD. In Posttraumatic Stress Disorder: Issues and Controversies (ed. Rosen, G. M.), pp. 101–126. Wiley: Chichester, England.Google Scholar
Orr, SP, Metzger, LJ, Lasko, NB, Macklin, ML, Hu, FB, Shalev, AY, Pitman, RK, Harvard/Veterans Affairs Post-traumatic Stress Disorder Twin Study Investigators (2003) Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure: association with posttraumatic stress disorder. Archives of General Psychiatry 60, 283–288.CrossRefGoogle ScholarPubMed
Orr, SP, Pitman, RK, Lasko, NB, Herz, LR (1993) Psychophysiologic assessment of posttraumatic stress disorder imagery in World War II and Korean Combat Veterans. Journal of Abnormal Psychology 102, 152–159.Google Scholar
Orr, SP, Roth, WT (2000) Psychophysiological assessment: clinical applications for PTSD. Journal of Affective Disorders 61, 225–240.Google Scholar
Osuch, EA, Benson, B, Geraci, M, Podell, D, Herscovitch, P, McCann, UD, Post, RM (2001) Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biological Psychiatry 50, 246–253.Google Scholar
Pitman, RK, Gilbertson, MW, Gurvits, TV, May, FS, Lasko, NB, Metzger, LJ, Shenton, ME, Yehuda, R, Orr, SP (2006) Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure. Annals of the New York Academy of Sciences 1071, 242–254.Google Scholar
Pitman, RK, Orr, SP, Forgue, DF, Altman, B, de Jong, JB, Herz, LR (1990) Psychophysiologic responses to combat imagery of Vietnam veterans with posttraumatic stress disorder versus other anxiety disorders. Journal of Abnormal Psychology 99, 49–54.Google Scholar
Pitman, RK, Orr, SP, Forgue, DF, de Jong, JB, Claiborn, JM (1987) Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Archives of General Psychiatry 44, 970–975.Google Scholar
Selzer, ML (1971) The Michigan alcoholism screening test: the quest for a new diagnostic instrument. American Journal of Psychiatry 127, 1653–1658.Google Scholar
Shalev, AY, Orr, SP, Pitman, RK (1992) Psychophysiologic response during script-driven imagery as an outcome measure in posttraumatic stress disorder. Journal of Clinical Psychiatry 53, 324–326.Google Scholar
Shalev, AY, Orr, SP, Pitman, RK (1993) Psychophysiologic assessment of traumatic imagery in Israeli civilian patients with posttraumatic stress disorder. American Journal of Psychiatry 150, 620–624.Google Scholar
Shin, LM, Bush, G, Milad, MR, Lasko, NB, Brohawn, KH, Hughes, KC, Macklin, ML, Gold, AL, Karpf, RD, Orr, SP, Rauch, SL, Pitman, RK (2011) Exaggerated activation of dorsal anterior cingulate cortex during cognitive interference: a monozygotic twin study of posttraumatic stress disorder. American Journal of Psychiatry 168, 979–985.Google Scholar
Shin, LM, Lasko, NB, Macklin, ML, Karpf, RD, Milad, MR, Orr, SP, Goetz, JM, Fischman, MD, Rauch, SL, Pitman, RK (2009) Resting metabolic activity in the cingulate cortex and vulnerability to posttraumatic stress disorder. Archives of General Psychiatry 66, 1099–1107.Google Scholar
Shin, LM, McNally, RJ, Kosslyn, SM, Thompson, WL, Rauch, SL, Alpert, NM, Metzger, LJ, Lasko, NB, Orr, SP, Pitman, RK (1999) Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. American Journal of Psychiatry 156, 575–584.Google Scholar
Shin, LM, Orr, SP, Carson, MA, Rauch, SL, Macklin, ML, Lasko, NB, Peters, PM, Metzger, LJ, Dougherty, DD, Cannistraro, PA, Alpert, NM, Fischman, AJ, Pitman, RK (2004) Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry 61, 168–176.Google Scholar
Shin, LM, Wright, CI, Cannistraro, PA, Wedig, MM, McMullin, K, Martis, B, Macklin, ML, Lasko, NB, Cavanagh, SR, Krangel, TS, Orr, SP, Pitman, RK, Whalen, PJ, Rauch, SL (2005) A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry 62, 273–281.Google Scholar
Strachan, E, Hunt, C, Afari, N, Duncan, G, Noonan, C, Schur, E, Watson, N, Goldberg, J, Buchwald, D (2013) University of Washington twin registry: poised for the next generation of twin research. Twin Research & Human Genetics 16, 455–462.Google Scholar
Talairach, J, Tournoux, P (1988) Co-Planar Stereotaxic Atlas of the Human Brain 3-Dimensional Proportional System: An Approach to Cerebral Imaging (Trans. M. Rayport). Thieme Medical Publishers: New York, NY.Google Scholar
VanElzakker, MB, Dahlgren, MK, Davis, FC, Dubois, S, Shin, LM (2014) From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders. Neurobiology of Learning & Memory 133, 3–18.Google Scholar
Weathers, FW, Keane, TM, Davidson, JRT (2001) Clinician-administered PTSD scale: a review of the first ten years of research. Depression & Anxiety 13, 132–156.Google Scholar
Yehuda, R, LeDoux, J (2007) Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 56, 19–32.Google Scholar
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