Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-19T10:04:17.842Z Has data issue: false hasContentIssue false

Childhood and adult trauma both correlate with dorsal anterior cingulate activation to threat in combat veterans

Published online by Cambridge University Press:  18 October 2012

R. J. Herringa*
Affiliation:
Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
M. L. Phillips
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Heath Park, Cardiff, UK
J. C. Fournier
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
D. M. Kronhaus
Affiliation:
St Catharine's College, Cambridge, UK Computer Laboratory, University of Cambridge, UK
A. Germain
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
*
*Address for correspondence: R. J. Herringa, M.D., Ph.D., Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, 6001 Research Park Blvd, Madison, WI 53719, USA. (Email: [email protected])

Abstract

Background

Prior studies of adult post-traumatic stress disorder (PTSD) suggest abnormal functioning of prefrontal and limbic regions. Cumulative childhood and adult trauma exposures are major risk factors for developing adult PTSD, yet their contribution to neural dysfunction in PTSD remains poorly understood. This study aimed to examine the neural correlates of childhood and adult trauma exposure and post-traumatic stress symptoms (PTSS) within a single model.

Method

Medication-free male combat veterans (n = 28, average age 26.6 years) with a wide range of PTSS were recruited from the community between 2010 and 2011. Subjects completed an emotional face-morphing task while undergoing functional magnetic resonance imaging (fMRI). Clinical ratings included the Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ) and Combat Exposure Scale (CES). A priori regions were examined through multivariate voxelwise regression in SPM8, using depressive symptoms and IQ as covariates.

Results

In the angry condition, CAPS scores correlated positively with activation in the medial prefrontal cortex [mPFC; Brodmann area (BA) 10, z = 3.51], hippocampus (z = 3.47), insula (z = 3.62) and, in earlier blocks, the amygdala. CES and CTQ correlated positively with activation in adjacent areas of the dorsal anterior cingulate cortex (dACC; BA 32, z = 3.70 and BA 24, z = 3.88 respectively). In the happy condition, CAPS, CTQ and CES were not correlated significantly with activation patterns.

Conclusions

dACC activation observed in prior studies of PTSD may be attributable to the cumulative effects of childhood and adult trauma exposure. By contrast, insula, hippocampus and amygdala activation may be specific to PTSS. The specificity of these results to threat stimuli, but not to positive stimuli, is consistent with abnormalities in threat processing associated with PTSS.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012 

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

Almeida, JR, Kronhaus, DM, Sibille, EL, Langenecker, SA, Versace, A, Labarbara, EJ, Phillips, ML (2011). Abnormal left-sided orbitomedial prefrontal cortical-amygdala connectivity during happy and fear face processing: a potential neural mechanism of female MDD. Frontiers in Psychiatry 2, 69.CrossRefGoogle ScholarPubMed
Andersen, SL, Tomada, A, Vincow, ES, Valente, E, Polcari, A, Teicher, MH (2008). Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. Journal of Neuropsychiatry and Clinical Neurosciences 20, 292301.CrossRefGoogle ScholarPubMed
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.CrossRefGoogle ScholarPubMed
Bernstein, EM, Putnam, FW (1986). Development, reliability, and validity of a dissociation scale. Journal of Nervous and Mental Disease 174, 727735.CrossRefGoogle ScholarPubMed
Blair, JR, Spreen, O (1989). Predicting premorbid IQ: a revision of the National Adult Reading Test. Clinical Neuropsychologist 3, 129136.CrossRefGoogle 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, 7590.Google ScholarPubMed
Brewin, CR, Andrews, B, Valentine, JD (2000). Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. Journal of Consulting and Clinical Psychology 68, 748766.CrossRefGoogle ScholarPubMed
Brohawn, KH, Offringa, R, Pfaff, DL, Hughes, KC, Shin, LM (2010). The neural correlates of emotional memory in posttraumatic stress disorder. Biological Psychiatry 68, 10231030.CrossRefGoogle ScholarPubMed
Burgos-Robles, A, Vidal-Gonzalez, I, Quirk, GJ (2009). Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. Journal of Neuroscience 29, 84748482.CrossRefGoogle ScholarPubMed
Dannlowski, U, Stuhrmann, A, Beutelmann, V, Zwanzger, P, Lenzen, T, Grotegerd, D, Domschke, K, Hohoff, C, Ohrmann, P, Bauer, J, Lindner, C, Postert, C, Konrad, C, Arolt, V, Heindel, W, Suslow, T, Kugel, H (2012). Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biological Psychiatry 71, 286293.CrossRefGoogle ScholarPubMed
Edmiston, EE, Wang, F, Mazure, CM, Guiney, J, Sinha, R, Mayes, LC, Blumberg, HP (2011). Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Archives of Pediatrics and Adolescent Medicine 165, 10691077.CrossRefGoogle ScholarPubMed
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 8593.CrossRefGoogle ScholarPubMed
Etkin, A, Wager, TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry 164, 14761488.CrossRefGoogle ScholarPubMed
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.Google Scholar
Francati, V, Vermetten, E, Bremner, JD (2007). Functional neuroimaging studies in posttraumatic stress disorder: review of current methods and findings. Depression and Anxiety 24, 202218.CrossRefGoogle ScholarPubMed
Grabenhorst, F, Rolls, ET (2011). Value, pleasure and choice in the ventral prefrontal cortex. Trends in Cognitive Sciences 15, 5667.CrossRefGoogle ScholarPubMed
Hanson, JL, Chung, MK, Avants, BB, Shirtcliff, EA, Gee, JC, Davidson, RJ, Pollak, SD (2010). Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk. Journal of Neuroscience 30, 74667472.CrossRefGoogle ScholarPubMed
Helzer, JE, Kraemer, HC, Krueger, RF, Wittchen, H-U, Sirovatka, PJ, Regier, DA (eds) (2008). Dimensional Approaches in Diagnostic Classification: Refining the Research Agenda for DSM-V. American Psychiatric Association: Arlington, VA.Google Scholar
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748751.CrossRefGoogle Scholar
Keane, T, Fairbank, J, Caddell, J, Zimering, R, Taylor, K, Mora, C (1989). Clinical evaluation of a measure to assess combat exposure. Psychological Assessment 1, 5355.CrossRefGoogle Scholar
Lanius, RA, Vermetten, E, Loewenstein, RJ, Brand, B, Schmahl, C, Bremner, JD, Spiegel, D (2010). Emotion modulation in PTSD: clinical and neurobiological evidence for a dissociative subtype. American Journal of Psychiatry 167, 640647.CrossRefGoogle ScholarPubMed
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience 10, 434445.CrossRefGoogle ScholarPubMed
Milad, MR, Pitman, RK, Ellis, CB, Gold, AL, Shin, LM, Lasko, NB, Zeidan, MA, Handwerger, K, Orr, SP, Rauch, SL (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological Psychiatry 66, 10751082.CrossRefGoogle ScholarPubMed
Milad, MR, Rauch, SL, Pitman, RK, Quirk, GJ (2006). Fear extinction in rats: implications for human brain imaging and anxiety disorders. Biological Psychology 73, 6171.CrossRefGoogle ScholarPubMed
Phillips, ML, Ladouceur, CD, Drevets, WC (2008). A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 829857.CrossRefGoogle ScholarPubMed
Quirk, GJ, Mueller, D (2008). Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33, 5672.CrossRefGoogle ScholarPubMed
Rauch, SL, Shin, LM, Phelps, EA (2006). Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research – past, present, and future. Biological Psychiatry 60, 376382.CrossRefGoogle ScholarPubMed
Rougemont-Bücking, A, Linnman, C, Zeffiro, TA, Zeidan, MA, Lebron-Milad, K, Rodriguez-Romaguera, J, Rauch, SL, Pitman, RK, Milad, MR (2011). Altered processing of contextual information during fear extinction in PTSD: an fMRI study. CNS Neuroscience and Therapeutics 17, 227236.CrossRefGoogle ScholarPubMed
Scher, CD, Stein, MB, Asmundson, GJ, McCreary, DR, Forde, DR (2001). The childhood trauma questionnaire in a community sample: psychometric properties and normative data. Journal of Traumatic Stress 14, 843857.CrossRefGoogle Scholar
Shackman, AJ, Salomons, TV, Slagter, HA, Fox, AS, Winter, JJ, Davidson, RJ (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience 12, 154167.CrossRefGoogle ScholarPubMed
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, 979985.CrossRefGoogle ScholarPubMed
Shin, LM, Lasko, NB, Macklin, ML, Karpf, RD, Milad, MR, Orr, SP, Goetz, JM, Fischman, AJ, Rauch, SL, Pitman, RK (2009). Resting metabolic activity in the cingulate cortex and vulnerability to posttraumatic stress disorder. Archives of General Psychiatry 66, 10991107.CrossRefGoogle ScholarPubMed
Shin, LM, Liberzon, I (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169191.CrossRefGoogle ScholarPubMed
Sierra-Mercado, D, Padilla-Coreano, N, Quirk, GJ (2011). Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear. Neuropsychopharmacology 36, 529538.CrossRefGoogle ScholarPubMed
van Wingen, GA, Geuze, E, Vermetten, E, Fernández, G (2011 a). Perceived threat predicts the neural sequelae of combat stress. Molecular Psychiatry 16, 664671.CrossRefGoogle ScholarPubMed
van Wingen, GA, Geuze, E, Vermetten, E, Fernandez, G (2011 b). The neural consequences of combat stress: long-term follow-up. Molecular Psychiatry 17, 116118.CrossRefGoogle ScholarPubMed
Vidal-Gonzalez, I, Vidal-Gonzalez, B, Rauch, SL, Quirk, GJ (2006). Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learning and Memory 13, 728733.CrossRefGoogle ScholarPubMed
Weathers, FW, Keane, TM, Davidson, JR (2001). Clinician-administered PTSD scale: a review of the first ten years of research. Depression and Anxiety 13, 132156.CrossRefGoogle Scholar
Wilber, AA, Walker, AG, Southwood, CJ, Farrell, MR, Lin, GL, Rebec, GV, Wellman, CL (2011). Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction. Neuroscience 174, 115131.CrossRefGoogle ScholarPubMed