Skip to main content Accessibility help
×
Home

Neural indicators of interpersonal anger as cause and consequence of combat training stress symptoms

  • G. Gilam (a1) (a2), T. Lin (a1) (a2), E. Fruchter (a3) and T. Hendler (a1) (a2) (a4) (a5)

Abstract

Background

Angry outbursts are an important feature of various stress-related disorders, and commonly lead to aggression towards other people. Findings regarding interpersonal anger have linked the ventromedial prefrontal cortex (vmPFC) to anger regulation and the locus coeruleus (LC) to aggression. Both regions were previously associated with traumatic and chronic stress symptoms, yet it is unclear if their functionality represents a consequence of, or possibly also a cause for, stress symptoms. Here we investigated the relationship between the neural trajectory of these indicators of anger and the development and manifestation of stress symptoms.

Method

A total of 46 males (29 soldiers, 17 civilians) participated in a prospective functional magnetic resonance imaging experiment in which they played a modified interpersonal anger-provoking Ultimatum Game (UG) at two-points. Soldiers were tested at the beginning and end of combat training, while civilians were tested at the beginning and end of civil service. We assumed that combat training would induce chronic stress and result in increased stress symptoms.

Results

Soldiers showed an increase in stress symptoms following combat training while civilians showed no such change following civil service. All participants were angered by the modified UG irrespective of time point. Higher post-combat training stress symptoms were associated with lower pre-combat training vmPFC activation and with higher activation increase in the LC between pre- and post-combat training.

Conclusions

Results suggest that during anger-provoking social interactions, flawed vmPFC functionality may serve as a causal risk factor for the development of stress symptoms, and heightened reactivity of the LC possibly reflects a consequence of stress-inducing combat training. These findings provide potential neural targets for therapeutic intervention and inoculation for stress-related psychopathological manifestations of anger.

Copyright

Corresponding author

*Address for correspondence: T. Hendler and G. Gilam, Tel Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Weizmann 6, Tel Aviv, 64239, Israel. (Email: talma@tlvmc.gov.il) [T.H.] (Email: gadi.gilam@gmail.com) [G.G.]

References

Hide All
Admon, R, Lubin, G, Rosenblatt, JD, Stern, O, Kahn, I, Assaf, M, Hendler, T (2013 a). Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans. Cerebral Cortex 23, 2835.
Admon, R, Milad, MR, Hendler, T (2013 b). A causal model of post-traumatic stress disorder: disentangling predisposed from acquired neural abnormalities. Trends in Cognitive Sciences 17, 337347.
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th edn. American Psychiatric Publishing: Arlington, VA.
Arnsten, AFT, Raskind, MA, Taylor, FB, Connor, DF (2015). The effects of stress exposure on prefrontal cortex: translating basic research into successful treatments for post-traumatic stress disorder. Neurobiology of Stress 1, 8999.
Astafiev, SV, Snyder, AZ, Shulman, GL, Corbetta, M (2010). Comment on “Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI” and “Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area”. Science 328, 309.
Aston-Jones, G, Valentino, RJ, Van Bockstaele, EJ, Meyerson, AT (1994). Locus coeruleus, stress, and PTSD: neurobiological and clinical parallels. In Catecholamine Function in Posttraumatic Stress Disorder: Emerging Concepts Progress in Psychiatry, no. 42 (ed. Murburg, MM), pp. 1762. American Psychiatric Association: Arlington, VA.
Baldwin, DS (2006). Serotonin noradrenaline reuptake inhibitors: a new generation of treatment for anxiety disorders. International Journal of Psychiatry in Clinical Practice 10, 1215.
Bardeen, JR, Kumpula, MJ, Orcutt, HK (2013). Emotion regulation difficulties as a prospective predictor of posttraumatic stress symptoms following a mass shooting. Journal of Anxiety Disorders 27, 188196.
Beckham, JC, Feldman, ME, Kirby, AC, Hertzberg, MA, Moore, SD (1997). Interpersonal violence and its correlates in Vietnam veterans with chronic posttraumatic stress disorder. Journal of Clinical Psychology 53, 859869.
Beckham, JC, Moore, SD, Reynolds, V (2000). Interpersonal hostility and violence in Vietnam combat veterans with chronic posttraumatic stress disorder: a review of theoretical models and empirical evidence. Aggression and Violent Behavior 5, 451466.
Bernton, E, Hoover, D, Galloway, R, Popp, K (1995). Adaptation to chronic stress in military trainees. Annals of the New York Academy of Sciences 774, 217231.
Berridge, CW (2008). Noradrenergic modulation of arousal. Brain Research Reviews 58, 117.
Berridge, CW, Waterhouse, BD (2003). The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Research Reviews 42, 3384.
Bremner, JD, Krystal, JH, Southwick, SM, Charney, DS (1996). Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 23, 3951.
Canli, T, Lesch, K-P (2007). Long story short: the serotonin transporter in emotion regulation and social cognition. Nature Neuroscience 10, 11031109.
Carroll, EM, Rueger, DB, Foy, DW, Donahoe, CP (1985). Vietnam combat veterans with posttraumatic stress disorder: analysis of marital and cohabitating adjustment. Journal of Abnormal Psychology 94, 329337.
Chemtob, CM, Hamada, RS, Roitblat, HL, Muraoka, MY (1994). Anger, impulsivity, and anger control in combat-related posttraumatic stress disorder. Journal of Consulting and Clinical Psychology 62, 827832.
Chemtob, CM, Novaco, RW, Hamada, RS, Gross, DM (1997 a). Cognitive–behavioral treatment for severe anger in posttraumatic stress disorder. Journal of Consulting and Clinical Psychology 65, 184189.
Chemtob, CM, Novaco, RW, Hamada, RS, Gross, DM, Smith, G (1997 b). Anger regulation deficits in combat-related posttraumatic stress disorder. Journal of Traumatic Stress 10, 1736.
Corbetta, M, Patel, G, Shulman, GL (2008). The reorienting system of the human brain: from environment to theory of mind. Neuron 58, 306324.
Crockett, MJ, Clark, L, Tabibnia, G, Lieberman, MD, Robbins, TW (2008). Serotonin modulates behavioral reactions to unfairness. Science 320, 17391739.
Cukor, J, Wyka, K, Jayasinghe, N, Difede, J (2010). The nature and course of subthreshold PTSD. Journal of Anxiety Disorders 24, 918923.
Davidson, RJ, Putnam, KM, Larson, CL (2000). Dysfunction in the neural circuitry of emotion regulation – a possible prelude to violence. Science 289, 591594.
Day, AL, Livingstone, HA (2001). Chronic and acute stressors among military personnel: do coping styles buffer their negative impact on health? Journal of Occupational Health Psychology 6, 348360.
Emanuele, E, Brondino, N, Bertona, M, Re, S, Geroldi, D (2008). Relationship between platelet serotonin content and rejections of unfair offers in the Ultimatum Game. Neuroscience Letters 437, 158161.
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 8593.
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.
Foa, EB, Cashman, L, Jaycox, L, Perry, K (1997). The validation of a self-report measure of posttraumatic stress disorder: the Posttraumatic Diagnostic Scale. Psychological Assessment 9, 445451.
Forbes, D, Creamer, M, Biddle, D (2001). The validity of the PTSD Checklist as a measure of symptomatic change in combat-related PTSD. Behaviour Research and Therapy 39, 977986.
Forbes, D, Parslow, R, Creamer, M, Allen, N, McHugh, T, Hopwood, M (2008). Mechanisms of anger and treatment outcome in combat veterans with posttraumatic stress disorder. Journal of Traumatic Stress 21, 142149.
Frewen, PA, Lanius, RA (2006). Toward a psychobiology of posttraumatic self-dysregulation: reexperiencing, hyperarousal, dissociation, and emotional numbing. Annals of the New York Academy of Sciences 1071, 110124.
George, SA, Knox, D, Curtis, AL, Aldridge, JW, Valentino, RJ, Liberzon, I (2013). Altered locus coeruleus–norepinephrine function following single prolonged stress. European Journal of Neuroscience 37, 901909.
Gilam, G, Hendler, T (2015). Deconstructing anger in the human brain. In Social Behavior from Rodents to Humans: Neural Foundations and Clinical Implications. Current Topics in Behavioral Neurosciences (ed. Wöhr, M and Krach, S), pp. 117. Springer: Berlin Heidelberg.
Gilam, G, Hendler, T (2016). With love, from me to you: embedding social interactions in affective neuroscience. Neuroscience and Biobehavioral Reviews 68, 590601.
Gilam, G, Lin, T, Raz, G, Azrielant, S, Fruchter, E, Ariely, D, Hendler, T (2015). Neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions. NeuroImage 120, 400411.
Grubaugh, AL, Magruder, KM, Waldrop, AE, Elhai, JD, Knapp, RG, Frueh, BC (2005). Subthreshold PTSD in primary care: prevalence, psychiatric disorders, healthcare use, and functional status. Journal of Nervous and Mental Disease 193, 658664.
Haden, SC, Scarpa, A (2007). The noradrenergic system and its involvement in aggressive behaviors. Aggression and Violent Behavior 12, 115.
Haller, J, Makara, GB, Kruk, MR (1997). Catecholaminergic involvement in the control of aggression: hormones, the peripheral sympathetic, and central noradrenergic systems. Neuroscience and Biobehavioral Reviews 22, 8597.
Heinrichs, M, Wagner, D, Schoch, W, Soravia, LM, Hellhammer, DH, Ehlert, U (2005). Predicting posttraumatic stress symptoms from pretraumatic risk factors: a 2-year prospective follow-up study in firefighters. American Journal of Psychiatry 162, 22762286.
Jakupcak, M, Conybeare, D, Phelps, L, Hunt, S, Holmes, HA, Felker, B, Klevens, M, McFall, ME (2007). Anger, hostility, and aggression among Iraq and Afghanistan war veterans reporting PTSD and subthreshold PTSD. Journal of Traumatic Stress 20, 945954.
Jakupcak, M, Tull, MT (2005). Effects of trauma exposure on anger, aggression, and violence in a nonclinical sample of men. Violence and Victims 20, 589598.
Jordan, BK, Marmar, CR, Fairbank, JA, Schlenger, WE (1992). Problems in families of male Vietnam veterans with posttraumatic stress disorder. Journal of Consulting and Clinical Psychology 60, 916926.
Keren, NI, Lozar, CT, Harris, KC, Morgan, PS, Eckert, MA (2009). In vivo mapping of the human locus coeruleus. NeuroImage 47, 12611267.
Keynan, JN, Meir-Hasson, Y, Gilam, G, Cohen, A, Jackont, G, Kinreich, S, Ikar, L, Or-Borichev, A, Etkin, A, Gyurak, A, Klovatch, I, Intrator, N, Hendler, T (2016). Limbic activity modulation guided by functional magnetic resonance imaging-inspired electroencephalography improves implicit emotion regulation. Biological Psychiatry 80, 490496.
Kumpula, MJ, Orcutt, HK, Bardeen, JR, Varkovitzky, RL (2011). Peritraumatic dissociation and experiential avoidance as prospective predictors of posttraumatic stress symptoms. Journal of Abnormal Psychology 120, 617627.
Liddell, BJ, Brown, KJ, Kemp, AH, Barton, MJ, Das, P, Peduto, A, Gordon, E, Williams, LM (2005). A direct brainstem–amygdala–cortical ‘alarm’ system for subliminal signals of fear. NeuroImage 24, 235243.
Lin, T, Vaisvaser, S, Fruchter, E, Admon, R, Wald, I, Pine, DS, Bar-Haim, Y, Hendler, T (2015). A neurobehavioral account for individual differences in resilience to chronic military stress. Psychological Medicine 45, 10111023.
Lommen, MJJ, Engelhard, IM, van de Schoot, R, van den Hout, MA (2014). Anger: cause or consequence of posttraumatic stress? A prospective study of Dutch soldiers. Journal of Traumatic Stress 27, 200207.
MacManus, D, Rona, R, Dickson, H, Somaini, G, Fear, N, Wessely, S (2015). Aggressive and violent behavior among military personnel deployed to Iraq and Afghanistan: prevalence and link with deployment and combat exposure. Epidemiologic Reviews 37, 196212.
McFall, M, Fontana, A, Raskind, M, Rosenheck, R (1999). Analysis of violent behavior in Vietnam combat veteran psychiatric inpatients with posttraumatic stress disorder. Journal of Traumatic Stress 12, 501517.
McHugh, T, Forbes, D, Bates, G, Hopwood, M, Creamer, M (2012). Anger in PTSD: is there a need for a concept of PTSD-related posttraumatic anger? Clinical Psychology Review 32, 93104.
Meffert, SM, Metzler, TJ, Henn-Haase, C, McCaslin, S, Inslicht, S, Chemtob, C, Neylan, T, Marmar, CR (2008). A prospective study of trait anger and PTSD symptoms in police. Journal of Traumatic Stress 21, 410416.
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.
Miles, SR, Menefee, DS, Wanner, J, Teten Tharp, A, Kent, TA (2016). The relationship between emotion dysregulation and impulsive aggression in veterans with posttraumatic stress disorder symptoms. Journal of Interpersonal Violence 31, 17951816.
Minzenberg, MJ, Watrous, AJ, Yoon, JH, La, C, Ursu, S, Carter, CS (2010). Response to comment on “Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI”. Science 328, 309.
Novaco, RW, Chemtob, CM (2002). Anger and combat-related posttraumatic stress disorder. Journal of Traumatic Stress 15, 123132.
Olatunji, BO, Ciesielski, BG, Tolin, DF (2010). Fear and loathing: a meta-analytic review of the specificity of anger in PTSD. Behavior Therapy 41, 93105.
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, 833857.
Pitman, RK, Rasmusson, AM, Koenen, KC, Shin, LM, Orr, SP, Gilbertson, MW, Milad, MR, Liberzon, I (2012). Biological studies of post-traumatic stress disorder. Nature Reviews Neuroscience 13, 769787.
Quirk, GJ, Beer, JS (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology 16, 723727.
Sanfey, AG, Rilling, JK, Aronson, JA, Nystrom, LE, Cohen, JD (2003). The neural basis of economic decision-making in the Ultimatum Game. Science 300, 17551758.
Sara, SJ, Bouret, S (2012). Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron 76, 130141.
Scherer, KR (2005). What are emotions? And how can they be measured? Social Science Information 44, 695729.
Schmidt, C, Peigneux, P, Maquet, P, Phillips, C (2010). Response to comment on “Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area”. Science 328, 309.
Seligowski, AV, Lee, DJ, Bardeen, JR, Orcutt, HK (2015). Emotion regulation and posttraumatic stress symptoms: a meta-analysis. Cognitive Behaviour Therapy 44, 87102.
Siever, LJ (2008). Neurobiology of aggression and violence. American Journal of Psychiatry 165, 429442.
Southwick, SM, Bremner, JD, Rasmusson, A, Morgan, CA III, Arnsten, A, Charney, DS (1999). Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry 46, 11921204.
Stemmler, G (2010). Somatovisceral activation during anger. In International Handbook of Anger (ed. Potegal, M, Stemmler, G and Spielberger, C), pp. 103121. Springer: New York.
Taylor, MK, Sausen, KP, Potterat, EG, Mujica-Parodi, LR, Reis, JP, Markham, AE, Padilla, GA, Taylor, DL (2007). Stressful military training: endocrine reactivity, performance, and psychological impact. Aviation, Space, and Environmental Medicine 78, 11431149.
Valentino, RJ, Van Bockstaele, E (2008). Convergent regulation of locus coeruleus activity as an adaptive response to stress. European Journal of Pharmacology 583, 194203.
van Zuiden, M, Kavelaars, A, Rademaker, AR, Vermetten, E, Heijnen, CJ, Geuze, E (2011). A prospective study on personality and the cortisol awakening response to predict posttraumatic stress symptoms in response to military deployment. Journal of Psychiatric Research 45, 713719.
Vedantham, K, Brunet, A, Neylan, TC, Weiss, DS, Mannar, CR (2000). Neurobiological findings in posttraumatic stress disorder: a review. Dialogues in Clinical Neuroscience 2, 2329.
Weathers, F, Huska, J, Keane, T (1991). The PTSD Checklist Military Version (PCL-M). National Center for PTSD: Boston, MA.
Yoon, H-K, Lee, H-J, Kim, L, Lee, M-S, Ham, B-J (2012). Impact of tryptophan hydroxylase 2 G-703 T polymorphism on anger-related personality traits and orbitofrontal cortex. Behavioural Brain Research 231, 105110.
Young, SN, Leyton, M (2002). The role of serotonin in human mood and social interaction: insight from altered tryptophan levels. Pharmacology Biochemistry and Behavior 71, 857865.

Keywords

Type Description Title
UNKNOWN
Supplementary materials

Gilam supplementary material
Gilam supplementary material 1

 Unknown (10.6 MB)
10.6 MB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed