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Chapter 12 - The Immune System and Anxiety Disorders

Published online by Cambridge University Press:  02 September 2021

By
Vasiliki Michopoulos  and
Tanja Jovanovic
Edited by
Golam Khandaker ,
Neil Harrison ,
Edward Bullmore  and
Robert Dantzer
Golam Khandaker
Affiliation:
University of Cambridge
Neil Harrison
Affiliation:
Cardiff University Brain Research Imaging Centre (CUBRIC)
Edward Bullmore
Affiliation:
University of Cambridge
Robert Dantzer
Affiliation:
University of Texas, MD Anderson Cancer Center
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Summary

Anxiety disorders, including post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD) and phobias (including social phobia and agoraphobia), are the most common (1) and most economically costly psychiatric conditions (2). All anxiety disorders are characterized by pathological fear reactions and/or anxiety (3) in response to stimuli specific to each disorder in the absence of danger (4). Impairments in the ability to extinguish learned fear in response to specific stimuli and to learn safety behaviours are also cardinal characteristics of anxiety disorders (4). Because anxiety disorders are highly comorbid with other psychiatric conditions and adverse physical health conditions that increase mortality, including cardiovascular disease, obesity and diabetes (1,5), biomedical research has focused on defining the mechanisms underlying anxiety disorders.

Type
Chapter
Information
Textbook of Immunopsychiatry , pp. 233 - 257
Publisher: Cambridge University Press
Print publication year: 2021

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References

Kessler, RC, Berglund, P, Demler, O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry. 2005;62(6):593–602.CrossRefGoogle ScholarPubMed
Gustavsson, A, Svensson, M, Jacobi, F, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(10):718–79.CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington; 2013.Google Scholar
Singewald, N, Schmuckermair, C, Whittle, N, Holmes, A, Ressler, KJ. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacology & Therapeutics. 2015;149:150–90.Google Scholar
Boscarino, JA. Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Annals of the New York Academy of Sciences. 2004;1032:141–53.Google Scholar
Haroon, E, Raison, CL, Miller, AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37(1):137–62.Google Scholar
Kessler, RC, Sonnega, A, Bromet, E, Hughes, M, Nelson, CB. Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry. 1995;52(12):1048–60.CrossRefGoogle ScholarPubMed
Norrholm, SD, Glover, EM, Stevens, JS, et al. Fear load: the psychophysiological over-expression of fear as an intermediate phenotype associated with trauma reactions. Int J Psychophysiol. 2015; 98(2 Pt 2):270–5.CrossRefGoogle ScholarPubMed
Norrholm, SD, Jovanovic, T, Olin, IW, et al. Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity. Biological Psychiatry. 2011;69(6):556–63.Google Scholar
Jovanovic, T, Norrholm, SD, Blanding, NQ, et al. Impaired fear inhibition is a biomarker of PTSD but not depression. Depress Anxiety. 2010;27(3):244–51.Google Scholar
Michopoulos, V, Norrholm, SD, Jovanovic, T. Diagnostic biomarkers for posttraumatic stress disorder: promising horizons from translational neuroscience research. Biological Psychiatry. 2015;78(5):344–53.Google Scholar
Michopoulos, V, Rothbaum, AO, Jovanovic, T, et al. Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma. The American Journal of Psychiatry. 2015;172(4):353–62.CrossRefGoogle Scholar
O’Donovan, A, Ahmadian, AJ, Neylan, TC, et al. Current posttraumatic stress disorder and exaggerated threat sensitivity associated with elevated inflammation in the Mind Your Heart Study. Brain Behav Immun. 2017;60:198–205.Google Scholar
Guo, M, Liu, T, Guo, JC, et al. Study on serum cytokine levels in posttraumatic stress disorder patients. Asian Pac J Trop Med. 2012;5(4):323–5.Google Scholar
Zhou, J, Nagarkatti, P, Zhong, Y, et al. Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder. PloS One. 2014;9(4):e94075.Google Scholar
Plantinga, L, Bremner, JD, Miller, AH, et al. Association between posttraumatic stress disorder and inflammation: a twin study. Brain Behav Immun. 2013;30:125–32.Google Scholar
Sumner, JA, Chen, Q, Roberts, AL, et al. Cross-sectional and longitudinal associations of chronic posttraumatic stress disorder with inflammatory and endothelial function markers in women. Biological Psychiatry. 2017;82(12):875–84.Google Scholar
von Kanel, R, Hepp, U, Kraemer, B, et al. Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. Journal of Psychiatric Research. 2007;41(9):744–52.Google Scholar
Oglodek, EA, Szota, AM, Mos, DM, Araszkiewicz, A, Szromek, AR. Serum concentrations of chemokines (CCL-5 and CXCL-12), chemokine receptors (CCR-5 and CXCR-4), and IL-6 in patients with posttraumatic stress disorder and avoidant personality disorder. Pharmacol Rep. 2015;67(6):1251–8.Google Scholar
Dalgard, C, Eidelman, O, Jozwik, C, et al. The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder. Transl Psychiatry. 2017;7(2):e1025.CrossRefGoogle ScholarPubMed
Lindqvist, D, Wolkowitz, OM, Mellon, S, et al. Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain Behav Immun. 2014;42:81–8.Google Scholar
Lindqvist, D, Dhabhar, FS, Mellon, SH, et al. Increased pro-inflammatory milieu in combat related PTSD – a new cohort replication study. Brain Behav Immun. 2017;59:260–4.Google Scholar
Bruenig, D, Mehta, D, Morris, CP, et al. Correlation between interferon gamma and interleukin 6 with PTSD and resilience. Psychiatry Research. 2017;260:193–8.Google Scholar
Mendoza, C, Barreto, GE, Avila-Rodriguez, M, Echeverria, V. Role of neuroinflammation and sex hormones in war-related PTSD. Molecular and Cellular Endocrinology. 2016;434:266–77.CrossRefGoogle ScholarPubMed
John-Henderson, NA, Marsland, AL, Kamarck, TW, Muldoon, MF, Manuck, SB. Childhood socioeconomic status and the occurrence of recent negative life events as predictors of circulating and stimulated levels of interleukin-6. Psychosom Med. 2016;78(1):91–101.Google Scholar
Devoto, C, Arcurio, L, Fetta, J, et al. Inflammation relates to chronic behavioral and neurological symptoms in military personnel with traumatic brain injuries. Cell Transplant. 2017;26(7):1169–77.Google Scholar
Tursich, M, Neufeld, RW, Frewen, PA, et al. Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis. Transl Psychiatry. 2014;4:e413.Google Scholar
Tietjen, GE, Khubchandani, J, Herial, NA, Shah, K. Adverse childhood experiences are associated with migraine and vascular biomarkers. Headache. 2012;52(6):920–9.CrossRefGoogle ScholarPubMed
Hartwell, KJ, Moran-Santa Maria, MM, Twal, WO, et al. Association of elevated cytokines with childhood adversity in a sample of healthy adults. Journal of Psychiatric Research. 2013;47(5):604–10.CrossRefGoogle Scholar
Smith, AK, Conneely, KN, Kilaru, V, et al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(6):700–8.Google ScholarPubMed
Gouin, JP, Glaser, R, Malarkey, WB, Beversdorf, D, Kiecolt-Glaser, JK. Childhood abuse and inflammatory responses to daily stressors. Ann Behav Med. 2012;44(2):287–92.Google Scholar
Kiecolt-Glaser, JK, Gouin, JP, Weng, NP, et al. Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation. Psychosom Med. 2011;73(1):16–22.Google Scholar
Danese, A, Pariante, CM, Caspi, A, Taylor, A, Poulton, R. Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(4):1319–24.Google Scholar
Rooks, C, Veledar, E, Goldberg, J, Bremner, JD, Vaccarino, V. Early trauma and inflammation: role of familial factors in a study of twins. Psychosom Med. 2012;74(2):146–52.Google Scholar
Matthews, KA, Chang, YF, Thurston, RC, Bromberger, JT. Child abuse is related to inflammation in mid-life women: role of obesity. Brain Behav Immun. 2014;36:29–34.Google Scholar
Bertone-Johnson, ER, Whitcomb, BW, Missmer, SA, Karlson, EW, Rich-Edwards, JW. Inflammation and early-life abuse in women. Am J Prev Med. 2012;43(6):611–20.Google Scholar
Lin, JE, Neylan, TC, Epel, E, O’Donovan, A. Associations of childhood adversity and adulthood trauma with C-reactive protein: a cross-sectional population-based study. Brain Behav Immun. 2016;53:105–12.Google Scholar
Holliday, SB, DeSantis, A, Germain, A, et al. Deployment length, inflammatory markers, and ambulatory blood pressure in military couples. Mil Med. 2017;182(7):e1892-e9.Google Scholar
Hussein, S, Dalton, B, Willmund, GD, Ibrahim, MAA, Himmerich, H. A systematic review of tumor necrosis factor-alpha in post-traumatic stress disorder: evidence from human and animal studies. Psychiatr Danub. 2017;29(4):407–20.Google Scholar
Waheed, A, Dalton, B, Wesemann, U, Ibrahim, MAA, Himmerich, H. A systematic review of interleukin-1beta in post-traumatic stress disorder: evidence from human and animal studies. J Interferon Cytokine Res. 2018;38(1):1–11.Google Scholar
Passos, IC, Vasconcelos-Moreno, MP, Costa, LG, et al. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry. 2015;2(11):1002–12.Google Scholar
Jergovic, M, Bendelja, K, Savic Mlakar, A, et al. Circulating levels of hormones, lipids, and immune mediators in post-traumatic stress disorder – a 3-month follow-up study. Front Psychiatry. 2015;6:49.Google Scholar
Song, Y, Zhou, D, Guan, Z, Wang, X. Disturbance of serum interleukin-2 and interleukin-8 levels in posttraumatic and non-posttraumatic stress disorder earthquake survivors in northern China. Neuroimmunomodulation. 2007;14(5):248–54.Google Scholar
Teche, SP, Rovaris, DL, Aguiar, BW, et al. Resilience to traumatic events related to urban violence and increased IL10 serum levels. Psychiatry Research. 2017;250:136–40.Google Scholar
Jergovic, M, Bendelja, K, Vidovic, A, et al. Patients with posttraumatic stress disorder exhibit an altered phenotype of regulatory T cells. Allergy Asthma Clin Immunol. 2014;10(1):43.Google Scholar
Altemus, M, Cloitre, M, Dhabhar, FS. Enhanced cellular immune response in women with PTSD related to childhood abuse. The American Journal of Psychiatry. 2003;160(9):1705–7.Google Scholar
Masoudzadeh, A, Modanloo Kordi, M, Ajami, A, Azizi, A. Evaluation of cortisol level and cell-mediated immunity response changes in individuals with post-traumatic stress disorder as a consequence of war. Med Glas (Zenica). 2012;9(2):218–22.Google Scholar
Rohleder, N, Joksimovic, L, Wolf, JM, Kirschbaum, C. Hypocortisolism and increased glucocorticoid sensitivity of pro-Inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder. Biological Psychiatry. 2004;55(7):745–51.Google Scholar
Gill, J, Vythilingam, M, Page, GG. Low cortisol, high DHEA, and high levels of stimulated TNF-alpha, and IL-6 in women with PTSD. J Trauma Stress. 2008;21(6):530–9.Google Scholar
Kawamura, N, Kim, Y, Asukai, N. Suppression of cellular immunity in men with a past history of posttraumatic stress disorder. American Journal of Psychiatry. 2001;158(3):484–6.Google Scholar
Vidovic, A, Gotovac, K, Vilibic, M, et al. Repeated assessments of endocrine- and immune-related changes in posttraumatic stress disorder. Neuroimmunomodulation. 2011;18(4):199–211.Google Scholar
Boscarino, JA, Chang, J. Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications. Psychosom Med. 1999;61(3):378–86.Google Scholar
Afzali, B, Lombardi, G, Lechler, RI, Lord, GM. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148(1):32–46.Google Scholar
Heinzelmann, M, Gill, J. Epigenetic mechanisms shape the biological response to trauma and risk for PTSD: a critical review. Nurs Res Pract. 2013;2013:417010.Google Scholar
Bam, M, Yang, X, Zumbrun, EE, et al. Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation. Sci Rep. 2016;6:31209.Google Scholar
Kuan, PF, Waszczuk, MA, Kotov, R, et al. An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders. Transl Psychiatry. 2017;7(6):e1158.Google Scholar
Uddin, M, Galea, S, Chang, SC, et al. Gene expression and methylation signatures of MAN2C1 are associated with PTSD. Dis Markers. 2011;30(2–3):111–21.Google Scholar
Uddin, M, Aiello, AE, Wildman, DE, et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(20):9470–5.Google Scholar
Miller, MW, Maniates, H, Wolf, EJ, et al. CRP polymorphisms and DNA methylation of the AIM2 gene influence associations between trauma exposure, PTSD, and C-reactive protein. Brain Behav Immun. 2018;67:194–202.Google Scholar
Pace, TW, Wingenfeld, K, Schmidt, I, et al. Increased peripheral NF-kappaB pathway activity in women with childhood abuse-related posttraumatic stress disorder. Brain Behav Immun. 2012;26(1):13–7.Google Scholar
Sarapas, C, Cai, G, Bierer, LM, et al. Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers. 2011;30(2–3):101–10.Google Scholar
O’Donovan, A, Sun, B, Cole, S, et al. Transcriptional control of monocyte gene expression in post-traumatic stress disorder. Dis Markers. 2011;30(2–3):123–32.Google Scholar
Guardado, P, Olivera, A, Rusch, HL, et al. Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-kappaB) systems is associated with posttraumatic stress disorder in military personnel. J Anxiety Disord. 2016;38:9–20.CrossRefGoogle ScholarPubMed
Segman, RH, Shefi, N, Goltser-Dubner, T, et al. Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Molecular Psychiatry. 2005;10(5):500–13, 425.Google Scholar
Zieker, J, Zieker, D, Jatzko, A, et al. Differential gene expression in peripheral blood of patients suffering from post-traumatic stress disorder. Molecular Psychiatry. 2007;12(2):116–8.Google Scholar
Yehuda, R, Cai, G, Golier, JA, et al. Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biological Psychiatry. 2009;66(7):708–11.Google Scholar
Mehta, D, Gonik, M, Klengel, T, et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Archives of General Psychiatry. 2011;68(9):901–10.Google Scholar
Chitrala, KN, Nagarkatti, P, Nagarkatti, M. Prediction of possible biomarkers and novel pathways conferring risk to post-traumatic stress disorder. PloS One. 2016;11(12):e0168404.Google Scholar
Bam, M, Yang, X, Zumbrun, EE, et al. Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation. Transl Psychiatry. 2017;7(8):e1222.CrossRefGoogle ScholarPubMed
Wingo, AP, Almli, LM, Stevens, JJ, et al. DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression. Nature Communications. 2015;6:10106.Google Scholar
Bam, M, Yang, X, Zhou, J, et al. Evidence for epigenetic regulation of pro-inflammatory cytokines, interleukin-12 and interferon gamma, in peripheral blood mononuclear cells from PTSD patients. J Neuroimmune Pharmacol. 2016;11(1):168–81.Google Scholar
Guffanti, G, Galea, S, Yan, L, et al. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology. 2013;38(12):3029–38.Google Scholar
Bruenig, D, Mehta, D, Morris, CP, et al. Genetic and serum biomarker evidence for a relationship between TNFalpha and PTSD in Vietnam war combat veterans. Compr Psychiatry. 2017;74:125–33.Google Scholar
Vogelzangs, N, Beekman, AT, de Jonge, P, Penninx, BW. Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry. 2013;3:e249.Google Scholar
Pitsavos, C, Panagiotakos, DB, Papageorgiou, C, et al. Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study. Atherosclerosis. 2006;185(2):320–6.Google Scholar
Brennan, AM, Fargnoli, JL, Williams, CJ, et al. Phobic anxiety is associated with higher serum concentrations of adipokines and cytokines in women with diabetes. Diabetes Care. 2009;32(5):926–31.Google Scholar
O’Donovan, A, Hughes, BM, Slavich, GM, et al. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships. Brain Behav Immun. 2010;24(7):1074–7.Google Scholar
Michopoulos, V, Powers, A, Gillespie, CF, Ressler, KJ, Jovanovic, T. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology. 2017;42(1):254–70.Google Scholar
Belem da Silva, CT, Costa, MA, Bortoluzzi, A, et al. Cytokine levels in panic disorder: evidence for a dose-response relationship. Psychosom Med. 2017;79(2):126–32.Google Scholar
Tang, Z, Ye, G, Chen, X, et al. Peripheral proinflammatory cytokines in Chinese patients with generalised anxiety disorder. Journal of Affective Disorders. 2018;225:593–8.Google Scholar
Glaus, J, von Kanel, R, Lasserre, AM, et al. The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: results from a large longitudinal population-based study. Depress Anxiety. 2018;35(4):360–71.CrossRefGoogle ScholarPubMed
Vieira, MM, Ferreira, TB, Pacheco, PA, et al. Enhanced Th17 phenotype in individuals with generalized anxiety disorder. J Neuroimmunol. 2010;229(1–2):212–8.Google Scholar
Hoge, EA, Brandstetter, K, Moshier, S, et al. Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder. Depress Anxiety. 2009;26(5):447–55.Google Scholar
Rapaport, MH, Stein, MB. Serum cytokine and soluble interleukin-2 receptors in patients with panic disorder. Anxiety. 1994;1(1):22–5.Google Scholar
Koh, KB, Lee, Y. Reduced anxiety level by therapeutic interventions and cell-mediated immunity in panic disorder patients. Psychother Psychosom. 2004;73(5):286–92.Google Scholar
Tukel, R, Arslan, BA, Ertekin, BA, et al. Decreased IFN-gamma and IL-12 levels in panic disorder. Journal of Psychosomatic Research. 2012;73(1):63–7.Google Scholar
Renna, ME, O’Toole, MS, Spaeth, PE, Lekander, M, Mennin, DS. The association between anxiety, traumatic stress, and obsessive-compulsive disorders and chronic inflammation: A systematic review and meta-analysis. Depress Anxiety. 2018;35(11):1081–94.Google Scholar
Costello, H, Gould, RL, Abrol, E, Howard, R. Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder. BMJ Open. 2019;9(7):e027925.Google Scholar
Quagliato, LA, Nardi, AE. Cytokine alterations in panic disorder: A systematic review. Journal of Affective Disorders. 2018;228:91–6.Google Scholar
Miller, AH, Raison, CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34.Google Scholar
Koo, JW, Duman, RS. IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(2):751–6.Google Scholar
Maier, SF, Watkins, LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev. 1998;105(1):83–107.Google Scholar
Bierhaus, A, Wolf, J, Andrassy, M, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(4):1920–5.Google Scholar
Maslanik, T, Mahaffey, L, Tannura, K, et al. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure. Brain Behav Immun. 2013;28:54–62.Google Scholar
Iwata, M, Ota, KT, Duman, RS. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun. 2013;31:105–14.Google Scholar
Nance, DM, Sanders, VM. Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun. 2007;21(6):736–45.Google Scholar
Tan, KS, Nackley, AG, Satterfield, K, et al. Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms. Cell Signal. 2007;19(2):251–60.Google Scholar
Rhen, T, Cidlowski, JA. Antiinflammatory action of glucocorticoids–new mechanisms for old drugs. The New England Journal of Medicine. 2005;353(16):1711–23.Google Scholar
Yehuda, R, Boisoneau, D, Lowy, MT, Giller, EL, Jr. Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. Archives of General Psychiatry. 1995;52(7):583–93.Google Scholar
de Kloet, CS, Vermetten, E, Geuze, E, et al. Elevated plasma corticotrophin-releasing hormone levels in veterans with posttraumatic stress disorder. Progress in Brain Research. 2008;167:287–91.Google Scholar
Baker, DG, Ekhator, NN, Kasckow, JW, et al. Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. The American Journal of Psychiatry. 2005;162(5):992–4.Google Scholar
Yehuda, R, Golier, JA, Kaufman, S. Circadian rhythm of salivary cortisol in Holocaust survivors with and without PTSD. The American Journal of Psychiatry. 2005;162(5):998–1000.Google Scholar
Mason, JW, Giller, EL, Kosten, TR, Ostroff, RB, Podd, L. Urinary free-cortisol levels in posttraumatic stress disorder patients. J Nerv Ment Dis. 1986;174(3):145–9.CrossRefGoogle ScholarPubMed
Staufenbiel, SM, Penninx, BW, Spijker, AT, Elzinga, BM, van Rossum, EF. Hair cortisol, stress exposure, and mental health in humans: a systematic review. Psychoneuroendocrinology. 2013;38(8):1220–35.Google Scholar
Mantella, RC, Butters, MA, Amico, JA, et al. Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder. Psychoneuroendocrinology. 2008;33(6):773–81.Google Scholar
Vreeburg, SA, Zitman, FG, van Pelt, J, et al. Salivary cortisol levels in persons with and without different anxiety disorders. Psychosom Med. 2010;72(4):340–7.Google Scholar
Coryell, W, Noyes, R, Jr., Schlechte, J. The significance of HPA axis disturbance in panic disorder. Biological Psychiatry. 1989;25(8):989–1002.Google Scholar
Meewisse, ML, Reitsma, JB, de Vries, GJ, Gersons, BP, Olff, M. Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. Br J Psychiatry. 2007;191:387–92.Google Scholar
Freidenberg, BM, Gusmano, R, Hickling, EJ, et al. Women with PTSD have lower basal salivary cortisol levels later in the day than do men with PTSD: a preliminary study. Physiology & Behavior. 2010;99(2):234–6.Google Scholar
Maes, M, Lin, A, Bonaccorso, S, et al. Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia. Acta Psychiatr Scand. 1998;98(4):328–35.Google Scholar
Fossey, MD, Lydiard, RB, Ballenger, JC, et al. Cerebrospinal fluid corticotropin-releasing factor concentrations in patients with anxiety disorders and normal comparison subjects. Biological Psychiatry. 1996;39(8):703–7.Google Scholar
Jolkkonen, J, Lepola, U, Bissette, G, Nemeroff, C, Riekkinen, P. CSF corticotropin-releasing factor is not affected in panic disorder. Biological Psychiatry. 1993;33(2):136–8.Google Scholar
Shea, A, Walsh, C, Macmillan, H, Steiner, M. Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology. 2005;30(2):162–78.Google Scholar
Dieleman, GC, Huizink, AC, Tulen, JH, et al. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis. Psychoneuroendocrinology. 2015;51:135–50.Google Scholar
Southwick, SM, Bremner, JD, Rasmusson, A, et al. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry. 1999;46(9):1192–204.Google Scholar
Blechert, J, Michael, T, Grossman, P, Lajtman, M, Wilhelm, FH. Autonomic and respiratory characteristics of posttraumatic stress disorder and panic disorder. Psychosom Med. 2007;69(9):935–43.Google Scholar
Cohen, H, Benjamin, J, Geva, AB, et al. Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks. Psychiatry Research. 2000;96(1):1–13.CrossRefGoogle ScholarPubMed
Thayer, JF, Friedman, BH, Borkovec, TD. Autonomic characteristics of generalized anxiety disorder and worry. Biological Psychiatry. 1996;39(4):255–66.Google Scholar
Delahanty, DL, Nugent, NR, Christopher, NC, Walsh, M. Initial urinary epinephrine and cortisol levels predict acute PTSD symptoms in child trauma victims. Psychoneuroendocrinology. 2005;30(2):121–8.Google Scholar
Geracioti, TD, Jr., Baker, DG, Ekhator, NN, et al. CSF norepinephrine concentrations in posttraumatic stress disorder. The American Journal of Psychiatry. 2001;158(8):1227–30.Google Scholar
Blanchard, EB, Kolb, LC, Prins, A, Gates, S, McCoy, GC. Changes in plasma norepinephrine to combat-related stimuli among Vietnam veterans with posttraumatic stress disorder. J Nerv Ment Dis. 1991;179(6):371–3.Google Scholar
Geracioti, TD, Jr., Baker, DG, Kasckow, JW, et al. Effects of trauma-related audiovisual stimulation on cerebrospinal fluid norepinephrine and corticotropin-releasing hormone concentrations in post-traumatic stress disorder. Psychoneuroendocrinology. 2008;33(4):416–24.Google Scholar
Alvares, GA, Quintana, DS, Kemp, AH, et al. Reduced heart rate variability in social anxiety disorder: associations with gender and symptom severity. PloS One. 2013;8(7):e70468.Google Scholar
Bornas, X, Llabres, J, Noguera, M, et al. Fear induced complexity loss in the electrocardiogram of flight phobics: a multiscale entropy analysis. Biological Psychology. 2006;73(3):272–9.Google Scholar
Chalmers, JA, Quintana, DS, Abbott, MJ, Kemp, AH. Anxiety disorders are associated with reduced heart rate variability: a meta-analysis. Front Psychiatry. 2014;5:80.Google Scholar
Gill, J, Lee, H, Barr, T, et al. Lower health related quality of life in U.S. military personnel is associated with service-related disorders and inflammation. Psychiatry Research. 2014;216(1):116–22.Google Scholar
Dennis, PA, Weinberg, JB, Calhoun, PS, et al. An investigation of vago-regulatory and health-behavior accounts for increased inflammation in posttraumatic stress disorder. Journal of Psychosomatic Research. 2016;83:33–9.Google Scholar
Bryant, PA, Trinder, J, Curtis, N. Sick and tired: does sleep have a vital role in the immune system? Nat Rev Immunol. 2004;4(6):457–67.Google Scholar
Meier-Ewert, HK, Ridker, PM, Rifai, N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43(4):678–83.Google Scholar
Vgontzas, AN, Papanicolaou, DA, Bixler, EO, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. The Journal of Clinical Endocrinology and Metabolism. 1999;84(8):2603–7.Google Scholar
Vgontzas, AN, Zoumakis, E, Bixler, EO, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. The Journal of Clinical Endocrinology and Metabolism. 2004;89(5):2119–26.Google Scholar
Khaodhiar, L, Ling, PR, Blackburn, GL, Bistrian, BR. Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity. JPEN J Parenter Enteral Nutr. 2004;28(6):410–5.Google Scholar
Pierce, GL, Kalil, GZ, Ajibewa, T, et al. Anxiety independently contributes to elevated inflammation in humans with obesity. Obesity (Silver Spring). 2017;25(2):286–9.Google Scholar
O’Donovan, A, Cohen, BE, Seal, KH, et al. Elevated risk for autoimmune disorders in iraq and afghanistan veterans with posttraumatic stress disorder. Biological Psychiatry. 2015;77(4):365–74.Google Scholar
Celano, CM, Daunis, DJ, Lokko, HN, Campbell, KA, Huffman, JC. Anxiety disorders and cardiovascular disease. Curr Psychiatry Rep. 2016;18(11):101.Google Scholar
Fu, SS, McFall, M, Saxon, AJ, et al. Post-traumatic stress disorder and smoking: a systematic review. Nicotine Tob Res. 2007;9(11):1071–84.Google Scholar
Morissette, SB, Tull, MT, Gulliver, SB, Kamholz, BW, Zimering, RT. Anxiety, anxiety disorders, tobacco use, and nicotine: a critical review of interrelationships. Psychol Bull. 2007;133(2):245–72.Google Scholar
Frohlich, M, Sund, M, Lowel, H, et al. Independent association of various smoking characteristics with markers of systemic inflammation in men. Results from a representative sample of the general population (MONICA Augsburg Survey 1994/95). Eur Heart J. 2003;24(14):1365–72.Google Scholar
Jamal, O, Aneni, EC, Shaharyar, S, et al. Cigarette smoking worsens systemic inflammation in persons with metabolic syndrome. Diabetol Metab Syndr. 2014;6:79.Google Scholar
Eraly, SA, Nievergelt, CM, Maihofer, AX, et al. Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry. 2014;71(4):423–31.Google Scholar
Breen, MS, Maihofer, AX, Glatt, SJ, et al. Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry. 2015;20(12):1538–45.Google Scholar
Pervanidou, P, Kolaitis, G, Charitaki, S, et al. Elevated morning serum interleukin (IL)-6 or evening salivary cortisol concentrations predict posttraumatic stress disorder in children and adolescents six months after a motor vehicle accident. Psychoneuroendocrinology. 2007;32(8–10):991–9.CrossRefGoogle ScholarPubMed
Cohen, M, Meir, T, Klein, E, et al. Cytokine levels as potential biomarkers for predicting the development of posttraumatic stress symptoms in casualties of accidents. International Journal of Psychiatry in Medicine. 2011;42(2):117–31.CrossRefGoogle ScholarPubMed
Michopoulos, V, Beurel, E, Gould, F, et al. Association of prospective risk for chronic PTSD symptoms with low TNFalpha and IFNgamma concentrations in the immediate aftermath of trauma exposure. The American Journal of Psychiatry. 2019;177(1):58–65.Google Scholar
Fonzo, GA, Ramsawh, HJ, Flagan, TM, et al. Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders. Br J Psychiatry. 2015;206(3):206–15.Google Scholar
Killgore, WD, Britton, JC, Schwab, ZJ, et al. Cortico-limbic responses to masked affective faces across ptsd, panic disorder, and specific phobia. Depress Anxiety. 2014;31(2):150–9.Google Scholar
Monk, CS, Telzer, EH, Mogg, K, et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Archives of General Psychiatry. 2008;65(5):568–76.Google Scholar
Stevens, JS, Kim, YJ, Galatzer-Levy, IR, et al. Amygdala reactivity and anterior cingulate habituation predict posttraumatic stress disorder symptom maintenance after acute civilian trauma. Biological Psychiatry. 2017;81(12):1023–9.Google Scholar
Inagaki, TK, Muscatell, KA, Irwin, MR, Cole, SW, Eisenberger, NI. Inflammation selectively enhances amygdala activity to socially threatening images. NeuroImage. 2012;59(4):3222–6.Google Scholar
Muscatell, KA, Dedovic, K, Slavich, GM, et al. Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress. Brain Behav Immun. 2015;43:46–53.Google Scholar
Harrison, NA, Brydon, L, Walker, C, et al. Neural origins of human sickness in interoceptive responses to inflammation. Biological Psychiatry. 2009;66(5):415–22.Google Scholar
Labrenz, F, Ferri, F, Wrede, K, et al. Altered temporal variance and functional connectivity of BOLD signal is associated with state anxiety during acute systemic inflammation. NeuroImage. 2019;184:916–24.Google Scholar
Fani, N, Jovanovic, T, Ely, TD, et al. Neural correlates of attention bias to threat in post-traumatic stress disorder. Biological Psychology. 2012;90(2):134–42.Google Scholar
Banich, MT, Mackiewicz, KL, Depue, BE, et al. Cognitive control mechanisms, emotion and memory: a neural perspective with implications for psychopathology. Neuroscience and Biobehavioral Reviews. 2009;33(5):613–30.Google Scholar
Cui, H, Zhang, J, Liu, Y, et al. Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. Hum Brain Mapp. 2016;37(4):1459–73.Google Scholar
Etkin, A, Wager, TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American Journal of Psychiatry. 2007;164(10):1476–88.CrossRefGoogle ScholarPubMed
Eisenberger, NI, Lieberman, MD. Why rejection hurts: a common neural alarm system for physical and social pain. Trends Cogn Sci. 2004;8(7):294–300.Google Scholar
Shin, LM, Bush, G, Whalen, PJ, et al. Dorsal anterior cingulate function in posttraumatic stress disorder. J Trauma Stress. 2007;20(5):701–12.Google Scholar
Pannu Hayes, J, Labar, KS, Petty, CM, McCarthy, G, Morey, RA. Alterations in the neural circuitry for emotion and attention associated with posttraumatic stress symptomatology. Psychiatry Research. 2009;172(1):7–15.Google Scholar
Felmingham, KL, Williams, LM, Kemp, AH, et al. Anterior cingulate activity to salient stimuli is modulated by autonomic arousal in posttraumatic stress disorder. Psychiatry Research. 2009;173(1):59–62.Google Scholar
Eisenberger, NI, Lieberman, MD, Satpute, AB. Personality from a controlled processing perspective: an fMRI study of neuroticism, extraversion, and self-consciousness. Cogn Affect Behav Neurosci. 2005;5(2):169–81.Google Scholar
O’Connor, MF, Irwin, MR, Wellisch, DK. When grief heats up: pro-inflammatory cytokines predict regional brain activation. NeuroImage. 2009;47(3):891–6.Google Scholar
Harrison, NA, Brydon, L, Walker, C, et al. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biological Psychiatry. 2009;66(5):407–14.Google Scholar
Capuron, L, Pagnoni, G, Demetrashvili, M, et al. Anterior cingulate activation and error processing during interferon-alpha treatment. Biological Psychiatry. 2005;58(3):190–6.CrossRefGoogle ScholarPubMed
Simmons, A, Strigo, IA, Matthews, SC, Paulus, MP, Stein, MB. Initial evidence of a failure to activate right anterior insula during affective set shifting in posttraumatic stress disorder. Psychosom Med. 2009;71(4):373–7.Google Scholar
Fani, N, King, TZ, Jovanovic, T, et al. White matter integrity in highly traumatized adults with and without post-traumatic stress disorder. Neuropsychopharmacology. 2012;37(12):2740–6.Google Scholar
van Rooij, SJH, Stevens, JS, Ely, TD, et al. The role of the hippocampus in predicting future posttraumatic stress disorder symptoms in recently traumatized civilians. Biological Psychiatry. 2017;84(2):106–15.Google Scholar
Harrison, NA, Doeller, CF, Voon, V, Burgess, N, Critchley, HD. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism. Biological Psychiatry. 2014;76(7):585–93.Google Scholar
Eisenberger, NI, Inagaki, TK, Rameson, LT, Mashal, NM, Irwin, MR. An fMRI study of cytokine-induced depressed mood and social pain: the role of sex differences. NeuroImage. 2009;47(3):881–90.Google Scholar
Hannestad, J, Subramanyam, K, Dellagioia, N, et al. Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans. J Nucl Med. 2012;53(4):601–7.Google Scholar
O’Donovan, A, Chao, LL, Paulson, J, et al. Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans. Psychoneuroendocrinology. 2015;51:557–66.Google Scholar
Ekdahl, CT, Claasen, JH, Bonde, S, Kokaia, Z, Lindvall, O. Inflammation is detrimental for neurogenesis in adult brain. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(23):13632–7.Google Scholar
Cunningham, C, Wilcockson, DC, Campion, S, Lunnon, K, Perry, VH. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci. 2005;25(40):9275–84.Google Scholar
Mehta, ND, Haroon, E, Xu, X, et al. Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: preliminary results. Brain Behav Immun. 2018;73:725–30.Google Scholar
Kraynak, TE, Marsland, AL, Hanson, JL, Gianaros, PJ. Retrospectively reported childhood physical abuse, systemic inflammation, and resting corticolimbic connectivity in midlife adults. Brain Behav Immun. 2019;82:203–13.Google Scholar
Dunn, AJ, Wang, J, Ando, T. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Advances in Experimental Medicine and Biology. 1999;461:117–27.Google Scholar
Schwarcz, R. The kynurenine pathway of tryptophan degradation as a drug target. Curr Opin Pharmacol. 2004;4(1):12–7.Google Scholar
Haroon, E, Fleischer, CC, Felger, JC, et al. Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Molecular Psychiatry. 2016;21(10):1351–7.Google Scholar
Tavares, RG, Tasca, CI, Santos, CE, et al. Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes. Neurochem Int. 2002;40(7):621–7.Google Scholar
Haroon, E, Woolwine, BJ, Chen, X, et al. IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology. 2014;39(7):1777–85.Google Scholar
Jing, H, Hao, Y, Bi, Q, Zhang, J, Yang, P. Intra-amygdala microinjection of TNF-alpha impairs the auditory fear conditioning of rats via glutamate toxicity. Neurosci Res. 2015;91:34–40.Google Scholar
Hao, Y, Jing, H, Bi, Q, et al. Intra-amygdala microinfusion of IL-6 impairs the auditory fear conditioning of rats via JAK/STAT activation. Behavioural Brain Research. 2014;275:88–95.Google Scholar
Crowley, T, Cryan, JF, Downer, EJ, O’Leary, OF. Inhibiting neuroinflammation: the role and therapeutic potential of GABA in neuro-immune interactions. Brain Behav Immun. 2016;54:260–77.Google Scholar
Miller, MW, Lin, AP, Wolf, EJ, Miller, DR. Oxidative stress, inflammation, and neuroprogression in chronic PTSD. Harv Rev Psychiatry. 2018;26(2):57–69.Google Scholar
Rosso, IM, Weiner, MR, Crowley, DJ, et al. Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy. Depress Anxiety. 2014;31(2):115–23.Google Scholar
Long, Z, Medlock, C, Dzemidzic, M, et al. Decreased GABA levels in anterior cingulate cortex/medial prefrontal cortex in panic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2013;44:131–5.Google Scholar
Goddard, AW, Mason, GF, Almai, A, et al. Reductions in occipital cortex GABA levels in panic disorder detected with 1h-magnetic resonance spectroscopy. Archives of General Psychiatry. 2001;58(6):556–61.Google Scholar
Michels, L, Schulte-Vels, T, Schick, M, et al. Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings. Psychiatry Research. 2014;224(3):288–95.Google Scholar
Borovac Stefanovic, L, Kalinic, D, Mimica, N, et al. Oxidative status and the severity of clinical symptoms in patients with post-traumatic stress disorder. Ann Clin Biochem. 2015;52(Pt 1):95–104.Google Scholar
Atli, A, Bulut, M, Bez, Y, et al. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors. Eur Arch Psychiatry Clin Neurosci. 2016;266(4):329–36.Google Scholar
Neylan, TC, Sun, B, Rempel, H, et al. Suppressed monocyte gene expression profile in men versus women with PTSD. Brain Behav Immun. 2011;25(3):524–31.Google Scholar
Glatt, SJ, Tylee, DS, Chandler, SD, et al. Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines: a pilot study. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(4):313–26.Google Scholar
Tylee, DS, Chandler, SD, Nievergelt, CM, et al. Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: a pilot study. Psychoneuroendocrinology. 2015;51:472–94.Google Scholar
Logue, MW, Smith, AK, Baldwin, C, et al. An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress. Psychoneuroendocrinology. 2015;57:1–13.Google Scholar
Bruenig, D, Morris, CP, Mehta, D, et al. Nitric oxide pathway genes (NOS1AP and NOS1) are involved in PTSD severity, depression, anxiety, stress and resilience. Gene. 2017;625:42–8.Google Scholar
Bulut, M, Selek, S, Bez, Y, et al. Reduced PON1 enzymatic activity and increased lipid hydroperoxide levels that point out oxidative stress in generalized anxiety disorder. Journal of Affective Disorders. 2013;150(3):829–33.Google Scholar
Ozdemir, O, Selvi, Y, Ozkol, H, et al. Comparison of superoxide dismutase, glutathione peroxidase and adenosine deaminase activities between respiratory and nocturnal subtypes of patients with panic disorder. Neuropsychobiology. 2012;66(4):244–51.Google Scholar
Rossi, S, Sacchetti, L, Napolitano, F, et al. Interleukin-1beta causes anxiety by interacting with the endocannabinoid system. J Neurosci. 2012;32(40):13896–905.Google Scholar
Mandolesi, G, Bullitta, S, Fresegna, D, et al. Interferon-gamma causes mood abnormalities by altering cannabinoid CB1 receptor function in the mouse striatum. Neurobiol Dis. 2017;108:45–53.Google Scholar
Yang, L, Wang, M, Guo, YY, et al. Systemic inflammation induces anxiety disorder through CXCL12/CXCR4 pathway. Brain Behav Immun. 2016;56:352–62.Google Scholar
Heinisch, S, Kirby, LG. SDF-1alpha/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus. Neuropharmacology. 2010;58(2):501–14.Google Scholar
Gibney, SM, McGuinness, B, Prendergast, C, Harkin, A, Connor, TJ. Poly I:C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression. Brain Behav Immun. 2013;28:170–81.Google Scholar
Wang, Z, Caughron, B, Young, MRI. Posttraumatic stress disorder: an immunological disorder? Front Psychiatry. 2017;8:222.Google Scholar
Michopoulos, V, Jovanovic, T. Chronic inflammation: a new therapeutic target for post-traumatic stress disorder? Lancet Psychiatry. 2015;2(11):954–5.Google Scholar
Brenner, LA, Stearns-Yoder, KA, Hoffberg, AS, et al. Growing literature but limited evidence: a systematic review regarding prebiotic and probiotic interventions for those with traumatic brain injury and/or posttraumatic stress disorder. Brain Behav Immun. 2017;65:57–67.Google Scholar
Gocan, AG, Bachg, D, Schindler, AE, Rohr, UD. Balancing steroidal hormone cascade in treatment-resistant veteran soldiers with PTSD using a fermented soy product (FSWW08): a pilot study. Horm Mol Biol Clin Investig. 2012;10(3):301–14.Google Scholar
Su, KP, Matsuoka, Y, Pae, CU. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders. Clin Psychopharmacol Neurosci. 2015;13(2):129–37.Google Scholar
Uher, R, Tansey, KE, Dew, T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. The American Journal of Psychiatry. 2014;171(12):1278–86.Google Scholar
Raison, CL, Rutherford, RE, Woolwine, BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70(1):31–41.Google Scholar
Tucker, P, Ruwe, WD, Masters, B, et al. Neuroimmune and cortisol changes in selective serotonin reuptake inhibitor and placebo treatment of chronic posttraumatic stress disorder. Biological Psychiatry. 2004;56(2):121–8.Google Scholar
Kao, CY, He, Z, Zannas, AS, et al. Fluoxetine treatment prevents the inflammatory response in a mouse model of posttraumatic stress disorder. Journal of Psychiatric Research. 2016;76:74–83.Google Scholar
Hou, R, Ye, G, Liu, Y, et al. Effects of SSRIs on peripheral inflammatory cytokines in patients with Generalized Anxiety Disorder. Brain Behav Immun. 2019;81:105–10.Google Scholar
Himmerich, H, Willmund, GD, Zimmermann, P, et al. Serum concentrations of TNF-alpha and its soluble receptors during psychotherapy in German soldiers suffering from combat-related PTSD. Psychiatr Danub. 2016;28(3):293–8.Google Scholar
Hoge, EA, Bui, E, Palitz, SA, et al. The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder. Psychiatry Research. 2018;262:328–32.Google Scholar
Memon, AA, Sundquist, K, Ahmad, A, et al. Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients treated with mindfulness-based therapy or cognitive behavioral therapy in primary health care. Psychiatry Research. 2017;254:311–6.Google Scholar
Sumner, JA, Chen, Q, Roberts, AL, et al. Posttraumatic stress disorder onset and inflammatory and endothelial function biomarkers in women. Brain Behav Immun. 2018;69:203–9.Google Scholar
Heath, NM, Chesney, SA, Gerhart, JI, et al. Interpersonal violence, PTSD, and inflammation: potential psychogenic pathways to higher C-reactive protein levels. Cytokine. 2013;63(2):172–8.Google Scholar
Miller, RJ, Sutherland, AG, Hutchison, JD, Alexander, DA. C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder: a pilot study. Cytokine. 2001;13(4):253–5.Google Scholar
Bersani, FS, Wolkowitz, OM, Lindqvist, D, et al. Global arginine bioavailability, a marker of nitric oxide synthetic capacity, is decreased in PTSD and correlated with symptom severity and markers of inflammation. Brain Behav Immun. 2016;52:153–60.Google Scholar
Miller, K, Driscoll, D, Smith, LM, Ramaswamy, S. The role of inflammation in late-life post-traumatic stress disorder. Mil Med. 2017;182(11):e1815-e8.Google Scholar
Rosen, RL, Levy-Carrick, N, Reibman, J, et al. Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks. Journal of Psychiatric Research. 2017;89:14–21.Google Scholar
Sondergaard, HP, Hansson, LO, Theorell, T. The inflammatory markers C-reactive protein and serum amyloid A in refugees with and without posttraumatic stress disorder. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004;342(1–2):93–8.Google Scholar
McCanlies, EC, Araia, SK, Joseph, PN, et al. C-reactive protein, interleukin-6, and posttraumatic stress disorder symptomology in urban police officers. Cytokine. 2011;55(1):74–8.Google Scholar
Muhtz, C, Godemann, K, von Alm, C, et al. Effects of chronic posttraumatic stress disorder on metabolic risk, quality of life, and stress hormones in aging former refugee children. J Nerv Ment Dis. 2011;199(9):646–52.Google Scholar
Maes, M, Lin, AH, Delmeire, L, et al. Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biological Psychiatry. 1999;45(7):833–9.CrossRefGoogle ScholarPubMed
Newton, TL, Fernandez-Botran, R, Miller, JJ, Burns, VE. Interleukin-6 and soluble interleukin-6 receptor levels in posttraumatic stress disorder: associations with lifetime diagnostic status and psychological context. Biological Psychology. 2014;99:150–9.Google Scholar
Oganesyan, LP, Mkrtchyan, GM, Sukiasyan, SH, Boyajyan, AS. Classic and alternative complement cascades in post-traumatic stress disorder. Bull Exp Biol Med. 2009;148(6):859–61.Google Scholar
Spivak, B, Shohat, B, Mester, R, et al. Elevated levels of serum interleukin-1 beta in combat-related posttraumatic stress disorder. Biological Psychiatry. 1997;42(5):345–8.Google Scholar
Naude, PJW, Roest, AM, Stein, DJ, de Jonge, P, Doornbos, B. Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study. World J Biol Psychiatry. 2018;6:1–10.Google Scholar
Copeland, WE, Shanahan, L, Worthman, C, Angold, A, Costello, EJ. Generalized anxiety and C-reactive protein levels: a prospective, longitudinal analysis. Psychol Med. 2012;42(12):2641–50.Google Scholar
Khandaker, GM, Zammit, S, Lewis, G, Jones, PB. Association between serum C-reactive protein and DSM-IV generalized anxiety disorder in adolescence: findings from the ALSPAC cohort. Neurobiol Stress. 2016;4:55–61.Google Scholar
Bankier, B, Barajas, J, Martinez-Rumayor, A, Januzzi, JL. Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. Eur Heart J. 2008;29(18):2212–7.Google Scholar
Wagner, EY, Wagner, JT, Glaus, J, et al. Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study. PloS One. 2015;10(4):e0123757.Google Scholar
Brambilla, F, Bellodi, L, Perna, G, et al. Plasma interleukin-1 beta concentrations in panic disorder. Psychiatry Research. 1994;54(2):135–42.Google Scholar
Brambilla, F, Bellodi, L, Perna, G. Plasma levels of tumor necrosis factor-alpha in patients with panic disorder: effect of alprazolam therapy. Psychiatry Research. 1999;89(1):21–7.CrossRefGoogle ScholarPubMed

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