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A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

  • P. J. Kennedy (a1) (a2), J. F. Cryan (a1) (a3), E. M. M. Quigley (a1) (a4), T. G. Dinan (a1) (a2) and G. Clarke (a1) (a2)...
Abstract
Background

Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS.

Method

Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST.

Results

The hypothalamic–pituitary–adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups.

Conclusions

Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

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Copyright
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence http://creativecommons.org/licenses/by/3.0/
Corresponding author
* Address for correspondence: Dr G. Clarke, Department of Psychiatry/Alimentary Pharmabiotic Centre, 1.15 Biosciences Institute, University College Cork, Cork, Ireland. (Email: G.Clarke@ucc.ie)
References
Hide All
Allen, AP, Kennedy, PJ, Cryan, JF, Dinan, TG, Clarke, G (2014). Biological and psychological markers of stress in humans: focus on the Trier Social Stress Test. Neuroscience and Biobehavioral Reviews 38, 94124.
Bender, R, Lange, S (2001). Adjusting for multiple testing – when and how? Journal of Clinical Epidemiology 54, 343349.
Blanchard, EB, Lackner, JM, Jaccard, J, Rowell, D, Carosella, AM, Powell, C, Sanders, K, Krasner, S, Kuhn, E (2008). The role of stress in symptom exacerbation among IBS patients. Journal of Psychosomatic Research 64, 119128.
Bohmelt, AH, Nater, UM, Franke, S, Hellhammer, DH, Ehlert, U (2005). Basal and stimulated hypothalamic-pituitary-adrenal axis activity in patients with functional gastrointestinal disorders and healthy controls. Psychosomatic Medicine 67, 288294.
Browne, RW, Kantarci, A, Lamonte, MJ, Andrews, CA, Hovey, KM, Falkner, KL, Cekici, A, Stephens, D, Genco, RJ, Scannapieco, FA, Van Dyke, TE, Wactawski-Wende, J (2013). Performance of multiplex cytokine assays in serum and saliva among community-dwelling postmenopausal women. PLoS One 8, e59 498.
Buysse, DJ, Reynolds, CF 3rd, Monk, TH, Berman, SR, Kupfer, DJ (1989). The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research 28, 193213.
Campisi, J, Bravo, Y, Cole, J, Gobeil, K (2012). Acute psychosocial stress differentially influences salivary endocrine and immune measures in undergraduate students. Physiology and Behavior 107, 317321.
Chitkara, DK, van Tilburg, MA, Blois-Martin, N, Whitehead, WE (2008). Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review. American Journal of Gastroenterology 103, 765774; quiz 775.
Chopra, KK, Ravindran, A, Kennedy, SH, Mackenzie, B, Matthews, S, Anisman, H, Bagby, RM, Farvolden, P, Levitan, RD (2009). Sex differences in hormonal responses to a social stressor in chronic major depression. Psychoneuroendocrinology 34, 12351241.
Clarke, G, McKernan, DP, Gaszner, G, Quigley, EM, Cryan, JF, Dinan, TG (2012). A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of toll-like receptor activation in irritable bowel syndrome. Frontiers in Pharmacology 3, 90.
Clarke, G, Quigley, EMM, Cryan, JF, Dinan, TG (2009). Irritable bowel syndrome: towards biomarker identification. Trends in Molecular Medicine 15, 478489.
Cohen, J (1988). Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum: Hillsdale, NJ.
Coutinho, SV, Plotsky, PM, Sablad, M, Miller, JC, Zhou, H, Bayati, AI, McRoberts, JA, Mayer, EA (2002). Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. American Journal of Physiology. Gastrointestinal and Liver Physiology 282, G307G316.
Dickerson, SS, Kemeny, ME (2004). Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychological Bulletin 130, 355391.
Dinan, TG, Quigley, EM, Ahmed, SM, Scully, P, O'Brien, S, O'Mahony, L, O'Mahony, S, Shanahan, F, Keeling, PW (2006). Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology 130, 304311.
Drossman, DA, Camilleri, M, Mayer, EA, Whitehead, WE (2002). AGA technical review on irritable bowel syndrome. Gastroenterology 123, 21082131.
Elsenbruch, S, Lucas, A, Holtmann, G, Haag, S, Gerken, G, Riemenschneider, N, Langhorst, J, Kavelaars, A, Heijnen, CJ, Schedlowski, M (2006). Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome. American Journal of Gastroenterology 101, 23002307.
Feise, RJ (2002). Do multiple outcome measures require p-value adjustment? BMC Medical Research Methodology 2, 8.
Francis, CY, Morris, J, Whorwell, PJ (1997). The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Alimentary Pharmacology and Therapeutics 11, 395402.
Fukudo, S, Suzuki, J (1987). Colonic motility, autonomic function, and gastrointestinal hormones under psychological stress on irritable bowel syndrome. Tohoku Journal of Experimental Medicine 151, 373385.
Grenham, S, Clarke, G, Cryan, JF, Dinan, TG (2011). Brain-gut-microbe communication in health and disease. Frontiers in Physiology 2, 94.
Heitkemper, MM, Cain, KC, Deechakawan, W, Poppe, A, Jun, SE, Burr, RL, Jarrett, ME (2012). Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome. Neurogastroenterology and Motility 24, 626631, e270-1.
Jarrett, M, Heitkemper, M, Cain, K, Burr, R, Hertig, V (2000). Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Digestive Diseases and Sciences 45, 952959.
Kennedy, PJ, Clarke, G, O'Neill, A, Groeger, JA, Quigley, EMM, Shanahan, F, Cryan, JF, Dinan, TG (2013). Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory. Psychological Medicine. Published online: 29 August 2013 . doi:0.1017/S0033291713002171.
Khalfa, S, Isabelle, P, Jean-Pierre, B, Manon, R (2002). Event-related skin conductance responses to musical emotions in humans. Neuroscience Letters 328, 145149.
Kiecolt-Glaser, JK, McGuire, L, Robles, TF, Glaser, R (2002). Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology. Annual Review of Psychology 53, 83107.
Kimura, K, Izawa, S, Sugaya, N, Ogawa, N, Yamada, KC, Shirotsuki, K, Mikami, I, Hirata, K, Nagano, Y, Hasegawa, T (2013). The biological effects of acute psychosocial stress on delay discounting. Psychoneuroendocrinology 38, 23002308.
Kirschbaum, C, Pirke, K, Hellhammer, D (1993). The 'Trier Social Stress Test’ – a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28, 7681.
Kroenke, K, Spitzer, RL, Williams, JB (2001). The PHQ-9: validity of a brief depression severity measure. Journal of General Internal Medicine 16, 606613.
Kudielka, BM, Hellhammer, DH, Kirschbaum, C (eds) (2007). Ten Years of Research with the Trier Social Stress Test – Revisited. Guilford Press: New York.
Liebregts, T, Adam, B, Bredack, C, Roth, A, Heinzel, S, Lester, S, Downie-Doyle, S, Smith, E, Drew, P, Talley, NJ, Holtmann, G (2007). Immune activation in patients with irritable bowel syndrome. Gastroenterology 132, 913920.
Longstreth, GF, Thompson, WG, Chey, WD, Houghton, LA, Mearin, F, Spiller, RC (2006). Functional bowel disorders. Gastroenterology 130, 14801491.
Manabe, N, Tanaka, T, Hata, J, Kusunoki, H, Haruma, K (2009). Pathophysiology underlying irritable bowel syndrome – from the viewpoint of dysfunction of autonomic nervous system activity. Journal of Smooth Muscle Research 45, 1523.
Mayer, EA (2000). The neurobiology of stress and gastrointestinal disease. Gut 47, 861869.
Mayer, EA, Aziz, Q, Coen, S, Kern, M, Labus, JS, Lane, R, Kuo, B, Naliboff, B, Tracey, I (2009). Brain imaging approaches to the study of functional GI disorders: a Rome working team report. Neurogastroenterology and Motility 21, 579596.
McKernan, DP, Gaszner, G, Quigley, EM, Cryan, JF, Dinan, TG (2011). Altered peripheral toll-like receptor responses in the irritable bowel syndrome. Alimentary Pharmacology and Therapeutics 33, 10451052.
Moloney, RD, O'Leary, OF, Felice, D, Bettler, B, Dinan, TG, Cryan, JF (2012). Early-life stress induces visceral hypersensitivity in mice. Neuroscience Letters 512, 99102.
Monteleone, P, Scognamiglio, P, Canestrelli, B, Serino, I, Monteleone, A, Maj, M (2011). Asymmetry of salivary cortisol and α-amylase responses to psychosocial stress in anorexia nervosa but not in bulimia nervosa. Psychological Medicine 41, 19631969.
Murray, CD, Flynn, J, Ratcliffe, L, Jacyna, MR, Kamm, MA, Emmanuel, AV (2004). Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome. Gastroenterology 127, 16951703.
Ohman, L, Simren, M (2010). Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nature Reviews. Gastroenterology and Hepatology 7, 163173.
O'Mahony, SM, Marchesi, JR, Scully, P, Codling, C, Ceolho, AM, Quigley, EM, Cryan, JF, Dinan, TG (2009). Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biological Psychiatry 65, 263267.
Pace, TW, Negi, LT, Dodson-Lavelle, B, Ozawa-de Silva, B, Reddy, SD, Cole, SP, Danese, A, Craighead, LW, Raison, CL (2013). Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein from before to after training in foster care program adolescents. Psychoneuroendocrinology 38, 294299.
Posserud, I, Agerforz, P, Ekman, R, Bjornsson, ES, Abrahamsson, H, Simren, M (2004). Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut 53, 11021108.
Pruessner, JC, Dedovic, K, Khalili-Mahani, N, Engert, V, Pruessner, M, Buss, C, Renwick, R, Dagher, A, Meaney, MJ, Lupien, S (2008). Deactivation of the limbic system during acute psychosocial stress: evidence from positron emission tomography and functional magnetic resonance imaging studies. Biological Psychiatry 63, 234240.
Pruessner, JC, Kirschbaum, C, Meinlschmid, G, Hellhammer, DH (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28, 916931.
Spiegel, BM (2009). The burden of IBS: looking at metrics. Current Gastroenterology Reports 11, 265269.
Suarez-Hitz, KA, Otto, B, Bidlingmaier, M, Schwizer, W, Fried, M, Ehlert, U (2012). Altered psychobiological responsiveness in women with irritable bowel syndrome. Psychosomatic Medicine 74, 221231.
Sugaya, N, Izawa, S, Kimura, K, Ogawa, N, Yamada, KC, Shirotsuki, K, Mikami, I, Hirata, K, Nagano, Y, Nomura, S, Shimada, H (2012). Adrenal hormone response and psychophysiological correlates under psychosocial stress in individuals with irritable bowel syndrome. International Journal of Psychophysiology 84, 3944.
Tanaka, T, Manabe, N, Hata, J, Kusunoki, H, Ishii, M, Sato, M, Kamada, T, Shiotani, A, Haruma, K (2008). Characterization of autonomic dysfunction in patients with irritable bowel syndrome using fingertip blood flow. Neurogastroenterology and Motility 20, 498504.
Tillisch, K, Mayer, EA, Labus, JS, Stains, J, Chang, L, Naliboff, BD (2005). Sex specific alterations in autonomic function among patients with irritable bowel syndrome. Gut 54, 13961401.
Tramullas, M, Dinan, TG, Cryan, JF (2012). Chronic psychosocial stress induces visceral hyperalgesia in mice. Stress 15, 281292.
Vege, SS, Locke, GR, Weaver, AL, Farmer, SA, Melton, LJ, NJ, T (2004). Functional gastrointestinal disorders among people with sleep disturbances: a population-based study. Mayo Clinic Proceedings 79, 15011506.
Walter, S, Bodemar, G, Hallböök, O, Thorell, L (2008). Sympathetic (electrodermal) activity during repeated maximal rectal distensions in patients with irritable bowel syndrome and constipation. Neurogastroenterology and Motility 20, 4352.
Wang, Z, Ocampo, MA, Pang, RD, Bota, M, Bradesi, S, Mayer, EA, Holschneider, DP (2013). Alterations in prefrontal-limbic functional activation and connectivity in chronic stress-induced visceral hyperalgesia. PLoS One 8, e59 138.
Watson, D, Clark, LA, Tellegen, A (1988). Development and validation of brief measures of positive and negative affect: the PANAS scales. Journal of Personality and Social Psychology 54, 10631070.
Wilson, A, Longstreth, GF, Knight, K, Wong, J, Wade, S, Chiou, CF, Barghout, V, Frech, F, Ofman, JJ (2004). Quality of life in managed care patients with irritable bowel syndrome. Managed Care Interface 17, 2428, 34.
Wright, CE, Valdimarsdottir, HB, Erblich, J, Bovbjerg, DH (2007). Poor sleep the night before an experimental stress task is associated with reduced cortisol reactivity in healthy women. Biological Psychology 74, 319327.
Zigmond, AS, Snaith, RP (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica 67, 361370.
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