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Reduction in the occurrence of distressing involuntary memories following propranolol or hydrocortisone in healthy women

  • Sunjeev K. Kamboj (a1), An Tong Gong (a1), ZhiHui Sim (a1), Adrihani A. Rashid (a1), Ami Baba (a1), Georges Iskandar (a2), Ravi K. Das (a1) and H. Valerie Curran (a1)...

Abstract

Background

Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear.

Method

Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a ‘trauma film’. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested.

Results

While neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group.

Conclusions

Overall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.

Copyright

Corresponding author

Author for correspondence: Sunjeev K. Kamboj, E-mail: sunjeev.kamboj@ucl.ac.uk

Footnotes

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*

ATG, ZS and AAR contributed equally to this work.

Footnotes

References

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Antony, JW, Ferreira, CS, Norman, KA and Wimber, M (2017) Retrieval as a fast route to memory consolidation. Trends in Cognitive Sciences 21, 573576.
Born, J, Hitzler, V, Pietrowsky, R, Pauschinger, P and Fehm, H (1988) Influences of cortisol on auditory evoked potentials (AEPs) and mood in humans. Neuropsychobiology 20, 145151.
Brewin, CR (2001) A cognitive neuroscience account of posttraumatic stress disorder and its treatment. Behaviour Research and Therapy 39, 373393.
Brewin, CR (2011) The nature and significance of memory disturbance in posttraumatic stress disorder. Annual Review of Clinical Psychology 7, 203227.
Brewin, CR (2014) Episodic memory, perceptual memory, and their interaction: foundations for a theory of posttraumatic stress disorder. Psychological Bulletin 140, 6997.
Brewin, CR and Holmes, EA (2003) Psychological theories of posttraumatic stress disorder. Clinical Psychology Review 23, 339376.
Buchanan, TW and Lovallo, WR (2001) Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology 26, 307317.
Chou, C-Y, La Marca, R, Steptoe, A and Brewin, CR (2014 a) Biological responses to trauma and the development of intrusive memories: an analog study with the trauma film paradigm. Biological Psychology 103, 135143.
Chou, CY, Marca, RL, Steptoe, A and Brewin, CR (2014 b) Heart rate, startle response, and intrusive trauma memories. Psychophysiology 51, 236246.
Das, R, Tamman, A, Nikolova, V, Freeman, T, Bisby, J, Lazzarino, A and Kamboj, SK (2016) Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma. Psychological Medicine 46, 17491759.
de Quervain, D, Schwabe, L and Roozendaal, B (2017) Stress, glucocorticoids and memory: implications for treating fear-related disorders. Nature Reviews Neuroscience 18, 719.
Diamond, DM, Fleshner, M, Ingersoll, N and Rose, G (1996) Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behavioral Neuroscience 110, 661.
Dudai, Y (2004) The neurobiology of consolidations, or, how stable is the engram? Annual Review of Psychology 55, 5186.
Enewold, L, Brinton, LA, McGlynn, KA, Zahm, SH, Potter, JF and Zhu, K (2010) Oral contraceptive use among women in the military and the general US population. Journal of Women's Health 19, 839845.
Gaffey, AE, Wirth, MM, Hoks, RM, Jahn, AL and Abercrombie, HC (2014) Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies. Stress 17, 314320.
Graebener, AH, Michael, T, Holz, E and Lass-Hennemann, J (2017) Repeated cortisol administration does not reduce intrusive memories – a double blind placebo controlled experimental study. European Neuropsychopharmacology 27, 11321143.
Hauser, TU, Allen, M, Purg, N, Moutoussis, M, Rees, G and Dolan, RJ (2017) Noradrenaline blockade specifically enhances metacognitive performance. eLife 6, e24901.
Holmes, EA and Bourne, C (2008) Inducing and modulating intrusive emotional memories: a review of the trauma film paradigm. Acta Psychologica 127, 553566.
Holmes, EA, James, EL, Kilford, EJ and Deeprose, C (2010) Key steps in developing a cognitive vaccine against traumatic flashbacks: Visuospatial Tetris versus verbal Pub Quiz. PLoS One 5, e13706.
Horsch, A, Vial, Y, Favrod, C, Harari, MM, Blackwell, SE, Watson, P, Iyadurai, L, Bonsall, MB and Holmes, EA (2017) Reducing intrusive traumatic memories after emergency caesarean section: a proof-of-principle randomized controlled study. Behaviour Research and Therapy 94, 3647.
Iyadurai, L, Blackwell, SE, Meiser-Stedman, R, Watson, PC, Bonsall, MB, Geddes, JR, Nobre, AC and Holmes, EA (2018) Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial. Molecular Psychiatry 23, 674682.
Iyadurai, L, Visser, RM, Lau-Zhu, A, Porcheret, K, Horsch, A, Holmes, EA and James, EL (2019) Intrusive memories of trauma: a target for research bridging cognitive science and its clinical application. Clinical Psychology Review 69, 6782.
Kamboj, SK, Krol, KM and Curran, HV (2015) A specific association between facial disgust recognition and estradiol levels in naturally cycling women. PLoS One 10, e0122311.
Kessler, RC, Sonnega, A, Bromet, E, Hughes, M and Nelson, CB (1995) Posttraumatic stress disorder in the National Comorbidity Survey. Archives of General Psychiatry 52, 10481060.
Kirschbaum, C, Wolf, OT, May, M, Wippich, W and Hellhammer, DH (1996) Stress-and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults. Life Sciences 58, 14751483.
Kuhlmann, S, Kirschbaum, C and Wolf, OT (2005) Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words. Neurobiology of Learning and Memory 83, 158162.
Lonergan, MH, Olivera-Figueroa, LA, Pitman, RK and Brunet, A (2013) Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis. Journal of Psychiatry & Neuroscience 38, 222231.
Maheu, FS, Joober, R, Beaulieu, S and Lupien, SJ (2004) Differential effects of adrenergic and corticosteroid hormonal systems on human short-and long-term declarative memory for emotionally arousing material. Behavioral Neuroscience 118, 420428.
McGaugh, JL (2004) The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience 27, 128.
Miller, R, Stalder, T, Jarczok, M, Almeida, DM, Badrick, E, Bartels, M, Boomsma, DI, Coe, CL, Dekker, MC, Donzella, B, Fischer, JE, Gunnar, MR, Kumari, M, Lederbogen, F, Power, C, Ryff, CD, Subramanian, SV, Tiemeier, H, Watamura, SE and Kirschbaum, C (2016) The CIRCORT database: reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies. Psychoneuroendocrinology 73, 1623.
Pitman, RK, Sanders, KM, Zusman, RM, Healy, AR, Cheema, F, Lasko, NB, Cahill, L and Orr, SP (2002) Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biological Psychiatry 51, 189192.
Rattel, JA, Grünberger, LM, Reichenberger, J, Liedlgruber, M, Miedl, SF, Blechert, J and Wilhelm, FH (2019) Frequency of intrusions and appraisal of related distress after analogue trauma: a comparative ecological momentary assessment methods study. Cognitive Therapy and Research 43, 174184.
Roche, DJ, King, AC, Cohoon, AJ and Lovallo, WR (2013) Hormonal contraceptive use diminishes salivary cortisol response to psychosocial stress and naltrexone in healthy women. Pharmacology Biochemistry and Behavior 109, 8490.
Rombold, F, Wingenfeld, K, Renneberg, B, Schwarzkopf, F, Hellmann-Regen, J, Otte, C and Roepke, S (2016) Impact of exogenous cortisol on the formation of intrusive memories in healthy women. Journal of Psychiatric Research 83, 7178.
Roozendaal, B (2000) Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 25, 213238.
Roozendaal, B (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiology of Learning and Memory 78, 578595.
Schelling, G, Stoll, C, Kapfhammer, H-P, Rothenhäusler, H-B, Krauseneck, T, Durst, K, Haller, M and Briegel, J (1999) The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors. Critical Care Medicine 27, 26782683.
Schelling, G, Briegel, J, Roozendaal, B, Stoll, C, Rothenhäusler, H-B and Kapfhammer, H-P (2001) The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biological Psychiatry 50, 978985.
Shadmehr, R and Holcomb, HH (1997) Neural correlates of motor memory consolidation. Science 277, 821825.
Sijbrandij, M, Kleiboer, A, Bisson, JI, Barbui, C and Cuijpers, P (2015) Pharmacological prevention of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis. The Lancet Psychiatry 2, 413421.
Soni, M, Curran, VH and Kamboj, SK (2013) Identification of a narrow post-ovulatory window of vulnerability to distressing involuntary memories in healthy women. Neurobiology of Learning and Memory 104, 3238.
Talarico, JM and Rubin, DC (2003) Confidence, not consistency, characterizes flashbulb memories. Psychological Science 14, 455461.
van Ast, VA, Cornelisse, S, Marin, M-F, Ackermann, S, Garfinkel, SN and Abercrombie, HC (2013) Modulatory mechanisms of cortisol effects on emotional learning and memory: novel perspectives. Psychoneuroendocrinology 38, 18741882.
Van Stegeren, AH (2008) The role of the noradrenergic system in emotional memory. Acta Psychologica 127, 532541.

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