Klasik korku koşullaması, klinik öncesi çalışmalarda travma sonrası stres bozukluğunu (TSSB) modellemede kullanılmaktadır. Yeniden-bütünleştirme sürecinde anılar belleğe geri çağrıldığında, bellek değişime açık bir hale gelir ve müdahale edilmeye uygundur. Koşullu uyarana (KU’lu uyaran) maruz bırakma ile tetiklenen yeniden-bütünleştirme sürecindeki müdahalelerin sadece maruz bırakılan KU’lu uyaranın tetiklediği korku tepkisinde azalmaya neden olduğu, korku ile ilişkili diğer ipuçlarına genellenmediği gözlenmiştir. Ancak günlük yaşamda, birden çok KU, korku uyandıran olayla ilişkilendirilebilir. Bu nedenle, son çalışmalarda tüm korku belleğinin yenidenbütünleştirme sürecine girmesine yol açtığı düşünülen, koşulsuz uyaran (KU’suz uyaran) ile geri çağırma prosedürüne odaklanılmıştır. KU’suz uyaran ile geri-çağırma ile tetiklenen yeniden-bütünleştirme sürecinde uygulanan müdahalelerin daha etkili olduğu düşünülmektedir. Bu derleme çalışmasında, KU’lu uyaran veya KU’suz uyaran ile aktive edilmiş korku belleği çalışmalara atıfta bulunularak, edinilmiş korkunun davranışsal ve farmakolojik müdahalelerle nasıl söndürülebileceğinden bahsedilmektedir. Ayrıca, korku belleğinde rol oynayan beyin bölgeleri ve cinsiyet farklılıklarının etkisi de ele alınmıştır. Bu derlemenin amacı, korku bozukluklarının daha etkili tedavi yaklaşımlarıyla nasıl çözülebileceğine yönelik alana katkıda bulunmaktır.
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Interventions on Fear Memory for the Prevention of Post-Traumatic Stress Disorder
Year 2023,
Volume: 10 Issue: 3, 396 - 412, 30.09.2023
The classical fear conditioning is extensively used in preclinical studies as an animal model for post traumatic stress disorder (PTSD). During the reconsolidation process, when memories are retrieved, the memory becomes susceptible to change and amenable to intervention. Interventions applied during the reconsolidation process triggered by exposure to a conditioned stimulus (CS) primarily lead to a decrease in fear responses triggered only by the exposed CS, without generalizing to other fear-related cues. However, in real-life scenarios, multiple CS’s can be linked to fear-inducing events. Therefore, recent studies have focused on the reactivation procedure with an unconditioned stimulus (US), which is believed to result in the reconsolidation of the entire fear memory. Interventions applied during the reconsolidation process that are triggered by US-based retrieval are considered more effective. Grounding on the fear memory studies activated by either CS or US, this review study discussed how acquired fear can be extinguished through behavioral and pharmacological interventions. Additionally, the brain regions involved in fear memory and the impact of gender differences on fear memory were also addressed. The aim of this review was to contribute to the field by exploring more effective treatment approaches for fear disorders.
Agren, T., Engman, J., Frick, A., Björkstrand, J., Larsson, E. M., Furmark, T. ve Fredrikson, M. (2012). Disruption of reconsolidation erases a fear memory trace in the human amygdala. Science, 337(6101), 1550–1552. https://doi.org/10.1126/science.1223006
Amaral, O. B., Luft, T., Cammarota, M., Izquierdo, I.ve Roesler, R. (2007). Temporary inactivation of the dorsal hippocampus induces a transient impairment in retrieval of aversive memory. Behavioural Brain Research, 180(2), 113–118. https://doi.org/10.1016/j.bbr.2007.02.031
American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Publishing, Inc.
An, B., Kim, J., Park, K., Lee, S., Song, S. ve Choi, S. (2017). Amount of fear extinction changes its underlying mechanisms. eLife, 6, e25224. https://doi.org/10.7554/eLife.25224
Armstrong, T., Federman, S., Hampson, K., Crabtree, O. ve Olatunji, B. O. (2021). Fear Learning in Veterans with Combat-Related PTSD Is Linked to Anxiety Sensitivity: Evidence From Self-Report and Pupillometry. Behavior Therapy, 52(1), 149–161. https://doi.org/10.1016/j.beth.2020.03.006
Bechara, A., Tranel, D., Damasio, H., Adolphs, R., Rockland, C.ve Damasio, A. R. (1995). Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science, 269(5227), 1115–1118. https://doi.org/10.1126/science.7652558
Björkstrand, J., Agren, T., Åhs, F., Frick, A., Larsson, E. M., Hjorth, O., Furmark, T. ve Fredrikson, M. (2016). Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior. Current Biology: CB, 26(19), 2690–2695. https://doi.org/10.1016/j.cub.2016.08.022
Bouton, M. E. (2002). Context, ambiguity, and unlearning: sources of relapse after behavioral extinction. Biological Psychiatry, 52(10), 976–986. https://doi.org/10.1016/s0006-3223(02)01546-9
Bouton, M. E. (2004). Context and behavioral processes in extinction. Learning & Memory, 11(5), 485-494. https://doi.org/10.1101/lm.78804
Bouton, M. E. ve Bolles, R. C. (1979). Contextual control of the extinction of conditioned fear. Learning and Motivation, 10(4), 445–466. https://doi.org/10.1016/0023-9690(79)90057-2
Bouton, M. E. ve Ricker, S. T. (1994). Renewal of extinguished responding in a second context. Animal Learning & Behavior, 22, 317-324. https://doi.org/10.3758/BF03209840
Briscione, M. A., Michopoulos, V., Jovanovic, T. ve Norrholm, S. D. (2017). Neuroendocrine Underpinnings of Increased Risk for Posttraumatic Stress Disorder in Women. In Vitamins and Hormones, 103, 53–83. https://doi.org/10.1016/bs.vh.2016.08.003
Brunet, A., Orr, S. P., Tremblay, J., Robertson, K., Nader, K. ve Pitman, R. K. (2008). Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. Journal of Psychiatric Research, 42(6), 503–506. https://doi.org/10.1016/j.jpsychires.2007.05.006
Brunet, A., Saumier, D., Liu, A., Streiner, D. L., Tremblay, J.ve Pitman, R. K. (2018). Reduction of PTSD symptoms with Pre-reactivation propranolol therapy: A randomized controlled trial. The American Journal of Psychiatry, 175(5), 427–433. https://doi.org/10.1176/appi.ajp.2017.17050481
Cahill, L., Prins, B., Weber, M. ve McGaugh, J. L. (1994). Beta-adrenergic activation and memory for emotional events. Nature, 371(6499), 702–704. https://doi.org/10.1038/371702a0
Chen, L., Huang, S., Yang, C., Wu, F., Zheng, Q., Yan, H., Yan, J., Luo, Y. ve Galaj, E. (2021). Blockade of β-Adrenergic Receptors by Propranolol Disrupts Reconsolidation of Drug Memory and Attenuates Heroin Seeking. Frontiers In Pharmacology, 12, 686845. https://doi.org/10.3389/fphar.2021.686845
Christiansen, D. M. ve Hansen, M. (2015). Accounting for sex differences in PTSD: A multi-variable mediation model. European Journal Of Psychotraumatology, 6, 26068. https://doi.org/10.3402/ejpt.v6.26068
Davis, M. (1997). Neurobiology of fear responses: The role of the amygdala. The Journal of Neuropsychiatry and Clinical Neurosciences, 9(3), 382–402. https://doi.org/10.1176/jnp.9.3.382
Delgado, M. R., Olsson, A. ve Phelps, E. A. (2006). Extending animal models of fear conditioning to humans. Biological Psychology, 73(1), 39–48. https://doi.org/10.1016/j.biopsycho.2006.01.006
Duvarcı, S. ve Nader, K. (2004). Characterization of fear memory reconsolidation. Journal of Neuroscience, 24(42), 9269–9275. https://doi.org/10.1523/JNEUROSCI.2971-04.2004
Fendt, M. ve Fanselow, M. S. (1999). The neuroanatomical and neurochemical basis of conditioned fear. Neuroscience and Biobehavioral Reviews, 23(5), 743–760. https://doi.org/10.1016/s0149-7634(99)00016-0
Finnie, P. S. B. ve Nader, K. (2012). The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation. Neuroscience & Biobehavioral Reviews, 36(7), 1667–1707. https://doi.org/10.1016/j.neubiorev.2012.03.008
Furmark, T., Fischer, H., Wik, G., Larsson, M. ve Fredrikson, M. (1997). The amygdala and individual differences in human fear conditioning. Neuroreport, 8(18), 3957–3960. https://doi.org/10.1097/00001756-199712220-00021
Goodman, J. ve Packard, M. G. (2019). There Is More Than One Kind of Extinction Learning. Frontiers in Systems Neuroscience, 13, 16. https://doi.org/10.3389/fnsys.2019.00016
Hassija, C. M. ve Gray, M. J. (2007). Behavioral interventions for trauma and posttraumatic stress disorder. International Journal of Behavioral Consultation and Therapy, 3(2), 166-175. http://dx.doi.org/10.1037/h0100797
Holmes, E. A., James, E. L., Coode-Bate, T. ve Deeprose, C. (2009). Can playing the computer game "Tetris" reduce the build-up of flashbacks for trauma? A proposal from cognitive science. PloS One, 4(1), e4153. https://doi.org/10.1371/journal.pone.0004153
Kimerling, R., Ouimette, P. ve Wolfe, J. (Edl.). (2002). Gender and PTSD. Guilford Press.
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