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Stress-related cognitive style is related to volumetric change of the hippocampus and FK506 binding protein 5 polymorphism in post-traumatic stress disorder

Published online by Cambridge University Press:  07 September 2020

Je-Yeon Yun ,
Min Jin Jin ,
Sungkean Kim  and
Seung-Hwan Lee Open the ORCID record for Seung-Hwan Lee [Opens in a new window]
Je-Yeon Yun
Affiliation:
Seoul National University Hospital, Seoul, Republic of Korea Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea
Min Jin Jin
Affiliation:
Department of Psychiatry, Wonkwang University Hospital, Iksan, Republic of Korea Institute of General Education, Kongju National University, Gongju, Republic of Korea
Sungkean Kim
Affiliation:
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
Seung-Hwan Lee*
Affiliation:
Clinical Emotion and Cognition Research Clinical Emotion and Cognition Research Laboratory, Inje University, Goyang, Republic of Korea Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
*
Author for correspondence: Seung-Hwan Lee, E-mail: [email protected]
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Abstract

Background

Patients with post-traumatic stress disorder (PTSD) show a different stress-related cognitive style compared with healthy controls (HC). The FK506 binding protein 5 gene (FKBP5), one of the PTSD known risk factors, is involved in the stress response through the hypothalamic-pituitary-adrenal axis and brain volumetric alterations. The present study aimed to uncover the neural correlates of stress-related cognitive styles through the analysis of the regional brain volumes and FKBP5 genotype in patients with PTSD compared with HC.

Methods

In this study, 51 patients with PTSD and 94 HC were assessed for stress-related cognitive styles, PTSD symptoms severity, and genotype of FKBP5 single nucleotide polymorphisms, and underwent T1-weighted structural magnetic resonance imaging. Diagnosis-by-genotype interaction for regional brain volumes was examined in 16 brain regions of interest.

Results

Patients with PTSD showed significantly higher levels of catastrophizing, ruminative response, and repression, and reduced distress aversion and positive reappraisal compared with HC (p < 0.001). Significant diagnosis-by-genotype interactions for regional brain volumes were observed for bilateral hippocampi and left frontal operculum. A significant positive correlation between the severity of the repression and left hippocampal volume was found in a subgroup of patients with PTSD with FKBP5 rs3800373 (AA genotype) or rs1360780 (CC genotype).

Conclusions

The present study showed the influences of FKBP5 genotype on the distorted cognitive styles in PTSD by measuring the volumetric alteration of hippocampal regions, providing a possible role of the hippocampus and left frontal operculum as significant neurobiological correlates of PTSD.

Keywords

FK506 binding protein 5 gene (FKBP5)hippocampuspost-traumatic stress disorderstress-related cognitive style
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 7 , May 2022 , pp. 1243 - 1254
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Afifi, T. O., Asmundson, G. J., Taylor, S., & Jang, K. L. (2010). The role of genes and environment on trauma exposure and posttraumatic stress disorder symptoms: A review of twin studies. Clinical Psychology Review, 30, 101–112.CrossRefGoogle ScholarPubMed
Beck, A. T., & Kovacs, M. (1979). Assessment of suicidal intention: The scale for suicide ideation. Journal of Consulting and Clinical Psychology, 47, 343–352.CrossRefGoogle ScholarPubMed
Benjet, C., Bromet, E., Karam, E. G., Kessler, R. C., McLaughlin, K. A., Ruscio, A. M., … Koenen, K. C. (2016). The epidemiology of traumatic event exposure worldwide: Results from the world mental health survey consortium. Psychological Medicine, 46, 327–343.CrossRefGoogle ScholarPubMed
Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C., Mercer, K. B., … Ressler, K. J. (2008). Association of fkbp5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299, 1291–1305.CrossRefGoogle ScholarPubMed
Butler, O., Herr, K., Willmund, G., Gallinat, J., Zimmermann, P., & Kuhn, S. (2018). Neural correlates of response bias: Larger hippocampal volume correlates with symptom aggravation in combat-related posttraumatic stress disorder. Psychiatry Research Neuroimaging, 279, 1–7.CrossRefGoogle ScholarPubMed
Carvalho, C. M., Coimbra, B. M., Ota, V. K., Mello, M. F., & Belangero, S. I. (2017). Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis as risk factors for posttraumatic stress disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 174, 671–682.CrossRefGoogle Scholar
Chawla, N., & Ostafin, B. (2007). Experiential avoidance as a functional dimensional approach to psychopathology: An empirical review. Journal of Clinical Psychology, 63, 871–890.CrossRefGoogle Scholar
Chen, X., Chen, Z., Dong, Z., Liu, M., & Yu, S. (2018). Morphometric changes over the whole brain in caffeine-containing combination-analgesic-overuse headache. Molecular Pain, 14, 1744806918778641.CrossRefGoogle ScholarPubMed
Elman, I., Lowen, S., Frederick, B. B., Chi, W., Becerra, L., & Pitman, R. K. (2009). Functional neuroimaging of reward circuitry responsivity to monetary gains and losses in posttraumatic stress disorder. Biological Psychiatry, 66, 1083–1090.CrossRefGoogle ScholarPubMed
Fani, N., King, T. Z., Reiser, E., Binder, E. B., Jovanovic, T., Bradley, B., & Ressler, K. J. (2014). Fkbp5 genotype and structural integrity of the posterior cingulum. Neuropsychopharmacology, 39, 1206–1213.CrossRefGoogle ScholarPubMed
Fani, N., King, T. Z., Shin, J., Srivastava, A., Brewster, R. C., Jovanovic, T., … Ressler, K. J. (2016). Structural and functional connectivity in posttraumatic stress disorder: Associations with fkbp5. Depression and Anxiety, 33, 300–307.CrossRefGoogle ScholarPubMed
Fanselow, M. S., & LeDoux, J. E. (1999). Why we think plasticity underlying pavlovian fear conditioning occurs in the basolateral amygdala. Neuron, 23, 229–232.CrossRefGoogle ScholarPubMed
Fitzgerald, J. M., Gorka, S. M., Kujawa, A., DiGangi, J. A., Proescher, E., Greenstein, J. E., … Phan, K. L. (2018). Neural indices of emotional reactivity and regulation predict course of PTSD symptoms in combat-exposed veterans. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 82, 255–262.CrossRefGoogle ScholarPubMed
Gamez, W., Chmielewski, M., Kotov, R., Ruggero, C., & Watson, D. (2011). Development of a measure of experiential avoidance: The multidimensional experiential avoidance questionnaire. Psychological Assessment, 23, 692–713.CrossRefGoogle ScholarPubMed
Garfinkel, S. N., Abelson, J. L., King, A. P., Sripada, R. K., Wang, X., Gaines, L. M., & Liberzon, I. (2014). Impaired contextual modulation of memories in PTSD: An fMRI and psychophysiological study of extinction retention and fear renewal. The Journal of Neuroscience, 34, 13435–13443.CrossRefGoogle ScholarPubMed
Garnefski, N., & Kraaij, V. (2007). The cognitive emotion regulation questionnaire: Psychometric features and prospective relationships with depression and anxiety in adults. European Journal of Psychological Assessment, 23, 141–149.CrossRefGoogle Scholar
Gellatly, R., & Beck, A. T. (2016). Catastrophic thinking: A transdiagnostic process across psychiatric disorders. Cognitive Therapy and Research, 40, 441–452.CrossRefGoogle Scholar
Ghasemi, M., Kordi, M., Asgharipour, N., Esmaeili, H., & Amirian, M. (2017). The effect of a positive reappraisal coping intervention and problem-solving skills training on coping strategies during waiting period of iui treatment: An rct. International Journal of Reproductive Biomedicine (Yazd, Iran), 15, 687–696.Google Scholar
Haukoos, J. S., & Lewis, R. J. (2005). Advanced statistics: Bootstrapping confidence intervals for statistics with ‘difficult’ distributions. Academic Emergency Medicine, 12, 360–365.CrossRefGoogle ScholarPubMed
Hawn, S. E., Sheerin, C. M., Lind, M. J., Hicks, T. A., Marraccini, M. E., Bountress, K., … Amstadter, A. B. (2019). Gxe effects of fkbp5 and traumatic life events on PTSD: A meta-analysis. Journal of Affective Disorders, 243, 455–462.CrossRefGoogle ScholarPubMed
Hayes, S. C., Wilson, K. G., Gifford, E. V., Follette, V. M., & Strosahl, K. (1996). Experimental avoidance and behavioral disorders: A functional dimensional approach to diagnosis and treatment. Journal of Consulting and Clinical Psychology, 64, 1152–1168.CrossRefGoogle ScholarPubMed
Holmes, S. E., Girgenti, M. J., Davis, M. T., Pietrzak, R. H., DellaGioia, N., Nabulsi, N., … Esterlis, I. (2017). Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings of the National Academy of Sciences of the United States of America, 114, 8390–8395.CrossRefGoogle ScholarPubMed
Hulbert, J. C., Henson, R. N., & Anderson, M. C. (2016). Inducing amnesia through systemic suppression. Nature Communications, 7, 11003.CrossRefGoogle ScholarPubMed
Jaspar, M., Manard, M., Dideberg, V., Bours, V., Maquet, P., & Collette, F. (2016). Influence of COMT genotype on antero-posterior cortical functional connectivity underlying interference resolution. Cerebral Cortex (New York, N.Y.: 1991), 26, 498–509.Google ScholarPubMed
Joseph, R. (1998). Traumatic amnesia, repression, and hippocampus injury due to emotional stress, corticosteroids and enkephalins. Child Psychiatry and Human Development, 29, 169–185.CrossRefGoogle ScholarPubMed
Kim, S. H. (2004). A study on relationships among the stressful events, cognntive emotion regulation strategies and psychological well-being. The Catholic University of Korea, Seoul, Republic of Korea.Google Scholar
Kim, S., Jeon, H., Jang, K. I., Kim, Y. W., Im, C. H., & Lee, S. H. (2019). Mismatch negativity and cortical thickness in patients with schizophrenia and bipolar disorder. Schizophrenia Bulletin, 45(2), 425–435.CrossRefGoogle ScholarPubMed
Kim, S. J., Kim, J. H., & Youn, S. C. (2010). Validation of the Korean-ruminative response scale (K-RRS). Korean Journal of Clinical Psychology, 29, 1–19.Google Scholar
Kim, S. J., Kwon, J. H., Yang, E. J., Kim, J. H., Yoo, B. H., & Lee, D. S. (2013). Confirmatory factor analysis of Korean-ruminative response scale in patients with depressive disorders. Cognitive Behavioral Therapy in Korea, 13, 133–147.Google Scholar
King, A. P., Block, S. R., Sripada, R. K., Rauch, S., Giardino, N., Favorite, T., … Liberzon, I. (2016). Altered default mode network (DMN) resting state functional connectivity following a mindfulness-based exposure therapy for posttraumatic stress disorder (PTSD) in combat veterans of Afghanistan and Iraq. Depression and Anxiety, 33, 289–299.CrossRefGoogle ScholarPubMed
Kocsel, N., Szabo, E., Galambos, A., Edes, A., Pap, D., Elliott, R., … Kokonyei, G. (2017). Trait rumination influences neural correlates of the anticipation but not the consumption phase of reward processing. Frontiers in Behavioral Neuroscience, 11, 85.CrossRefGoogle Scholar
Lappalainen, T., & Greally, J. M. (2017). Associating cellular epigenetic models with human phenotypes. Nature Reviews Genetics, 18, 441–451.CrossRefGoogle ScholarPubMed
Levy-Gigi, E., Szabo, C., Kelemen, O., & Keri, S. (2013). Association among clinical response, hippocampal volume, and fkbp5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biological Psychiatry, 74, 793–800.CrossRefGoogle ScholarPubMed
Liberzon, I., & Abelson James, L. (2016). Context processing and the neurobiology of post-traumatic stress disorder. Neuron, 92, 14–30.CrossRefGoogle ScholarPubMed
Logue, M. W., van Rooij, S. J. H., Dennis, E. L., Davis, S. L., Hayes, J. P., Stevens, J. S., … Morey, R. A. (2018). Smaller hippocampal volume in posttraumatic stress disorder: A multisite enigma-PGC study: Subcortical volumetry results from posttraumatic stress disorder consortia. Biological Psychiatry, 83, 244–253.CrossRefGoogle ScholarPubMed
Loureiro, M., Kramar, C., Renard, J., Rosen, L. G., & Laviolette, S. R. (2016). Cannabinoid transmission in the hippocampus activates nucleus accumbens neurons and modulates reward and aversion-related emotional salience. Biological Psychiatry, 80, 216–225.CrossRefGoogle ScholarPubMed
Marin, M. F., Song, H., VanElzakker, M. B., Staples-Bradley, L. K., Linnman, C., Pace-Schott, E. F., … Milad, M. R. (2016). Association of resting metabolism in the fear neural network with extinction recall activations and clinical measures in trauma-exposed individuals. American Journal of Psychiatry, 173, 930–938.CrossRefGoogle ScholarPubMed
McNerney, M. W., Sheng, T., Nechvatal, J. M., Lee, A. G., Lyons, D. M., Soman, S., … Adamson, M. M. (2018). Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation. PLoS ONE, 13, e0192222.CrossRefGoogle ScholarPubMed
Musazzi, L., Tornese, P., Sala, N., & Popoli, M. (2018). What acute stress protocols can tell us about PTSD and stress-related neuropsychiatric disorders. Frontiers in Pharmacology, 9, 758.CrossRefGoogle ScholarPubMed
Namburi, P., Al-Hasani, R., Calhoon, G. G., Bruchas, M. R., & Tye, K. M. (2016). Architectural representation of valence in the limbic system. Neuropsychopharmacology, 41, 1697–1715.CrossRefGoogle ScholarPubMed
Nelson, M. D., & Tumpap, A. M. (2017). Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: A meta-analytic study. CNS Spectrums, 22, 363–372.CrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S. (1991). Responses to depression and their effects on the duration of depressive episodes. Journal of Abnormal Psychology, 100, 569–582.CrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S., & Morrow, J. (1991). A prospective study of depression and posttraumatic stress symptoms after a natural disaster: The 1989 Loma Prieta earthquake. Journal of Personality and Social Psychology, 61, 115–121.CrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S., Wisco, B. E., & Lyubomirsky, S. (2008). Rethinking rumination. Perspectives on Psychological Science, 3, 400–424.CrossRefGoogle ScholarPubMed
Oh, S. M., Min, K. J., & Park, D. B. (1999). A study on the standardization of the hospital anxiety and depression scale of Koreans. Journal of Korean Neuropsychiatric Association, 38, 289–296.Google Scholar
Panizzon, M. S., Fennema-Notestine, C., Eyler, L. T., Jernigan, T. L., Prom-Wormley, E., Neale, M., … Kremen, W. S. (2009). Distinct genetic influences on cortical surface area and cortical thickness. Cerebral Cortex (New York. NY), 19, 2728–2735.Google ScholarPubMed
Park, M. R. (2013). Experiential avoidance and emotional coping ability on posttraumatic growth. Department of Psychiatry, Chungbuk University, Republic of Korea.Google Scholar
Pernet, C. R., Wilcox, R. R., & Rousselet, G. A. (2013). Robust correlation analyses: False positive and power validation using a new open source matlab toolbox. Frontiers in Psychology, 3, 606.CrossRefGoogle ScholarPubMed
Qiao, L., Wei, D. T., Li, W. F., Chen, Q. L., Che, X. W., Li, B. B., … Liu, Y. J. (2013). Rumination mediates the relationship between structural variations in ventrolateral prefrontal cortex and sensitivity to negative life events. Neuroscience, 255, 255–264.CrossRefGoogle ScholarPubMed
Rangaprakash, D., Dretsch, M. N., Venkataraman, A., Katz, J. S., Denney, T. S. Jr., & Deshpande, G. (2018). Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma. Human Brain Mapping, 39, 264–287.CrossRefGoogle ScholarPubMed
Ruscio, J. (2008). Constructing confidence intervals for Spearman's rank correlation with ordinal data: A simulation study comparing analytic and bootstrap methods. Journal of Modern Applied Statistical Methods, 7, 7.CrossRefGoogle Scholar
Scheuer, S., Ising, M., Uhr, M., Otto, Y., von Klitzing, K., & Klein, A. M. (2016). Fkbp5 polymorphisms moderate the influence of adverse life events on the risk of anxiety and depressive disorders in preschool children. Journal of Psychiatric Research, 72, 30–36.CrossRefGoogle ScholarPubMed
Schleinitz, D., DiStefano, J. K., & Kovacs, P. (2011). Targeted SNP genotyping using the taqman® assay. In DiStefano, J. K. (Ed.), Disease gene identification: Methods and protocols (pp. 77–87). Totowa, NJ: Humana Press.CrossRefGoogle Scholar
Schlund, M. W., Magee, S., & Hudgins, C. D. (2011). Human avoidance and approach learning: Evidence for overlapping neural systems and experiential avoidance modulation of avoidance neurocircuitry. Behavioural Brain Research, 225, 437–448.CrossRefGoogle ScholarPubMed
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., … Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27, 2349–2356.CrossRefGoogle ScholarPubMed
Shalev, A., Liberzon, I., & Marmar, C. (2017). Post-traumatic stress disorder. The New England Journal of Medicine, 376, 2459–2469.CrossRefGoogle ScholarPubMed
Shin, M. S., Park, K. B., Oh, K. J., & Kim, Z. S. (1990). A study of suicidal ideation among high school students: The structural relation among depression, hopelessness, and suicidal ideation. Korean Journal of Clinical Psychology, 9, 1–19.Google Scholar
Shou, H., Yang, Z., Satterthwaite, T. D., Cook, P. A., Bruce, S. E., Shinohara, R. T., … Sheline, Y. I. (2017). Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD. NeuroImage Clinical, 14, 464–470.CrossRefGoogle ScholarPubMed
Stein, M. B., Jang, K. L., Taylor, S., Vernon, P. A., & Livesley, W. J. (2002). Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: A twin study. American Journal of Psychiatry, 159, 1675–1681.CrossRefGoogle ScholarPubMed
Stevens, J. S., Reddy, R., Kim, Y. J., van Rooij, S. J. H., Ely, T. D., Hamann, S., … Jovanovic, T. (2018). Episodic memory after trauma exposure: Medial temporal lobe function is positively related to re-experiencing and inversely related to negative affect symptoms. NeuroImage Clinical, 17, 650–658.CrossRefGoogle ScholarPubMed
Stice, E., Yokum, S., Burger, K. S., Epstein, L. H., & Small, D. M. (2011). Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. The Journal of Neuroscience, 31, 4360–4366.CrossRefGoogle Scholar
Sullivan, D. R., Marx, B., Chen, M. S., Depue, B. E., Hayes, S. M., & Hayes, J. P. (2019). Behavioral and neural correlates of memory suppression in PTSD. Journal of Psychiatric Research, 112, 30–37.CrossRefGoogle ScholarPubMed
Tamman, A. J. F., Sippel, L. M., Han, S., Neria, Y., Krystal, J. H., Southwick, S. M., … Pietrzak, R. H. (2019). Attachment style moderates effects of fkbp5 polymorphisms and childhood abuse on post-traumatic stress symptoms: Results from the national health and resilience in veterans study. The World Journal of Biological Psychiatry, 20(4), 289–300.CrossRefGoogle ScholarPubMed
Tovote, P., Fadok, J. P., & Lüthi, A. (2015). Neuronal circuits for fear and anxiety. Nature Reviews Neuroscience, 16, 317.CrossRefGoogle ScholarPubMed
Tozzi, L., Carballedo, A., Wetterling, F., McCarthy, H., O'Keane, V., Gill, M., … Frodl, T. (2016). Single-nucleotide polymorphism of the fkbp5 gene and childhood maltreatment as predictors of structural changes in brain areas involved in emotional processing in depression. Neuropsychopharmacology, 41, 487–497.CrossRefGoogle ScholarPubMed
Treynor, W., Gonzalez, R., & Nolen-Hoeksema, S. (2003). Rumination reconsidered: A psychometric analysis. Cognitive Therapy and Research, 27, 247–259.CrossRefGoogle Scholar
Weathers, F. W., Blake, D. D., Schnurr, P. P., Kaloupek, D. G., Marx, B. P., & Keane, T. M. (2013a). The clinician-administered PTSD scale for DSM-5 (caps-5).Google Scholar
Weathers, F. W., Blake, D. D., Schnurr, P. P., Kaloupek, D. G., Marx, B. P., & Keane, T. M/ (2013b). The life events checklist for DSM-5 (lec-5).Google Scholar
Weathers, F. W., Litz, B. T., Keane, T. M., Palmieri, P. A., Marx, B. P., & Schnurr, P.P. (2013c). The PTSD checklist for DSM-5 (pcl-5).Google Scholar
Woon, F. L., Sood, S., & Hedges, D. W. (2010). Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: A meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34, 1181–1188.CrossRefGoogle ScholarPubMed
Zhang, X. D., Yin, Y., Hu, X. L., Duan, L., Qi, R., Xu, Q., … Li, L. J. (2017). Altered default mode network configuration in posttraumatic stress disorder after earthquake: A resting-stage functional magnetic resonance imaging study. Medicine, 96, e7826.CrossRefGoogle ScholarPubMed
Zigmond, A. S., & Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67, 361–370.CrossRefGoogle ScholarPubMed
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