Hostname: page-component-848d4c4894-ndmmz Total loading time: 0 Render date: 2024-06-01T07:41:04.265Z Has data issue: false hasContentIssue false
  • English
  • Français

Childhood trauma and amygdala nuclei volumes in youth at risk for mental illness

Published online by Cambridge University Press:  17 September 2020

Nikita Nogovitsyn Open the ORCID record for Nikita Nogovitsyn [Opens in a new window] ,
Jean Addington ,
Roberto Souza ,
Thea J. Placsko ,
Jacqueline Stowkowy ,
JianLi Wang ,
Benjamin I. Goldstein ,
Signe Bray ,
Catherine Lebel  and
Valerie H. Taylor
...Show all authors
Nikita Nogovitsyn*
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Jean Addington
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Roberto Souza
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Thea J. Placsko
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Jacqueline Stowkowy
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
JianLi Wang
Affiliation:
Work & Mental health Research Unit, Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Benjamin I. Goldstein
Affiliation:
Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Departments of Psychiatry and Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Signe Bray
Affiliation:
Department of Radiology, University of Calgary, Calgary, Alberta, Canada Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada Child & Adolescent Imaging Research (CAIR) Program, Calgary, Alberta, Canada
Catherine Lebel
Affiliation:
Department of Radiology, University of Calgary, Calgary, Alberta, Canada Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada Child & Adolescent Imaging Research (CAIR) Program, Calgary, Alberta, Canada
Valerie H. Taylor
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
Sidney H. Kennedy
Affiliation:
Department of Psychiatry, University Health Network, Toronto, Ontario, Canada Department of Psychiatry, St. Michael's Hospital, Toronto, Ontario, Canada Arthur Sommer Rotenberg Chair in Suicide and Depression Studies, St. Michael's Hospital, Toronto, Ontario, Canada Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
Glenda MacQueen
Affiliation:
Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
*
Author for correspondence: Nikita Nogovitsyn, E-mail: n.nogovitsyn@ucalgary.ca
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth.

Methods

Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure.

Results

Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment.

Conclusion

The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.

Keywords

Adolescenceamygdalaanxietyclinical high riskdepressionrisktrauma
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 6 , April 2022 , pp. 1192 - 1199
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aas, M., Navari, S., Gibbs, A., Mondelli, V., Fisher, H. L., Morgan, C., … Dazzan, P. (2012). Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis? Schizophrenia Research, 137(1–3), 73–79.CrossRefGoogle Scholar
Abdi, H., & Williams, L. J. (2010). Principal component analysis. Wiley Interdisciplinary Reviews: Computational Statistics, 2(4), 433–459. doi:10.1002/wics.101.CrossRefGoogle Scholar
Addington, J., Goldstein, B. I., Wang, J. L., Kennedy, S. H., Bray, S., Lebel, C., … MacQueen, G. (2018). Youth at-risk for serious mental illness: Methods of the PROCAN study. BMC Psychiatry, 18(1), 219.CrossRefGoogle ScholarPubMed
Addington, J., Liu, L., Goldstein, B. I., Wang, J., Kennedy, S. H., Bray, S., … MacQueen, G. (2019). Clinical staging for youth at-risk for serious mental illness. Early Intervention in Psychiatry, 13(6), 1416–1423.CrossRefGoogle ScholarPubMed
Andersen, S. L., Tomada, A., Vincow, E. S., Valente, E., Polcari, A., & Teicher, M. H. (2008). Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. The Journal of Neuropsychiatry and Clinical Neurosciences, 20(3), 292–301.CrossRefGoogle ScholarPubMed
Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561–571.CrossRefGoogle ScholarPubMed
Calem, M., Bromis, K., McGuire, P., Morgan, C., & Kempton, M. J. (2017). Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples. NeuroImage: Clinical, 14, 471–479.CrossRefGoogle ScholarPubMed
Carr, C. P., Martins, C. M. S., Stingel, A. M., Lemgruber, V. B., & Juruena, M. F. (2013). The role of early life stress in adult psychiatric disorders. The Journal of Nervous and Mental Disease, 201(12), 1007–1020.CrossRefGoogle ScholarPubMed
Davidson, R. J., & McEwen, B. S. (2012). Social influences on neuroplasticity: Stress and interventions to promote well-being. Nature Neuroscience, 15(5), 689–695.CrossRefGoogle ScholarPubMed
Dear, B. F., Titov, N., Sunderland, M., McMillan, D., Anderson, T., Lorian, C., & Robinson, E. (2011). Psychometric comparison of the generalized anxiety disorder scale-7 and the Penn state worry questionnaire for measuring response during treatment of generalised anxiety disorder. Cognitive Behaviour Therapy, 40(3), 216–227.CrossRefGoogle ScholarPubMed
Gerritsen, L., Kalpouzos, G., Westman, E., Simmons, A., Wahlund, L.-O., Bäckman, L., … Wang, H.-X. (2015). The influence of negative life events on hippocampal and amygdala volumes in old age: A life-course perspective. Psychological Medicine, 45(6), 1219–1228.CrossRefGoogle ScholarPubMed
Gorka, A. X., Hanson, J. L., Radtke, S. R., & Hariri, A. R. (2014). Reduced hippocampal and medial prefrontal gray matter mediate the association between reported childhood maltreatment and trait anxiety in adulthood and predict sensitivity to future life stress. Biology of Mood & Anxiety Disorders, 4(1), 12.CrossRefGoogle ScholarPubMed
Grant, M. M., Cannistraci, C., Hollon, S. D., Gore, J., & Shelton, R. (2011). Childhood trauma history differentiates amygdala response to sad faces within MDD. Journal of Psychiatric Research, 45(7), 886–895.CrossRefGoogle ScholarPubMed
Guadagno, A., Wong, T. P., & Walker, C. D. (2018). Morphological and functional changes in the preweaning basolateral amygdala induced by early chronic stress associate with anxiety and fear behavior in adult male, but not female rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 81, 25–37. doi:10.1016/j.pnpbp.2017.09.025.CrossRefGoogle Scholar
Hayes, A. F. (2015). An index and test of linear moderated mediation. Multivariate Behavioral Research, 50(1), 1–22.CrossRefGoogle ScholarPubMed
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biological Psychiatry, 49(12), 1023–1039.CrossRefGoogle ScholarPubMed
Hibar, D. P., Westlye, L. T., Van Erp, T. G. M. M., Rasmussen, J., Leonardo, C. D., Faskowitz, J., … Andreassen, O. A. (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry, 21(12), 1710–1716. doi:10.1038/mp.2015.227.CrossRefGoogle ScholarPubMed
Hoy, K., Barrett, S., Shannon, C., Campbell, C., Watson, D., Rushe, T., … Mulholland, C. (2012). Childhood trauma and hippocampal and amygdalar volumes in first-episode psychosis. Schizophrenia Bulletin, 38(6), 1162–1169.CrossRefGoogle ScholarPubMed
Iglesias, J. E., Augustinack, J. C., Nguyen, K., Player, C. M., Player, A., Wright, M., … Van Leemput, K. (2015). A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI. NeuroImage, 115, 117–137.CrossRefGoogle ScholarPubMed
Janak, P. H., & Tye, K. M. (2015). From circuits to behaviour in the amygdala. Nature, 517(7534), 284–292.CrossRefGoogle ScholarPubMed
Janssen, I., Krabbendam, L., Bak, M., Hanssen, M., Vollebergh, W., de Graaf, R., & van Os, J. (2004). Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatrica Scandinavica, 109(1), 38–45.CrossRefGoogle ScholarPubMed
Kessler, R. C., Andrews, G., Colpe, L. J., Hiripi, E., Mroczek, D. K., Normand, S. L. T., … Zaslavsky, A. M. (2002). Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychological Medicine, 32(6), 959–976.CrossRefGoogle ScholarPubMed
Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., … Williams, D. R. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. British Journal of Psychiatry, 197(5), 378–385.CrossRefGoogle ScholarPubMed
Kuhn, M., & Johnson, K. (2013). Applied predictive modeling (Vol. 26). New York: Springer.CrossRefGoogle Scholar
LoPilato, A. M., Goines, K., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., … Walker, E. F. (2019). Impact of childhood adversity on corticolimbic volumes in youth at clinical high-risk for psychosis. Schizophrenia Research, 213, 48–55. doi:10.1016/j.schres.2019.01.048.CrossRefGoogle ScholarPubMed
Lupien, S. J., Juster, R.-P., Raymond, C., & Marin, M.-F. (2018). The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Frontiers in Neuroendocrinology, 49, 91–105. doi:10.1016/J.YFRNE.2018.02.001.CrossRefGoogle ScholarPubMed
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10(6), 434–445. doi:10.1038/nrn2639.CrossRefGoogle ScholarPubMed
Mackinnon, D. P., Warsi, G., & Dwyer, J. H. (1995). A simulation study of mediated effect measures. Multivariate Behavioral Research, 30(1), 41.CrossRefGoogle ScholarPubMed
Macqueen, G. M., Hassel, S., Arnott, S. R., Addington, J., Bowie, C. R., Bray, S. L., … Kennedy, S. H. (2019). The Canadian Biomarker Integration Network in Depression (CAN-BIND): Magnetic resonance imaging protocols. Journal of Psychiatry & Neuroscience, 44(4), 223–236.CrossRefGoogle ScholarPubMed
Malykhin, N. V., Carter, R., Hegadoren, K. M., Seres, P., & Coupland, N. J. (2012). Fronto-limbic volumetric changes in major depressive disorder. Journal of Affective Disorders, 136(3), 1104–1113.CrossRefGoogle ScholarPubMed
McGlashan, T. H., Walsh, B., & Woods, S. (2010). The psychosis-risk syndrome: Handbook for diagnosis and follow-up. New York: Oxford University Press.Google Scholar
McGorry, P. D., Hickie, I. B., Yung, A. R., Pantelis, C., & Jackson, H. J. (2006). Clinical staging of psychiatric disorders: A heuristic framework for choosing earlier, safer and more effective interventions. Australian and New Zealand Journal of Psychiatry, 40(8), 616–622.CrossRefGoogle ScholarPubMed
Morgan, C., & Fisher, H. (2006). Environment and schizophrenia: Environmental factors in schizophrenia: Childhood trauma--A critical review. Schizophrenia Bulletin, 33(1), 3–10.CrossRefGoogle ScholarPubMed
Olivares, J., García-López, L. J., & Hidalgo, M. D. (2001). The social phobia scale and the social interaction anxiety scale: Factor structure and reliability in a Spanish-speaking population. Journal of Psychoeducational Assessment, 19(1), 69–80.CrossRefGoogle Scholar
Oshri, A., Gray, J. C., Owens, M. M., Liu, S., Duprey, E. B., Sweet, L. H., & MacKillop, J. (2019). Adverse childhood experiences and amygdalar reduction: High-resolution segmentation reveals associations with subnuclei and psychiatric outcomes. Child Maltreatment, 24(4), 400–410. doi:107755951983949.CrossRefGoogle ScholarPubMed
Paquola, C., Bennett, M. R., & Lagopoulos, J. (2016). Understanding heterogeneity in grey matter research of adults with childhood maltreatment—A meta-analysis and review. Neuroscience & Biobehavioral Reviews, 69, 299–312.CrossRefGoogle ScholarPubMed
Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48, 175–187.CrossRefGoogle ScholarPubMed
Rau, A. R., Chappell, A. M., Butler, T. R., Ariwodola, O. J., & Weiner, J. L. (2015). Increased basolateral amygdala pyramidal cell excitability may contribute to the anxiogenic phenotype induced by chronic early-life stress. Journal of Neuroscience, 35(26), 9730–9740.CrossRefGoogle Scholar
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., … Keller, M. B. (2003). The 16-item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression. Biological Psychiatry, 54(5), 573–583.CrossRefGoogle ScholarPubMed
Sah, P., Faber, E. S. L., Lopez De ArmentiaA, M., & Power, J. (2003). The amygdaloid complex: Anatomy and physiology. Physiological Reviews, 83(3), 803–834.CrossRefGoogle ScholarPubMed
Saygin, Z. M., Kliemann, D., Iglesias, J. E., van der Kouwe, A. J. W., Boyd, E., & Reuter, M., … Alzheimer's Disease Neuroimaging Initiative. (2017). High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: Manual segmentation to automatic atlas. NeuroImage, 155, 370–382.CrossRefGoogle ScholarPubMed
Stowkowy, J., Goldstein, B. I., MacQueen, G. M., Wang, J., Kennedy, S. H., Bray, S., … Addington, J. (2019). Trauma in youth at-risk for serious mental illness. The Journal of Nervous and Mental Disease, 208(1), 70–76.CrossRefGoogle Scholar
Teicher, M. H., & Parigger, A. (2015). The ‘maltreatment and abuse chronology of exposure’ (MACE) scale for the retrospective assessment of abuse and neglect during development. PLoS One, 10(2), e0117423. doi:10.1371/journal.pone.0117423.CrossRefGoogle ScholarPubMed
Teicher, M. H., & Samson, J. A. (2016). Annual research review: Enduring neurobiological effects of childhood abuse and neglect. Journal of Child Psychology and Psychiatry, 57(3), 241–266.CrossRefGoogle ScholarPubMed
Teicher, M. H., Samson, J. A., Anderson, C. M., & Ohashi, K. (2016). The effects of childhood maltreatment on brain structure, function and connectivity. Nature Reviews Neuroscience, 17, 652–666.CrossRefGoogle ScholarPubMed
Tripathi, S. J., Chakraborty, S., Srikumar, B. N. N., Raju, T. R. R., & Shankaranarayana Rao, B. S. S. (2019). Basolateral amygdalar inactivation blocks chronic stress-induced lamina-specific reduction in prefrontal cortex volume and associated anxiety-like behavior. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 88, 194–207. doi:10.1016/J.PNPBP.2018.07.016.CrossRefGoogle ScholarPubMed
Vyas, A., Bernal, S., & Chattarji, S. (2003). Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Research, 965(1–2), 290–294.CrossRefGoogle ScholarPubMed
Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S. (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. Journal of Neuroscience, 22(15), 6810–6818.CrossRefGoogle ScholarPubMed
Whittle, S., Dennison, M., Vijayakumar, N., Simmons, J. G., Yücel, M., Lubman, D. I., … Allen, N. B. (2013). Childhood maltreatment and psychopathology affect brain development during adolescence. Journal of the American Academy of Child & Adolescent Psychiatry, 52(9), 940–952.e1.CrossRefGoogle ScholarPubMed
Williams, L. M., Debattista, C., Duchemin, A.-M., Schatzberg, A. F., & Nemeroff, C. B. (2016). Childhood trauma predicts antidepressant response in adults with major depression: Data from the randomized international study to predict optimized treatment for depression. Translational Psychiatry, 6(5), e799–e799. doi:10.1038/tp.2016.61.CrossRefGoogle Scholar
Yang, H. (2013). The case for being automatic: Introducing the automatic linear modeling (LINEAR) procedure in SPSS statistics. Multiple Linear Regression Viewpoints, 39(2), 27–37.Google Scholar
Yang, R. J., Mozhui, K., Karlsson, R.-M., Cameron, H. A., Williams, R. W., & Holmes, A. (2008). Variation in mouse basolateral amygdala volume is associated with differences in stress reactivity and fear learning. Neuropsychopharmacology, 33(11), 2595–2604. doi:10.1038/sj.npp.1301665.CrossRefGoogle ScholarPubMed
Supplementary material: File

Nogovitsyn et al. supplementary material

Nogovitsyn et al. supplementary material 1

Download Nogovitsyn et al. supplementary material(File)
File 23.8 KB
Supplementary material: File

Nogovitsyn et al. supplementary material

Nogovitsyn et al. supplementary material 2

Download Nogovitsyn et al. supplementary material(File)
File 58.4 KB
Supplementary material: File

Nogovitsyn et al. supplementary material

Nogovitsyn et al. supplementary material 3

Download Nogovitsyn et al. supplementary material(File)
File 14.1 KB