Childhood trauma-related brain alterations in bipolar disorder: an ENIGMA-Bipolar Disorder study

Poster No:

458 

Submission Type:

Abstract Submission 

Authors:

Yann Quide1, Leonardo Tozzi2, Maria Dauvermann3, Emma Corley4, Andrea Fernandes4, Leila Nabulsi5, Roberto Goya-Maldonado6, Klaus Berger7, Marco Hermesdorf7, Tamsyn van Rheenen8, Elysha Ringin8, Susan Rossell9, Lisa Furlong8, Tilo Kircher10, Frederike Stein11, Udo Dannlowski12, Dominik Grotegerd12, Jair Soares13, Mon-Ju Wu14, Giovana Zunta-Soares14, Benson Mwangi14, Joaquim Radua15, Enric Vilajosana15, Eduard Vieta16, Melissa Green17, Francesco Benedetti18, Elisa Melloni18, Gloria Roberts19, Philip Mitchell19, Jonathan Savitz20, Lakshmi Yatham21, Josselin Houenou22, Marion Leboyer23, Sophia Thomopoulos5, Paul Thompson5, Yanghee Im5, Melody Kang5, Ole Andreassen24, Chris Ching5, Dara Cannon25

Institutions:

1School of Psychology, UNSW Sydney, Sydney, NSW, Australia, 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States, 3Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom, 4University of Galway, Ireland, Galway, Ireland, 5University of Southern California, Los Angeles, CA, United States, 6Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany, 7Institute of Epidemiology and Social Medicine, University of Muenster, Münster, North Rhine-Westphalia, Germany, 8Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia, 9Centre for Mental Health and Brain Sciences, Swinburne University, Melbourne, VIC, Australia, 10Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Hesse, Germany, 11Department of Psychiatry and Psychotherapy, University of Marburg, Germany, Marburg, Hesse, Germany, 12Institute for Translational Psychiatry, University of Münster, Münster, North Rhine-Westphalia, Germany, 13UT Health Science Center at Houston, Houston, TX, United States, 14UTHealth Houston, Houston, TX, United States, 15Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 16Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain, 17School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia, 18Psychiatry & Clinical Psychobiology, IRCCS Scientific Institute Ospedale San Raffaele, Milan, Italy, 19University of New South Wales, Sydney, NSW, Australia, 20Laureate Institute for Brain Research, Tulsa, OK, United States, 21University of British Columbia, Vancouver, BC, Canada, 22Université Paris-Saclay, Paris, France, 23INSERM U955 Team, Créteil, France, 24University of Oslo, Oslo, Norway, 25University of Galway, Galway, Ireland

First Author:

Yann Quide  
School of Psychology, UNSW Sydney
Sydney, NSW, Australia

Co-Author(s):

Leonardo Tozzi  
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine
Stanford, CA, United States
Maria Dauvermann  
Institute for Mental Health, School of Psychology, University of Birmingham
Birmingham, United Kingdom
Emma Corley  
University of Galway, Ireland
Galway, Ireland
Andrea Fernandes  
University of Galway, Ireland
Galway, Ireland
Leila Nabulsi  
University of Southern California
Los Angeles, CA, United States
Roberto Goya-Maldonado  
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen
Göttingen, Germany
Klaus Berger  
Institute of Epidemiology and Social Medicine, University of Muenster
Münster, North Rhine-Westphalia, Germany
Marco Hermesdorf  
Institute of Epidemiology and Social Medicine, University of Muenster
Münster, North Rhine-Westphalia, Germany
Tamsyn van Rheenen  
Department of Psychiatry, University of Melbourne
Melbourne, VIC, Australia
Elysha Ringin  
Department of Psychiatry, University of Melbourne
Melbourne, VIC, Australia
Susan Rossell  
Centre for Mental Health and Brain Sciences, Swinburne University
Melbourne, VIC, Australia
Lisa Furlong  
Department of Psychiatry, University of Melbourne
Melbourne, VIC, Australia
Tilo Kircher  
Department of Psychiatry and Psychotherapy, University of Marburg
Marburg, Hesse, Germany
Frederike Stein  
Department of Psychiatry and Psychotherapy, University of Marburg, Germany
Marburg, Hesse, Germany
Udo Dannlowski  
Institute for Translational Psychiatry, University of Münster
Münster, North Rhine-Westphalia, Germany
Dominik Grotegerd  
Institute for Translational Psychiatry, University of Münster
Münster, North Rhine-Westphalia, Germany
Jair Soares  
UT Health Science Center at Houston
Houston, TX, United States
Mon-Ju Wu  
UTHealth Houston
Houston, TX, United States
Giovana Zunta-Soares  
UTHealth Houston
Houston, TX, United States
Benson Mwangi  
UTHealth Houston
Houston, TX, United States
Joaquim Radua  
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Barcelona, Spain
Enric Vilajosana  
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Barcelona, Spain
Eduard Vieta  
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)
Barcelona, Spain
Melissa Green  
School of Clinical Medicine, UNSW Sydney
Sydney, NSW, Australia
Francesco Benedetti  
Psychiatry & Clinical Psychobiology, IRCCS Scientific Institute Ospedale San Raffaele
Milan, Italy
Elisa Melloni  
Psychiatry & Clinical Psychobiology, IRCCS Scientific Institute Ospedale San Raffaele
Milan, Italy
Gloria Roberts  
University of New South Wales
Sydney, NSW, Australia
Philip Mitchell  
University of New South Wales
Sydney, NSW, Australia
Jonathan Savitz  
Laureate Institute for Brain Research
Tulsa, OK, United States
Lakshmi Yatham  
University of British Columbia
Vancouver, BC, Canada
Josselin Houenou  
Université Paris-Saclay
Paris, France
Marion Leboyer  
INSERM U955 Team
Créteil, France
Sophia Thomopoulos  
University of Southern California
Los Angeles, CA, United States
Paul Thompson  
University of Southern California
Los Angeles, CA, United States
Yanghee Im  
University of Southern California
Los Angeles, CA, United States
Melody Kang  
University of Southern California
Los Angeles, CA, United States
Ole Andreassen  
University of Oslo
Oslo, Norway
Chris Ching  
University of Southern California
Los Angeles, CA, United States
Dara Cannon  
University of Galway
Galway, Ireland

Introduction:

Childhood trauma is experienced by more than 50% of people with severe psychiatric disorders (Devi et al., 2019; Xie et al., 2018) and is a major risk factor for bipolar disorder (BD) (Palmier-Claus et al., 2016). Previous studies have investigated associations between childhood trauma, brain morphology, and the likelihood of developing BD. However, most studies have been conducted in small samples using heterogeneous methods (e.g., different brain imaging processing methods, childhood trauma assessments), resulting in inconsistent findings (see Quidé et al., 2020, for a review). Our study from the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder working group (ENIGMA-BD) aims to determine the impact of childhood trauma on brain morphology in BD.

Methods:

Fifteen independent cross-sectional samples, including 744 BD cases (55% females) and 1810 healthy controls (HCs; 58% females) were collated via ENIGMA-BD. Severity of childhood trauma was measured using the Childhood Trauma Questionnaire (CTQ) (Bernstein et al., 2003) at all sites. Structural 3D T1-weighted brain MRI scans were processed using FreeSurfer (Fischl et al., 2002) and measures of subcortical volumes (16 regions), cortical thickness and surface area (68 regions from the Desikan-Killiany atlas; Desikan et al., 2006) were extracted. Data were quality-checked using standard ENIGMA pipelines and harmonised for site differences using ComBat (Radua et al., 2020). Linear regressions were used to determine the associations between BD diagnosis (BD versus HC), severity of childhood trauma (CTQ total scores) and their interaction on brain morphology. Age, sex, and total intracranial volumes (for subcortical volume analyses only) were included as covariates. False-Discovery Rate correction (q<0.05) was applied to account for the number of regions included (separate analyses for subcortical volumes, cortical thickness and surface area). Additional analyses investigated the associations of specific childhood trauma domains (emotional, physical, sexual abuse, and emotional and physical neglect) and their interactions with group on brain morphology, accounting for each other.

Results:

Fifty-nine percent of BD cases (N=440) and 31% of HCs (N=562) reported moderate-to-extreme levels of exposure to at least one type of trauma measured by the CTQ. A diagnosis of BD was significantly associated with larger bilateral lateral ventricles and smaller bilateral hippocampi and amygdalar volumes (all q<0.013), and with widespread patterns of thinner cortex (55 regions out of 68; all q<0.05). When examining the association between brain morphology and severity of the different childhood trauma domains, we found a significant group-by-sexual abuse interaction in the left medial orbitofrontal gyrus (mOFC; q=0.005). A subsequent moderation analysis indicated that the severity of sexual abuse was significantly associated with thicker mOFC in HCs (b=0.007, p<0.001), and with thinner mOFC in BD (b=-0.006, p=0.028).

Conclusions:

In the largest analysis to date, BD was associated with a widespread pattern of thinner cortex and smaller subcortical volumes, while childhood sexual abuse was associated with thinner mOFC in BD, and thicker mOFC in HCs. Thicker left mOFC in HCs may reflect compensatory or adaptative mechanisms in relation to resilience to childhood sexual abuse, whereas thinner mOFC in BD may reflect maladaptive mechanisms, potentially underlining commonly reported aberrant emotion regulation in BD. Future functional studies are underway to confirm this interpretation.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Modeling and Analysis Methods:

Multivariate Approaches 2

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Anatomy and Functional Systems
Cortical Anatomy and Brain Mapping
Subcortical Structures

Keywords:

Affective Disorders
Psychiatric Disorders
STRUCTURAL MRI
Trauma

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

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Structural MRI

For human MRI, what field strength scanner do you use?

3.0T

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Free Surfer

Provide references using APA citation style.

Bernstein, D. P., Stein, J. A., Newcomb, M. D., Walker, E., Pogge, D., Ahluvalia, T., Stokes, J., Handelsman, L., Medrano, M., Desmond, D., & Zule, W. (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl, 27(2), 169-190.
Desikan, R. S., Segonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., Buckner, R. L., Dale, A. M., Maguire, R. P., Hyman, B. T., Albert, M. S., & Killiany, R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968-980.
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., Montillo, A., Makris, N., Rosen, B., & Dale, A. M. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341-355.
Quidé, Y., Tozzi, L., Corcoran, M., Cannon, D. M., & Dauvermann, M. R. (2020). The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress. Neuropsychiatr Dis Treat., 16, 3095-3115.
Radua, J., Vieta, E., Shinohara, R., Kochunov, P., Quidé, Y., Green, M. J., Weickert, C. S., Weickert, T., Bruggemann, J., Kircher, T., Nenadic, I., Cairns, M. J., Seal, M., Schall, U., Henskens, F., Fullerton, J. M., Mowry, B., Pantelis, C., Lenroot, R., …, ENIGMA Consortium collaborators (2020). Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA. NeuroImage, 218, 116956.
Devi, F., Shahwan, S., Teh, W. L., Sambasivam, R., Zhang, Y. J., Lau, Y. W., Ong, S. H., Fung, D., Gupta, B., Chong, S. A., & Subramaniam, M. (2019). The prevalence of childhood trauma in psychiatric outpatients. Ann Gen Psychiatry, 18, 15.
Palmier-Claus, J. E., Berry, K., Bucci, S., Mansell, W., & Varese, F. (2016). Relationship between childhood adversity and bipolar affective disorder: systematic review and meta-analysis. The British Journal of Psychiatry, 209(6):454-459
Xie, P., Wu, K., Zheng, Y., Guo, Y., Yang, Y., He, J., Ding, Y., & Peng, H. (2018). Prevalence of childhood trauma and correlations between childhood trauma, suicidal ideation, and social support in patients with depression, bipolar disorder, and schizophrenia in southern China. J Affect Disord, 228, 41-48.

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