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Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort

  • Leonardo Tozzi (a1) (a2), Lisa Garczarek (a1), Deborah Janowitz (a3), Dan J. Stein (a4), Katharina Wittfeld (a3) (a5), Henrik Dobrowolny (a1), Jim Lagopoulos (a6) (a7), Sean N. Hatton (a6), Ian B. Hickie (a6), Angela Carballedo (a8), Samantha J. Brooks (a4) (a9), Daniella Vuletic (a4), Anne Uhlmann (a4) (a10), Ilya M. Veer (a11), Henrik Walter (a11), Robin Bülow (a12), Henry Völzke (a13), Johanna Klinger-König (a3), Knut Schnell (a14) (a15) (a16), Dieter Schoepf (a17), Dominik Grotegerd (a18), Nils Opel (a18), Udo Dannlowski (a18), Harald Kugel (a19), Elisabeth Schramm (a20) (a21), Carsten Konrad (a22) (a23), Tilo Kircher (a23), Dilara Jüksel (a23), Igor Nenadić (a23), Axel Krug (a23), Tim Hahn (a18), Olaf Steinsträter (a23) (a24), Ronny Redlich (a18), Dario Zaremba (a18), Bartosz Zurowski (a25), Cynthia H.Y. Fu (a26) (a27), Danai Dima (a28) (a29), James Cole (a28), Hans J. Grabe (a3), Colm G. Connolly (a30) (a31), Tony T. Yang (a30) (a32), Tiffany C. Ho (a30) (a33), Kaja Z. LeWinn (a30) (a32), Meng Li (a34), Nynke A. Groenewold (a4), Lauren E. Salminen (a35), Martin Walter (a1) (a34) (a36), Alan N Simmons (a37) (a38), Theo G.M. van Erp (a39), Neda Jahanshad (a35), Bernhard T. Baune (a18) (a40) (a41) (a42), Nic J.A. van der Wee (a43), Marie-Jose van Tol (a44), Brenda W.J.H. Penninx (a45), Derrek P. Hibar (a39), Paul M. Thompson (a35), Dick J. Veltman (a45), Lianne Schmaal (a46) (a47), Thomas Frodl (a1) (a6) (a48) and ‘for the ENIGMA-MDD Consortium’ (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a8) (a9) (a10) (a11) (a12) (a13) (a14) (a15) (a16) (a17) (a18) (a19) (a20) (a21) (a22) (a23) (a24) (a25) (a26) (a27) (a28) (a29) (a30) (a31) (a32) (a33) (a34) (a35) (a36) (a37) (a38) (a39) (a40) (a41) (a42) (a43) (a44) (a45) (a46) (a47) (a48)...

Abstract

Background

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Methods

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

Results

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Conclusions

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Copyright

Corresponding author

Author for correspondence: Thomas Frodl, E-mail: Thomas.Frodl@med.ovgu.de

Footnotes

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Contributed equally.

Footnotes

References

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Bernet, CZ and Stein, MB (1999) Relationship of childhood maltreatment to the onset and course of major depression in adulthood. Depression and Anxiety 9, 169174.
Bernstein, DP, Fink, L, Handelsman, L, Foote, J, Lovejoy, M, Wenzel, K, Sapareto, E and Ruggiero, J (1994) Initial reliability and validity of a new retrospective measure of child abuse and neglect. American Journal of Psychiatry 151, 11321136.
Canu, E, Kostic, M, Agosta, F, Munjiza, A, Ferraro, PM, Pesic, D, Copetti, M, Peljto, A, Lecic Tosevski, D and Filippi, M (2015) Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity. Journal of Neurology 262, 12551265.
Chaney, A, Carballedo, A, Amico, F, Fagan, A, Skokauskas, N, Meaney, J and Frodl, T (2014) Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants. Journal of Psychiatry and Neuroscience 39, 5059.
Dannlowski, U, Stuhrmann, A, Beutelmann, V, Zwanzger, P, Lenzen, T, Grotegerd, D, Domschke, K, Hohoff, C, Ohrmann, P, Bauer, J, Lindner, C, Postert, C, Konrad, C, Arolt, V, Heindel, W, Suslow, T and Kugel, H (2012) Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biological Psychiatry 71, 286293.
Davey, J, Thompson, HE, Hallam, G, Karapanagiotidis, T, Murphy, C, De Caso, I, Krieger-Redwood, K, Bernhardt, BC, Smallwood, J and Jefferies, E (2016) Exploring the role of the posterior middle temporal gyrus in semantic cognition: integration of anterior temporal lobe with executive processes. Neuroimage 137, 165177.
Desikan, RS, Segonne, F, Fischl, B, Quinn, BT, Dickerson, BC, Blacker, D, Buckner, RL, Dale, AM, Maguire, RP, Hyman, BT, Albert, MS and Killiany, RJ (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31, 968980.
Edmiston, EE, Wang, F, Mazure, CM, Guiney, J, Sinha, R, Mayes, LC and Blumberg, HP (2011) Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Archives of Pediatrics and Adolescent Medicine 165, 10691077.
Etkin, A, Egner, T and Kalisch, R (2011) Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 8593.
Everaerd, D, Klumpers, F, Zwiers, M, Guadalupe, T, Franke, B, van Oostrom, I, Schene, A, Fernandez, G and Tendolkar, I (2016) Childhood abuse and deprivation are associated with distinct sex-dependent differences in brain morphology. Neuropsychopharmacology 41, 17161723.
Fallucca, E, MacMaster, FP, Haddad, J, Easter, P, Dick, R, May, G, Stanley, JA, Rix, C and Rosenberg, DR (2011) Distinguishing between major depressive disorder and obsessive-compulsive disorder in children by measuring regional cortical thickness. Archives of General Psychiatry 68, 527533.
Farah, MJ, Shera, DM, Savage, JH, Betancourt, L, Giannetta, JM, Brodsky, NL, Malmud, EK and Hurt, H (2006) Childhood poverty: specific associations with neurocognitive development. Brain Research 1110, 166174.
Feder, A, Nestler, EJ and Charney, DS (2009) Psychobiology and molecular genetics of resilience. Nature Review Neuroscience 10, 446457.
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, van der Kouwe, A, Killiany, R, Kennedy, D, Klaveness, S, Montillo, A, Makris, N, Rosen, B and Dale, AM (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341355.
Frodl, TS, Koutsouleris, N, Bottlender, R, Born, C, Jager, M, Scupin, I, Reiser, M, Moller, HJ and Meisenzahl, EM (2008) Depression-related variation in brain morphology over 3 years: effects of stress? Archives of General Psychiatry 65, 11561165.
Frodl, T, Reinhold, E, Koutsouleris, N, Reiser, M and Meisenzahl, EM (2010) Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression. Journal of Psychiatric Research 44, 799807.
Frodl, T, Janowitz, D, Schmaal, L, Tozzi, L, Dobrowolny, H, Stein, DJ, Veltman, DJ, Wittfeld, K, van Erp, TG, Jahanshad, N, Block, A, Hegenscheid, K, Volzke, H, Lagopoulos, J, Hatton, SN, Hickie, IB, Frey, EM, Carballedo, A, Brooks, SJ, Vuletic, D, Uhlmann, A, Veer, IM, Walter, H, Schnell, K, Grotegerd, D, Arolt, V, Kugel, H, Schramm, E, Konrad, C, Zurowski, B, Baune, BT, van der Wee, NJ, van Tol, MJ, Penninx, BW, Thompson, PM, Hibar, DP, Dannlowski, U and Grabe, HJ (2017) Childhood adversity impacts on brain subcortical structures relevant to depression. Journal of Psychiatric Research 86, 5865.
Fu, H, Feng, T, Qin, J, Wang, T, Wu, X, Cai, Y, Lan, L and Yang, T (2018) Reported prevalence of childhood maltreatment among Chinese college students: a systematic review and meta-analysis. PLoS ONE 13, e0205808.
Garavan, H, Hester, R, Murphy, K, Fassbender, C and Kelly, C (2006) Individual differences in the functional neuroanatomy of inhibitory control. Brain Research 1105, 130142.
Hillis, S, Mercy, J, Amobi, A and Kress, H (2016) Global prevalence of past-year violence against children: a systematic review and minimum estimates. Pediatrics 137, e20154079.
Ho, TC, Dennis, EL, Thompson, PM and Gotlib, IH (2018) Network-based approaches to examining stress in the adolescent brain. Neurobiology of Stress 8, 147157.
Kelly, PA, Viding, E, Wallace, GL, Schaer, M, De Brito, SA, Robustelli, B and McCrory, EJ (2013) Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability? Biological Psychiatry 74, 845852.
Kole, MH, Czeh, B and Fuchs, E (2004) Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress. Hippocampus 14, 742751.
Lambert, HK, King, KM, Monahan, KC and McLaughlin, KA (2017) Differential associations of threat and deprivation with emotion regulation and cognitive control in adolescence. Development and Psychopathology 29, 929940.
Leeb, RT, Paulozzi, L, Melanson, C, Simon, T and Arias, I (2008) Child Maltreatment Surveillance: Uniform Definitions for Public Health and Recommended Data Elements. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control.
Levens, SM and Phelps, EA (2010) Insula and orbital frontal cortex activity underlying emotion interference resolution in working memory. Journal of Cognitive Neuroscience 22, 27902803.
Lim, L, Hart, H, Mehta, M, Worker, A, Simmons, A, Mirza, K and Rubia, K (2018) Grey matter volume and thickness abnormalities in young people with a history of childhood abuse. Psychological Medicine 48, 10341046.
Macqueen, G and Frodl, T (2010) The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Molecular Psychiatry 16, 252264.
Magarinos, AM, McEwen, BS, Flugge, G and Fuchs, E (1996) Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. Journal of Neuroscience 16, 35343540.
McLaughlin, KA, Sheridan, MA and Lambert, HK (2014 a) Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience. Neuroscience & Biobehavioural Reviews 47, 578591.
McLaughlin, KA, Sheridan, MA, Winter, W, Fox, NA, Zeanah, CH and Nelson, CA (2014 b) Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biological Psychiatry 76, 629638.
Nanni, V, Uher, R and Danese, A (2012) Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry 169, 141151.
Newbury, JB, Arseneault, L, Moffitt, TE, Caspi, A, Danese, A, Baldwin, JR and Fisher, HL (2018) Measuring childhood maltreatment to predict early-adult psychopathology: comparison of prospective informant-reports and retrospective self-reports. Journal of Psychiatric Research 96, 5764.
Ongur, D and Price, JL (2000) The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cerebral Cortex 10, 206219.
Phillips, ML, Ladouceur, CD and Drevets, WC (2008) A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 829, 833857.
Riedel, M, Möller, HJ, Obermeier, M, Schennach-Wolff, R, Bauer, M, Adli, M, Kronmüller, K, Nickel, T, Brieger, P, Laux, G, Bender, W, Heuser, I, Zeiler, J, Gaebel, W and Seemüller, F (2010) Response and remission criteria in major depression–a validation of current practice. Journal of Psychiatric Research 44, 10631068.
Ritchie, SJ, Tucker-Drob, EM, Cox, SR, Dickie, DA, Del, CVHM, Corley, J, Royle, NA, Redmond, P, Munoz Maniega, S, Pattie, A, Aribisala, BS, Taylor, AM, Clarke, TK, Gow, AJ, Starr, JM, Bastin, ME, Wardlaw, JM and Deary, IJ (2017) Risk and protective factors for structural brain ageing in the eighth decade of life. Brain Structure and Function 222, 34773490.
Saxe, R and Kanwisher, N (2003) People thinking about thinking people. The role of the temporo-parietal junction in “theory of mind”. Neuroimage 19, 18351842.
Schmaal, L, Hibar, DP, Samann, PG, Hall, GB, Baune, BT, Jahanshad, N, Cheung, JW, van Erp, TGM, Bos, D, Ikram, MA, Vernooij, MW, Niessen, WJ, Tiemeier, H, Hofman, A, Wittfeld, K, Grabe, HJ, Janowitz, D, Bulow, R, Selonke, M, Volzke, H, Grotegerd, D, Dannlowski, U, Arolt, V, Opel, N, Heindel, W, Kugel, H, Hoehn, D, Czisch, M, Couvy-Duchesne, B, Renteria, ME, Strike, LT, Wright, MJ, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Martin, NG, Gillespie, NA, Goya-Maldonado, R, Gruber, O, Kramer, B, Hatton, SN, Lagopoulos, J, Hickie, IB, Frodl, T, Carballedo, A, Frey, EM, van Velzen, LS, Penninx, B, van Tol, MJ, van der Wee, NJ, Davey, CG, Harrison, BJ, Mwangi, B, Cao, B, Soares, JC, Veer, IM, Walter, H, Schoepf, D, Zurowski, B, Konrad, C, Schramm, E, Normann, C, Schnell, K, Sacchet, MD, Gotlib, IH, MacQueen, GM, Godlewska, BR, Nickson, T, McIntosh, AM, Papmeyer, M, Whalley, HC, Hall, J, Sussmann, JE, Li, M, Walter, M, Aftanas, L, Brack, I, Bokhan, NA, Thompson, PM and Veltman, DJ (2017) Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Molecular Psychiatry 22, 900909.
Sheridan, MA and McLaughlin, KA (2014) Dimensions of early experience and neural development: deprivation and threat. Trends in Cognitive Science 18, 580585.
Steele, VR, Aharoni, E, Munro, GE, Calhoun, VD, Nyalakanti, P, Stevens, MC, Pearlson, G and Kiehl, KA (2013) A large scale (N = 102) functional neuroimaging study of response inhibition in a Go/NoGo task. Behavioural Brain Research 256, 529536.
Teicher, MH, Anderson, CM, Ohashi, K and Polcari, A (2014) Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula. Biological Psychiatry 76, 297305.
Teicher, MH, Samson, JA, Anderson, CM and Ohashi, K (2016) The effects of childhood maltreatment on brain structure, function and connectivity. Nature Review Neuroscience 17, 652666.
van Harmelen, AL, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Aleman, A, Spinhoven, P, van Buchem, MA, Zitman, FG, Penninx, BW and Elzinga, BM (2010) Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biological Psychiatry 68, 832838.
Wellman, CL (2001) Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. Journal of Neurobiology 49, 245253.
WHO (2016). Childhood Maltreatment. Geneva: WHO.
Wise, T, Radua, J, Via, E, Cardoner, N, Abe, O, Adams, TM, Amico, F, Cheng, Y, Cole, JH, de Azevedo Marques Perico, C, Dickstein, DP, Farrow, TF, Frodl, T, Wagner, G, Gotlib, IH, Gruber, O, Ham, BJ, Job, DE, Kempton, MJ, Kim, MJ, Koolschijn, PC, Malhi, GS, Mataix-Cols, D, McIntosh, AM, Nugent, AC, O'Brien, JT, Pezzoli, S, Phillips, ML, Sachdev, PS, Salvadore, G, Selvaraj, S, Stanfield, AC, Thomas, AJ, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Young, AH, Fu, CH, Cleare, AJ and Arnone, D (2016) Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Molecular Psychiatry; 22(10):14551463.
Woolley, CS, Gould, E, Frankfurt, M and McEwen, BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. Journal of Neuroscience 10, 40354039.
Yang, S, Cheng, Y, Mo, Y, Bai, Y, Shen, Z, Liu, F, Li, N, Jiang, L, Chen, W, Lu, Y, Sun, X and Xu, X (2017) Childhood maltreatment is associated with gray matter volume abnormalities in patients with first-episode depression. Psychiatry Research: Neuroimaging 268, 2734.

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