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Internalizing Symptoms and Adverse Childhood Experiences Associated With Functional Connectivity in a Middle Childhood Sample

Published:April 25, 2022DOI:https://doi.org/10.1016/j.bpsc.2022.04.001

      Abstract

      Background

      Research has found overlapping associations in adults of resting-state functional connectivity (RSFC) to both internalizing disorders (e.g., depression, anxiety) and a history of traumatic events. The present study aimed to extend this previous research to a younger sample by examining RSFC associations with both internalizing symptoms and adverse childhood experiences (ACEs) in middle childhood.

      Methods

      We used generalized linear mixed models to examine associations between a priori within- and between-network RSFC with child-reported internalizing symptoms and ACEs using the Adolescent Brain Cognitive Development dataset (N = 10,168, mean age = 9.95 years, SD = 0.627).

      Results

      We found that internalizing symptoms and ACEs were associated with both multiple overlapping and unique RSFC network patterns. Both ACEs and internalizing symptoms were associated with a reduced anticorrelation between the default mode network and the dorsal attention network. However, internalizing symptoms were uniquely associated with lower within-network default mode network connectivity, while ACEs were uniquely associated with both lower between-network connectivity of the auditory network and cingulo-opercular network, and higher within-network frontoparietal network connectivity.

      Conclusions

      The present study points to overlap in the RSFC associations with internalizing symptoms and ACEs, as well as important areas of specificity in RSFC associations. Many of the RSFC associations found have been previously implicated in attentional control functions, including modulation of attention to sensory stimuli. This may have critical importance in understanding internalizing symptoms and outcomes of ACEs.

      Keywords

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      References

        • Gilbert R.
        • Widom C.S.
        • Browne K.
        • Fergusson D.
        • Webb E.
        • Janson S.
        Burden and consequences of child maltreatment in high-income countries.
        Lancet. 2009; 373: 68-81
        • Edwards V.J.
        • Holden G.W.
        • Felitti V.J.
        • Anda R.F.
        Relationship between multiple forms of childhood maltreatement and adult mental health in community respondents: Results from the adverse childhood experiences study.
        Am J Psychiatry. 2003; 160: 1453-1460
        • Widom C.S.
        • DuMont K.
        • Czaja S.J.
        A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up.
        Arch Gen Psychiatry. 2007; 64: 49-56
        • Teicher M.H.
        • Samson J.A.
        • Anderson C.M.
        • Ohashi K.
        The effects of childhood maltreatment on brain structure, function and connectivity.
        Nat Rev Neurosci. 2016; 17: 652-666
        • Herzog J.I.
        • Schmahl C.
        Adverse childhood experiences and the consequences on neurobiological, psychosocial, and somatic conditions across the lifespan.
        Front Psychiatry. 2018; 9: 420
        • Weissman D.G.
        • Jenness J.L.
        • Colich N.L.
        • Miller A.B.
        • Sambrook K.A.
        • Sheridan M.A.
        • McLaughlin K.A.
        Altered neural processing of threat-related information in children and adolescents exposed to violence: A transdiagnostic mechanism contributing to the emergence of psychopathology.
        J Am Acad Child Adolesc Psychiatry. 2020; 59: 1274-1284
        • Gordon E.M.
        • Laumann T.O.
        • Adeyemo B.
        • Huckins J.F.
        • Kelley W.M.
        • Petersen S.E.
        Generation and evaluation of a cortical area parcellation from resting-state correlations.
        Cereb Cortex. 2016; 26: 288-303
        • Coste C.P.
        • Kleinschmidt A.
        Cingulo-opercular network activity maintains alertness.
        Neuroimage. 2016; 128: 264-272
        • Hamilton J.P.
        • Furman D.J.
        • Chang C.
        • Thomason M.E.
        • Dennis E.
        • Gotlib I.H.
        Default-mode and task-positive network activity in major depressive disorder: Implications for adaptive and maladaptive rumination.
        Biol Psychiatry. 2011; 70: 327-333
        • Mao Y.
        • Xiao H.
        • Ding C.
        • Qiu J.
        The role of attention in the relationship between early life stress and depression.
        Sci Rep. 2020; 10: 6154
        • Yu M.
        • Linn K.A.
        • Shinohara R.T.
        • Oathes D.J.
        • Cook P.A.
        • Duprat R.
        • et al.
        Childhood trauma history is linked to abnormal brain connectivity in major depression [published correction appears in Proc Natl Acad Sci U S A 2019; 116:13146].
        Proc Natl Acad Sci U S A. 2019; 116: 8582-8590
        • Lanssens A.
        • Pizzamiglio G.
        • Mantini D.
        • Gillebert C.R.
        Role of the dorsal attention network in distracter suppression based on features.
        Cogn Neurosci. 2020; 11: 37-46
        • van den Heuvel M.P.
        • Hulshoff Pol H.E.
        Exploring the brain network: A review on resting-state fMRI functional connectivity.
        Eur Neuropsychopharmacol. 2010; 20: 519-534
        • Gabbay V.
        • Ely B.A.
        • Li Q.
        • Bangaru S.D.
        • Panzer A.M.
        • Alonso C.M.
        • et al.
        Striatum-based circuitry of adolescent depression and anhedonia.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 628-641.e13
        • Sheline Y.I.
        • Price J.L.
        • Yan Z.
        • Mintun M.A.
        Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus.
        Proc Natl Acad Sci U S A. 2010; 107: 11020-11025
        • Dannlowski U.
        • Stuhrmann A.
        • Beutelmann V.
        • Zwanzger P.
        • Lenzen T.
        • Grotegerd D.
        • et al.
        Limbic scars: Long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging.
        Biol Psychiatry. 2012; 71: 286-293
        • Herringa R.J.
        • Birn R.M.
        • Ruttle P.L.
        • Burghy C.A.
        • Stodola D.E.
        • Davidson R.J.
        • Essex M.J.
        Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence.
        Proc Natl Acad Sci U S A. 2013; 110: 19119-19124
        • Hulvershorn L.A.
        • Cullen K.R.
        • Francis M.
        • Westlund M.
        Developmental resting state functional connectivity for clinicians.
        Curr Behav Neurosci Rep. 2014; 1: 161-169
        • Rabany L.
        • Diefenbach G.J.
        • Bragdon L.B.
        • Pittman B.P.
        • Zertuche L.
        • Tolin D.F.
        • et al.
        Resting-state functional connectivity in generalized anxiety disorder and social anxiety disorder: Evidence for a dimensional approach.
        Brain Connect. 2017; 7: 289-298
        • Williams L.M.
        Precision psychiatry: A neural circuit taxonomy for depression and anxiety.
        Lancet Psychiatry. 2016; 3: 472-480
        • Raichle M.E.
        The brain’s default mode network.
        Annu Rev Neurosci. 2015; 38: 433-447
        • Xiong H.
        • Guo R.J.
        • Shi H.W.
        Altered default mode network and salience network functional connectivity in patients with generalized anxiety disorders: An ICA-based resting-state fMRI study.
        Evid Based Complement Alternat Med. 2020; 2020: 4048916
        • Lui S.
        • Wu Q.
        • Qiu L.
        • Yang X.
        • Kuang W.
        • Chan R.C.K.
        • et al.
        Resting-state functional connectivity in treatment-resistant depression.
        Am J Psychiatry. 2011; 168: 642-648
        • Geng H.
        • Li X.
        • Chen J.
        • Li X.
        • Gu R.
        Decreased intra- and inter-salience network functional connectivity is related to trait anxiety in adolescents.
        Front Behav Neurosci. 2016; 9: 350
        • Sikora M.
        • Heffernan J.
        • Avery E.T.
        • Mickey B.J.
        • Zubieta J.K.
        • Peciña M.
        Salience network functional connectivity predicts placebo effects in major depression.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2016; 1: 68-76
        • Sylvester C.M.
        • Barch D.M.
        • Corbetta M.
        • Power J.D.
        • Schlaggar B.L.
        • Luby J.L.
        Resting state functional connectivity of the ventral attention network in children with a history of depression or anxiety.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 1326-1336.e5
        • Sylvester C.M.
        • Corbetta M.
        • Raichle M.E.
        • Rodebaugh T.L.
        • Schlaggar B.L.
        • Sheline Y.I.
        • et al.
        Functional network dysfunction in anxiety and anxiety disorders.
        Trends Neurosci. 2012; 35: 527-535
        • Liu J.
        • Xu P.
        • Zhang J.
        • Jiang N.
        • Li X.
        • Luo Y.
        Ventral attention-network effective connectivity predicts individual differences in adolescent depression.
        J Affect Disord. 2019; 252: 55-59
        • Kaufman J.
        Child abuse and psychiatric illness.
        Biol Psychiatry. 2012; 71: 280-281
        • De Bellis M.D.
        • Zisk A.
        The biological effects of childhood trauma.
        Child Adolesc Psychiatr Clin N Am. 2014; 23 (vii): 185-222
        • Olson E.A.
        • Kaiser R.H.
        • Pizzagalli D.A.
        • Rauch S.L.
        • Rosso I.M.
        Anhedonia in trauma-exposed individuals: Functional connectivity and decision-making correlates.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2018; 3: 959-967
        • Kaiser R.H.
        • Andrews-Hanna J.R.
        • Wager T.D.
        • Pizzagalli D.A.
        Large-scale network dysfunction in major depressive disorder: A meta-analysis of resting-state functional connectivity.
        JAMA Psychiatry. 2015; 72: 603-611
        • Popovic D.
        • Ruef A.
        • Dwyer D.B.
        • Antonucci L.A.
        • Eder J.
        • Sanfelici R.
        • et al.
        Traces of trauma: A multivariate pattern analysis of childhood trauma, brain structure, and clinical phenotypes.
        Biol Psychiatry. 2020; 88: 829-842
        • McLaughlin K.A.
        • Weissman D.
        • Bitrán D.
        Childhood adversity and neural development: A systematic review.
        Annu Rev Dev Psychol. 2019; 1: 277-312
        • Grant K.E.
        • Compas B.E.
        • Thurm A.E.
        • McMahon S.D.
        • Gipson P.Y.
        Stressors and child and adolescent psychopathology: Measurement issues and prospective effects.
        J Clin Child Adolesc Psychol. 2004; 33: 412-425
        • Tiet Q.Q.
        • Bird H.R.
        • Hoven C.W.
        • Moore R.
        • Wu P.
        • Wicks J.
        • et al.
        Relationship between specific adverse life events and psychiatric disorders.
        J Abnorm Child Psychol. 2001; 29: 153-164
        • Philip N.S.
        • Sweet L.H.
        • Tyrka A.R.
        • Price L.H.
        • Bloom R.F.
        • Carpenter L.L.
        Decreased default network connectivity is associated with early life stress in medication-free healthy adults.
        Eur Neuropsychopharmacol. 2013; 23: 24-32
        • Sripada R.K.
        • Swain J.E.
        • Evans G.W.
        • Welsh R.C.
        • Liberzon I.
        Childhood poverty and stress reactivity are associated with aberrant functional connectivity in default mode network.
        Neuropsychopharmacology. 2014; 39: 2244-2251
        • van der Werff S.J.A.
        • Pannekoek J.N.
        • Veer I.M.
        • van Tol M.J.
        • Aleman A.
        • Veltman D.J.
        • et al.
        Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus.
        Child Abuse Negl. 2013; 37: 1021-1029
        • Zhou A.M.
        • Buss K.A.
        Trajectories of internalizing symptoms in early childhood: Associations with maternal internalizing symptoms and child physiology.
        Dev Psychobiol. 2021; 63: 1295-1308
        • Shanahan L.
        • Calkins S.D.
        • Keane S.P.
        • Kelleher R.
        • Suffness R.
        Trajectories of internalizing symptoms across childhood: The roles of biological self-regulation and maternal psychopathology.
        Dev Psychopathol. 2014; 26: 1353-1368
        • Whitfield-Gabrieli S.
        • Wendelken C.
        • Nieto-Castañón A.
        • Bailey S.K.
        • Anteraper S.A.
        • Lee Y.J.
        • et al.
        Association of intrinsic brain architecture with changes in attentional and mood symptoms during development.
        JAMA Psychiatry. 2020; 77: 378-386
        • Karcher N.R.
        • Michelini G.
        • Kotov R.
        • Barch D.M.
        Associations between resting-state functional connectivity and a hierarchical dimensional structure of psychopathology in middle childhood.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2021; 6: 508-517
        • Barch D.M.
        • Belden A.C.
        • Tillman R.
        • Whalen D.
        • Luby J.L.
        Early childhood adverse experiences, inferior frontal gyrus connectivity, and the trajectory of externalizing psychopathology.
        J Am Acad Child Adolesc Psychiatry. 2018; 57: 183-190
        • Barch D.M.
        • Albaugh M.D.
        • Avenevoli S.
        • Chang L.
        • Clark D.B.
        • Glantz M.D.
        • et al.
        Demographic, physical and mental health assessments in the adolescent brain and cognitive development study: Rationale and description.
        Dev Cogn Neurosci. 2018; 32: 55-66
        • Garavan H.
        • Bartsch H.
        • Conway K.
        • Decastro A.
        • Goldstein R.Z.
        • Heeringa S.
        • et al.
        Recruiting the ABCD sample: Design considerations and procedures.
        Dev Cogn Neurosci. 2018; 32: 16-22
        • ClinicalTrials.gov
        Computerized screening of comorbidity in adolescents with substance or psychiatric disorders. NCT01866956.
        • Kaufman J.
        • Birmaher B.
        • Brent D.
        • Rao U.
        • Flynn C.
        • Moreci P.
        • et al.
        Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 980-988
        • Townsend L.
        • Kobak K.
        • Kearney C.
        • Milham M.
        • Andreotti C.
        • Escalera J.
        • et al.
        Development of three web-based computerized versions of the Kiddie Schedule for Affective Disorders and Schizophrenia child psychiatric diagnostic interview: Preliminary validity data.
        J Am Acad Child Adolesc Psychiatry. 2020; 59: 309-325
        • Karcher N.R.
        • Barch D.M.
        • Avenevoli S.
        • Savill M.
        • Huber R.S.
        • Simon T.J.
        • et al.
        Assessment of the Prodromal Questionnaire-Brief Child Version for measurement of self-reported psychoticlike experiences in childhood.
        JAMA Psychiatry. 2018; 75: 853-861
        • Casey B.J.
        • Cannonier T.
        • Conley M.I.
        • Cohen A.O.
        • Barch D.M.
        • Heitzeg M.M.
        • et al.
        The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites.
        Dev Cogn Neurosci. 2018; 32: 43-54
        • Hagler Jr., D.J.
        • Hatton S.N.
        • Cornejo M.D.
        • Makowski C.
        • Fair D.A.
        • Dick A.S.
        • et al.
        Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.
        Neuroimage. 2019; 202: 116091
        • Fair D.A.
        • Miranda-Dominguez O.
        • Snyder A.Z.
        • Perrone A.
        • Earl E.A.
        • Van A.N.
        • et al.
        Correction of respiratory artifacts in MRI head motion estimates.
        Neuroimage. 2020; 208: 116400
        • Bates D.
        • Mächler M.
        • Bolker B.
        • Walker S.
        Fitting linear mixed-effects models using lme4.
        J Stat Softw. 2015; 67: 1-48
        • Maguire-Jack K.
        • Lanier P.
        • Lombardi B.
        Investigating racial differences in clusters of adverse childhood experiences.
        Am J Orthopsychiatry. 2020; 90: 106-114
        • Sacks V.
        • Murphey D.
        The prevalence of adverse childhood experiences, nationally, by state, and by race or ethnicity. Child Trends.
        (Available at) (Accessed September 2, 2021)
        • Yu M.
        • Linn K.A.
        • Cook P.A.
        • Phillips M.L.
        • McInnis M.
        • Fava M.
        • et al.
        Statistical harmonization corrects site effects in functional connectivity measurements from multi-site fMRI data.
        Hum Brain Mapp. 2018; 39: 4213-4227
        • Fortin J.P.
        • Parker D.
        • Tunç B.
        • Watanabe T.
        • Elliott M.A.
        • Ruparel K.
        • et al.
        Harmonization of multi-site diffusion tensor imaging data.
        Neuroimage. 2017; 161: 149-170
        • Kim Y.K.
        • Yoon H.K.
        Common and distinct brain networks underlying panic and social anxiety disorders.
        Prog Neuropsychopharmacol Biol Psychiatry. 2018; 80: 115-122
        • Boshuisen M.L.
        • Ter Horst G.J.
        • Paans A.M.J.
        • Reinders A.A.T.S.
        • den Boer J.A.
        rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest.
        Biol Psychiatry. 2002; 52: 126-135
        • Lai C.H.
        • Wu Y.T.
        The explorative analysis to revise fear network model for panic disorder: Functional connectome statistics.
        Medicine (Baltimore). 2016; 95: e3597
        • Cui H.
        • Zhang J.
        • Liu Y.
        • Li Q.
        • Li H.
        • Zhang L.
        • et al.
        Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder.
        Hum Brain Mapp. 2016; 37: 1459-1473
        • Shang J.
        • Lui S.
        • Meng Y.
        • Zhu H.
        • Qiu C.
        • Gong Q.
        • et al.
        Alterations in low-level perceptual networks related to clinical severity in PTSD after an earthquake: A resting-state fMRI study.
        PLoS One. 2014; 9: e96834
        • Conio B.
        • Magioncalda P.
        • Martino M.
        • Tumati S.
        • Capobianco L.
        • Escelsior A.
        • et al.
        Opposing patterns of neuronal variability in the sensorimotor network mediate cyclothymic and depressive temperaments.
        Hum Brain Mapp. 2019; 40: 1344-1352
        • Yan C.G.
        • Chen X.
        • Li L.
        • Castellanos F.X.
        • Bai T.J.
        • Bo Q.J.
        • et al.
        Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.
        Proc Natl Acad Sci U S A. 2019; 116: 9078-9083
        • Davey C.G.
        • Breakspear M.
        • Pujol J.
        • Harrison B.J.
        A brain model of disturbed self-appraisal in depression.
        Am J Psychiatry. 2017; 174: 895-903
        • King A.
        • Hinckley E.
        • Sripada C.
        • Liberzon I.
        Altered anterior and posterior default mode (DMN) connectivity with dorsal attention (DAN) and frontoparietal (FPCN) networks during an interoception task associated with PTSD avoidant symptoms and treatment response to psychotherapy.
        Biol Psychiatry. 2020; 87: S360
        • Mitra A.
        • Raichle M.E.
        Principles of cross-network communication in human resting state fMRI.
        Scand J Psychol. 2018; 59: 83-90
        • Owens M.M.
        • Yuan D.
        • Hahn S.
        • Albaugh M.
        • Allgaier N.
        • Chaarani B.
        • et al.
        Investigation of psychiatric and neuropsychological correlates of default mode network and dorsal attention network anticorrelation in children.
        Cereb Cortex. 2020; 30: 6083-6096
        • van der Werff S.J.A.
        • Pannekoek J.N.
        • Veer I.M.
        • van Tol M.J.
        • Aleman A.
        • Veltman D.J.
        • et al.
        Resting-state functional connectivity in adults with childhood emotional maltreatment.
        Psychol Med. 2013; 43: 1825-1836
        • Dick A.S.
        • Lopez D.A.
        • Watts A.L.
        • Heeringa S.
        • Reuter C.
        • Bartsch H.
        • et al.
        Meaningful associations in the adolescent brain cognitive development study.
        Neuroimage. 2021; 239: 118262
        • Keller A.S.
        • Leikauf J.E.
        • Holt-Gosselin B.
        • Staveland B.R.
        • Williams L.M.
        Paying attention to attention in depression [published correction appears in Transl Psychiatry 2020; 10:64].
        Transl Psychiatry. 2019; 9: 279
        • Zhang Z.
        • Telesford Q.K.
        • Giusti C.
        • Lim K.O.
        • Bassett D.S.
        Choosing wavelet methods, filters, and lengths for functional brain network construction.
        PLoS One. 2016; 11e0157243
        • Resick P.A.
        • Schnicke M.K.
        Cognitive processing therapy for sexual assault victims.
        J Consult Clin Psychol. 1992; 60: 748-756
        • Marek S.
        • Dosenbach N.U.F.
        The frontoparietal network: Function, electrophysiology, and importance of individual precision mapping.
        Dialogues Clin Neurosci. 2018; 20: 133-140
        • Uddin L.Q.
        Salience processing and insular cortical function and dysfunction.
        Nat Rev Neurosci. 2015; 16: 55-61
        • Vossel S.
        • Geng J.J.
        • Fink G.R.
        Dorsal and ventral attention systems: Distinct neural circuits but collaborative roles.
        Neuroscientist. 2014; 20: 150-159