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Internalizing Symptoms & 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

      Introduction

      Research has found overlapping associations in adults of resting state functional connectivity (RSFC) to both internalizing disorders (e.g., depression, anxiety) as well as 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.

      Method

      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, Mage(years)= 9.95, SDage(years)= 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.
        The Lancet. 2009; 373: 68-81
        • Edwards V.
        • Holden G.
        • Felitti V.
        • Anda R.
        Relationship Between Multiple Forms of Childhood Maltreatement and Adult Mental Health in Community Respondents: Results From the Adverse Childhood Experiences Study.
        The American Journal of Psychiatry. 2003; 8: 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.
        Archives of General 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.
        Nature Reviews Neuroscience. 2016; 17: 652-666
        • Herzog J.I.
        • Schmahl C.
        Adverse childhood experiences and the consequences on neurobiological, psychosocial, and somatic conditions across the lifespan.
        Frontiers in Psychiatry. 2018; 9: 1-8
        • 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.
        Journal of the American Academy of Child and Adolescent 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.
        Cerebral 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.
        Biological 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.
        Scientific Reports. 2020; 10: 1-10
      1. Keller AS, Leikauf JE, Holt-Gosselin B, Staveland BR, Williams LM (2019, December 1): Paying attention to attention in depression. Translational Psychiatry, vol. 9. Nature Publishing Group, pp 1–12.

        • 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.
        Proceedings of the National Academy of Sciences of the United States of America. 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.
        Cognitive Neuroscience. 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.
        European Neuropsychopharmacology. 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.
        Journal of the American Academy of Child and Adolescent Psychiatry. 2013; 52 (e13): 628-641
        • 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.
        Proceedings of the National Academy of Sciences of the United States of America. 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.
        Biological Psychiatry. 2012; 71: 286-293
        • Herringa R.J.
        • Birn R.M.
        • Ruttle P.L.
        • Burghy C.A.
        • Stodola D.E.
        • Davidson R.J.
        Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence.
        Proceedings of the National Academy of Sciences of the United States of America. 2013; 110: 19119-19124
        • Hulvershorn L.
        • Cullen K.
        • Francis M.
        • Westlund M.
        Developmental Resting State Functional Connectivity for Clinicians.
        Current Behavioral Neuroscience. 2014; 3: 161-169
        • 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
        • 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 Connectivity. 2017; 7: 289-298
        • Williams L.M.
        Precision psychiatry: A neural circuit taxonomy for depression and anxiety.
        The Lancet Psychiatry. 2016; 3: 472-480
        • Raichle M.E.
        The Brain’s Default Mode Network.
        Annual Review of Neuroscience. 2015; 38: 433-447
      2. Xiong H, Guo RJ, Shi HW (2020): Altered Default Mode Network and Salience Network Functional Connectivity in Patients with Generalized Anxiety Disorders: An ICA-Based Resting-State fMRI Study. Evidence-based Complementary and Alternative Medicine 2020. https://doi.org/10.1155/2020/4048916

        • Lui S.
        • Wu Q.
        • Qiu L.
        • Yang X.
        • Kuang W.
        • Chan R.C.K.
        • et al.
        Resting-state functional connectivity in treatment-resistant depression.
        American Journal of 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.
        Frontiers in Behavioral Neuroscience. 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.
        Biological Psychiatry: Cognitive Neuroscience and 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.
        Journal of the American Academy of Child and Adolescent Psychiatry. 2013; 52: 1326
      3. Sylvester CM, Corbetta M, Raichle ME, Rodebaugh TL, Schlaggar BL, Sheline YI, et al. (2012, September): Functional network dysfunction in anxiety and anxiety disorders. Trends in Neurosciences, vol. 35. NIH Public Access, pp 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.
        Journal of Affective Disorders. 2019; 252: 55-59
        • Kaufman J.
        Child abuse and psychiatric illness.
        Biological Psychiatry. 2012; 71: 280-281
      4. de Bellis MD, Zisk A (2014): The Biological Effects of Childhood Trauma. Child and Adolescent Psychiatric Clinics of North America, vol. 23. pp 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.
        Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2018; 3: 959-967
        • 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.
        Biological Psychiatry. 2020; 88: 829-842
        • McLaughlin K.A.
        • Weissman D.
        • Bitrán D.
        Childhood Adversity and Neural Development: A Systematic Review.
        Annual Review of Developmental Psychology. 2019; 1: 277-312
        • Grant K.
        • Compas B.
        • Thurm A.
        • McMahon S.
        • Gipson P.
        Stressors and Child Adolescent Psychopathology: Measurement Issues and Prospective Effects.
        Journal of Clinical Child and Adolescent Psychology. 2004; 33: 412-425
        • Tiet Q.
        • Bird H.
        • Hoven C.
        • Moor R.
        • Wu P.
        • Wicks J.
        • et al.
        Relationship Between Specific Adverse Life Events and Psychiatric Disorders.
        Journal of Abnormal Child Psychology. 2001; 29: 153-164
        • Philip N.
        • Sweet L.
        • Tyrka A.
        • Price L.
        • Bloom R.
        • Carpenter L.
        Decreased Default Network Connectivity is Associated with Early Life Stress in MEdication-Free Healthy Adults.
        European Neuropsychopharmacology. 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 and Neglect. 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.
        Developmental psychobiology. 2021; 63: 1295
        • 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.
        Development and psychopathology. 2014; 26: 1353
        • 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.
        Biological Psychiatry: Cognitive Neuroscience and 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.
        Journal of the American Academy of Child & Adolescent 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.
        Developmental Cognitive Neuroscience. 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.
        Developmental Cognitive Neuroscience. 2018; 32: 16-22
      5. Kobak KA, Kaufman JR (2013): Computerized screening of comorbidity in adolescents with substance or psychiatric disorders. Anxiety Disorders and Depression. La Jolaa, CA.

        • 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.
        Journal of the American Academy of Child and Adolescent 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.
        Journal of the American Academy of Child and Adolescent 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.
        Developmental Cognitive Neuroscience. 2018; 32: 43-54
      6. Hagler D, Hatton S, Makowski C, Cornejo D, Fair D, Dick AS, et al. (2018): Image processing and analysis methods for the Adolescent Brain Cognitive Development Study. bioRxiv 457739.

        • Bates D.
        • Mächler M.
        • Bolker B.M.
        • Walker S.C.
        Fitting linear mixed-effects models using lme4.
        Journal of Statistical Software. 2015; 67https://doi.org/10.18637/jss.v067.i01
        • Maguire-Jack K.
        • Lanier P.
        • Lombardi B.
        Investigating Racial Differences in Clusters of Adverse Childhood Experiences.
        American Journal of Orthopsychiatry. 2019; https://doi.org/10.1037/ort0000405
        • Sacks V.
        • Murphey D.
        The prevalence of adverse childhood experiences, nationally, by state, and by race or ethnicity. Research brief.
        Child Trends. 2018; : 1-20
        • 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.
        Human Brain Mapping. 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
      7. Kim YK, Yoon HK (2018, January 3): Common and distinct brain networks underlying panic and social anxiety disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 80. Elsevier Inc., pp 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.
        Biological Psychiatry. 2002; 52: 126-135
        • Lai C.H.
        • Wu Y te
        The explorative analysis to revise fear network model for panic disorder functional connectome statistics.
        Medicine (United States). 2016; 95e3597
        • 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.
        Human Brain Mapping. 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; 9e96834
        • 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.
        Human Brain Mapping. 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.
        Proceedings of the National Academy of Sciences of the United States of America. 2019; 116: 9078-9083
        • Davey C.G.
        • Breakspear M.
        • Pujol J.
        • Harrison B.J.
        A brain model of disturbed self-appraisal in depression.
        American Journal of 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.
        Biological Psychiatry. 2020; 87: S360
        • Mitra A.
        • Raichle M.E.
        Principles of cross-network communication in human resting state fMRI.
        Scandinavian Journal of Psychology. 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.
        Cerebral 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.
        Psychological Medicine. 2013; 43: 1825-1836
        • Marek S.
        • Dosenbach N.U.F.
        The frontoparietal network: Function, electrophysiology, and importance of individual precision mapping.
        Dialogues in Clinical Neuroscience. 2018; 20: 133-141
        • 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; 11https://doi.org/10.1371/journal.pone.0157243
      8. Steven Dick A, Lopez DA, Watts AL, Heeringa S, Reuter C, Bartsch H, et al. (2021): Meaningful Associations in the Adolescent Brain Cognitive Development Study. bioRxiv 2020.09.01.276451.

        • Hagler 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
        • Resick P.A.
        • Schnicke M.K.
        Cognitive Processing Therapy for Sexual Assault Victims.
        Journal of Consulting and Clinical Psychology. 1992; 60: 748-756
        • Uddin L.Q.
        Salience processing and insular cortical function and dysfunction.
        Nature Reviews Neuroscience. 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