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Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents’ Neural Responses to Cognitive Conflict

Published:March 27, 2022DOI:https://doi.org/10.1016/j.bpsc.2022.03.007

      Abstract

      Background

      Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leveraged both cross-sectional and longitudinal data from early childhood into adolescence.

      Methods

      For this study, 89 participants were recruited from a large longitudinal research study on early-life temperament to investigate associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15) as well as associations of anxiety and irritability symptoms measured cross-sectionally at age 15 with neural substrates of conflict and error processing assessed at age 15 using the flanker task.

      Results

      Results of whole-brain multivariate linear models revealed that anxiety at age 15 was uniquely associated with decreased neural response to conflict across multiple regions implicated in attentional control and conflict adaptation. Conversely, irritability at age 15 was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict.

      Conclusions

      Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.

      Keywords

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      References

        • Brotman M.A.
        • Schmajuk M.
        • Rich B.A.
        • Dickstein D.P.
        • Guyer A.E.
        • Costello E.J.
        • et al.
        Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children.
        Biol Psychiatry. 2006; 60: 991-997
        • Savage J.
        • Verhulst B.
        • Copeland W.
        • Althoff R.R.
        • Lichtenstein P.
        • Roberson-Nay R.
        A genetically informed study of the longitudinal relation between irritability and anxious/depressed symptoms.
        J Am Acad Child Adolesc Psychiatry. 2015; 54: 377-384
        • Copeland W.E.
        • Brotman M.A.
        • Costello E.J.
        Normative irritability in youth: Developmental findings from the Great Smoky Mountains Study.
        Am Acad Child Adolesc Psychiatry. 2015; 54: 635-642
        • McTeague L.M.
        • Huemer J.
        • Carreon D.M.
        • Jiang Y.
        • Eickhoff S.B.
        • Etkin A.
        Identification of common neural circuit disruptions in cognitive control across psychiatric disorders.
        Am J Psychiatry. 2017; 174: 676-685
        • Cardinale E.M.
        • Subar A.R.
        • Brotman M.A.
        • Leibenluft E.
        • Kircanski K.
        • Pine D.S.
        Inhibitory control and emotion dysregulation: A framework for research on anxiety.
        Dev Psychopathol. 2019; 31: 859-869
        • Nigg J.T.
        Annual Research Review: On the relations among self-regulation, self-control, executive functioning, effortful control, cognitive control, impulsivity, risk-taking, and inhibition for developmental psychopathology.
        J Child Psychol Psychiatry. 2017; 58: 361-383
        • Miyake A.
        • Friedman N.P.
        • Emerson M.J.
        • Witzki A.H.
        • Howerter A.
        • Wager T.D.
        The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis.
        Cogn Psychol. 2000; 41: 49-100
        • Filippi C.A.
        • Subar A.R.
        • Sachs J.F.
        • Kircanski K.
        • Buzzell G.
        • Pagliaccio D.
        • et al.
        Developmental pathways to social anxiety and irritability: The role of the ERN.
        Dev Psychopathol. 2020; 32: 897-907
        • Meyer A.
        • Hajcak G.
        • Glenn C.R.
        • Kujawa A.J.
        • Klein D.N.
        Error-related brain activity is related to aversive potentiation of the startle response in children, but only the ERN is associated with anxiety disorders.
        Emotion. 2017; 17: 487-496
        • Moser J.S.
        The nature of the relationship between anxiety and the error-related negativity across development.
        Curr Behav Neurosci Rep. 2017; 4: 309-321
        • Moser J.S.
        • Moran T.P.
        • Schroder H.S.
        • Donnellan M.B.
        • Yeung N.
        On the relationship between anxiety and error monitoring: A meta-analysis and conceptual framework.
        Front Hum Neurosci. 2013; 7: 466
        • Smith A.R.
        • White L.K.
        • Leibenluft E.
        • McGlade A.L.
        • Heckelman A.C.
        • Haller S.P.
        • et al.
        The heterogeneity of anxious phenotypes: Neural responses to errors in treatment-seeking anxious and behaviorally inhibited youths.
        J Am Acad Child Adolesc Psychiatry. 2020; 59: 759-769
        • Buzzell G.A.
        • Morales S.
        • Bowers M.E.
        • Troller-Renfree S.V.
        • Chronis-Tuscano A.
        • Pine D.S.
        • et al.
        Inhibitory control and set shifting describe different pathways from behavioral inhibition to socially anxious behavior.
        Dev Sci. 2021; 24: e13040
        • Valadez E.A.
        • Troller-Renfree S.V.
        • Buzzell G.A.
        • Henderson H.A.
        • Chronis-Tuscano A.
        • Pine D.S.
        • Fox N.A.
        Behavioral inhibition and dual mechanisms of anxiety risk: Disentangling neural correlates of proactive and reactive control.
        JCPP Adv. 2021; 1: e12022
        • Derakshan N.
        • Eysenck M.W.
        Anxiety, processing efficiency, and cognitive performance: New developments from attentional control theory.
        European Psychologist. 2009; 14: 168-176
        • Eysenck M.W.
        • Derakshan N.
        • Santos R.
        • Calvo M.G.
        Anxiety and cognitive performance: Attentional control theory.
        Emotion. 2007; 7: 336-353
        • Venables N.C.
        • Foell J.
        • Yancey J.R.
        • Kane M.J.
        • Engle R.W.
        • Patrick C.J.
        Quantifying inhibitory control as externalizing proneness: A cross-domain model.
        Clinical Psychological Science. 2018; 6: 561-580
        • Fishburn F.A.
        • Hlutkowsky C.O.
        • Bemis L.M.
        • Huppert T.J.
        • Wakschlag L.S.
        • Perlman S.B.
        Irritability uniquely predicts prefrontal cortex activation during preschool inhibitory control among all temperament domains: A LASSO approach.
        Neuroimage. 2019; 184: 68-77
        • Li Y.
        • Grabell A.S.
        • Wakschlag L.S.
        • Huppert T.J.
        • Perlman S.B.
        The neural substrates of cognitive flexibility are related to individual differences in preschool irritability: A fNIRS investigation.
        Dev Cogn Neurosci. 2017; 25: 138-144
        • Liuzzi M.T.
        • Kryza-Lacombe M.
        • Christian I.R.
        • Palumbo D.E.
        • Amir N.
        • Wiggins J.L.
        Neural and behavioral correlates of inhibitory control in youths with varying levels of irritability.
        J Affect Disord. 2020; 273: 567-575
        • Tseng W.L.
        • Deveney C.M.
        • Stoddard J.
        • Kircanski K.
        • Frackman A.E.
        • Yi J.Y.
        • et al.
        Brain mechanisms of attention orienting following frustration: Associations with irritability and age in youths.
        Am J Psychiatry. 2019; 176: 67-76
        • Dugré J.R.
        • Potvin S.
        Developmental multi-trajectory of irritability, anxiety, and hyperactivity as psychological markers of heterogeneity in childhood aggression.
        Psychol Med. 2022; 52: 241-250
        • Pagliaccio D.
        • Pine D.S.
        • Barch D.M.
        • Luby J.L.
        • Leibenluft E.
        Irritability trajectories, cortical thickness, and clinical outcomes in a sample enriched for preschool depression.
        J Am Acad Child Adolesc Psychiatry. 2018; 57: 336-342.e6
        • Feng X.
        • Shaw D.S.
        • Silk J.S.
        Developmental trajectories of anxiety symptoms among boys across early and middle childhood.
        J Abnorm Psychol. 2008; 117: 32-47
        • Kessel E.M.
        • Meyer A.
        • Hajcak G.
        • Dougherty L.R.
        • Torpey-Newman D.C.
        • Carlson G.A.
        • Klein D.N.
        Transdiagnostic factors and pathways to multifinality: The error-related negativity predicts whether preschool irritability is associated with internalizing versus externalizing symptoms at age 9.
        Dev Psychopathol. 2016; 28: 913-926
        • Kircanski K.
        • White L.K.
        • Tseng W.L.
        • Wiggins J.L.
        • Frank H.R.
        • Sequeira S.
        • et al.
        A latent variable approach to differentiating neural mechanisms of irritability and anxiety in youth.
        JAMA Psychiatry. 2018; 75: 631-639
        • Stoddard J.
        • Tseng W.L.
        • Kim P.
        • Chen G.
        • Yi J.
        • Donahue L.
        • et al.
        Association of irritability and anxiety with the neural mechanisms of implicit face emotion processing in youths with psychopathology.
        JAMA Psychiatry. 2017; 74: 95-103
        • Cardinale E.M.
        • Pagliaccio D.
        • Swetlitz C.
        • Grassie H.
        • Abend R.
        • Costa V.
        • et al.
        Deliberative choice strategies in youths: Relevance to transdiagnostic anxiety symptoms.
        Clin Psychol Sci. 2021; 9: 979-989
        • Hane A.A.
        • Fox N.A.
        • Henderson H.A.
        • Marshall P.J.
        Behavioral reactivity and approach-withdrawal bias in infancy.
        Dev Psychol. 2008; 44: 1491-1496
        • Michalska K.J.
        • Feldman J.S.
        • Ivie E.J.
        • Shechner T.
        • Sequeira S.
        • Averbeck B.
        • et al.
        Early-childhood social reticence predicts SCR-BOLD coupling during fear extinction recall in preadolescent youth.
        Dev Cogn Neurosci. 2019; 36: 100605
        • Jarcho J.M.
        • Davis M.M.
        • Shechner T.
        • Degnan K.A.
        • Henderson H.A.
        • Stoddard J.
        • et al.
        Early-childhood social reticence predicts brain function in preadolescent youths during distinct forms of peer evaluation.
        Psychol Sci. 2016; 27: 821-835
        • 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
        • Achenbach T.M.
        • Ruffle T.M.
        The Child Behavior Checklist and related forms for assessing behavioral/emotional problems and competencies.
        Pediatr Rev. 2000; 21: 265-271
        • Wiggins J.L.
        • Mitchell C.
        • Stringaris A.
        • Leibenluft E.
        Developmental trajectories of irritability and bidirectional associations with maternal depression.
        J Am Acad Child Adolesc Psychiatry. 2014; 53: 1191-1205.e4
        • Birmaher B.
        • Khetarpal S.
        • Brent D.
        • Cully M.
        • Balach L.
        • Kaufman J.
        • Neer S.M.
        The Screen for Child Anxiety Related Emotional Disorders (SCARED): Scale construction and psychometric characteristics.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 545-553
        • Stringaris A.
        • Goodman R.
        • Ferdinando S.
        • Razdan V.
        • Muhrer E.
        • Leibenluft E.
        • Brotman M.A.
        The Affective Reactivity Index: A concise irritability scale for clinical and research settings.
        J Child Psychol Psychiatry. 2012; 53: 1109-1117
        • Egner T.
        • Hirsch J.
        The neural correlates and functional integration of cognitive control in a Stroop task.
        Neuroimage. 2005; 24: 539-547
        • Jiang J.
        • Beck J.
        • Heller K.
        • Egner T.
        An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands.
        Nat Commun. 2015; 6: 8165
        • Aron A.R.
        • Robbins T.W.
        • Poldrack R.A.
        Inhibition and the right inferior frontal cortex: one decade on.
        Trends Cogn Sci. 2014; 18: 177-185
        • Uddin L.Q.
        • Nomi J.S.
        • Hébert-Seropian B.
        • Ghaziri J.
        • Boucher O.
        Structure and function of the human insula.
        J Clin Neurophysiol. 2017; 34: 300-306
        • McLaughlin K.A.
        • King K.
        Developmental trajectories of anxiety and depression in early adolescence.
        J Abnorm Child Psychol. 2015; 43: 311-323
        • Wittfoth M.
        • Buck D.
        • Fahle M.
        • Herrmann M.
        Comparison of two Simon tasks: Neuronal correlates of conflict resolution based on coherent motion perception.
        Neuroimage. 2006; 32: 921-929
        • Meyer A.
        A biomarker of anxiety in children and adolescents: A review focusing on the error-related negativity (ERN) and anxiety across development.
        Dev Cogn Neurosci. 2017; 27: 58-68
        • Dehaene S.
        • Posner M.I.
        • Tucker D.M.
        Localization of a neural system for error detection and compensation.
        Psychol Sci. 1994; 5: 303-305
        • Ridderinkhof K.R.
        The role of the medial frontal cortex in cognitive control.
        Science. 2004; 306: 443-447
        • Fitzgerald K.D.
        • Liu Y.
        • Stern E.R.
        • Welsh R.C.
        • Hanna G.L.
        • Monk C.S.
        • et al.
        Reduced error-related activation of dorsolateral prefrontal cortex across pediatric anxiety disorders.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 1183-1191.e1
        • Meyer A.
        • Weinberg A.
        • Klein D.N.
        • Hajcak G.
        The development of the error-related negativity (ERN) and its relationship with anxiety: Evidence from 8 to 13 year-olds.
        Dev Cogn Neurosci. 2012; 2: 152-161
        • Aebi M.
        • Plattner B.
        • Metzke C.W.
        • Bessler C.
        • Steinhausen H.C.
        Parent- and self-reported dimensions of oppositionality in youth: Construct validity, concurrent validity, and the prediction of criminal outcomes in adulthood.
        J Child Psychol Psychiatry. 2013; 54: 941-949
        • Stringaris A.
        • Zavos H.
        • Leibenluft E.
        • Maughan B.
        • Eley T.C.
        Adolescent irritability: Phenotypic associations and genetic links with depressed mood.
        Am J Psychiatry. 2012; 169: 47-54
        • Tseng W.L.
        • Moroney E.
        • Machlin L.
        • Roberson-Nay R.
        • Hettema J.M.
        • Carney D.
        • et al.
        Test-retest reliability and validity of a frustration paradigm and irritability measures.
        J Affect Disord. 2017; 212: 38-45
        • Dougherty L.R.
        • Galano M.M.
        • Chad-Friedman E.
        • Olino T.M.
        • Bufferd S.J.
        • Klein D.N.
        Using item response theory to compare irritability measures in early adolescent and childhood samples.
        Assessment. 2021; 28: 918-927
        • Stringaris A.
        • Cohen P.
        • Pine D.S.
        • Leibenluft E.
        Adult outcomes of youth irritability: A 20-year prospective community-based study.
        Am J Psychiatry. 2009; 166: 1048-1054
        • Pine D.S.
        • Cohen P.
        • Brook J.
        Adolescent fears as predictors of depression.
        Biol Psychiatry. 2001; 50: 721-724