Timing and Type of Early Psychopathology Symptoms Predict Longitudinal Change in Cortical Thickness From Middle Childhood Into Early Adolescence

      Abstract

      Background

      Early-life experiences have profound effects on functioning in adulthood. Altered cortical development may be one mechanism through which early-life experiences, including poverty and psychopathology symptoms, affect outcomes. However, there is little prospective research beginning early in development that combines clinician-rated psychopathology symptoms and multiwave magnetic resonance imaging to examine when these relationships emerge.

      Methods

      Children from the Preschool Depression Study who completed diagnostic interviews at three different developmental stages (preschool, school age, early adolescent) and up to three magnetic resonance imaging scans beginning in middle childhood participated in this study (N = 138). Multilevel models were used to calculate intercepts and slopes of cortical thickness within a priori cortical regions of interest. Linear regressions probed how early-life poverty and psychopathology (depression, anxiety, and externalizing symptoms at separate developmental periods) related to intercept/slope.

      Results

      Collectively, experiences during the preschool period predicted reduced cortical thickness, via either reduced intercept or accelerated thinning (slope). Early-life poverty predicted intercepts within sensory and sensory-motor integration regions. Beyond poverty, preschool anxiety symptoms predicted intercepts within the insula, subgenual cingulate, and inferior parietal cortex. Preschool externalizing symptoms predicted accelerated thinning within prefrontal and parietal cortices. Depression and anxiety/externalizing symptoms at later ages were not significant predictors.

      Conclusions

      Early childhood is a critical period of risk; experiences at this developmental stage specifically have the potential for prolonged influence on brain development. Negative early experiences collectively predicted reduced cortical thickness, but the specific neural systems affected aligned with those typically implicated in these individual disorders/experiences.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Staff R.T.
        • Murray A.D.
        • Ahearn T.S.
        • Mustafa N.
        • Fox H.C.
        • Whalley L.J.
        Childhood socioeconomic status and adult brain size: Childhood socioeconomic status influences adult hippocampal size.
        Ann Neurol. 2012; 71: 653-660
        • Cohen R.A.
        • Grieve S.
        • Hoth K.F.
        • Paul R.H.
        • Sweet L.
        • Tate D.
        • et al.
        Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei.
        Biol Psychiatry. 2006; 59: 975-982
        • Hanson J.L.
        • Hair N.
        • Shen D.G.
        • Shi F.
        • Gilmore J.H.
        • Wolfe B.L.
        • Pollak S.D.
        Family poverty affects the rate of human infant brain growth.
        PLoS One. 2013; 8e80954
        • Luby J.L.
        • Baram T.Z.
        • Rogers C.E.
        • Barch D.M.
        Neurodevelopmental optimization after early-life adversity: Cross-species studies to elucidate sensitive periods and brain mechanisms to inform early intervention.
        Trends Neurosci. 2020; 43: 744-751
        • Luby J.L.
        • Belden A.C.
        • Jackson J.J.
        • Lessov-Schlaggar C.N.
        • Harms M.P.
        • Tillman R.
        • et al.
        Early childhood depression and alterations in the trajectory of gray matter maturation in middle childhood and early adolescence.
        JAMA Psychiatry. 2016; 73: 31-38
        • Whittle S.
        • Vijayakumar N.
        • Simmons J.G.
        • Allen N.B.
        Internalizing and externalizing symptoms are associated with different trajectories of cortical development during late childhood.
        J Am Acad Child Adolesc Psychiatry. 2020; 59: 177-185
        • Merz E.C.
        • He X.
        • Noble K.G.
        • Pediatric Imaging, Neurocognition, and Genetics Study
        Anxiety, depression, impulsivity, and brain structure in children and adolescents.
        Neuroimage Clin. 2018; 20: 243-251
        • Kaczkurkin A.N.
        • Park S.S.
        • Sotiras A.
        • Moore T.M.
        • Calkins M.E.
        • Cieslak M.
        • et al.
        Evidence for dissociable linkage of dimensions of psychopathology to brain structure in youths.
        Am J Psychiatry. 2019; 176: 1000-1009
        • Merikangas K.R.
        • He J.P.
        • Burstein M.
        • Swanson S.A.
        • Avenevoli S.
        • Cui L.
        • et al.
        Lifetime prevalence of mental disorders in U.S. adolescents: Results from the National comorbidity Survey Replication—Adolescent Supplement (NCS-A).
        J Am Acad Child Adolesc Psychiatry. 2010; 49: 980-989
        • Amlien I.K.
        • Fjell A.M.
        • Tamnes C.K.
        • Grydeland H.
        • Krogsrud S.K.
        • Chaplin T.A.
        • et al.
        Organizing principles of human cortical development—Thickness and area from 4 to 30 years: Insights from comparative primate neuroanatomy.
        Cereb Cortex. 2016; 26: 257-267
        • Walhovd K.B.
        • Fjell A.M.
        • Giedd J.
        • Dale A.M.
        • Brown T.T.
        Through thick and thin: A need to reconcile contradictory results on trajectories in human cortical development.
        Cereb Cortex. 2017; 27: 1472-1481
        • Ducharme S.
        • Albaugh M.D.
        • Nguyen T.V.
        • Hudziak J.J.
        • Mateos-Pérez J.M.
        • Labbe A.
        • et al.
        Trajectories of cortical thickness maturation in normal brain development—The importance of quality control procedures.
        Neuroimage. 2016; 125: 267-279
        • Huttenlocher P.R.
        Synaptic density in human frontal cortex—Developmental changes and effects of aging.
        Brain Res. 1979; 163: 195-205
        • Petanjek Z.
        • Judaš M.
        • Šimic G.
        • Rasin M.R.
        • Uylings H.B.
        • Rakic P.
        • Kostovic I.
        Extraordinary neoteny of synaptic spines in the human prefrontal cortex.
        Proc Natl Acad Sci U S A. 2011; 108: 13281-13286
        • Parker N.
        • Patel Y.
        • Jackowski A.P.
        • Pan P.M.
        • Salum G.A.
        • Pausova Z.
        • et al.
        Assessment of neurobiological mechanisms of cortical thinning during childhood and adolescence and their implications for psychiatric disorders.
        JAMA Psychiatry. 2020; 77: 1127-1136
        • Sotiras A.
        • Toledo J.B.
        • Gur R.E.
        • Gur R.C.
        • Satterthwaite T.D.
        • Davatzikos C.
        Patterns of coordinated cortical remodeling during adolescence and their associations with functional specialization and evolutionary expansion.
        Proc Natl Acad Sci U S A. 2017; 114: 3527-3532
        • Fjell A.M.
        • Grydeland H.
        • Krogsrud S.K.
        • Amlien I.
        • Rohani D.A.
        • Ferschmann L.
        • et al.
        Development and aging of cortical thickness correspond to genetic organization patterns.
        Proc Natl Acad Sci U S A. 2015; 112: 15462-15467
        • Shaw P.
        • Kabani N.J.
        • Lerch J.P.
        • Eckstrand K.
        • Lenroot R.
        • Gogtay N.
        • et al.
        Neurodevelopmental trajectories of the human cerebral cortex.
        J Neurosci. 2008; 28: 3586-3594
        • Sotiras A.
        • Resnick S.M.
        • Davatzikos C.
        Finding imaging patterns of structural covariance via non-negative matrix factorization.
        Neuroimage. 2015; 108: 1-16
        • Newman E.
        • Thompson W.K.
        • Bartsch H.
        • Hagler Jr., D.J.
        • Chen C.H.
        • Brown T.T.
        • et al.
        Anxiety is related to indices of cortical maturation in typically developing children and adolescents.
        Brain Struct Funct. 2016; 221: 3013-3025
        • McLaughlin K.A.
        • Sheridan M.A.
        • Winter W.
        • Fox N.A.
        • Zeanah C.H.
        • Nelson C.A.
        Widespread reductions in cortical thickness following severe early-life deprivation: A neurodevelopmental pathway to attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2014; 76: 629-638
        • Ducharme S.
        • Hudziak J.J.
        • Botteron K.N.
        • Albaugh M.D.
        • Nguyen T.V.
        • Karama S.
        • et al.
        Decreased regional cortical thickness and thinning rate are associated with inattention symptoms in healthy children.
        J Am Acad Child Adolesc Psychiatry. 2012; 51: 18-27.e2
        • Willner C.J.
        • Gatzke-Kopp L.M.
        • Bray B.C.
        The dynamics of internalizing and externalizing comorbidity across the early school years.
        Dev Psychopathol. 2016; 28: 1033-1052
        • Blair C.
        • Raver C.C.
        Poverty, stress, and brain development: New directions for prevention and intervention.
        Acad Pediatr. 2016; 16: S30-S36
        • McDermott C.L.
        • Seidlitz J.
        • Nadig A.
        • Liu S.
        • Clasen L.S.
        • Blumenthal J.D.
        • et al.
        Longitudinally mapping childhood socioeconomic status associations with cortical and subcortical morphology.
        J Neurosci. 2019; 39: 1365-1373
        • Hair N.L.
        • Hanson J.L.
        • Wolfe B.L.
        • Pollak S.D.
        Association of Child Poverty, brain development, and academic achievement.
        JAMA Pediatr. 2015; 169: 822-829
        • Wadsworth M.E.
        • Achenbach T.M.
        Explaining the link between low socioeconomic status and psychopathology: Testing two mechanisms of the social causation hypothesis.
        J Consult Clin Psychol. 2005; 73: 1146-1153
        • Luby J.L.
        • Heffelfinger A.
        • Koenig-McNaught A.L.
        • Brown K.
        • Spitznagel E.
        The Preschool Feelings Checklist: A brief and sensitive screening measure for depression in young children.
        J Am Acad Child Adolesc Psychiatry. 2004; 43: 708-717
        • Belden A.C.
        • Thomson N.R.
        • Luby J.L.
        Temper tantrums in healthy versus depressed and disruptive preschoolers: Defining tantrum behaviors associated with clinical problems.
        J Pediatr. 2008; 152: 117-122
        • Barch D.M.
        • Shirtcliff E.A.
        • Elsayed N.M.
        • Whalen D.
        • Gilbert K.
        • Vogel A.C.
        • et al.
        Testosterone and hippocampal trajectories mediate relationship of poverty to emotion dysregulation and depression.
        Proc Natl Acad Sci U S A. 2020; 117: 22015-22023
        • Egger H.L.
        • Erkanli A.
        • Keeler G.
        • Potts E.
        • Walter B.K.
        • Angold A.
        Test-retest reliability of the preschool age psychiatric assessment (PAPA).
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 538-549
        • Angold A.
        • Costello E.J.
        The child and adolescent psychiatric assessment (CAPA).
        J Am Acad Child Adolesc Psychiatry. 2000; 39: 39-48
        • McLoyd V.C.
        Socioeconomic disadvantage and child development.
        Am Psychol. 1998; 53: 185-204
        • King L.S.
        • Dennis E.L.
        • Humphreys K.L.
        • Thompson P.M.
        • Gotlib I.H.
        Cross-sectional and longitudinal associations of family income-to-needs ratio with cortical and subcortical brain volume in adolescent boys and girls.
        Dev Cogn Neurosci. 2020; 44: 100796
        • Noble K.G.
        • Houston S.M.
        • Brito N.H.
        • Bartsch H.
        • Kan E.
        • Kuperman J.M.
        • et al.
        Family income, parental education and brain structure in children and adolescents.
        Nat Neurosci. 2015; 18: 773-778
        • Luby J.
        • Allen N.
        • Estabrook R.
        • Pine D.S.
        • Rogers C.
        • Krogh-Jespersen S.
        • et al.
        Mapping infant neurodevelopmental precursors of mental disorders: How synthetic cohorts & computational approaches can be used to enhance prediction of early childhood psychopathology.
        Behav Res Ther. 2019; 123: 103484
        • Etkin A.
        • Wager T.D.
        Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia.
        Am J Psychiatry. 2007; 164: 1476-1488
        • Arnsten A.F.
        The emerging neurobiology of attention deficit hyperactivity disorder: The key role of the prefrontal association cortex.
        J Pediatr. 2009; 154: I-S43
        • Makris N.
        • Biederman J.
        • Valera E.M.
        • Bush G.
        • Kaiser J.
        • Kennedy D.N.
        • et al.
        Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder.
        Cereb Cortex. 2007; 17: 1364-1375
        • Kumar U.
        • Arya A.
        • Agarwal V.
        Neural alterations in ADHD children as indicated by voxel-based cortical thickness and morphometry analysis.
        Brain Dev. 2017; 39: 403-410
        • Vaidya C.J.
        Neurodevelopmental abnormalities in ADHD.
        Curr Top Behav Neurosci. 2012; 9: 49-66
        • Sacchet M.D.
        • Camacho M.C.
        • Livermore E.E.
        • Thomas E.A.C.
        • Gotlib I.H.
        Accelerated aging of the putamen in patients with major depressive disorder.
        J Psychiatry Neurosci. 2017; 42: 164-171
        • Whittle S.
        • Lichter R.
        • Dennison M.
        • Vijayakumar N.
        • Schwartz O.
        • Byrne M.L.
        • et al.
        Structural brain development and depression onset during adolescence: A prospective longitudinal study.
        Am J Psychiatry. 2014; 171: 564-571