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. 2022 Mar 15;23(6):3176.
doi: 10.3390/ijms23063176.

Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample

Jalmar Teeuw  1 , Marieke Klein  2   3   4 , Nina Roth Mota  3   4 , Rachel M Brouwer  1   5 , Dennis van 't Ent  6 , Zyneb Al-Hassaan  1 , Barbara Franke  3   4   7 , Dorret I Boomsma  6   8 , Hilleke E Hulshoff Pol  1   9
Affiliations

Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample

Jalmar Teeuw et al. Int J Mol Sci. .

Abstract

Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers, and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and the brain volumes and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) with magnetic resonance imaging in the BrainSCALE cohort, which consisted of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years for the twins. Genetic covariance modeling based on the classical twin design, extended to also include siblings of twins, showed that genes influence externalizing behavior and changes therein (h2 up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation rph up to +0.20) and lower MD (rph up to -0.20), with sizeable genetic correlations (FA ra up to +0.42; MD ra up to -0.33). The cortical gray matter (CGM; rph up to -0.20) and cerebral white matter (CWM; rph up to +0.20) volume were phenotypically but not genetically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence of the same genetic factor.

Keywords: adolescence; externalizing behavior; genetic correlation; gray matter volume; heritability; longitudinal; magnetic resonance imaging; white matter integrity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Phenotypic development of externalizing behavior throughout adolescence. Measurements are based on the externalizing scale of the Child Behavior Checklist and Youth Self Report. Data points are plotted for the untransformed scores on the y-axis. Estimates of sex and age regression coefficients and p-value were obtained from the longitudinal genetic model on the log10-transformed scores. Abbreviations (in alphabetical order): CBCL = child behavior checklist; CI = confidence interval; n.s. = not significant; YSR = youth self-report.
Figure 2
Figure 2
Development of global brain structures for boys and girls throughout adolescence. Sex effects for total (sub)cortical gray matter volume and cerebral white matter volume are plotted after simultaneous regression of total brain volume. The effect of sex was significant for all six global brain structures; the exact effect sizes and p-values of sex and age are reported in Supplementary Data File F2. Abbreviation (in alphabetical order): CI = confidence interval; n.s. = not significant.
Figure 3
Figure 3
Associations between externalizing behavior and global brain structures throughout adolescence. Phenotypic association (rph) of the log10-transformed scores of externalizing behavior on the CBCL or YSR questionnaire with Z-standardized measures of global brain structures (only listing uncorrected p < 0.05 significant associations). Bar charts display the total variance explained by the phenotypic (light gray) and genetic (dark gray) associations. Abbreviations (in alphabetical order): CBCL = Child Behavior Check List; FA = fractional anisotropy; MD = mean diffusivity; YSR = Youth Self Report.
Figure 4
Figure 4
Longitudinal structural equation model applied to the longitudinal data on brain and behavior. Boxes represent observed measures of behavior and/or brain features; circles represent the latent factors for additive genetic (blue), common environment (orange), and unique environment (green). Path coefficients between the latent factors and observed measures are estimated by the model. For simplicity, this model is shown for only one member of the family. The full model includes three family members, where latent genetic factors between family members are correlated depending on their relationship (i.e., correlation of 1.0 for MZ twins, 0.5 for DZ twins and between twin and sibling pairs), common environmental factors between family members are always shared (i.e., correlation of 1.0), and unique environment factors are uncorrelated by definition.
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References

    1. Christenson J.D., Crane D.R., Malloy J., Parker S. The Cost of Oppositional Defiant Disorder and Disruptive Behavior: A Review of the Literature. J. Child Fam. Stud. 2016;25:2649–2658. doi: 10.1007/s10826-016-0430-9. - DOI
    1. Achenbach T.M., Reschorla L.A. Manual for the ASEBA School-Age Forms and Profiles. Achenbach; Burlington, VT, USA: 2001.
    1. Bongers I.L., Koot H.M., van der Ende J., Verhulst F.C. Developmental Trajectories of Externalizing Behaviors in Childhood and Adolescence. Child Dev. 2004;75:1523–1537. doi: 10.1111/j.1467-8624.2004.00755.x. - DOI - PubMed
    1. Van Lier P.A., Verhulst F.C., Van Der Ende J., Crijnen A.A. Classes of disruptive behaviour in a sample of young elementary school children. J. Child Psychol. Psychiatry. 2003;44:377–387. doi: 10.1111/1469-7610.00128. - DOI - PubMed
    1. Van Hazebroek B.C.M., Blokland A.A.J., Wermink H.T., De Keijser J.W., Popma A., Van Domburgh L. Delinquent Development Among Early-Onset Offenders: Identifying and Characterizing Trajectories Based on Frequency Across Types of Offending. Crim. Justice Behav. 2019;46:1542–1565. doi: 10.1177/0093854819876306. - DOI

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