Anxious/depressed symptoms are related to microstructural maturation of white matter in typically developing youths

AbstractThere are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.

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Maturity of brain structures and white matter connectomes, and their relationship with psychiatric symptoms in youth

10.1101/2020.03.02.20029488 ◽

2020 ◽

Author(s):

Alex Luna ◽

Joel Bernanke ◽

Jiook Cha ◽

Jonathan Posner

Keyword(s):

White Matter ◽

Child Behavior ◽

Child Behavior Checklist ◽

Psychiatric Symptoms ◽

Flanker Task ◽

Brain Network ◽

Single Type ◽

Age Difference ◽

Imaging Data ◽

Global Assessment Scale

AbstractBackgroundBrain neuromaturation can be indexed using brain predicted age difference (BrainPAD), a metric derived by the application of machine learning (ML) algorithms to neuroimaging. Previous studies in youth have been limited to a single type of imaging data, single ML approach, or specific psychiatric condition. Here, we use multimodal neuroimaging and an ensemble ML algorithm to estimate BrainPAD and examine its relationship with broad measures of symptoms and functioning in youth.MethodsWe used neuroimaging from eligible participants in the Healthy Brain Network (HBN, N = 498). Participants with a Child Behavior Checklist Total Problem T-Score < 60 were split into training (N=215) and test sets (N=48). Morphometry estimates (from structural MRI), white matter connectomes (from diffusion MRI), or both were fed to an automated ML pipeline to develop BrainPAD models. The most accurate model was applied to a held-out evaluation set (N=249), and the association with several psychometrics was estimated.ResultsModels using morphometry and connectomes together had a mean absolute error of 1.16 years, outperforming unimodal models. After dividing participants into positive, normal, and negative BrainPAD groups, negative BrainPAD values were associated with more symptoms on the Child Behavior Checklist (negative=71.6, normal 59.0, p=0.011) and lower functioning on the Children’s Global Assessment Scale (negative=49.3, normal=58.3, p=0.002). Higher scores were associated with better performance on the Flanker task (positive=62.4, normal=52.5, p=0.006).ConclusionThese findings suggest that a multimodal approach, in combination with an ensemble method, yields a robust biomarker correlated with clinically relevant measures in youth.

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Microstructural development across white matter from 9-13 years

10.1101/2021.06.04.447102 ◽

2021 ◽

Author(s):

Clare E Palmer ◽

Diliana Pecheva ◽

John Rehner Iversen ◽

Donald J Hagler ◽

Leo Sugrue ◽

...

Keyword(s):

White Matter ◽

Statistical Power ◽

Diffusion Tensor ◽

Microstructural Development ◽

Global Changes ◽

Cross Sectional ◽

Microstructural Changes ◽

Age Related ◽

Subcortical Regions ◽

Spatially Varying

Development in late childhood has been associated with microstructural changes in white matter (WM) that are hypothesized to underpin concurrent changes in cognitive and behavioral function. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that can probe microstructural changes within hindered and restricted compartments providing greater specificity than diffusion tensor imaging for characterizing intracellular diffusion. Using RSI, we modelled voxelwise restricted isotropic, N0, and anisotropic, ND, diffusion across the brain and measured cross-sectional and longitudinal age associations in a large sample (n=8,039) aged 9-13 years from the Adolescent Brain and Cognitive Development (ABCD) StudySM. Participants showed global increases in N0 and ND across WM with age. When controlling for global RSI measures (averaged across WM), we found smaller age-related associations in frontal regions, reflective of more protracted development of frontal WM. Moreover, variability in the development of restricted diffusion in subcortical regions and along particular gray-white matter boundaries was independent of the global developmental effect. Using the ABCD sample, we have unprecedented statistical power to estimate developmental effects with high precision. Our analyses reveal spatially-varying maturational changes for different regions, independent of global changes. This non-uniformity may reflect age-dependent development of distinct cognitive and behavioral processes.

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Consistency of Fractional Anisotropy Values Using Different Combinations of b-Value and Time of Echo (TE) in Diffusion Tensor Imaging of Normal Brain White Matter

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2018/38089.12315 ◽

2018 ◽

Author(s):

Rahul P Kotian ◽

K Prakashini ◽

Sreekumaran Nair ◽

M Satish Babu

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

B Value ◽

Normal Brain ◽

Brain White Matter

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Prenatal maternal and childhood bisphenol a exposure and brain structure and behavior of young children

Environmental Health ◽

10.1186/s12940-019-0528-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 7

Author(s):

Melody N. Grohs ◽

◽

Jess E. Reynolds ◽

Jiaying Liu ◽

Jonathan W. Martin ◽

...

Keyword(s):

White Matter ◽

Bisphenol A ◽

Child Behavior ◽

Brain Structure ◽

Child Behavior Checklist ◽

Mean Diffusivity ◽

Internalizing Behavior ◽

Spot Urine ◽

White Matter Microstructure ◽

The Relationship

Abstract Background Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children’s brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior. Methods Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3–4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2–5 years (3.7 ± 0.8 years). Associations between prenatal maternal and childhood BPA and children’s fractional anisotropy and mean diffusivity of 10 isolated white matter tracts were investigated, controlling for urinary creatinine, child sex, and age at the time of MRI. Post-hoc analyses examined if alterations in white matter mediated the relationship of BPA and children’s scores on the Child Behavior Checklist (CBCL). Results Prenatal maternal urinary BPA was significantly associated with child mean diffusivity in the splenium and right inferior longitudinal fasciculus. Splenium diffusivity mediated the relationship between maternal prenatal BPA levels and children’s internalizing behavior (indirect effect: β = 0.213, CI [0.0167, 0.564]). No significant associations were found between childhood BPA and white matter microstructure. Conclusions This study provides preliminary evidence for the neural correlates of BPA exposure in humans. Our findings suggest that prenatal maternal exposure to BPA may lead to alterations in white matter microstructure in preschool aged children, and that such alterations mediate the relationship between early life exposure to BPA and internalizing problems.

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Multimodal white matter imaging to investigate reduced fractional anisotropy and its age-related decline in schizophrenia

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2014.05.004 ◽

2014 ◽

Vol 223 (2) ◽

pp. 148-156 ◽

Cited By ~ 29

Author(s):

Peter Kochunov ◽

Joshua Chiappelli ◽

Susan N. Wright ◽

Laura M. Rowland ◽

Beenish Patel ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Age Related

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Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

10.1101/677898 ◽

2019 ◽

Author(s):

Yaron Caspi ◽

Rachel M. Brouwer ◽

Hugo G. Schnack ◽

Marieke E. van de Nieuwenhuijzen ◽

Wiepke Cahn ◽

...

Keyword(s):

Mixed Model ◽

Linear Mixed Model ◽

Brain Aging ◽

Age Groups ◽

Direct Calculation ◽

Normal Brain ◽

Intracranial Volume ◽

Cross Sectional ◽

Age Related ◽

Fourth Decade

AbstractNormal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N=482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line and applying a global linear mixed model fitting. We report statistically significant increases in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decreases in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinal setup are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.

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Mütterliche Belastung bei Kindern mit Williams-Beuren-Syndrom, Down-Syndrom, geistiger Behinderung nichtsyndromaler Ätiologie im Vergleich zu der nichtbehinderter Kinder

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024//1422-4917.29.4.285 ◽

2001 ◽

Vol 29 (4) ◽

pp. 285-295 ◽

Cited By ~ 4

Author(s):

A. Gosch

Keyword(s):

Child Behavior ◽

Child Behavior Checklist ◽

Kindliches Verhalten

Zusammenfassung: Fragestellung: In der vorliegenden Studie sollte geklärt werden, ob sich Mütter von Kindern mit geistiger Behinderung unterschiedlicher Ätiologie (Williams-Beuren-Syndrom - WBS, Down-Syndrom - DS, nichtsyndromaler Ätiologie - LB/GB) von Müttern nichtbehinderter Kinder in ihrem Belastungserleben unterscheiden. Methodik: Es wurden 85 Mütter von Kindern mit WBS, DS, LB/GB und Mütter von nichtbehinderten Kindern (VG) mithilfe des Patenting Stress Indexes (PSI) befragt. Den Müttern wurde zusätzlich die Child Behavior Checklist (CBCL) vorgelegt, um kindliche Verhaltensauffälligkeiten zu erfassen. Die Parallelisierung fand anhand desAlters der Kinder, des Geschlechts und der Wortschatztestleistung im Hamburg Wechsler Intelligenztest (HAWIK-R) statt. Ergebnisse: Mütter von Kindern mit WBS und DS weisen einen signifikanten höheren PSI-Gesamtstresswert auf als Mütter von Kindern mit LB/GB und VG. Dieses Ergebnis ist auf signifikante Unterschiede zwischen den Gruppen bezüglich des kindbezogenen Stresses, aber nicht der elternbezogenen Belastung, zurückzuführen. Auf Subskalenebene des Kinderbereichs fühlen sich Mütter von Kindern mit WBS und DS im Vergleich zu den anderen beiden Gruppen signifikant durch die kindlichen Anforderungen und dem wenig akzeptablen Verhalten ihres Kindes belastet. Mütter von Kindern mit LB/GB beschreiben sich ebenfalls als signifikant belasteter durch ein unakzeptables kindliches Verhalten als Mütter normalentwickelter Kinder. Mütter von Kindern mit WBS schätzen ihre Belastung durch ein hyperaktives Verhalten, eine geringe Anpassungsfähigkeit und größere Stimmungslabilität ihrer Kinder signifikant höher ein als Mütter der anderen drei Gruppen. Bezüglich des Erwachsenenbereichs schätzen sich Mütter von Kindern mit DS als signifikant depressiver und weniger kompetent in ihrem Erziehungsverhalten ein und geben mehr Gesundheitssorgen an als Mütter der anderen drei Gruppen. Mütter von Kindern mit LB/GB fühlen sich im Vergleich zu den anderen Gruppen am wenigsten durch partnerschaftliche Probleme belastet und in ihrer elterlichen Rolle eingeschränkt. Kein Zusammenhang kann zwischen dem kindlichen Alter, dem sozioökonomischen Status und dem Belastungsgrad gesehen werden, allerdings korrelieren der Grad der geistigen Behinderung als auch der Verhaltensauffälligkeiten signifikant mit dem mütterlichen Belastungsgrad. Schlussfolgerung: Es kann festgehalten werden, dass es sowohl allgemeine Belastungsfaktoren wie die hohen Anforderungen durch das Kind und sein unakzeptableres Verhalten gibt, die mit einer kindlichen Behinderung einhergehen als auch spezifische, die mit dem Verhaltensphänotyp eines Syndroms assoziiert sind.

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Anwendbarkeit der Child Behavior Checklist bei entwicklungsgestörten Kindern

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024//1422-4917.27.3.183 ◽

1999 ◽

Vol 27 (3) ◽

pp. 183-188 ◽

Cited By ~ 16

Author(s):

M. Noterdaeme ◽

F. Minow ◽

H. Amorosa

Keyword(s):

Child Behavior ◽

Child Behavior Checklist ◽

Soziale Probleme

Zusammenfassung: Frage: Die Child Behavior Checklist (CBCL) wird in großen, unausgelesenen Stichproben verwendet, um Verhaltensauffälligkeiten bei Kindern und Jugendlichen zu erfassen. In der hier vorgelegten Arbeit wird untersucht, inwieweit sich die CBCL eignet, um die bei einer Stichprobe entwicklungsgestörter Kinder typischerweise auftretenden Probleme zu erfassen. Methodik: Es wurden zwei Stichproben entwicklungsgestörter Kinder, bei denen Schwierigkeiten im Bereich der Sprache und der Kommunikation bestanden, untersucht. Es handelte sich um 34 Kinder mit einem frühkindlichen Autismus und 34 alters-, geschlechts- und intelligenzparallelisierte Kinder mit einer spezifischen Sprachentwicklungsstörung. Bei den zwei Stichproben wurde im Rahmen der routinemäßigen Abklärung der Symptomatik die CBCL ausgefüllt. Ergebnisse: Die Hälfte der sprachgestörten Kinder hatten im CBCL-Gesamtscore Werte im klinischen Bereich. Bei diesen Kindern sind die Probleme vor allem auf den Skalen «Aufmerksamkeitsstörungen», «Soziale Probleme» und «Zurückgezogenheit» anzutreffen. Etwa zwei Drittel der autistischen Kinder werden auf den oben genannten Syndromskalen als auffällig eingestuft. 32 der 34 autistischen Kinder erreichen auf der Skala V «Schizoid/Zwanghaft» auffällige Werte, während dies nur für ein sprachgestörtes Kind der Fall ist. Die Einzelitem-Analyse zeigt, daß in beiden Stichproben überdurchschnittlich häufig über entwicklungsbezogene Probleme (Sprechprobleme, Einnässen…) berichtet wird. Schlußfolgerungen: Die CBCL ist geeignet, um die bei entwicklungsgestörten Kindern charakteristischen Verhaltensauffälligkeiten zu erfassen. Diese Auffälligkeite n werden sowohl auf der Ebene der Syndromskalen wie auch durch Einzelitems erfaßt. Hohe Werte auf der Skala «Schizoid/Zwanghaft» sollten bei diesen Kindern Anlaß zu einer gezielten diagnostischen Abklärung eines frühkindlichen Autismus geben.

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