Dataset Information

Deviations from normative brain white and gray matter structure are associated with psychopathology in youth.

ABSTRACT: Combining imaging modalities and metrics that are sensitive to various aspects of brain structure and maturation may help identify individuals that show deviations in relation to same-aged peers, and thus benefit early-risk-assessment for mental disorders. We used one timepoint multimodal brain imaging, cognitive, and questionnaire data from 1280 eight- to twenty-one-year-olds from the Philadelphia Neurodevelopmental Cohort. We estimated age-related gray and white matter properties and estimated individual deviation scores using normative modeling. Next, we tested for associations between the estimated deviation scores, and with psychopathology domain scores and cognition. More negative deviations in DTI-based fractional anisotropy (FA) and the first principal eigenvalue of the diffusion tensor (L1) were associated with higher scores on psychosis positive and prodromal symptoms and general psychopathology. A more negative deviation in cortical thickness (CT) was associated with a higher general psychopathology score. Negative deviations in global FA, surface area, L1 and CT were also associated with poorer cognitive performance. No robust associations were found between the deviation scores based on CT and DTI. The low correlations between the different multimodal magnetic resonance imaging-based deviation scores suggest that psychopathological burden in adolescence can be mapped onto partly distinct neurobiological features.

SUBMITTER: Kjelkenes R

PROVIDER: S-EPMC9637865 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Deviations from normative brain white and gray matter structure are associated with psychopathology in youth.

Kjelkenes Rikka R Wolfers Thomas T Alnæs Dag D Norbom Linn B LB Voldsbekk Irene I Holm Madelene M Dahl Andreas A Berthet Pierre P Tamnes Christian K CK Marquand Andre F AF Westlye Lars T LT

Developmental cognitive neuroscience 20221101

Combining imaging modalities and metrics that are sensitive to various aspects of brain structure and maturation may help identify individuals that show deviations in relation to same-aged peers, and thus benefit early-risk-assessment for mental disorders. We used one timepoint multimodal brain imaging, cognitive, and questionnaire data from 1280 eight- to twenty-one-year-olds from the Philadelphia Neurodevelopmental Cohort. We estimated age-related gray and white matter properties and estimated ...[more]

PMID: 36332329

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Project description:The heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology. For each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n = 195). Individuals with schizophrenia (n = 322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual. Compared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region. Furthermore, 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59 ± 2%, p < 0.001). Thus, while infra-normal deviations were common among patients, their anatomical loci were highly inconsistent between individuals. Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r = -0.17, p = 0.006). We conclude that anatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.

Project description:ImportanceMaternal tobacco use during pregnancy (MTDP) remains a major public health challenge. However, the complete spectrum of effects of MTDP is not fully understood.ObjectivesTo examine the longitudinal associations of MTDP and children's brain morphometric subcortical volume and gray-white matter contrast (GWC) development.Design, setting, and participantsCohort study of children aged 9 to 10 years at wave 1 (October 2016 to October 2018) and at a 2-year follow-up (wave 2; August 2018 to January 2021; aged 11-12 years) across 21 US sites in the Adolescent Brain Cognitive Development (ABCD) Study. Data were analyzed from October 2023 to October 2024.ExposureMTDP.Main outcomes and measuresMorphometric brain measures of subcortical volume and GWC.ResultsAmong the 11 448 children (51.5% male; 13.1% Black; 24.0% Hispanic; and 52.9% White) at wave 1, 1607 (16.6%; 95% CI, 13.0%-20.2%) were identified with MTDP exposure. At wave 1, children with MTDP exposure (vs no exposure) exhibited lower GWC in widespread brain regions primarily located in the frontal (eg, superior frontal; regression coefficient [B] = -0.0019; SE, 0.0006; P = .004), parietal (eg, supramarginal; B = -0.0021; SE, 0.0007; P = .002) and temporal lobes (eg, middle temporal; B = -0.0024; SE, 0.0007; P < .001). These differences in GWC continued to be significant at wave 2. In regard to subcortical volume, children with MTDP exposure demonstrated smaller volume of the lateral ventricle (B = -257.5; SE, 78.6; P = .001) and caudate (B = -37.7; SE, 14.0; P = .01) in the left hemisphere at wave 1, and lower volume of the caudate in both left (B = -48.7; SE, 15.9; P = .002) and right hemisphere (B = -45.5; SE, 16.1; P = .01) at wave 2.Conclusions and relevanceThis cohort study found that MTDP exposure was associated with lower GWC across the whole cortex and smaller caudate nuclei volume compared with no exposure, signifying the importance of preventing MTDP and necessitating further research on this topic.

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Deviations from normative brain white and gray matter structure are associated with psychopathology in youth.

Publications

Deviations from normative brain white and gray matter structure are associated with psychopathology in youth.

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