373. Adolescence is Associated with Genomically Patterned Consolidation of the Hubs of the Human Brain Connectome

Whitaker, Kirstie; Vértes, Petra E.; Romero-García, Rafael; Váša, František; Moutoussis, Michael; Prabhub, Gita; Weiskopf, Nikolaus; Callaghan, Martina F.; Wagstyl, Konrad; Rittman, Timothy; Tait, Roger; Ooi, Cinly; Suckling, John; Inkster, Becky; Fonagy, Peter; Dolan, Raymond J.; Jones, Peter; Goodyer, Ian; Consortium, The NSPN; Bullmore, Edward T.

doi:10.1016/j.biopsych.2017.02.390

Cited by 15 publications

(12 citation statements)

References 13 publications

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“…Consistent with this interpretation, previous studies have shown that whole-genome transcriptional profiles co-located with adolescent myelination of structural covariance network hubs were enriched for genes associated with schizophrenia [47]; and that schizophrenia cases, compared to healthy controls, had reduced degree of cortical hubs in morphometric similarity networks that were co-located with cortically patterned expression of schizophrenia-related genes [16].…”

Section: /21supporting

confidence: 63%

The genetic relationships between brain structure and schizophrenia

Stauffer

Bethlehem

Dorfschmidt

et al. 2023

Preprint

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Recent studies suggest shared genetic effects on both schizophrenia and brain structure, but it has been challenging to specify which genes mediate this pleiotropic association. We accessed genome-wide association data on schizophrenia (N=69,369 cases; 236,642 controls), and on three magnetic resonance imaging (MRI) metrics (surface area, cortical thickness, neurite density index) measured at 180 cortical areas (N=36,843). Using Hi-C-coupled MAGMA, we identified 61 genes that were significantly associated with both schizophrenia and one or more MRI metrics. Whole genome analysis demonstrated significant genetic covariation between schizophrenia and area or thickness of most cortical regions. Genetic similarity between cortical areas was strongly coupled to covariance of their MRI metrics, and genetic covariation between schizophrenia and cortical regional phenotypes was greatest in the hubs of the corresponding structural covariance network. Three genomic regions, on chromosomes 3p21, 17q21 and 11p11, were enriched for neurodevelopmental processes and consistently implicated in these pleiotropic associations between schizophrenia and cortical network organization.

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Section: /21supporting

confidence: 63%

The genetic relationships between brain structure and schizophrenia

Stauffer

Bethlehem

Dorfschmidt

et al. 2023

Preprint

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“…The error in estimating each gene's PLS 1 weight was assessed by bootstrapping (resampling with replacement of the 34 brain regions), and the ratio of the weight of each gene to its bootstrap standard error was used to calculate the Z scores and, hence, rank the genes according to their contribution to PLS 1 (Whitaker et al, 2016). Genes with large positive PLS 1 weights correspond to genes that have higher than average expression in regions where the association between CP volume and TSPO is more strongly positive.…”

Section: Imaging Transcriptomicsmentioning

confidence: 99%

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

Althubaity

Schubert

Martins

et al. 2021

Preprint

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Background: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods: 51 depressed participants (HDRS score >13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. Results: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r=0.28, p=0.02), prefrontal cortex (r=0.24, p=0.04), and insular cortex (r=0.24, p=0.04), but not with the peripheral inflammatory markers: CRP levels (r=0.07, p=0.53), IL-6 (r=-0.08, p=0.61), and TNF-α (r=-0.06, p=0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r=0.34, p=0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. Conclusion: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

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“…The mapping from each region in the 318-region subdivision of the Desikan Killiany atlas (Fig. 2I) was based on the mapping used in Seidlitz et al (2018), originally performed by Vértes et al (2016) and Whitaker et al (2017). These prior studies used the closely related DK-308 parcellation (Romero-Garcia et al, 2012), which is an asymmetric version of the DK-318 atlas.…”

Section: Cortical Parcellationmentioning

confidence: 99%

MIND Networks: Robust Estimation of Structural Similarity from Brain MRI

Sebenius

Seidlitz

Warrier

et al. 2022

Preprint

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Structural similarity networks are a central focus of magnetic resonance imaging (MRI) research into human brain connectomes in health and disease. We present Morphometric INverse Divergence (MIND), a robust method to estimate within-subject structural similarity between cortical areas based on the Kullback-Leibler divergence between the multivariate distributions of their structural features. Compared to the prior approach of morphometric similarity networks (MSNs) on N>10,000 data from the ABCD cohort, MIND networks were more consistent with known cortical symmetry, cytoarchitecture, and (in N=19 macaques) gold-standard tract-tracing connectivity, and were more invariant to cortical parcellation. Importantly, MIND networks were remarkably coupled with cortical gene co-expression, providing fresh evidence for the unified architecture of brain structure and transcription. Using kinship (N=1282) and genetic data (N=4085), we characterized the heritability of MIND phenotypes, identifying stronger genetic influence on the relationship between structurally divergent regions compared to structurally similar regions. Overall, MIND presents a biologically-validated lens for analyzing the structural organization of the cortex using readily-available MRI measurements.

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373. Adolescence is Associated with Genomically Patterned Consolidation of the Hubs of the Human Brain Connectome

Cited by 15 publications

References 13 publications

The genetic relationships between brain structure and schizophrenia

The genetic relationships between brain structure and schizophrenia

Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

MIND Networks: Robust Estimation of Structural Similarity from Brain MRI

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