Multimodal neural correlates of childhood psychopathology
- McGill University, Canada
- University of Geneva, Switzerland
- National University of Singapore, Singapore
- Geneva University Hospitals, Switzerland
Abstract
Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples and robust to variations in analytical parameters. Although model parameters yielded statistically significant brain-behavior associations in unseen data, generalizability of the model was rather limited for all three latent components (r change from within- to out-of-sample statistics: LC1within=0.36, LC1out=0.03; LC2within=0.34, LC2out=0.05; LC3within=0.35, LC3out=0.07). Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.
Data availability
The ABCD data are publicly available via the NIMH Data Archive (https://nda.nih.gov/abcd/).The preprocessing pipeline can be found at https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/CBIG_fMRI_Preproc2016.Preprocessing code specific to this study can be found here: https://github.com/ThomasYeoLab/ABCD_scripts.The code for analyses can be found here: (https://github.com/valkebets/multimodal_psychopathology_components).
Article and author information
Author details
Funding
NUS Yong Loo Lin School of Medicine (NUHSRO/2020/124/TMR/LOA)
- BT Thomas Yeo
Singapore National Medical Research Council (OFLCG19May-0035; CTGIIT23jan-0001; OFIRG24jan-0030; STaR20nov-0003)
- BT Thomas Yeo
Singapore Ministry of Health (CG21APR1009)
- BT Thomas Yeo
Temasek Foundation (TF2223-IMH-01)
- BT Thomas Yeo
National Institutes of Health (R01MH133334)
- BT Thomas Yeo
Natural Sciences and Engineering Research Council of Canada (NSERC Discovery-1304413)
- Boris C Bernhardt
Canadian Institutes of Health Research (FDN-154298; PJT-174995)
- Boris C Bernhardt
Sick Kids Foundation (NI17-039)
- Boris C Bernhardt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethical review and approval of the protocol was obtained from the Institutional Review Board (IRB) at the University of California, San Diego, as well as from local IRB (Auchter et al., 2018; https://doi.org/10.1016/j.dcn.2018.04.003). Parents/guardians and children provided written assent (Clark et al., 2018; https://doi.org/10.1016/j.dcn.2017.06.005).
Copyright
© 2024, Royer et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 448
- views
-
- 88
- downloads
-
- 0
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Multimodal neural correlates of childhood psychopathology
eLife 13:e87992.
https://doi.org/10.7554/eLife.87992
Further reading
-
- Immunology and Inflammation
- Neuroscience
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however, few studies have investigated its role in neurodegenerative processes such as Alzheimer’s disease (AD). Here, we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in humans, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.
-
- Neuroscience
Historically, the creation of the parasympathetic division of the autonomic nervous system of the vertebrates is inextricably linked to the unification of the cranial and sacral autonomic outflows. There is an intriguing disproportion between the entrenchment of the notion of a ‘cranio-sacral’ pathway, which informs every textbook schematic of the autonomic nervous system since the early XXth century, and the wobbliness of its two roots: an anatomical detail overinterpreted by Walter Holbrook Gaskell (the ‘gap’ between the lumbar and sacral outflows), on which John Newport Langley grafted a piece of physiology (a supposed antagonism of these two outflows on external genitals), repeatedly questioned since, to little avail. I retrace the birth of a flawed scientific concept (the cranio-sacral outflow) and the way in which it ossified instead of dissipated. Then, I suggest that the critique of the ‘cranio-sacral outflow’ invites, in turn, a radical deconstruction of the very notion of a ‘parasympathetic’ outflow, and a more realistic description of the autonomic nervous system.
