Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures.

AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

A feasibility study of goal-directed network-based real-time fMRI neurofeedback for anhedonic depression.

Anhedonia is a hallmark symptom of depression that often lacks adequate interventions. The translational gap remains in clinical treatments based on neural substrates of anhedonia. Our pilot study found that depressed individuals depended less on goal-directed (GD) reward learning (RL), with reduced reward prediction error (RPE) BOLD signal. Previous studies have found that anhedonia is related to abnormal activities and/or functional connectivities of the central executive network (CEN) and salience network (SN), both of which belong to the goal-directed system. In addition, it was found that real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) could improve the balance between CEN and SN in healthy individuals. Therefore, we speculate that rt-fMRI NF of the CEN and SN associated with the GD system may improve depressive and/or anhedonic symptoms. Therefore, this study (1) will examine individuals with anhedonic depression using GD-RL behavioral task, combined with functional magnetic resonance imaging and computational modeling to explore the role of CEN/SN deficits in anhedonic depression; and (2) will utilize network-based rt-fMRI NF to investigate whether it is feasible to regulate the differential signals of brain CEN/SN of GD system through rt-fMRI NF to alleviate depressive and/or anhedonic symptoms. This study highlights the need to elucidate the intervention effects of rt-fMRI NF and the underlying computational network neural mechanisms.