Regularized CCA Identifies Sex-Specific Brain-Behavior Associations in Adolescent Psychopathology

This project investigates sex-specific associations between resting-state functional connectivity (rs-fMRI) and psychiatric symptoms in early adolescence using the ABCD dataset. Using Canonical Correlation Analysis (CCA) and rigorous cross-validation, we identify multivariate brain-behavior mappings across eight Child Behavior Checklist (CBCL) syndrome scales. In contrast to previous studies, we explicitly model sex differences in these brain-behavior associations, revealing distinct neural correlates for attention, thought, and internalizing problems in males and females. Our findings highlight the importance of considering sex-specific mechanisms in adolescent psychopathology and support the development of sex-informed clinical strategies.

📄 Read the paper here: DOI

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Data

Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development℠ (ABCD) Study (https://abcdstudy.org), publicly released in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9–10 and follow them over 10 years into early adulthood.

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Code Overview

This repository contains all scripts used to perform the regularized CCA analysis, cross-validation, and permutation testing.

• cca_abcd_rsfmri_cbcl.py — Main script for running CCA with cross-validation.
• cca_abcd_rsfmri_cbcl_utils.py — Utility functions for data loading and preprocessing.
• permutation_analysis.py — Script to perform permutation testing for full cohort and sex-stratified models.
• permutation_analysis_utils.py — Supporting functions for permutation training and correlation analysis.
• gather_cca_abcd_rsfmri_cbcl.py — Script to gather and summarize cross-validation results.
• launch_cca_abcd_rsfmri_cbcl.py — Helper script to launch CCA runs across parameter configurations.
• run_cca.sh — Slurm batch script to launch CCA jobs via launch_cca_abcd_rsfmri_cbcl.py.
• run_perm.sh — Slurm batch script to launch permutation analysis via permutation_analysis.py.

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Citation

If you use this codebase or reference this work in your research, please cite our corresponding paper:

L. Milecki, C. Gonzalez, E. Adeli, K. B. Nooner, M. R. Sabuncu, A. Kuceyeski, and Q. Zhao. ''Regularized CCA identifies sex-specific brain-behavior associations in adolescent psychopathology.'' Transl Psychiatry 15, 405 (2025). https://doi.org/10.1038/s41398-025-03678-9

Bibtex:
@article{
Milecki2025RegularizedPsychopathology,
title = {Regularized CCA identifies sex-specific brain-behavior associations in adolescent psychopathology},
volume = {15},
ISSN = {2158-3188},
url = {http://dx.doi.org/10.1038/s41398-025-03678-9},
DOI = {10.1038/s41398-025-03678-9},
number = {1},
journal = {Translational Psychiatry},
publisher = {Springer Science and Business Media LLC},
author = {Milecki, Leo and Gonzalez, Camila and Adeli, Ehsan and Nooner, Kate B. and Sabuncu, Mert R. and Kuceyeski, Amy and Zhao, Qingyu},
year = {2025},
month = oct
}