Linder, I. | Search bioRxiv

bioRxiv2026

Salience network expansion as a transdiagnostic neural marker for psychopathology risk in adolescence

Increased cortical surface area of the brain's salience network (SAL) has been observed in depression and appears to emerge during early adolescence. However, similar expansion has also been reported in bipolar disorder (BD), obsessive compulsive disorder (OCD), and other atypicalities of salience network function have been broadly implicated across multiple psychiatric conditions. Whether increased SAL surface area is specific to depression or related more generally with psychopathology remains unclear. Using data collected as part of the Adolescent Brain Cognitive Development (ABCD) Study (baseline: N = 7942; ages 9-10; Year 2: N = 5901; ages 11-12), we quantified individual SAL size and examined associations with dimensional symptoms from the Child Behavior Checklist. SAL surface area showed substantial inter-individual variability, with expansion occurring primarily through encroachment into the default mode (DMN), action-mode (AMN), and frontoparietal (FP) networks. Larger SAL size showed a modest positive association with depressive symptoms in the baseline sample, consistent with prior reports; however, this association did not replicate in the year 2 internal replication sample. Instead, associations with total problems were stronger and replicated across both timepoints, suggesting a subtle, dimensional relationship between SAL organization and general psychopathology burden. These findings suggest that individual differences in SAL organization may represent a broader transdiagnostic neural correlate of dimensional psychopathology rather than a disorder-specific neural signature.

neuroscience↗

bioRxiv2024

Reproducible Sex Differences in Personalized Functional Network Topography in Youth

BackgroundA key step towards understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organization at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organization of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex. AimsWe aimed to evaluate the impact of sex on the spatial organization of person-specific functional brain networks. MethodWe leveraged person-specific atlases of functional brain networks defined using non-negative matrix factorization in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalized additive models to uncover associations between sex and the spatial layout ("topography") of personalized functional networks (PFNs). Next, we trained support vector machines to classify participants sex from multivariate patterns of PFN topography. Finally, we leveraged transcriptomic data from the Allen Human Brain Atlas to evaluate spatial correlations between sex differences in PFN topography and gene expression. ResultsSex differences in PFN topography were greatest in association networks including the fronto-parietal, ventral attention, and default mode networks. Machine learning models trained on participants PFNs were able to classify participant sex with high accuracy. Brain regions with the greatest sex differences in PFN topography were enriched in expression of X-linked genes as well as genes expressed in astrocytes and excitatory neurons. ConclusionsSex differences in PFN topography are robust, replicate across large-scale samples of youth, and are associated with expression patterns of X-linked genes. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

neuroscience↗