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

Koirala, S.; Hermosillo, R.; Godfrey, K. J.; Anderson, M.; Lundquist, J.; Moser, J.; Feczko, E.; Miranda Dominguez, O.; Weldon, K. B.; Linder, I.; Mahmoudi, M.; Uddin, L. Q.; Nelson, S. M.; Elison, J. T.; Fair, D.; Tervo-Clemmens, B.

doi:10.64898/2026.10.28.762645

bioRxiv · 10.64898/2026.10.28.762645

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

Koirala, S.·Hermosillo, R.·Godfrey, K. J.·Anderson, M.·Lundquist, J.·Moser, J.·Feczko, E.·Miranda Dominguez, O.·Weldon, K. B.·Linder, I.·Mahmoudi, M.·Uddin, L. Q.·Nelson, S. M.·Elison, J. T.·Fair, D.·Tervo-Clemmens, B.

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Abstract

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.

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Koirala, S., Hermosillo, R., Godfrey, K. J., Anderson, M., Lundquist, J., Moser, J., Feczko, E., Miranda Dominguez, O., Weldon, K. B., Linder, I., Mahmoudi, M., Uddin, L. Q., Nelson, S. M., Elison, J. T., Fair, D., Tervo-Clemmens, B.. 2026-10-30. Salience network expansion as a transdiagnostic neural marker for psychopathology risk in adolescence. https://doi.org/10.64898/2026.10.28.762645

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