ArticleBMC psychiatry2026
A transdiagnostic niacin flushing biomarker with disorder-specific multivariate relationships in adolescent unipolar and bipolar depression.
Article in BMC psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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16 authors.
Funding
Abstract
backgroundIdentifying objective biomarkers for adolescent unipolar depression (UD) and bipolar depression (BD) remains a critical challenge. The niacin skin flushing response (NSFR) is a promising peripheral biomarker that is blunted in adults with mood disorders; however, its profile in adolescent and its multivariate relationships with behavioral phenotypes remain unestablished.
methodsWe conducted a comprehensive investigation of the NSFR in a large adolescent sample (N = 315), including 114 with BD, 46 with UD, and 155 healthy controls (HCs). We quantified NSFR features using a multi-parametric approach, alongside comprehensive clinical and cognitive profiling. Analyses included machine learning classification and sparse canonical correlation analysis (SCCA) to decipher multivariate NSFR-behavior relationships.
resultsBoth UD and BD groups exhibited significantly blunted NSFR compared to HCs, establishing it as a transdiagnostic feature. NSFR features differentiated patients from HCs (AUC-ROC up to 0.804) but not UD from BD. Critically, SCCA revealed disorder-specific relationship patterns: in UD, blunted NSFR was associated with anergia and anxiety-related symptoms, whereas in BD, it correlated with diurnal variation, anhedonia, non-suicidal self-injury, and cognitive changes in processing speed, continuous attention, and social cognition.
conclusionsThis study establishes blunted NSFR as a shared biological vulnerability in adolescent UD and BD. More importantly, clinical heterogeneity arises not from the biomarker itself, but from disorder-specific architectures linking this shared abnormality to distinct clinical and cognitive domains. Our findings support a paradigm shift toward a relationship-based framework for understanding psychiatric heterogeneity.
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