A recent groundbreaking study utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018 has uncovered a notable link between elevated albumin-bilirubin (ALBI) scores and depression in adults across the United States. Published in the 2025 edition of BMC Psychiatry, this investigation pioneers the exploration of ALBI—a biochemical index traditionally used to evaluate liver function—as a potential biomarker for mental health disorders. The findings offer intriguing insights that could revolutionize our understanding of the physiological underpinnings of depression, a condition that remains a leading cause of global disability and mortality.
Depression’s etiology is notably complex, encompassing biological, psychological, and socio-environmental components. Yet, the pathophysiological mechanisms underlying this mental health disorder remain incompletely characterized. The ALBI score, devised initially to provide objective evaluation of hepatic function through serum albumin and bilirubin levels, has demonstrated prognostic capacity in diverse clinical scenarios, including liver diseases and cardiovascular conditions. However, its relationship with neuropsychiatric manifestations has not been systematically examined until now.
The research team embarked on a population-based cross-sectional analysis using NHANES data derived from seven continuous survey cycles, representing a nationally representative cohort of American adults. ALBI scores were calculated using the formula combining logarithmic bilirubin concentrations with serum albumin levels, thus offering a composite metric reflective of liver functional status. Depression was quantitatively measured via the Patient Health Questionnaire-9 (PHQ-9), a validated instrument assessing the severity of depressive symptoms. This methodological framework allowed for sophisticated, weighted multivariable logistic regression analyses, ensuring adjustment for numerous potential confounders such as age, sex, race, socioeconomic status, lifestyle factors, and comorbidities.
Results from the statistical modeling revealed a robust association between higher ALBI scores and increased odds of depression. Specifically, individuals with ALBI values above -2.87 exhibited a 16% greater risk of depression compared to those with lower scores, after adjusting for demographic and clinical variables. The relationship was confirmed to be linear through advanced restricted cubic spline modeling, suggesting that incremental rises in ALBI correspond to proportionally higher depression risk. These associations persisted consistently across diverse subpopulations delineated by age, gender, ethnicity, educational attainment, smoking status, alcohol consumption, and diabetic status, indicating ALBI’s potential utility as an independent biomarker for depression risk.
Further analysis illuminated a dose-response gradient wherein higher ALBI scores aligned with escalating severity of depressive symptoms, underscoring the score’s possible relevance in both diagnosis and symptom monitoring. Importantly, the study also deployed Cox proportional hazards regression models to examine ALBI’s prognostic implications within the subset of individuals diagnosed with depression. Strikingly, each one-unit elevation in ALBI was associated with a nearly fourfold increase in all-cause mortality risk, underscoring the profound implications of liver function dysregulation on patient outcomes in mental health contexts.
Cancer-specific mortality was similarly elevated, with ALBI increments linked to more than a threefold increase in risk. Non-cancer mortality showed an even stronger correlation with ALBI, highlighting the systemic impacts potentially bridging hepatic dysfunction and broader health outcomes among depressed individuals. Kaplan-Meier survival analyses and nonlinear modeling via restricted cubic splines further illustrated these persistent, adverse mortality trends tied to rising ALBI, advocating for the consideration of biochemical markers in holistic depression management strategies.
While the pathophysiological processes connecting ALBI components to depression remain speculative, several plausible mechanisms warrant consideration. Albumin, a multifunctional serum protein, modulates inflammatory responses and oxidative stress, both of which have been implicated in depression pathogenesis. Elevated bilirubin levels, while traditionally regarded as markers of hepatic clearance functionality, have antioxidative capacities and may reflect subtle systemic disruptions affecting neuroinflammation or neurotransmitter balance. The interplay of these factors could contribute to neurobiological environments fostering depressive symptomatology.
This study opens new horizons for integrating metabolic and hepatic biomarkers into psychiatric evaluation frameworks. The ALBI score, derived from routine blood tests, offers a cost-effective, minimally invasive tool with promising predictive value for depression risk stratification and prognostication. Its incorporation into clinical practice could complement psychological assessments, facilitating earlier identification of at-risk individuals and personalized treatment approaches.
Moreover, these findings highlight the critical necessity for interdisciplinary research linking hepatology, psychiatry, and epidemiology. Future investigations should aim to elucidate causative pathways, explore longitudinal trajectories linking ALBI fluctuations to depression onset or progression, and evaluate the potential of ALBI-targeted interventions to ameliorate depressive outcomes. Expanding understanding in this domain may also shed light on the broader systemic nature of depression and the intricate connections between physical and mental health.
While cross-sectional in design and thus limited in establishing definitive causality, this study leverages rigorous statistical methodologies and a large, representative dataset, lending credibility to its conclusions. It emboldens the scientific and medical communities to explore novel biomarkers beyond traditional psychological metrics and underscores the multifaceted nature of depression research in the 21st century.
The convergence of hepatic physiology and mental health delineated here challenges previously siloed perspectives of organ-specific pathology, inviting holistic conceptual models. Given the global burden inflicted by depression, integrating ALBI score assessments with standard psychiatric evaluations offers a promising avenue for enhancing diagnostic precision and therapeutic efficacy. As such, these findings stand to impact public health policies, clinical guidelines, and future psychiatric research agendas.
In summary, this pioneering inquiry demonstrates a compelling association between high ALBI scores and increased depression risk as well as mortality among affected individuals. It advances the nascent field examining biochemical correlates of mental illness and suggests that liver function metrics could be harnessed to improve depression diagnosis, monitor disease severity, and predict long-term outcomes, thus potentially transforming patient care paradigms worldwide.
Subject of Research: The association between albumin-bilirubin (ALBI) scores and depression, and the prognostic implications of ALBI in depressive patients.
Article Title: NHANES 2005–2018 data reveal high albumin-bilirubin scores are associated with depression.
Article References:
Li, QZ., Tan, JX., Ruan, GT. et al. NHANES 2005–2018 data reveal high albumin-bilirubin scores are associated with depression. BMC Psychiatry 25, 660 (2025). https://doi.org/10.1186/s12888-025-07082-x
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