Plasma Inflammation and Plasticity Biomarkers Associated with Future Suicidal Ideation and Depression Severity in Mood Disorders: A Six-Month Prospective Study

Abstract Discerning potential associations between plasma biomarkers and the evolution of suicidal ideation (SI) in mood disorders could advance our understanding of disease progression. We evaluated a cohort of 149 mood disorder patients, assessing 32 plasma soluble proteins implicated in neuroplasticity and inflammation at baseline and six-month follow-up. The primary outcome was the occurrence of suicidal ideation during the six-month follow-up. Secondary outcomes included the presence of suicidal ideation and depression severity at six-month follow-up. We employed Principal Component Analysis and Elastic Net regression for feature extraction and selection. Selected markers were then examined in covariate-adjusted regression models. Our results showed that high baseline levels of interferon-γ and a pro-inflammatory principal component score were linked to the occurrence of SI during follow-up. At the six-month point, SI presence was associated with elevated interferon-γ, interleukin-1β, and diminished serotonin levels, with the latter connection dissipating post-adjustment. High interferon-γ, and low orexin-A at baseline were associated with increased depression severity at follow-up, with specific associations between interferon-γ and anxious symptoms, and orexin-A and atypical depressive symptoms. These findings identify elevated interferon-γ, interleukin-1β, and reduced orexin-A as potential biomarkers associated with the occurrence of SI and severity of depression in mood disorders over six months. With further validation in larger cohorts, these insights could enable more personalized risk assessment and intervention strategies, representing a step forward in improving therapeutic outcomes.