Work

Antidepressant Use and Circulating Lipoprotein(a) Levels: A UK Biobank Analysis Including LPA Variant Carriers

Year: 2026

Type: article

Abstract: Experimental studies suggest that serotonergic antidepressants may enhance hepatic uptake of lipoprotein(a) [Lp(a)] through serotonin-dependent endocytic pathways, but whether antidepressant use is associated with circulating Lp(a) concentrations in humans remains unknown. We evaluated the cross-sectional association between antidepressant use and circulating Lp(a) and apolipoprotein(a) [apo(a)] levels in a large population-based cohort. We analyzed UK Biobank data including serum Lp(a) measured by immunoturbidimetry (n=365,459) and plasma apo(a) quantified by Olink proteomics (n=38,937). Antidepressant use and Lp(a)/apo(a) measurements were ascertained at the same baseline assessment. Multivariable linear regression models assessed associations of three selective serotonin reuptake inhibitors (SSRIs; citalopram, sertraline, paroxetine), two tricyclic antidepressants (TCAs; imipramine, amitriptyline), and combined exposure groups with rank-based inverse normal transformed Lp(a) and apo(a) levels. Analyses were performed in the full cohort, restricted to European ancestry, and among carriers of the LPA variants rs3798220 and rs10455872. Across 112 prespecified models, no antidepressant was significantly associated with Lp(a) or apo(a) levels after Bonferroni correction (P < 4.5 × 10 -4 ). Regression coefficients were uniformly small with no consistent pattern in magnitude or direction. Results were consistent across Lp(a) and apo(a) assays and ancestry strata; carrier-restricted analyses were generally concordant but less precise because of smaller sample sizes. In this large cross-sectional population-based study, SSRI and TCA use were not associated with circulating Lp(a) or apo(a) levels. Small, dose-dependent, duration-dependent, or within-person treatment effects cannot be excluded. Further mechanistic and longitudinal studies are warranted to clarify serotonergic influences on Lp(a) metabolism.

Source: Journal of Lipid Research

DOI: 10.1016/j.jlr.2026.101174

Authors: Iosif Taleb, Courtney Astore, Kavita Praveen, Philip L.S.M. Gordts, Sotirios Tsimikas

Institutions: University of California San Diego, Ionis Pharmaceuticals (United States), University of Utah, University of Utah Health Care, UC San Diego Health System

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430