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Authors
Pinho, Cibele Martins
Olescowicz, Gislaine
Bevilacqua, Laura Menegatti
de Amorim, Gabriel Estevam Santos
Platt, Nicolle
da Silva Räder, Marcos Antonio
da Silveira Neto, Francisco
Kaster, Manuella Pinto
Prediger, Rui Daniel
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Funding
Funding for this research was provided by:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Universidade Federal De Santa Catarina
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Article History
Received: 5 December 2025
Accepted: 9 February 2026
First Online: 27 February 2026
Declarations
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: This study identifies sex-dependent alterations in emotional and social behaviors associated with low-density lipoprotein receptor (LDLr) deficiency, a well-established model of familial hypercholesterolemia. While hypercholesterolemia is primarily recognized for its cardiovascular impact, our findings reveal that LDLr deficiency also disrupts neural circuits involved in anxiety and sociability, effects that are particularly pronounced in females. We further show that reduced expression of catechol-O-methyltransferase (COMT) in the prefrontal cortex may represent a molecular correlate linking altered lipid metabolism to dopaminergic modulation of behavior. By characterizing social behavior as an underexplored dimension in dyslipidemia research, this study expands the understanding of LDLr-related phenotypes beyond metabolic dysfunction and suggests new avenues for investigating the neuropsychiatric burden of lipid disorders.
: The authors declare no competing interests.
