Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

Lysophosphatidic acid (LPA) species are bioactive lipids participating in neurodevelopmental processes. The aim was to investigate whether the relevant species of LPA were associated with clinical features of alcohol addiction. A total of 55 abstinent alcohol use disorder (AUD) patients were compared with 34 age/sex/body mass index-matched controls. Concentrations of total LPA and 16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA species were quantified and correlated with neuroplasticity-associated growth factors including brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-2, and neurotrophin-3 (NT-3). AUD patients showed dysexecutive syndrome (22.4%) and memory impairment (32.6%). Total LPA, 16:0-LPA, 18:0-LPA and 18:1-LPA concentrations, were decreased in the AUD group compared to control group. Total LPA, 16:0-LPA, 18:2-LPA and 20:4-LPA concentrations were decreased in men compared to women. Frontal lobe functions correlated with plasma LPA species. Alcohol-cognitive impairments could be related with the deregulation of the LPA species, especially in 16:0-LPA, 18:1-LPA and 20:4-LPA. Concentrations of BDNF correlated with total LPA, 18:2-LPA and 20:4-LPA species. The relation between LPA species and BDNF is interesting in plasticity and neurogenesis functions, their involvement in AUD might serve as a biomarker of cognitive impairment.The present study has been supported by the following programs and research projects: Subprograma Redes Temáticas RETICS (Red de Trastornos Adictivos RD16/0017/001 and RD12/0028/0021) funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO) and the European Regional and European Regional Development Funds/European Social Fund (ERDF/ESF); Proyectos de Investigación en Salud (PI16/01953, PI16/01698 and PI17/02026) funded by ISCIII and ERDF/ESF; Proyectos de Investigación en Drogodependencias (PND2017/043, PND2018/033, PND2018/044 and PND2019/040) funded by Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Sanidad, Secretaría de Estado de Sanidad and ERDF/ESF; Proyecto de Investigación en Salud (PI-0140-2018) funded by Consejería de Salud y Bienestar Social, Junta de Andalucía and ERDF/ESF. NGM holds a “Sara Borrell” research contract (CD19/00019) funded by ISCIII and ERDF/ESF. FJP, AS and JS hold a “Miguel Servet II” research contract (CPII19/00022, CPII19/00031 and CPII17/00024, respectively) funded by ISCIII and ERDF/ESF. RTF holds a Grant (2017 SGR 138) funded by Departament d’Economia i Coneixement de la Generalitat de Catalunya (CIBEROBN), ISCIII and ERDF/ESF.Ye