Sex Differences in Plasma Lysophosphatidic Acid Species in Patients with Alcohol and Cocaine Use Disorders

Abstract

Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in drug addiction. Recently, we reported alterations in the plasma concentrations of LPA species in patients with alcohol use disorder (AUD). As there are sex differences in drug addiction, the main aim of the present study was to investigate whether relevant LPA species (16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA) were associated with sex and/or substance use disorder (SUD). This exploratory study was conducted in 214 abstinent patients with lifetime SUD, and 91 healthy control subjects. The SUD group was divided according to the diagnosis of AUD and/or cocaine use disorder (CUD). Participants were clinically assessed, and plasma samples were collected to determine LPA species and total LPA. We found that LPA concentrations were significantly affected by sex, and women showed higher concentrations than men. In addition, there were significantly lower 16:0-LPA, 18:2-LPA and total LPA concentrations in patients with SUD than in controls. Namely, patients with CUD and AUD + CUD showed lower LPA concentrations than controls or patients with AUD. In conclusion, our data suggest that LPA species could be potential biomarkers for SUD in women and men, which could contribute to a better stratification of these patients in treatment programs.

Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders

“…Among the potential candidates, several preclinical studies have suggested a potential role of lysophosphatidic acid (LPA) in drug addiction [ 12 – 15 ], and other studies have linked LPA signaling to substance use disorders (SUD) and its comorbidity [ 16 – 18 ].…”

“…Previous studies from our group have suggested a potential role of LPA as a reliable biomarker for SUD, mainly in patients diagnosed with alcohol use disorder (AUD) [ 16 – 18 ]. Therefore, LPA could be a potential biomarker for mild cognitive impairment in abstinent patients with AUD [ 17 ], as well as plasma concentrations of ATX and LPA could be a preventive biomarker of liver disease in these patients with AUD [ 16 ].…”

“…Therefore, LPA could be a potential biomarker for mild cognitive impairment in abstinent patients with AUD [ 17 ], as well as plasma concentrations of ATX and LPA could be a preventive biomarker of liver disease in these patients with AUD [ 16 ]. In addition to these studies, we have recently explored the plasma concentrations of LPA in patients with SUD, but considering the different substance uses, and we have found that the concentration of the species of LPA are affected by the type of SUD [ 18 ]. In fact, patients diagnosed with CUD alone or in combination with AUD display lower LPA concentrations than healthy controls or patients with AUD, suggesting that a pathological use of cocaine is associated with alterations in plasma concentration of LPA species.…”

Sexual Differences in Addictions and Dual Disorders: Importance of Gender Perspective

“…Therefore, this Special Issue aims to update our knowledge of the sexual and gender differences found in research into addictions and dual diagnosis. Thus, the articles included in this special issue cover both issues related to gender [ 1 , 7 ] and sex [ 6 , 8 , 9 ], patients using various substances [ 1 , 6 , 7 ] or others with specific substance use disorders (SUDs) [ 8 , 9 ], and including both issues related to addictions [ 9 ] and dual diagnosis [ 1 , 6 , 7 , 8 ].…”

“…For their part, Flores-López et al (2002) [ 9 ] conducted an exploratory study to examine the plasma concentrations of lysophosphatidic acid (LPA, 1-acyl-2-hydroxy-sn-glycero-3-phosphate) species in women and men from a cohort of abstinent patients diagnosed with lifetime alcohol use disorder (AUD) and/or cocaine use disorder (CUD). The main results of their study were: (1) there are sex differences in LPA concentrations, which were higher in women; (2) there was a positive correlation between 16:0-LPA, 18:1-LPA, 18:2-LPA, 20:4-LPA, or total LPA concentrations and age in the SUD and control groups; (3) patients with SUD displayed lower 16:0-LPA, 18:2-LPA, and total LPA concentrations than healthy controls; (4) 16:0-LPA, 18:2-LPA, and total LPA concentrations were affected both by the diagnosis of a SUD and by sex, although there were no interactions between these two factors; and (5) the different species of LPA and total LPA concentrations were affected by the type of SUD: patients with CUD and AUD + CUD had lower LPA concentrations than the control or AUD groups.…”