Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder.

ABSTRACT

We have recently reported sex differences in the plasma concentrations of lysophosphatidic acid (LPA) and alterations in LPA species in patients with alcohol and cocaine use disorders. Preclinical evidence suggests a main role of lysophosphatidic acid (LPA) signaling in anxiogenic responses and drug addiction. To further explore the potential role of the LPA signaling system in sex differences and psychiatric comorbidity in cocaine use disorder (CUD), we conducted a cross-sectional study with 88 patients diagnosed with CUD in outpatient treatment and 60 healthy controls. Plasma concentrations of total LPA and LPA species (160, 180, 181, 182 and 204) were quantified and correlated with cortisol and tryptophan metabolites [tryptophan (TRP), serotonin (5-HT), kynurenine (KYN), quinolinic acid (QUIN) and kynurenic acid (KYNA)]. We found sexual dimorphism for the total LPA and most LPA species in the control and CUD groups. The total LPA and LPA species were not altered in CUD patients compared to the controls. There was a significant correlation between 182 LPA and age at CUD diagnosis (years) in the total sample, but total LPA, 160 LPA and 182 LPA correlated with age at onset of CUD in male patients. Women with CUD had more comorbid anxiety and eating disorders, whereas men had more cannabis use disorders. Total LPA, 180 LPA and 204 LPA were significantly decreased in CUD patients with anxiety disorders. Both 204 LPA and total LPA were significantly higher in women without anxiety disorders compared to men with and without anxiety disorders. Total LPA and 160 LPA were significantly decreased in CUD patients with childhood ADHD. Both 181 LPA and 204 LPA were significantly augmented in CUD patients with personality disorders. KYNA significantly correlated with total LPA, 160 LPA and 182 LPA species, while TRP correlated with the 181 LPA species. Our results demonstrate that LPA signaling is affected by sex and psychiatric comorbidity in CUD patients, playing an essential role in mediating their anxiety symptoms.