Involvement of the TRPV1 receptor and the endocannabinoid system in schizophrenia

• Published in: Brain research bulletin Vol. 215; p. 111007
• Main Authors: Huang, Junjie, Huang, Huan, Liu, Moyin, Yang, Wanlin, Wang, Huiling
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024; Elsevier
• Subjects: Adult; Arachidonic Acids - blood; Arachidonic Acids - metabolism; Cross-Sectional Studies; Endocannabinoids - blood; Endocannabinoids - metabolism; Female; Glycerides - blood; Glycerides - metabolism; Humans; Male; Middle Aged; Negative symptom; Polyunsaturated Alkamides - blood; Polyunsaturated Alkamides - metabolism; Receptor, Cannabinoid, CB1 - metabolism; Schizophrenia; Schizophrenia - blood; Schizophrenia - metabolism; The endocannabinoid system; Transient receptor potential vanilloid type 1; TRPV Cation Channels - metabolism; Young Adult; Schizophrenia; The endocannabinoid system; Negative symptom; Transient receptor potential vanilloid type 1
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2024.111007

Schizophrenia (SCZ) is a severe mental disorder, but its pathogenesis is still unknown, and its clinical treatment effect is very limited. Transient receptor potential vanilloid 1 (TRPV1) channel and the Endocannabinoid System (ECS)have been confirmed to be involved in the pathogenesis of SCZ, although their actions have not been fully clarified yet. The objective is to examine TRPV1 and ECS expression in the blood of schizophrenia patients and investigate their correlation with disease severity. This is a cross-sectional investigation. Peripheral blood samples were gathered from normal controls (NC, n=37), as well as individuals with schizophrenia, including first episode (n=30) and recurrent (n=30) cases. We employed western blot and ELISA techniques to quantify TRPV1, cannabinoid receptors 1(CB1), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), and assess the severity of the patient's symptoms by means of the PANSS scale. Compared to NC, TRPV1 levels showed a noticeable decrease in both first episode schizophrenia (f-SCZ group) and recurrent schizophrenia (r-SCZ group) subjects. Additionally, CB1 levels appeared increased in f-SCZ group. Furthermore, 2-AG levels were found to be elevated in both f-SCZ group and r-SCZ group compared to NC, whereas AEA levels were decreased in f-SCZ group but increased in r-SCZ group. Moreover, among schizophrenia patients, TRPV1 demonstrated a negative correlation with negative symptoms. Within r-SCZ subjects, CB1 displayed a negative correlation with relapse number, while 2-AG showed a correlation in the opposite direction. This study provides initial clinical evidence of changed TRPV1 expression in schizophrenia, potentially linked to negative symptoms. These results suggest a possible dysfunction of TRPV1 and the endocannabinoid system (ECS), which might offer new avenues for medical interventions. •TRPV1 and the ECS may be involved in the development of schizophrenia and its clinical course.•TRPV1 might negatively correlated with negative symptom severity.•CB1 and 2-AG was negatively and positively correlated with the number of relapses in r-SCZ group.•TRPV1 and the ECS could be considered as potential biomarker and therapeutic target.