Relationship between circulating plasma endocannabinoids in adolescents and maternal depressive symptoms

Psychopharmacology (Berl). 2025 Jun 18. doi: 10.1007/s00213-025-06831-w. Online ahead of print.

ABSTRACT

BACKGROUND: The endocannabinoid signaling system regulates stress and is implicated in depression, with altered circulating endocannabinoid concentrations frequently reported in adults with depression compared to without. Maternal depression is a well-established predictor of depressive symptoms in youth. However, few studies have examined the relationship between circulating endocannabinoids and susceptibility to psychiatric disorders during adolescence, a high-risk period for symptom onset. This study examines associations among adolescent depressive symptoms, maternal depressive symptoms, and circulating endocannabinoids in a heterogenous community sample of adolescents.

METHODS: This study reports on 77 adolescents (M ± SD = 13.36 ± 2.19 years, 51.9% female; 41.6% White Non-Hispanic, 41.6% Black Non-Hispanic, 5.2% Hispanic, 9.0% biracial) and their biological mothers. Depressive symptoms were measured in mothers and adolescents using the Beck Depression Inventory and Children’s Depression Inventory, respectively. Adolescent plasma concentrations of the endocannabinoids N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) were quantified using liquid chromatography-tandem mass spectrometry.

RESULTS: Over half (58.4%) of adolescents and 15.6% of mothers exceeded clinically significant depression cut-offs. Maternal and adolescent depressive symptoms were not significantly associated (R² = 0.120, p = 0.053). However, maternal (but not adolescent) depressive symptoms were positively associated with adolescent AEA concentrations, adjusting for covariates (R² = 0.332, p < 0.001). This association was moderated by adolescent depressive symptoms (p = 0.004; B=-0.2557), particularly when maternal symptoms were low. Adolescent or maternal symptoms were not significantly associated with adolescent 2-AG concentrations (R² = 0.097, p = 0.670 and R² = 0.098, p = 0.611, respectively).

CONCLUSION: Higher AEA concentrations may serve as a monitoring marker of familial susceptibility for depression during adolescence, including among adolescents with subthreshold symptoms. These results suggest the endocannabinoid system as a potential target for identifying risk and developing interventions during adolescence.

PMID:40531314 | DOI:10.1007/s00213-025-06831-w