Relationship between circulating plasma endocannabinoids in adolescents and maternal depressive symptoms

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.

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.

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).

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.