Jaster Alaina M, Ely Samantha L, Zundel Clara G, Gowatch Leah C, Shampine MacKenna, Carpenter Carmen, O'Mara Emilie, Bhogal Amanpreet, Tamimi Reem, Lewis Christine, Sharma Kamakashi, Losiowski Jennifer, Marusak Hilary A
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
School of Information, University of Michigan, Ann Arbor, MI, USA.
Psychopharmacology (Berl). 2025 Jun 18. doi: 10.1007/s00213-025-06831-w.
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 (R = 0.120, p = 0.053). However, maternal (but not adolescent) depressive symptoms were positively associated with adolescent AEA concentrations, adjusting for covariates (R = 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 (R = 0.097, p = 0.670 and R = 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.
内源性大麻素信号系统调节应激,与抑郁症有关,与无抑郁症的成年人相比,抑郁症成年人的循环内源性大麻素浓度经常出现改变。母亲患抑郁症是青少年出现抑郁症状的一个公认预测因素。然而,很少有研究探讨青少年时期(症状发作的高危期)循环内源性大麻素与精神疾病易感性之间的关系。本研究在一个异质性青少年社区样本中,考察青少年抑郁症状、母亲抑郁症状与循环内源性大麻素之间的关联。
本研究报告了77名青少年(平均年龄±标准差=13.36±2.19岁,51.9%为女性;41.6%为非西班牙裔白人,41.6%为非西班牙裔黑人,5.2%为西班牙裔,9.0%为混血儿)及其亲生母亲。分别使用贝克抑郁量表和儿童抑郁量表测量母亲和青少年的抑郁症状。采用液相色谱-串联质谱法定量青少年血浆中内源性大麻素N-花生四烯酰乙醇胺(花生四烯酸乙醇胺,AEA)和2-花生四烯酸甘油酯(2-AG)的浓度。
超过一半(58.4%)的青少年和15.6%的母亲超过了临床显著的抑郁临界值。母亲和青少年的抑郁症状无显著关联(R=0.120,p=0.053)。然而,在调整协变量后,母亲(而非青少年)的抑郁症状与青少年AEA浓度呈正相关(R=0.332,p<0.001)。这种关联受到青少年抑郁症状的调节(p=0.004;B=-0.2557),尤其是在母亲症状较轻时。青少年或母亲的症状与青少年2-AG浓度无显著关联(分别为R=0.097,p=0.670和R=0.098,p=0.611)。
较高的AEA浓度可能作为青少年抑郁症家族易感性的监测指标,包括症状未达临界值的青少年。这些结果表明内源性大麻素系统是青少年时期识别风险和制定干预措施的一个潜在靶点。