Gunay Aksu, Targum Steven D, Leow Alex D, Ajilore Olusola, Rasenick Mark M
Deparment of Psychiatry, University of Illinois College of Medicine, Chicago, IL, 60612, USA.
Department of Physiology and Biophysics, University of Illinois Chicago, Chicago, IL, 60612, USA.
Mol Psychiatry. 2025 Mar 4. doi: 10.1038/s41380-025-02941-1.
Previous studies have shown that the heterotrimeric G protein, Gsalpha (Gsα), is ensconced predominantly in lipid rafts in acutely depressed subjects with major depressive disorder (MDD) in contrast to healthy controls, and that effective antidepressant treatment (ADT) facilitates translocation of Gsα from lipid rafts. The measurement of Gsα via prostaglandin E1 stimulation of adenylyl cyclase (PGE1 stimulation) has been proposed as a peripheral biomarker for assessing clinical status in MDD. We examined the Gsα biomarker in a new study. PGE1 stimulation was used to assess the coupling of Gsα with platelet adenylyl cyclase in depressed subjects in active treatment and healthy controls. The Quick Inventory of Depressive Symptomatology (QIDS-C) measured thresholds of symptom severity at two study visits spaced 2 weeks apart. QIDS-C scores and PGE1 stimulated responses were stable between the two study visits. The QIDS-C was inversely correlated with PGE1 stimulated responses at each visit (r = -0.33, r = -0.60, respectively). MDD subjects with mild-moderate depressive symptoms (defined by QIDS-C ≥ 6) had significantly lower PGE1 stimulated responses than asymptomatic MDD subjects (QIDS-C < 6) or healthy controls (p = 0.001 and 0.002 respectively). MDD subjects with moderate depressive symptoms (QIDS-C ≥ 10) had the lowest PGE1 responses of all subjects (Fisher's exact = 0.012). These results support our earlier findings that a simple, high-throughput-capable platelet assay may be a useful biomarker to assess the clinical status of depressed subjects. Larger studies are needed to evaluate the utility of this biomarker for diagnosis and treatment response.
先前的研究表明，与健康对照相比，异源三聚体G蛋白Gsα在重度抑郁症（MDD）急性抑郁患者中主要存在于脂筏中，且有效的抗抑郁治疗（ADT）可促进Gsα从脂筏中易位。通过前列腺素E1刺激腺苷酸环化酶来测量Gsα（PGE1刺激）已被提议作为评估MDD临床状态的外周生物标志物。我们在一项新研究中检测了Gsα生物标志物。PGE1刺激用于评估正在接受积极治疗的抑郁症患者和健康对照中Gsα与血小板腺苷酸环化酶的偶联情况。抑郁症状快速清单（QIDS-C）在间隔2周的两次研究访视中测量症状严重程度阈值。两次研究访视之间，QIDS-C评分和PGE1刺激反应均稳定。每次访视时，QIDS-C与PGE1刺激反应呈负相关（分别为r = -0.33，r = -0.60）。有轻度至中度抑郁症状的MDD患者（由QIDS-C≥6定义）的PGE1刺激反应显著低于无症状的MDD患者（QIDS-C＜6）或健康对照（分别为p = 0.001和0.002）。有中度抑郁症状的MDD患者（QIDS-C≥10）的PGE1反应在所有受试者中最低（Fisher精确检验 = 0.012）。这些结果支持了我们早期的发现，即一种简单的、具有高通量能力的血小板检测方法可能是评估抑郁症患者临床状态的有用生物标志物。需要进行更大规模的研究来评估这种生物标志物在诊断和治疗反应方面的效用。
