Department of Biomedical Sciences and Biotechnologies - Biology and Genetic Division, University of Brescia, Viale Europa 11, Brescia, 25123, Italy.
BMC Psychiatry. 2012 Sep 18;12:145. doi: 10.1186/1471-244X-12-145.
In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD.
We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class.
These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models
Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathophysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.
近年来，与精神疾病相关的外周生物标志物的鉴定变得越来越重要，如重度抑郁症（MDD），因为这些生物标志物可能提高鉴别诊断过程的效率，并为新的抗抑郁药物提供靶点。最近的两个候选基因，ErbB3 和 Fgfr1，是生长因子，其 mRNA 水平在受双相情感障碍影响的患者的白细胞中发现发生改变。在此基础上，本研究旨在确定 ErbB3 和 Fgfr1 mRNA 水平是否可以作为 MDD 的生物标志物。
我们通过实时 PCR 测量 MDD 患者与对照组相比白细胞中 ErbB3 和 Fgfr1 mRNA 的表达水平。随后，为了评估 ErbB3 mRNA 水平是否受先前抗抑郁治疗的影响，我们将患者样本分层为两组，比较未用药和停药患者。此外，我们评估了 MDD 患者在抗抑郁治疗 12 周后的转录物水平，以及在应激大鼠的前额叶皮层中用相同类别的抗抑郁药物进行治疗后的转录物水平。
这些结果表明，与健康受试者相比，MDD 患者白细胞中的 ErbB3 而不是 Fgfr1 mRNA 水平降低。此外，在人类或动物模型中，ErbB3 水平不受抗抑郁治疗的影响。
我们的数据表明，ErbB3 可以被认为是 MDD 的生物标志物，其缺乏可能是该疾病病理生理学的基础，而不是治疗的结果。此外，该研究支持白细胞作为识别精神疾病生物标志物的外周系统的有用性。
