Wu Congchong, Lu Jing, Lu Shaojia, Huang Manli, Xu Yi
Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China; Brain Research Institute of Zhejiang University, Hangzhou, China.
J Psychiatr Res. 2020 Jul;126:92-97. doi: 10.1016/j.jpsychires.2020.05.010. Epub 2020 May 12.
Although studies have shown that severe anhedonia in patients with major depressive disorder (MDD) is associated with poor treatment outcomes, the biological mechanism of this feature is unclear. The aim of this study was to investigate the dysfunction of brain-derived neurotrophic factor (BDNF) metabolism, measured by the ratio of mature BDNF to precursor-BDNF, in MDD patients with severe anhedonia.
We measured plasma levels of mature BDNF (mBDNF), precursor-BDNF (proBDNF), tissue plasminogen activator (tPA) and tropomyosin-related kinase B (trkB) in outpatients with MDD with anhedonia (n = 26), outpatients with MDD without anhedonia (n = 29) and age- and sex-matched healthy controls (HCs, n = 38) by enzyme-linked immunosorbent assay kits, and we calculated the ratio of mBDNF to proBDNF (M/P). We compared these biological determinants among the three groups and explored the interrelationships between anhedonia severity and BDNF metabolism.
The levels of mBDNF, proBDNF, and tPA and the ratio of M/P were identified with highly significant differences among the three groups. Compared with MDD patients without anhedonia and healthy controls, MDD patients with anhedonia showed higher level of the ratio of M/P, and it was positively associated with the SHAPS scores in MDD patients. Compared to healthy controls, the plasma tPA concentrations were higher in MDD patients with anhedonia but were not different from those in MDD patients without anhedonia.
These results provide novel evidence regarding the relationship between anhedonia and plasma BDNF metabolism. The hypermetabolism of BDNF may be a function of anhedonia rather than other characteristics in MDD.
尽管研究表明，重度抑郁症（MDD）患者的严重快感缺乏与治疗效果不佳有关，但其生物学机制尚不清楚。本研究旨在探讨以成熟脑源性神经营养因子（BDNF）与前体BDNF的比值衡量的BDNF代谢功能障碍在伴有严重快感缺乏的MDD患者中的情况。
我们采用酶联免疫吸附测定试剂盒，测定了伴有快感缺乏的MDD门诊患者（n = 26）、不伴有快感缺乏的MDD门诊患者（n = 29）以及年龄和性别匹配的健康对照者（HCs，n = 38）血浆中成熟BDNF（mBDNF）、前体BDNF（proBDNF）、组织型纤溶酶原激活剂（tPA）和原肌球蛋白相关激酶B（trkB）的水平，并计算了mBDNF与proBDNF的比值（M/P）。我们比较了三组之间的这些生物学指标，并探讨了快感缺乏严重程度与BDNF代谢之间的相互关系。
三组之间mBDNF、proBDNF、tPA水平以及M/P比值存在高度显著差异。与不伴有快感缺乏的MDD患者和健康对照者相比，伴有快感缺乏的MDD患者的M/P比值更高，且与MDD患者的SHAPS评分呈正相关。与健康对照者相比，伴有快感缺乏的MDD患者血浆tPA浓度更高，但与不伴有快感缺乏的MDD患者无差异。
这些结果为快感缺乏与血浆BDNF代谢之间的关系提供了新的证据。BDNF的代谢亢进可能是MDD中快感缺乏而非其他特征的一种表现。
