Max Planck Institute of Psychiatry, Munich, Germany.
Transl Psychiatry. 2011 Dec 13;1(12):e58. doi: 10.1038/tp.2011.56.
Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.
目前使用的抗抑郁药会提高突触间隙中单胺类物质的水平。有充分的理由假设，这不是抗抑郁治疗活动的唯一来源，次级下游效应可能与缓解抑郁症状有关。我们试图通过在慢性帕罗西汀治疗后检测 DBA/2Ola 小鼠的代谢组学图谱，阐明单胺类物质再摄取抑制的下游受影响的生化途径。使用气相色谱-质谱分析方法进行代谢组学变化研究，并通过单变量和多变量统计分析来分析组间差异。受抗抑郁治疗影响的途径与能量代谢、氨基酸代谢和激素信号转导有关。鉴定出的途径揭示了进一步的抗抑郁治疗作用，并代表了药物开发努力的目标。中枢神经系统与血浆代谢物变化的比较确定 GABA、半乳糖-6-磷酸和亮氨酸作为评估外周抗抑郁治疗效果的生物标志物候选物。
