title: Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation.
abstract: 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.
authors: Max Planck Institute of Psychiatry, Munich, Germany.
authors: C
authors: C
authors: Webhofer
authors: P
authors: P
authors: Gormanns
authors: V
authors: V
authors: Tolstikov
authors: W
authors: W
authors: Zieglgänsberger
authors: I
authors: I
authors: Sillaber
authors: F
authors: F
authors: Holsboer
authors: C W
authors: CW
authors: Turck
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015415:Biomarkers / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D008811:Mice, Inbred DBA; D017374:Paroxetine / Q000494:pharmacology*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015306:Biogenic Monoamines; D015415:Biomarkers; D017374:Paroxetine