TY - JOUR
T1 - Metabolomic signatures of intravenous racemic ketamine associated remission in treatment-resistant depression
T2 - A pilot hypothesis generating study
AU - The Mood Disorders Precision Medicine Consortium (MDPMC)
AU - Singh, Balwinder
AU - MahmoudianDehkordi, Siamak
AU - Voort, Jennifer L.Vande
AU - Han, Xianlin
AU - Port, John D.
AU - Frye, Mark A.
AU - Kaddurah-Daouk, Rima
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/8
Y1 - 2022/8
N2 - In this pilot study (N = 9), we highlight new insights gained on ketamine's mechanism of action where we have mapped biochemical processes that are affected within 40 min of intravenous ketamine exposure. Targeting acylcarnitines, we demonstrated rapid utilization of short-chain acylcarnitines within 40 min of ketamine treatment followed by restoration within 24 h; this change in short chain acylcarnitine with rapid-acting antidepressant treatment is consistent with previous work identifying similar change but at 8-weeks with slower-acting SSRI treatment. Using a non-targeted metabolomics platform, we defined broader effects of ketamine on lipid metabolism and identified changes in triglyceride that correlate with ketamine response. This study provides novel insights into ketamine's action and highlighting a possible role for mitochondrial function and energy metabolism in ketamine's mechanism of action.
AB - In this pilot study (N = 9), we highlight new insights gained on ketamine's mechanism of action where we have mapped biochemical processes that are affected within 40 min of intravenous ketamine exposure. Targeting acylcarnitines, we demonstrated rapid utilization of short-chain acylcarnitines within 40 min of ketamine treatment followed by restoration within 24 h; this change in short chain acylcarnitine with rapid-acting antidepressant treatment is consistent with previous work identifying similar change but at 8-weeks with slower-acting SSRI treatment. Using a non-targeted metabolomics platform, we defined broader effects of ketamine on lipid metabolism and identified changes in triglyceride that correlate with ketamine response. This study provides novel insights into ketamine's action and highlighting a possible role for mitochondrial function and energy metabolism in ketamine's mechanism of action.
KW - Ketamine
KW - Metabolomics
KW - Treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=85133736747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85133736747&partnerID=8YFLogxK
U2 - 10.1016/j.psychres.2022.114655
DO - 10.1016/j.psychres.2022.114655
M3 - Article
C2 - 35738038
AN - SCOPUS:85133736747
SN - 0165-1781
VL - 314
JO - Psychiatry Research
JF - Psychiatry Research
M1 - 114655
ER -