| Autor: |
Flora Moujaes, Jie Lisa Ji, Masih Rahmati, Joshua Burt, Charles H. Schleifer, Brendan Adkinson, Aleksandar Savič, Nicole Santamauro, Zailyn Tamayo, Caroline Diehl, Antonija Kolobaric, Morgan Flynn, Nathalie M. Rieser, Clara Fonteneau, Terry Camarro, Junqian Xu, Youngsun T. Cho, Grega Repovš, Sarah K. Fineberg, Peter Morgan, Erich Seifritz, Franz X. Vollenweider, John Krystal, John D. Murray, Katrin H. Preller, Alan Anticevic |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.11.01.514692 |
| Popis: |
BackgroundKetamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.MethodsWe conducted a double-blind placebo-controlled study in which 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hour). We quantified resting-state functional connectivity via data-driven global brain connectivity, related it to individual ketamine-induced symptom variation, and compared it to cortical gene expression targets.ResultsWe found that: i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, implicating the role of SST and PVALB interneurons in ketamine’s acute effects; and iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.ConclusionsCollectively, these findings support the possibility for developing individually precise pharmacological biomarkers for treatment selection in psychiatry.FundingThis study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420); Swiss Neuromatrix Foundation (Grant No. 2016–0111m Grant No. 2015 – 010); Swiss National Science Foundation under the frame-work of Neuron Cofund (Grant No. 01EW1908), Usona Institute (2015 – 2056). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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