This single-blind placebo-controlled study (n=40) investigated the neural and behavioural effects of acute ketamine in healthy participants. Results revealed robust inter-individual variability in both neural and behavioural responses to ketamine, with data-driven individual symptom variation mapping onto distinct neural gradients.
Abstract of Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
“Background: Ketamine 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.
Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results: We 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, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry.”
Authors: Flora Moujaes, Jie L. Ji, Masih Rahmati, Joshua B. Burt, Charles Schleifer, Brendan D. Adkinson, Aleksandar Savic, Nicole Santamauro, Zailyn Tamayo, Caroline Diehl, Antonija Kolobaric, Morgan Flynn, Nathalie Rieser, Clara Fonteneau, Terry Camarro, Junqian Xu, Youngsun Cho, Grega Repovs, Sarah K. Fineberg, Peter T. Morgan, Erich Seifritz, Franz X. Vollenweider, John H. Krystal, John D. Murray, Katrin H. Preller & Alan Anticevic
Summary of Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
Introduction
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression, but individual differences in baseline molecular effects and brain function predict the degree to which an individual experiences specific acute ketamine-induced symptoms.
Ketamine’s effects have been extensively characterised by group studies, which typically involve recruiting a sample of patients, measuring brain activity before and after ketamine infusion, and then averaging the results across the patients to ascertain ketamine’s effects. Ketamine’s acute neural effects are less clear, and the majority of studies have used seed-based approaches that have led to contradictory results. There is evidence that these inconsistencies may stem in part from a failure to account for individual differences in ketamine response.
Find this paper
Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
https://doi.org/10.7554/eLife.84173
Open Access | Google Scholar | Backup | 🕊
Cite this paper (APA)
Moujaes, F., Ji, J. L., Rahmati, M., Burt, J. B., Schleifer, C., Adkinson, B. D., ... & Anticevic, A. (2024). Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. Elife, 13, e84173.
Study details
Compounds studied
Ketamine
Placebo
Topics studied
Healthy Subjects
Study characteristics
Placebo-Controlled
Single-Blind
Participants
40
Humans