biostudies-literatureMoujaes FUsona InstituteNCATS NIH HHSNational Institute on Alcohol Abuse and AlcoholismNIMH NIH HHSBrain and Behavior Research FoundationNIAAA NIH HHSNational Institutes of HealthHeffter Research InstituteSimons Foundation Autism Research InitiativeSwiss Neuromatrix FoundationSwiss National Science Foundation under the framework of Neuron CofundNIH HHSNational Science Foundatione84173https://www.ebi.ac.uk/biostudies/studies/S-EPMC11023699biostudies-literatureUnknown13<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>We found that: (i) both the neural and behavioreLifeKetamine induces multiple individually distinct whole-brain functional connectivity signatures.PMC110236992015 - 20562015276U01 MH121766Pilot AwardR01 MH108590R01 MH11274601EW1908UL1 TR001863R01 MH1121891-1904205R01MH1121895R01MH108590DP5 OD012109Young Investigator Award2016-0111P50 AA012870R01MH1127462P50AA012870-111U01MH121766DP5OD012109-01Vollenweider FXMurray JDMorgan PTRieser NAdkinson BDDiehl CKrystal JHCamarro TSavic AFlynn MSeifritz EKolobaric AAnticevic ARepovs GTamayo ZJi JLCho YMoujaes FSantamauro NXu JSchleifer CRahmati MFonteneau CBurt JBFineberg SKPreller KHfalseKetamine induces multiple individually distinct whole-brain functional connectivity signatures.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>We found that: (i) both the neural and behavior2024-01-01T00:00:00Z2024 Apr2026-06-02T10:26:23.966Z2025-04-06T00:48:44.866ZS-EPMC110236993862981110.7554/eLife.84173