Archives of General Psychiatry
September 1, 2005
John H. Krystal, Edward Perry, Ralitza Gueorguieva et al.
323 citations
Ketamine and amphetamine produce different patterns of psychotic and cognitive effects in healthy people. Ketamine causes perceptual changes, negative symptoms, and memory disruption, while amphetamine triggers hostility, grandiosity, and somatic concern. Both drugs produce positive symptoms and euphoria, but their interaction reveals three patterns: amphetamine reduces ketamine-induced working memory impairment; the drugs additively increase thought disorder, arousal, and euphoria; and their combined effect on psychosis is less than additive. These results suggest that glutamate and dopamine systems contribute differently to psychosis, thought disorder, and euphoria, and that boosting prefrontal dopamine may help cognitive problems linked to glutamate dysfunction.
bioRxiv Preprint Server
February 21, 2023
Naomi R. Driesen, Peter Herman, Margaret A. Rowland et al.
5 citations
preprint
Ketamine, an NMDAR antagonist, increased oxidative metabolism (CMRO2) and cerebral blood flow in the prefrontal cortex and other cortical regions, but did not alter resting-state cortical functional connectivity or brain-wide CBF-CMRO2 coupling. Higher baseline CMRO2 was associated with lower task-related prefrontal activation and greater working memory accuracy impairment under both saline and ketamine conditions. These findings suggest that CMRO2 and resting-state functional connectivity index distinct dimensions of neural activity, and that ketamine's impairment of working memory-related neural activity and performance relates to its induction of cortical metabolic activation.
iScience
January 16, 2026
Amir Valizadeh, John D Roache, Xinyu Zhang et al.
2 citations
Post-traumatic stress disorder varies greatly in its clinical and biological features, making treatment difficult. The largest randomized trial of ketamine for PTSD found no overall benefit over placebo, highlighting the need to identify which patients might respond. Using pre-treatment blood DNA methylation profiles and clinical data from that trial, machine learning models predicted treatment response. A model based on 1,208 methylation sites outperformed models using only clinical variables, and combining both data types improved accuracy further. The methylation-derived score identified responders with 92.9% accuracy. Predictive methylation sites were near genes involved in glutamatergic signaling, immune regulation, and known PTSD risk loci, suggesting peripheral DNA methylation patterns can guide precision pharmacotherapy for PTSD.