Molecular Psychiatry
October 3, 2018
Maurizio Fava, M. Freeman, M. Flynn et al.
438 citations
Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties...
Molecular Psychiatry
July 2018
Bashkim Kadriu, Philip W Gold, D A Luckenbaugh et al.
Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The...
Molecular Psychiatry
March 13, 2018
Panos Zanos, T. Gould
1,112 citations
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine’s widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the...
Molecular Psychiatry
February 27, 2018
Allison C. Nugent, Elizabeth D. Ballard, T. Gould et al.
254 citations
Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms,...
Molecular Psychiatry
November 21, 2017
Ning Yao, Olga Skiteva, Xue-Qin Zhang et al.
123 citations
Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether...
Molecular Psychiatry
October 3, 2017
Michelle Kokkinou, Abhishekh Hulegar Ashok, Oliver Howes
252 citations
Ketamine is a non-competitive antagonist at the N -methyl- d -aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute...
Molecular Psychiatry
April 11, 2017
Irina Esterlis, Nicole DellaGioia, Robert H Pietrzak et al.
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers...
Molecular Psychiatry
January 2017
Rodrigo Machado‐Vieira, Philip W Gold, D A Luckenbaugh et al.
We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key...
Molecular Psychiatry
January 2017
G A Vargish, K A Pelkey, X Yuan et al.
Placental transfer of Δ9-tetrahydrocannabinol (THC) during pregnancy has the potential to interfere with endogenous cannabinoid (CB) regulation of fetal nervous system development in utero. Here we examined the effect of maternal CB intake on mouse hippocampal interneurons largely focusing on cholecystokinin-expressing interneurons (CCK-INTs), a prominent CB subtype-1 receptor (CB1R) expressing...
Molecular Psychiatry
February 2016
D B McClatchy, J N Savas, S Martínez-Bartolomé et al.
Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative...
Molecular Psychiatry
June 9, 2015
Fabien Vinckier, Raphaël Gaillard, S Palminteri et al.
A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic...
Molecular Psychiatry
March 31, 2015
Jordi Riba, Marta Valle, Frederic Sampedro et al.
41 citations
Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control....
Molecular Psychiatry
September 2014
Georg Northoff, Etienne Sibille
Major depression is a complex and severe psychiatric disorder whose symptomatology encompasses a critical shift in awareness, especially in the balance from external to internal mental focus. This is reflected by unspecific somatic symptoms and the predominance of the own cognitions manifested in increased self-focus and rumination. We posit here that sufficient empirical data has accumulated...
Molecular Psychiatry
April 2014
J Iafrati, M J Orejarena, Olivier Lassalle et al.
Defective brain extracellular matrix (ECM) is a factor of vulnerability in various psychiatric diseases such as schizophrenia, depression and autism. The glycoprotein reelin is an essential building block of the brain ECM that modulates neuronal development and participates to the functions of adult central synapses. The reelin gene (RELN) is a strong candidate in psychiatric diseases of early...
Molecular Psychiatry
October 15, 2013
Gerard Sanacora, Mark A. Smith, Sanjeev Pathak et al.
234 citations
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the...
Molecular Psychiatry
January 3, 2012
J. Stone, C. Dietrich, R. Edden et al.
Preclinical studies suggest that ketamine-induced psychopathology is mediated, in part, by increased glutamate release, hypothesized to occur via inhibition of GABAergic interneurons. Using proton magnetic resonance spectroscopy (1H-MRS), we tested this hypothesis in healthy humans. Ketamine increased anterior cingulate cortex glutamate levels, which correlated with the degree of positive...
Molecular Psychiatry
July 12, 2011
J. Hirvonen, R. Goodwin, Cheng-Ta Li et al.
Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally...
Molecular Psychiatry
April 19, 2011
Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice.
Molecular Psychiatry
September 1, 2005
P Seeman, F Ko, T Tallerico
Although phencyclidine and ketamine are used to model a hypoglutamate theory of schizophrenia, their selectivity for NMDA receptors has been questioned. To determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the functional high-affinity state of the dopamine D2 receptor, D2High, their dissociation constants (Ki) were obtained on [3H]domperidone binding to human cloned...