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Ketamine schizophrenia

Ivan Koychev, John Francis William Deakin, Wael El-Deredy, Corinna Haenschel
BACKGROUND: Working memory (WM) deficits are a core feature of schizophrenia. Electrophysiological studies suggest that impaired early visual processing may contribute to impaired WM in the visual domain. Abnormal N-methyl-D-aspartate (NMDA) receptor function has been implicated both in WM and in early visual processing deficits in schizophrenia. We investigated whether ketamine, a noncompetitive NMDA antagonist, would replicate in healthy volunteers the WM performance and early visual processing abnormalities we and others have reported in patients with schizophrenia...
April 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Xin Wang, António Pinto-Duarte, M Margarita Behrens, Xianjin Zhou, Terrence J Sejnowski
Reduced expression of Sp4, the murine homolog of human SP4, a risk gene of multiple psychiatric disorders, led to N-methyl-D-aspartate (NMDA) hypofunction in mice, producing behavioral phenotypes reminiscent of schizophrenia, including hypersensitivity to ketamine. As accumulating evidence on molecular mechanisms and behavioral phenotypes established Sp4 hypomorphism as a promising animal model, systems-level neural circuit mechanisms of Sp4 hypomorphism, especially network dynamics underlying cognitive functions, remain poorly understood...
2018: PloS One
Wan-Ju Cheng, Chun-Hsin Chen, Chih-Ken Chen, Ming-Chyi Huang, Robert H Pietrzak, John H Krystal, Ke Xu
BACKGROUND: Ketamine has been used to probe the biology of psychosis and cognitive dysfunction in humans. High levels of ketamine abuse are associated with persisting psychosis (KPP) in a minority of users. However, relatively little is known about cognitive function among KPP patients and whether the cognitive impairments associated with KPP resemble those of schizophrenia (SZ). METHODS: We recruited 149 treatment-seeking patients, including nonpsychotic ketamine users (KNP, n=51), KPP (n=23), and SZ (n=75) patients...
March 3, 2018: Schizophrenia Research
Deepak Cyril D'Souza, Richard E Carson, Naomi Driesen, Jason Johannesen, Mohini Ranganathan, John H Krystal
BACKGROUND: Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. METHODS: In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects...
January 31, 2018: Biological Psychiatry
Marta Szlachta, Maciej Kuśmider, Paulina Pabian, Joanna Solich, Magdalena Kolasa, Dariusz Żurawek, Marta Dziedzicka-Wasylewska, Agata Faron-Górecka
G-protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 receptors and serotonin 5-HT1A and 5-HT2A receptors play an important role in neurotransmission and have been implicated in many human psychiatric disorders, including schizophrenia. Therefore, in this study, we investigated whether antipsychotic drugs (clozapine (CLZ) and haloperidol (HAL)) affected the formation of heterodimers of D2 -5-HT1A receptors as well as 5-HT1A -5-HT2A receptors. Proximity ligation assay (PLA) was used to accurately visualize, for the first time, GPCR heterodimers both at in vitro and ex vivo levels...
2018: Frontiers in Molecular Neuroscience
Nina Vanessa Kraguljac, Matthew Carle, Michael A Frölich, Steve Tran, Michael A Yassa, David Matthew White, Abhishek Reddy, Adrienne Carol Lahti
BACKGROUND: Converging evidence from neuroimaging and postmortem studies suggests that hippocampal subfields are differentially affected in schizophrenia. Recent studies report dentate gyrus dysfunction in chronic schizophrenia, but the underlying mechanisms remain to be elucidated. Here we sought to examine if this deficit is already present in first-episode psychosis, and if N-methyl-D-aspartate receptor hypofunction, a putative central pathophysiological mechanism in schizophrenia, experimentally induced by ketamine, would result in a similar abnormality...
March 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Kirsten Borup Bojesen, Kasper Aagaard Andersen, Sophie Nordahl Rasmussen, Lone Baandrup, Line Malmer Madsen, Birte Yding Glenthøj, Egill Rostrup, Brian Villumsen Broberg
Progressive loss of brain tissue is seen in some patients with schizophrenia and might be caused by increased levels of glutamate and resting cerebral blood flow (rCBF) alterations. Animal studies suggest that the normalisation of glutamate levels decreases rCBF and prevents structural changes in hippocampus. However, the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of humans has not been studied in the absence of antipsychotics and illness chronicity. Ketamine is a noncompetitive N -methyl-D-aspartate receptor antagonist that transiently induces schizophrenia-like symptoms and neurobiological disturbances in healthy volunteers (HVs)...
2018: Frontiers in Psychiatry
Thiebes Stephanie, Steinmann Saskia, Curic Stjepan, Polomac Nenad, Andreou Christina, Eichler Iris-Carola, Eichler Lars, Zöllner Christian, Gallinat Jürgen, Leicht Gregor, Mulert Christoph
Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Rafał Wojdacz, Łukasz Święcicki, Anna Antosik-Wójcińska
Electroconvulsive therapy (ECT) is the treatment method widely used in psychiatric disorders such as depression, bipolar disorder, schizophrenia and schizoaffective disorder. The advantage of ECT is therapeutic response that occurs significantly earlier than during pharmacotherapy. Initially ECTwas used without anesthesia. Then, in the 1950s procedures with general anesthesia were introduced to reduce the complications that may occur during a seizure caused by ECT, such as broken bones, teeth, tendon rupture, muscle damage...
December 30, 2017: Psychiatria Polska
Benneth Ben-Azu, Itivere Adrian Omogbiya, Adegbuyi Oladele Aderibigbe, Solomon Umukoro, Abayomi Mayowa Ajayi, Ezekiel O Iwalewa
The involvement of oxidative/nitrosative stress, cholinergic and inflammatory pathways have been reported to contribute to the pathophysiology of schizophrenia, a debilitating neuropsychiatric disorder. Our previous studies have shown that doxycycline (DOX), a notable member of tetracyclines with proven antioxidant and anti-inflammatory properties, attenuated psychotic-like behaviors induced by apomophine and ketamine (KET) in mice. This present study was designed to further evaluate in detail the ability of DOX and its combination with risperidone (RIS) to prevent and reverse KET-induced schizophrenic-like behaviors and the role of oxidative/nitrosative and cholinergic pathways in mice...
February 6, 2018: Brain Research Bulletin
Matteo Caloro, Giuseppa Calabrò, Eleonora de Pisa, Enrico Rosini, Georgios D Kotzalidis, Davide Lonati, Carlo Alessandro Locatelli, Pietro Papa, Fabrizio Schifano, Paolo Girardi
: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists...
February 2, 2018: Journal of Addiction Medicine
Timothy I Michaels, Lauren L Long, Ian H Stevenson, James J Chrobak, Chi-Ming A Chen
Disrupted neuronal oscillations have been identified as a potentially important biomarker for the perceptual and cognitive symptoms of schizophrenia. Emerging evidences suggest that interactions between different frequency bands, cross-frequency coupling (CFC), serve an important role in integrating sensory and cognitive information and may contribute to disease pathophysiology. In the present study, we investigated the effects of 14-day consecutive administration of ketamine (30 mg/kg i.p.) versus saline on alterations in amplitude and changes in the coupling of low-frequency (0-30 Hz) phase and high-frequency (30-115 Hz) amplitude in the CA1 hippocampus of Long Evans rats...
January 23, 2018: European Journal of Neuroscience
Nicholas E Clifton, Kerrie L Thomas, Jeremy Hall
Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia...
January 1, 2018: Journal of Psychopharmacology
Luis Rafael Leite Sampaio, Francisco Maurício Sales Cysne Filho, Jamily Cunha de Almeida, Danilo Dos Santos Diniz, Cláudio Felipe Vasconcelos Patrocínio, Caren Nádia Soares de Sousa, Manoel Cláudio Azevedo Patrocínio, Danielle S Macêdo, Silvânia Maria Mendes Vasconcelos
Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats...
January 11, 2018: Neuroscience
L Aparicio-Nava, L A Márquez-García, A Meneses
Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT5A receptor antagonist) were reported in the associative learning task of autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory (LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly aiming improving performance (conditioned response, CR), in this work autoshaping lever-press vs...
January 9, 2018: Behavioural Brain Research
Elena Martín-González, Ángeles Prados-Pardo, Santiago Mora, Pilar Flores, Margarita Moreno
RATIONALE: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. OBJECTIVES: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. METHODS: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP)...
January 8, 2018: Psychopharmacology
Mohamed A Sherif, Jose A Cortes-Briones, Mohini Ranganathan, Patrick D Skosnik
Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptors type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions...
December 15, 2017: European Journal of Neuroscience
William B Holliday, Kate Gurnsey, Robert A Sweet, Tobias Teichert
BACKGROUND: The amplitude of the auditory evoked N1 component that can be derived from noninvasive electroencephalographic recordings increases as a function of time between subsequent tones. N1 amplitudes in individuals with schizophrenia saturate at a lower asymptote, thus giving rise to a reduced dynamic range. Reduced N1 dynamic range is a putative electrophysiological biomarker of altered sensory memory function in individuals with the disease. To date, it is not clear what determines N1 dynamic range and what causes reduced N1 dynamic range in individuals with schizophrenia...
December 13, 2017: Journal of Psychiatry & Neuroscience: JPN
Daniela Cadinu, Ben Grayson, Giovanni Podda, Michael K Harte, Nazanin Doostdar, Joanna C Neill
Negative and cognitive deficit symptoms in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of cognitive dysfunction in the illness is urgently required to enhance the development of new improved therapeutic strategies. Careful validation of animal models that mimic the behaviour and pathology of complex psychiatric disorders is an essential step towards this goal. Non-competitive NMDAR (N-Methyl-d-aspartate receptor) antagonists e.g. phencyclidine (PCP), ketamine and dizocilpine (MK-801) can effectively replicate certain aspects of negative and cognitive deficits associated with schizophrenia in animals...
November 28, 2017: Neuropharmacology
Carlos M Coronel-Oliveros, Renny Pacheco-Calderón
Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60  h-1 ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages...
January 2018: Developmental Psychobiology
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