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Prediction of the Antidepressant Effect of Ketamine Based on Clinical Parameters and Intoxication Phenomenology
Andrashko, Veronika ; Horáček, Jiří (advisor) ; Papežová, Hana (referee) ; Juřica, Jan (referee)
Background: ketamine is a rapid and potent antidepressant treatment, however no sufficient predictors for tailored treatment have been identified to date. The aim of the thesis was to identify possible clinical and phenomenological characteristics, associated with better antidepressant response in patients receiving ketamine. Materials and methods: data from 86 depressed patients from cohorts A (2010-2015) and B (2018-2022) were utilized. All patients underwent ketamine infusion and demographic as well as clinical assessment (severity of depressive symptoms, subjective and objective anxiety and anhedonia before and after ketamine application). In addition, an electrocardiogram was taken to assess heart rate variability in cohort A and blood pressure, heart rate, and altered state of consciousness scales were recorded in cohort B during ketamine intoxication. Results: in cohort A, the use of higher doses of benzodiazepines was associated with worse response at day 3 (p = 0.04) and day 7 (p = 0.02) after ketamine administration. Responders showed higher heart rate (p = 0.001) and differed from nonresponders in heart rate variability (p = 0.011). In cohort B, responders reached higher values od systolic (p = 0.003) and diastolic (p = 0.005) blood pressure during intoxication, but not higher heart...
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Effect of ketamine on light-induced changes in the circadian system
Kratina, Alex ; Bendová, Zdeňka (advisor) ; Valeš, Karel (referee)
The circadian system is controlled by the suprachiasmatic nuclei of the hypothalamus (SCN) and ensures optimal timing of physiological processes. Synchronization of this system with external light conditions is based on the activation of NMDA receptors during light exposure in the subjective night. Ketamine is a non-competitive antagonist of NMDA receptors used as a safe anesthetic, whose subanesthetic doses act as an antidepressant with a rapid onset of action, and increase proliferation in some parts of the brain. There are hypotheses about the possible effect of subanesthetic doses of ketamine on the circadian system, altough this effect has not yet been tested. This work aims to investigate the effect of a single subanesthetic dose of ketamine on the circadian system of the rat, especially on light-induced changes in locomotor activity and light-induced markers in the SCN and dentate gyrus, which represents one of the strongly proliferative areas of the brain. Our results show that ketamine decreases light pulse-induced c-FOS protein expression in the SCN at the onset of the subjective night, but increases this expression in the dentate gyrus under the same conditions. Reduction of c-FOS expression in the SCN correlates with the behavioral output of the circadian system and thus suppresses the...
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Automated monitoring of behaviour as a new paradigm in the research of depressive disorder
Revayová, Anna ; Valeš, Karel (advisor) ; Kubik-Zahorodna, Agnieszka (referee)
The rapid antidepressant effect of ketamine changed the direction of the research of potential antidepressants and its effect was also evaluated in this thesis. However, the main focus of this thesis is a new methodological approach to the research of depressive disorder. The main interest lies with the evaluation of automated monitoring of behaviour in this research. The first aim of this thesis was to evaluate the antidepressant effect of ketamine in the forced swimming test using software enabling automated monitoring of behaviour. The second aim was to meassure the change in phosphorylated Mammalian target of rapamycin (mTOR), using Enzyme-Linked ImmunoSorbent Assay (ELISA). The last, but the most important aim of this thesis was to implement the utilization of Phenotyper boxes in the automated behavioural evaluation of the olfactory bulbectomy model of depressive disorder and also evaluate the effect of ketamine in this model. Ketamine did not show an antidepressant effect in forced swimming test, however this observation could be influenced by chosen dose and mouse strain. Sensitivity of the test to chosen experimental protocol shows insufficient validity of this test. Observed change in level of phosphorylated mTOR corresponded with the behavioural results. Data collected from Phenotyper...
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Clinical and experimental use of ketamine in psychiatry
Rydzyková, Tereza ; Tylš, Filip (advisor) ; Melkes, Barbora (referee)
Ketamine (NMDA receptor antagonist) is used primarily as an anesthetic in medicine. This paper deals with the use of ketamine in psychiatric research. A brief section approaching pharmacology and neurobiological effects of this substance, is followed by the main essay dealing within the first part with the use of ketamine as a potential new antidepressant drug. Preclinical and clinical studies demonstrating the effectiveness of this substance are described. Than neurobiological mechanisms underlying antidepressant action of ketamine are discussed. The second part of this review focuses on the use of ketamine as a pharmacological model of psychosis. Also published animal studies and studies administering ketamine in healthy subjects and schizophrenic patients are outlined. Subsequently neurobiological mechanism by which ketamine induces a psychotic state is proposed. Key words: Ketamine, NMDA receptor, schizophrenia, treatment-resistant depression, model of psychosis, antidepressant drug
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Automated monitoring of behaviour as a new paradigm in the research of depressive disorder
Revayová, Anna ; Valeš, Karel (advisor) ; Kubik-Zahorodna, Agnieszka (referee)
The rapid antidepressant effect of ketamine changed the direction of the research of potential antidepressants and its effect was also evaluated in this thesis. However, the main focus of this thesis is a new methodological approach to the research of depressive disorder. The main interest lies with the evaluation of automated monitoring of behaviour in this research. The first aim of this thesis was to evaluate the antidepressant effect of ketamine in the forced swimming test using software enabling automated monitoring of behaviour. The second aim was to meassure the change in phosphorylated Mammalian target of rapamycin (mTOR), using Enzyme-Linked ImmunoSorbent Assay (ELISA). The last, but the most important aim of this thesis was to implement the utilization of Phenotyper boxes in the automated behavioural evaluation of the olfactory bulbectomy model of depressive disorder and also evaluate the effect of ketamine in this model. Ketamine did not show an antidepressant effect in forced swimming test, however this observation could be influenced by chosen dose and mouse strain. Sensitivity of the test to chosen experimental protocol shows insufficient validity of this test. Observed change in level of phosphorylated mTOR corresponded with the behavioural results. Data collected from Phenotyper...
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Antidepressant effect of ketamine
Revayová, Anna ; Valeš, Karel (advisor) ; Šóš, Peter (referee)
Ketamine is used as an anaesthetic mainly in veterinary medicine and paediatrics. Thirteen years ago, interest in ketamine as an antidepressant emerged. Ketamine as an antidepressant works rapidly and is also effective in the case of patients suffering from treatment resistant depression.The main disadvantage of ketamine as an antidepressant is its psychotomimetic effect. Ketamine is an antagonist of the NMDA receptor, which has an important influence in brain activity. Through antagonism of this receptor, a large amount of processes can be affected, for example levels of glutamate, excitotoxicity, or density of other receptors. In addition, ketamine probably also affects the D2 receptors, but its role in this is uncertain. Ketamine influences synaptic plasticity and its effect can be modulated by repeated application, co-application with other drugs and other methods. Also gender seems to play role in the effect of ketamine. The aim of this work is to summarise possible mechanisms of effect of ketamine, its effect on synaptic plasticity and also possibilities of modulation of its effect. This thesis mentions the most important studies concerning ketamine as an antidepressant and possible future directions of research. Keywords: major depressive disorder, ketamine, antidepressant, NMDA antagonism,...
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Synthesis of isotopically labeled ketamine
Stuchlíková, Lucie ; Lešetický, Ladislav (advisor) ; Smrček, Stanislav (referee)
In this work were synthesized ketamine isotopomers. Ketamine is used in human medicine and veterinary sectors. It has very broad spectrum of pharmacological effects: anesthetic, analgesic, hallucinogenic, bronchodilator, cardiovascular and antidepressive, which is currently in the research. At first was synthesized precursor of ketamine, N- desmethylketamine which was subsequently labeled the deuterium, tritium and carbon- 14. For the determination of purity and identity mass spectrometry and nuclear magnetic resonance spectroscopy were used. KEY WORDS synthesis of ketamine, ketamine, N-desmethylketamine, nor-ketamine, isotopically labeled ketamine, deuterium, tritium, carbon-14.
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