Flegr J.,Charles University |
Preiss M.,Prague Psychiatric Center |
Klose J.,Central University of Costa Rica
PLoS ONE | Year: 2013
Background:The parasite Toxoplasma gondii influences the behaviour of infected animals and probably also personality of infected humans. Subjects with a Rhesus-positive blood group are protected against certain behavioural effects associated with Toxoplasma infection, including the deterioration of reaction times and personality factor shift.Methodology/Principal Findings:Here, we searched for differences in the toxoplasmosis-associated effects between RhD-positive and RhD-negative subjects by testing 502 soldiers with two personality tests and two intelligence tests. The infected subjects expressed lower levels of all potentially pathognomic factors measured with the N-70 questionnaire and in neurasthenia measured with NEO-PI-R. The RhD-positive, Toxoplasma-infected subjects expressed lower while RhD-negative, Toxoplasma-infected subjects expressed higher intelligence than their Toxoplasma-free peers. The observed Toxoplasma-associated differences were always larger in RhD-negative than in RhD-positive subjects.Conclusions:RhD phenotype plays an important role in the strength and direction of association between latent toxoplasmosis and not only psychomotor performance, but also personality and intelligence. © 2013 Flegr et al.
Vales K.,Academy of Sciences of the Czech Republic |
Svoboda J.,Academy of Sciences of the Czech Republic |
Benkovicova K.,Academy of Sciences of the Czech Republic |
Bubenikova-Valesova V.,Prague Psychiatric Center |
Stuchlik A.,Academy of Sciences of the Czech Republic
European Journal of Pharmacology | Year: 2010
The manipulation of glutamate neurotransmission could represent a potential strategy for the pharmacotherapy of schizophrenic symptoms. Preclinical studies suggest that two subtypes of metabotropic glutamate (mGlu) receptors such as mGlu2/3 and mGlu5 receptors have the potential to ameliorate deficits in schizophrenia. In our study we evaluated the role of a non-specific mGlu receptor agonist ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid; 1S,3R-ACPD), mGlu5 receptor agonist or positive modulators ((RS)-2-Chloro-5-hydroxyphenylglycine;CHPG; [(3-Fluoro-phenyl)methylene]hydrazone-3-fluorobenzaldehyde; DFB; 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; CDPPB) and a mGlu2/3 receptor agonist (2,2,2-Trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyrdinylmethyl)ethanesulfonamide hydrochloride; LY-487379) on performance in a cognitive task (Active Allothetic Place Avoidance) after sub-chronic administration of 5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imine; MK-801 The Active Allothetic Place Avoidance task is suitable for assessing the executive function and attention of animals and was previously validated for testing the effect of anti-psychotics. Application of the mGlu2/3 receptor agonist had no effect on cognitive impairment induced by MK-801. However, the mGlu5 receptor agonists ameliorated cognitive impairment induced by MK-801 without affecting locomotion. In conclusion, the mGlu5 receptor agonists could be effective in the treatment of cognitive deficits in patients with schizophrenia. However, the pro-cognitive effect of the agonist of mGlu2/3 receptors was not demonstrated in the present study. © 2010 Elsevier B.V.
Ricny J.,Prague Psychiatric Center
Neurochemical Research | Year: 2013
Overview of Szutowicz et al. (Neurochem Res 38(8):1523-1542, 2013), is focusing on specific features of acetyl-CoA metabolism in the cholinergic compartment of the brain. Authors are suggesting that deficit of that metabolite can act as a trigger for several cholinergic encephalopathies, with special emphasis on Alzheimer disease (AD). Central role of acetyl-CoA and its metabolic paths in neurodegeneration are charted starting from its synthesis in mitochondria, followed by utilization in energy metabolism, as well as transport into cytoplasm and participation in the synthesis and turnover of neurotransmitter acetylcholine to emergence of diseased states. Various putative pathogenic signals are evaluated that might be responsible for acetyl-CoA deficit ending up in development of neurodegeneration, unraveling exceptional susceptibility of cholinergic system. They are discussed in context of other existing alternative hypotheses on AD etiology. Overview is thoroughly documented (178 references) and is supported by results accomplished by extensive research in Prof. Szutowicz's laboratory (approximately 25 original papers). © 2013 Springer Science+Business Media New York.
Stein D.J.,University of Cape Town |
Ahokas A.,Mehilainen Clinic |
Marquez M.S.,Teaching and Research in Neuroscience |
Haschl C.,Prague Psychiatric Center |
And 5 more authors.
Journal of Clinical Psychiatry | Year: 2014
Background: Agomelatine was efficacious in reducing symptoms in a short-term placebo-controlled trial in generalized anxiety disorder (GAD) and in preventing relapse in a longer term placebo-controlled study. An additional short-term placebo-controlled study is required by regulatory agencies to confirm the efficacy of agomelatine in GAD. Method: This 12-week, placebo-controlled, double-blind, randomized, parallel group, international, multicenter study was designed to confirm the efficacy of agomelatine 25 50 mg/d in the treatment of patients with a primary D5M-IV- TR diagnosis of GAD. The primary outcome measure was the Hamilton Anxiety Rating Scale (HARS) total score. Assay sensitivity was evaluated by including an escitalopram (10 20 mg/d) group. Settings:The study was undertaken in 45 clinical centers in Argentina, Czech Republic, Finland, South Korea, Poland, Russia, and Slovakia from April 2010 to July 2011. Results: One hundred thirty-nine outpatients were included in the agomelatine group, 131 in the placebo group, and 142 in the escitalopram group. Agomelatine significantly reduced mean (SD) HARS total score (agomelatine-placebo difference: 4.71 [1.03], P< .0001) and had significant effects on secondary outcome measures, including psychic and somatic HARS subscales, response rate (estimate [standard error]) (agomelatine-placebo difference: 27.4% [5.9%], P <.0001), remission on the HARS (agomelatine-placebo difference: 16.8% [5.4%], P .002), Clinical Global Impressions- Severity of Illness scale (CGI-S) (P <.001), functional impairment (P< .0001), and sleep quality (P< .001). Findings were confirmed in the subset of more severely ill patients (HARS total score >25 with or without CGI S >5 at baseline). Agomelatine was well tolerated by patients, with no more adverse events than placebo. Escitalopram was similarly efficacious but was accompanied by a higher incidence of adverse events compared to placebo. Conclusions: In clinical practice, agomelatine has at least similar efficacy to that of escitalopram for the short-term treatment of GAD and is well tolerated. Trial Registration: Control led-Tria ls.com identifier: 1SRCTN03554974. © 2014 Physicians Postgraduate Press, Inc.
Rambousek L.,Institute of Chemical Technology Prague |
Rambousek L.,Academy of Sciences of the Czech Republic |
Kacer P.,Institute of Chemical Technology Prague |
Syslova K.,Institute of Chemical Technology Prague |
And 3 more authors.
Drug and Alcohol Dependence | Year: 2014
Background: Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother's health but also the developing fetus. To provide better insight into these risks, we performed the following experiments. Method: First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment. Results: We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure. Conclusion: We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure. © 2014 Elsevier Ireland Ltd.