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Metabolic disturbances are common in patients maintained on neuroleptics. These abnormalities significantly increase the physical comorbidity and mortality rates due to cardiovascular disease. We hypothesized that 5-HT receptor genes polymorphisms have associations with drug-induced metabolic syndrome development in schizophrenic patients.
Objectives
To investigate the role of polymorphic variants of serotonin receptors genes in the development of antipsychotic-induced metabolic syndrome.
Methods
467 patients with schizophrenia receiving long-term antipsychotic therapy were investigated. The mean age was 40.0±11.6 years. The standard phenol-chloroform method for DNA isolation was used. Genotyping was carried out on eight SNP’s of genes HTR1A, HTR2A, HTR3A and HTR2C with the MassARRAY® Analyzer 4 (Agena Bioscience™) using the set SEQUENOM Consumables iPLEX Gold 96 on the base The Core Facility “Medical Genomics”, Tomsk NRMC.
Results
The prevalence of metabolic syndrome was 26.1%. In the study sample, there were significantly more women with metabolic syndrome (56.6%) than men (43.4%) (p=0.002). The majority of patients with metabolic disturbances were aged >40 years (62.3%), versus 40.9% in the group without metabolic disorders (p<0.001). The duration of the disease was statistically significantly higher in the group of patients with metabolic syndrome (p=0.003). We did not find statistically significant associations of polymorphic variants of the studied genes with the development of the drug-induced metabolic syndrome.
Conclusions
Our results do not demonstrate any significant association between allelic variants of serotonin receptor genes and metabolic syndrome in patients with schizophrenia. Conflict of interest. The authors declare no conflict of interest. Supported by Grant of RSF 19-75-10012.
A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs’ affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice.
Method
Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery.
Results
The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity.
Conclusion
The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.
We here present two new methods for the characterization of fluorescent localization microscopy images obtained from immunostained brain tissue sections. Direct stochastic optical reconstruction microscopy images of 5-HT1A serotonin receptors and glial fibrillary acidic proteins in healthy cryopreserved brain tissues are analyzed. In detail, we here present two image processing methods for characterizing differences in receptor distribution on glial cells and their distribution on neural cells: One variant relies on skeleton extraction and adaptive thresholding, the other on k-means based discrete layer segmentation. Experimental results show that both methods can be applied for distinguishing classes of images with respect to serotonin receptor distribution. Quantification of nanoscopic changes in relative protein expression on particular cell types can be used to analyze degeneration in tissues caused by diseases or medical treatment.
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