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Evaluation Studies 2011; 32(Suppl 1): 53-56 PubMed PMID: 22167208 Citation  Keywords:  Abortion, Eugenic:statistics & numerical data, Abortion, Spontaneous:epidemiology, Antidepressive Agents:adverse effects, Case-Control Studies, Congenital Abnormalities:epidemiology, Czech Republic:epidemiology, Depression:drug therapy, Drug Information S.   

OBJECTIVES: Antidepressant drugs are used frequently during pregnancy. The risk assessment of SSRI exposure is still evaluated and re-opened due to studies indicating possible increase of inborn defects, neonatal abstinence syndrome and cognitive ability or behavioral defects.

METHODS: In our study, we prospectively followed groups of pregnancies in years 2002-2009, that were exposed to SSRI. As control group we used 1) women exposed to new atypical antidepressant and anti-psychotics - APD (risperidone, mirtazapine, venlafaxine, trazodone, aripiprazole, ziprasidone, olanzapine), 2) women exposed to nonteratogenic drugs and 3) the general population according to Institute of Health Informations and Statistics (ÚZIS.) Data were analyzed using software Statistica for Windows No.5.5.

RESULTS: The total number of queries on psychotropic drugs performs in CZTIS more than 30% of all calls, constantly. We enrolled a total of 43 women exposed to SSRI and 37 women (1x twins) exposed to new psychotropic drugs (APD) in the study. Exposure to SSRI was often associated with poly-therapy. The most frequent SSRI used were citalopram and/or escitalopram (56%), and setraline (26%). Other SSRI were used sporadically. We observed significantly higher frequency of elective terminations in group of SSRI and higher frequency of abortions a prematurity in APD group. Frequency of malformations does not varied, being in all groups in expected range.

CONCLUSIONS: We confirmed that SSRI exposure during pregnancy was not associated with the higher risk of major malformation. However, number of cases was low and did not allow the statistical treatment with higher power....

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Journal Article 2011; 32(2): 133-140 PubMed PMID: 21552194 Citation  Keywords:  Adult, Antioxidants:metabolism, Biomarkers:blood, Case-Control Studies, Comorbidity, Coronary Artery Disease:epidemiology, Depression:blood, Disease Progression, Fatigue Syndrome, Chronic:blood, Female, Glutathione Peroxidase:blood, Humans, Male, Middle A.   

BACKGROUND: Major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are two disorders accompanied by an upregulation of the inflammatory and oxidative and nitrosative (IO&NS) pathways and a decreased antioxidant status. Moreover, depression is accompanied by disorders in inflammatory and neuroprogressive (IN-PRO) pathways.

METHODS: This study examines whole blood glutathione peroxidase (GPX) in depression and in ME/CFS; GPX is an enzyme that reduces hydroperoxides by oxidizing glutathione and consequently protects the cells from oxidative damage. Blood was sampled in 39 patients with depression, 40 patients with ME/CFS and 24 normal volunteers. Whole blood was analysed for GPX activity using the Ransel assay (Randox). Severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF scale).

RESULTS: We found that whole blood GPX activity was significantly (p=0.001) lower in depressed patients than in normal controls and that there were no significant differences between ME/CFS and controls. In depression and ME/CFS, there were significant and inverse relationships between GPX activity and the FF items, depressed mood and autonomic symptoms. In depression, there were significant and negative correlations between whole blood GPX and the HDRS score and autonomic symptoms.

DISCUSSION: The results show that lowered whole blood GPX activity contributes to the lowered antioxidant status in depression. Since GPX activity is a predictor of neuroprogression and coronary artery disease (CAD), lowered GPX activity in depression contributes to the IN-PRO pathways and the comorbidity between depression and CAD. Our results suggest that patients with depression would benefit from Ebselen or a supplementation with glutathione, N-Acetyl-l-Cysteine and selenium....

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Clinical Trial 2011; 32(2): 141-147 PubMed PMID: 21552193 Citation  Keywords:  Adult, Antibodies:blood, Antipsychotic Agents:therapeutic use, Biomarkers:blood, Case-Control Studies, Dehydroepiandrosterone:analogs & derivatives, Female, Homocysteine:blood, Humans, Hydrocortisone:blood, Immunologic Factors:blood, Iodide Peroxidase:imm.   

OBJECTIVE: Serum levels of neuro- and immunomodulatory adrenal steroids together with selected hormonal, lipid and other relevant biochemical parameters were investigated to examine the differences between first-episode schizophrenia patients and age-matched healthy subjects, and the effect of treatment with atypical antipsychotics.

METHODS: The patient´s group consisted of 22 drug-naive patients (13 men and 9 women), diagnosed with schizophrenia according to ICD-10 criteria, before and after six-months treatment with atypical antipsychotics of olanzapine or non-olanzapine type. Biochemical markers included steroids cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxylated metabolites of dehydroepiandrosterone, prolactin, thyrotropin, free thyroxine, autoantibodies against thyroid peroxidase and thyroglobulin, glucose levels, four major lipid parameters, homocysteine and three other aminothiols. Steroids, prolactin and thyroid parameters were determined by radioimmunoassays, the other markers by standard biochemical methods.

RESULTS: Significantly lower dehydroepiandrosterone sulfate and of 7α-hydroxy- dehydroepiandrosterone levels than in controls were found in male patients. In the female group, the only difference in steroid spectra was significantly higher cortisolemia in the patients. The patients had also higher titres of autoantibodies against thyroid peroxidase. Compared to controls, the patients displayed worse lipid spectra, and higher homocysteinemia. Medication did not lead to significant changes in the parameters, with the exception of expected increase in prolactin levels in non-olanzapine treated subgroups.

CONCLUSION: Lower levels of 7α-hydroxydehydroepiandrosterone, abundant especially in brain, determined for the first time in schizophrenia patients, are in agreement with recent opinion of their neuroprotective and immunoprotective role. High levels of autoantibodies against thyroid peroxidase in the patients support the autoimmunity hypothesis of schizophrenia....

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Journal Article 2011; 32(1): 52-58 PubMed PMID: 21407155 Citation  Keywords:  Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Point Mutation, Polymorphism, Single Nucleotide, Schizophrenia:genetics,.   

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin/ insulin-like growth factor signalling in cells might underlie both structural and functional brain changes and peripheral abnormalities in schizophrenia. No associations between polymorphisms in the genes for insulin-like growth factor 1 or its receptor and schizophrenia have been reported. However, the insulin receptor substrates 1-4 linking both the insulin and insulin-like growth factor 1 receptors with intracellular pathways have not been extensively studied in schizophrenia. In this study, we therefore chose to study the insulin receptor substrate-4 (IRS-4) gene as a candidate gene in schizophrenia.

METHODS: The IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, followed by case-control analyses of 10 detected single nucleotide polymorphisms.

RESULTS: No significant genotype, allele or haplotype associations were found with the schizophrenia illness. However, one female patient with paranoid schizophrenia had an IRS-4 gene mutation at position 107863596, resulting in a change in amino acid coding from histidine to tyrosine at position 879.

CONCLUSIONS: Although this study supports the view that the IRS-4 gene is not of major importance for the aetiology of the vast majority of schizophrenia cases, our finding of this single patient with schizophrenia and a mutation in the IRS-4 gene may point to that the insulin/ insulin-like growth factor signalling system in cells is still of interest in the future search for schizophrenia genes....

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Journal Article 2010; 31(6): 747-753 PubMed PMID: 21196923 Citation  Keywords:  Anisotropy, Attention Deficit Disorder with Hyperactivity:diagnosis, Case-Control Studies, Child, Cognition, Diffusion Tensor Imaging, Executive Function, Female, Frontal Lobe:pathology, Functional Laterality, Humans, Male, Neuropsychological Tests,.   

UNLABELLED: Abnormalities of frontal white matter (WM) have been found in some children with ADHD. The purpose of this study was to explore the changes in WM in child patients with ADHD by DTI, which detects changes in WM microstructure based on properties of diffusion. We also expect to investigate the relationship between the changes in WM and executive function in child patients with ADHD. DTI was performed on 24 patients with ADHD and 20 healthy controls. A series of neuropsychological tests and a structural interview were conducted to assess the cognitive functions and clinical data of the ADHD patients and controls. Firstly, child patients with ADHD have higher fractional anisotropy (FA) values in WM in the right frontal region. Secondly, FA in right frontal WM is positively correlated with scores in the Stroop test.

CONCLUSIONS: Increased FA of right frontal WM implies a higher degree of myelination and lower degree of neural branching in WM, contributing to the neurological deficits of ADHD....

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Comparative Study 2010; 31(5): 679-683 PubMed PMID: 21173748 Citation  Keywords:  Adult, Biomarkers:blood, Blood Glucose:metabolism, Body Mass Index, Case-Control Studies, Comorbidity, Diabetes Mellitus:blood, Diabetes Mellitus, Type 2:blood, Enzyme-Linked Immunosorbent Assay, Female, Hemoglobin A, Glycosylated:metabolism, Humans, Insu.   

OBJECTIVES: Glycosylated haemoglobin (HbA1c), leptin, leptin soluble receptors (sOB-R) and free leptin index (FLI) may all be influenced by diabetes, but their associations remain unclear. Therefore, we put forward a hypothesis that serum leptin, sOBR and FLI might be parallel to Hb1c, as they all reflect the metabolic status.

DESIGN AND SETTING: We measured leptin and sOB-R concentrations in 97 obese non-diabetic (47 women and 50 men), and 65 obese diabetic (32 women and 33 men) humans, and examined whether they were related to HbA1c. Under the condition, the presence of diabetes was the only differentiating factor between two groups of frankly obese humans.

RESULTS: Non-diabetic vs. diabetic, median and interquartile range, respectively: Leptin (ng/ml), 30.83, 37.27 vs. 28.24, 23.34; p>0.05; sOB-R (ng/ml), 17.62, 17.05 vs. 21.81, 16.61, p<0.05; FLI, 231.23, 310.00 vs. 131.76, 157.68, p<0.05. To investigate the influence of HbA1c on leptin and sOB-R, both groups were divided into tertiles based on HbA1c. In diabetics, leptin did not differ between the high, intermediate, and low HbA1c levels subgroups, p>0.05, and leptin was not influenced by HbA1c levels: r=0.086; p>0.05. For sOB-R, respectively: p>0.05; r=0.080; p>0.05. In non-diabetics, respectively: p<0.05; r=0.2923; p<0.05 for leptin; and p<0.0001, r=0.5103; p<0.0001, for s-OB-R.

CONCLUSIONS: Not leptin alone but serum sOB-R and FLI are the markers of leptin action impairment in type 2 diabetes. Further, HbA1c is not associated with metabolic status of leptin in obese diabetic patients, whereas this association is found in obese non-diabetic humans....

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Comparative Study 2010; 31(5): 631-634 PubMed PMID: 21173745 Citation  Keywords:  Adult, Body Mass Index, Case-Control Studies, Cataplexy:diagnosis, Comorbidity, Czech Republic:epidemiology, Female, Humans, Male, Medical Records, Middle Aged, Narcolepsy:diagnosis, Obesity:diagnosis, Polysomnography, Sleep, Wakefulness,.   

BACKGROUND: Narcolepsy with cataplexy (NC) differs from narcolepsy without cataplexy (NwoC) in the cerebrospinal fluid levels of hypocretin. Since hypocretin is known to regulate not only wakefulness but also eating behaviour, we decided to compare the two entities for body mass index (BMI) and the presence of obesity.

METHODS: Clinical data on patients with NC and NwoC was studied and examined, including nocturnal polysomnography and the Multiple Sleep Latency Test (MSLT). The results were rated against a group of age- and sex-matched healthy controls.

RESULTS: The BMI in NC (29.1±SD=5.8) was significantly higher than in NwoC (25.4±4.4) or in the controls (25.8±3.9) (p<0.001, F=17.4, df= 323), while no difference in BMI was found between NwoC and the controls. The proportion of patients with BMI >30 was significantly greater in NC (39.0%) than in NwoC (13.8%) or than in the control group (13.0%). A negative correlation of BMI and sleep latency in MSLT (p=0.009) was found in the combined NC and NwoC groups.

CONCLUSION: Unlike NC, NwoC has neither a higher BMI nor a higher incidence of obesity than the general population....

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Journal Article 2010; 31(5): 717-723 PubMed PMID: 21173738 Citation  Keywords:  5,10-Methylenetetrahydrofolate Reductase (FADH2):genetics, Abortion, Habitual:enzymology, Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Poland, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymor.   

BACKGROUND: Recurrent miscarriages (RM) are significant social and clinical problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes involved in homocysteine and folate metabolism, including 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important risk factors for homocysteine accumulation and modulator of RM susceptibility. Therefore the aim of this study was to evaluate the frequency of MTHFR polymorphisms (677C>T, 1298A>C, and 1793G>A) in women with recurrent miscarriages.

MATERIAL AND METHODS: We have analyzed 104 Polish women with a history of 3 or more unexplained recurrent miscarriages in the first pregnancy trimester (6-13 gestation week). The control group consisted of 169 women without obstetrical complication, any history of miscarriage and with at least one live birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP methods.

RESULTS: For MTHFR 1793G>A polymorphism we have observed significant overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in the controls, OR=4.21, p=0.003). For 677C>T and 1298A>C we have shown lack of significant association with RM. Nevertheless, such significant association was observed if more than one mutated MTHFR variant was present in one patient.

CONCLUSIONS: Our research indicate the possible role of MTHFR 1793G>A polymorphism in pathogenesis of RM. The noticed tendency to more frequent occurrence of haplotypes of MTHFR gene including two or three mutated alleles showed the possibility of summarized amplification of these variants effect influencing RM susceptibility....

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