Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances.

Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required.

Suicide ideators and attempters with schizophrenia--the role of 5-HTTLPR, rs25531, and 5-HTT VNTR Intron 2 variants.

AIM: To examine the role of 5-HTTLPR, rs25531 and 5-HTT VNTR Intron 2 variants in subjects with psychotic disorders manifesting suicide ideation and behaviour. METHODS: The study included 519 subsequently hospitalized subjects who were genotyped for 5-HTTLPR, rs25531 and 5-HTT VNTR In2 variants. Clinical assessments included structured psychiatric interview, sociodemographic characteristics, suicide ideation and behaviour (SIBQ), severity of psychopathology (PANSS) and depression (CDSS). RESULTS: Three subgroups were identified: suicide attempters (N = 161), suicide ideators (N = 174) and subjects who never reported suicide ideation or behaviour (comparative group, N = 184). MAJOR FINDINGS: 1) Suicide attempters scored highest on the CDSS, while no differences between the three clinical subgroups were detected in the PANSS scores; 2) Suicide attempters were more frequently the carriers of L(A) allele, while subjects in the comparative group were more frequently the carriers of low expression 5-HTTLPR/5-HTT rs25531 haplotype SL(G); 3) No difference was found between the three clinical groups in the 5-HTT VNTR In2 variants; 4) Subjects with 5-HTTLPR/5-HTT rs25531 intermediate expression haplotype (L(A)L(G,)SL(A)) scored higher on the PANSS general psychopathology subscale; 5) There was no association between suicide attempt or ideation and 5-HTTLPR/In2 or 5-HTTLPR/rs25531/In2 haplotype distribution. CONCLUSION: The suicide ideators, attempters and controls did not differ significantly in 5-HTTLPR or 5-HTT VNTR In 2 variants, but 5-HTTLPR/5-HTT rs25531 haplotype might be a useful genetic marker in distinguishing these three clinical groups.

Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female patients with schizophrenia.

The objective of this study was to determine the association of 5-HT2C (serotonin 2C receptor) and MDR1 (multidrug resistant protein) genetic polymorphisms and antipsychotic-induced metabolic abnormalities among female patients with DSM IV schizophrenia spectrum disorders. We have previously reported the associations of -759CT 5-HT2C and G2677T and C3435T MDR1 genetic polymorphisms and olanzapine/risperidone-induced weight gain in a similar sample of patients. Here, we included a total of 101 previously non-medicated female patients treated with olanzapine/risperidone over a 3-month period. The variables analyzed included fasting glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride levels in blood, blood pressure and waist circumferences. We observed significant association of -759T 5-HT2C genetic variant and greater increase in waist circumference (P=0.03), fasting glucose level (P=0.046) and triglyceride level (P=0.045) in blood after a 3-month period. The 2677T and 3435T MDR1 genetic variants were significantly associated with the greater increase in fasting glucose level in blood when patients were using olanzapine (P<0.001 and P=0.028, respectively). Our data indicate a possible influence of -759CT 5-HT2C and MDR1 G2677T and C3435T MDR1 genetic polymorphisms on the development of metabolic abnormalities among female patients treated with olanzapine/risperidone.

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up.

The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.

EMG analysis of muscle load during simulation of characteristic postures in dinghy sailing.

AIM: The aim of this work was to establish the characteristic values of the particular electromyographic (EMG) indicators in the simulation of hiking in the laser-standard class in dinghy sailing. METHODS: Seven top-level competitors participated in the study (age: 21.1+/-2.5 years; height: 184.1+/-5.7 cm; weight: 78.4+/-3.7 kp). The 4 muscle groups analyzed were those which, according to expertise are exposed to the most strain during training and competition in all classes of dinghy sailing, as well as in the Olympic laser standard class (extensors of the lower leg, abdominal, lumbar and tibial muscles). A portable surface EMG apparatus was used for the recording of EMG signals. Digitized EMG data were full-wave rectified and smoothed. Their mean values during characteristic hiking positions (sitting--S, upright hiking--UH, leaning backwards hiking--LBH) were compared by means of repeated ANOVA measures. RESULTS: ANOVA showed significant differences for the absolute EMG signal between analyzed positions for quadriceps muscles (UH vs S, p < or = 0.001; LBH vs UH, p < or = 0.01), abdominal m (UH vs S, p < or = 0.001; LBH vs UH, p < or = 0.001), tibial m (UH vs S, p < or = 0.01; LBH vs UH, p < or = 0.05) and lumbar m (LBH vs UH, p < or = 0.01). According to results, the muscles most loaded are the quadriceps muscle of the thigh, followed by the abdominal muscles. CONCLUSIONS: The findings of this study allow for a better biomechanical understanding of the character of the load distribution in body musculature in positions characteristic of the laser-standard class sailing, and these insights might be applicable to other classes of dinghy sailing.

Similarities in the pattern of regional brain dysfunction in negative schizophrenia and unipolar depression: a single photon emission-computed tomography and auditory evoked potentials study.

1. Negative schizophrenic and unipolar depressive patients were clinically assessed. In addition to this SANS and HRSD tests were administered. 2. SPECT and AEP measurements were provided. SPECT resulted in quantified brain blood perfusion, by means of average "count/pixel" values in the brain regions of interest. AEPs resulted in stored multichannel signal waveforms. 3. Statistical analyses of blood perfusion measurement data revealed an overall similarity between these two disorders in the majority of brain regions. An exception to this are the regions: inferior temporalis, inferior occipitalis, hippocampus and the anterior basal ganglia. Both diagnostic groups manifested hypofrontality. In general, hypoperfusion of the left hemisphere was found, albeit displaying different patterns in the two groups investigated. 4. AEP latencies were prolonged and found to be similar in both diagnostic groups, whilst AEP amplitudes were smaller in schizophrenics compared to depressives.

Simple neuro-mechanical measure of the locomotor skill: an example of backward somersault.

We have studied skilled human locomotions in sports gymnastics by measurement and analysis of ground reaction force and myoelectric signals. Assuming the quality of performance to be a skill level criterion acquired signals were mathematically analyzed via basic signal processing and cross-correlation methods. The study of backward somersault yielded quantitative criteria of performance, proposing an original measure-an inter-muscular cross-correlation function. Besides motor learning, the quantification of movement skill introduced here also relates to possible applications in biocybernetics, robotics and rehabilitation medicine.

A marker-free method to estimate joint centre of rotation by video image processing.

A marker-free video measurement and image processing method that provides numerical estimation of the 2-D centre of rotation of one rigid segment is tested. The algorithm is based on binary region moment features. A comparison is made between this method and a marker-based one, where the location of the markers has been calculated in two ways. The algorithm is also extended to handle two rigid segments. The method is to be applied in human locomotion analysis in order to calculate the centre of rotation of the hip joint. It's accuracy has been tested by a comparison with in vivo radiological measurements on humans.

Method to evaluate the skill level in fast locomotion through myoelectric and kinetic signal analysis.

The paper describes a method aimed at providing objective diagnostic testing of skilled locomotor stereotypes. Bioelectric muscle activity indices and ground reaction force data are used to represent a movement structure, in a schematized way, using discrete states in time. Athletes were asked to perform one specific movement structure: a backward somersault from the standing position. Mathematical analyses of measured signals reveal the significance, for the skill level evaluation, of parameters reflecting the impulsive take-off force waveform and the symmetry in EMG activity of ankle extensor muscles, which therefore might be used as diagnostic criteria. Within technical limitations, this approach may also be applied to other locomotor patterns and possibly to monitor the progress in motorics in pathological locomotion. EMG telemetry could significantly enhance the method's scope.

Locomotion diagnostics: Some neuromuscular and robotic aspects.

Some aspects of neuromuscular function evaluation in fast sports locomotion are presented. The procedure of locomotion diagnostics and the underlying principles are discussed, and experimental data for their support are given. These data concern the evaluation of locomotor skill and of muscle fatigue. The approach processes some features similar to robotic systems study and is potentially applicable to other (ergonomic, medical) areas as well. Among the major limitations of the methodology are a relatively crude representation of the neuromuscular system, with only a few major muscles (and only in the lower extremities) monitored, and the fact that the EMG gives an indication of an actively generated muscle force only, and not of significant elastic force components.

Acute effect of electroconvulsive therapy on brain perfusion assessed by Tc99m-hexamethylpropyleneamineoxim and single photon emission computed tomography.

Regional cerebral blood flow (rCBF) was measured in relative terms with Tc99m-hexamethylpropyleneamineoxim and single photon emission computed tomography in 11 patients undergoing electroconvulsive therapy (ECT). The patients suffered from major depressive disorder (n = 8) or schizoaffective disorders (n = 3). rCBF was measured under general anesthesia 3 days prior to the ECT treatment and coinciding with the ECT stimulation. ECT caused a redistribution of the tracers uptake. The uptake became more pronounced in frontal parts of the brain and in the basal ganglia than in posterior parts of the cortex, and the thalamus. This selective effect of ECT on rCBF may be related to catecholaminergic projections to anterior parts of the brain.

Cerebral perfusion inhomogeneities in schizophrenia demonstrated with single photon emission computed tomography and Tc99m-hexamethylpropyleneamineoxim.

Cerebral blood flow was measured in relative terms with Tc99m-hexamethylpropyleneamineoxim (HMPAO) and single photon emission computed tomography (SPECT) in 28 female schizophrenic patients (20 acute and 8 chronic) classified according to DSM-III. Eleven normals served as controls. The acute patients were classified according to positive and negative symptoms. Patients with predominantly positive symptoms showed by and large normal and homogeneous cerebral isotope uptake. Those with negative symptoms, and the chronic patients, showed inhomogeneous tracer uptake with multiple regions of hypoperfusion in slices 4-6 cm above the orbitomeatal line. The findings support in principle the notion that schizophrenia with negative or chronic symptoms does not affect the whole brain homogeneously. Brain imaging with Tc99m-HMPAO and SPECT might be used to distinguish various types of schizophrenia.

Echocardiographic findings in children participating in swimming training.

In 72 children having a body surface area from 0.8 to 1.6 m2 who systematically trained in swimming at last for 1 year, or an average of 29.2 months, echocardiographic recordings were done to find out which changes result from systematic training. The results obtained were compared with values obtained in 72 normal children, having the same body area, but who did not actively engage in sports. The measurements and analyses showed that values of the left ventricular interior diameter (LVID), left atrium (LA), and heart depth (DS) were statistically significantly increased. The values of septum thickness (SE) and left ventricular posterior wall (LVPW) were a bit larger, but statistically not significant. Contractibility of the myocardium was also examined by measurement of the ejection fraction (EF), percentage of the shortening of the left ventricle (%FS), and average velocity of the circumferential shortening of the muscular fibers (VCF). The values obtained were within limits of normal values. Results of the analysis of the influence of sports training on echocardiographic dimensions indicated four positive correlations: left ventricular interior diameter in systole (LVIDs) and diastole (LVIDd), diameter of the left atrium (LA), and heart depth (DS). In recording echocardiograms in children, it is necessary to establish whether the child actively engages in sports beforehand since long-term training leads to changes of some heart structures, which may, if it is not known that the child is active in sports, lead to wrong conclusions that the finding is pathological.

Vasopressin and cardiovascular system in aging.

The studies concerned age-dependent peculiarities of the vasopressin effect on the hemodynamics and tone of the coronary vessels in dogs, the contraction of the isolated vascular strip in rats, and the hemodynamic and ECG indices in rabbits and in rats. The data obtained indicate the great sensitivity of old vessels to vasopressin. In aging, both humans and animals show a rise of vasopressin concentration in the blood. Age-dependent differences of the vasopressin effect on the kallikrein-kinin system, adenosine metabolism, the contents of prostaglandins and cyclic AMP have been established. High sensitivity to vasopressin in combination with its increased concentration in the blood is an important factor that contributes to the development of arterial hypertension and ischemic heart disease.