[Heritability of bipolar affective disorder--family study].

BACKGROUND/AIM: Bipolar affective disorder is mental disorder with polygenic type of heredity. Heritability--relation between genetic and environmental variance is used to estimate the level of influence of genetic variance to phenotype variance. Study results show decreasing trend in the value of heritability of bipolar affective disorder, thus indicating that this disorder is a complex behavioral threshold characteristic. Therefore, the aim of this study was to estimate the contribution of genetic variance to phenotype variance of bipolar affective disorder, i.e. to estimate heritability of this disorder. METHODS: By the use of a questionnaire, 80 patients with over crossed threshold for bipolar affective disorder were asked for functional information about the members of their families belonging to the first degree of relation (fathers, mothers and full-sibs). By using "Applet for calculating heritability for threshold traits (disease)", and regression analysis, heritability of bipolar affective disorder as well as its statistical significance, were estimated (chi2 test). RESULTS: Heritability and relationship of genetic and environmental variance of bipolar affective disorder is 0.2 with statistically significant difference from zero (p < 0.001). CONCLUSION: The estimated contribution of genetic variance to phenotype variance of bipolar affective disorder is low being 20%, while the contribution of environmental variance is 80%. This result contributes to the understanding of bipolar affective disorder as a complex behavioral threshold trait.

Population pharmacokinetic model of carbamazepine derived from routine therapeutic drug monitoring data.

The aim of the present study was to develop a population pharmacokinetic model of carbamazepine from routine therapeutic drug monitoring data. Steady-state carbamazepine plasma concentrations determined by homogenous enzyme immunoassay technique, dosing history including cotherapy, schedule of blood sampling, and patients' demographic characteristics were collected retrospectively from patients' chart histories. A one-compartment model was fitted to the data using nonlinear mixed effects modeling. The influence of weight, age, gender, smoking, allergy, carbamazepine daily dose, and cotherapy on clearance (CL/F) was evaluated. Additionally, bioavailability of controlled-release relative to immediate-release tablets was assessed. Two hundred sixty-five patients (423 concentrations) were used to develop a population pharmacokinetic model. The population estimate of CL/F from the base model was 5.14 L/h with interindividual variability of 50.20%. Patients' gender, age, smoking, allergy, cotherapy with lamotrigine and benzodiazepines had no effect on CL/F. Patient weight (WT), daily carbamazepine dose (DCBZ), daily dose of phenobarbitone (DPB) and valproic acid (VPA), when its daily dose exceeded 750 mg, significantly influenced CL/F and were included in the final model:[equation: see text] where VPA is 1 if dose is greater than 750 mg or 0 otherwise. No difference in bioavailability of carbamazepine between controlled- and immediate-release tablets was detected. The model predictions in the validation set had no bias and satisfactory precision. The model can be used for estimation of carbamazepine CL/F in individual patients in the postautoinduction phase and for selection of optimum dosing regimen in routine patient care.

Single-dose intravenous simvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in the rat.

The effect of acute pretreatment with a single dose of simvastatin (1 mg/kg, i.v.; 30 min before ischemia) on renal dysfunction caused by ischemia-reperfusion (I/R) injury in the rat was investigated. I/R injury was induced by clamping both renal vascular pedicles for 45 min, followed by 4 h of reperfusion with saline (2 ml/kg per hour). Simvastatin significantly improved both parameters of glomerular and tubular dysfunction (e.g., creatinine levels and fractional excretion of Na(+), respectively) and especially improved the histological score, compared to control I/R-injured rats treated with saline or 10% DMSO only.

[Comorbidity of migraine and somatic diseases].

INTRODUCTION: A 5-year prospective follow-up study was performed at the Institute of Mental Health in Belgrade, and it included adult patients diagnosed with migraine. MATERIAL AND METHODS: A protocol for prospective follow-up of comorbiditiy of migraine and somatic diseases was designed, whereas data were analyzed using standard statistical methods. RESULTS: The study comprised 381 patients, mean age 35.8 (range 19-60) years, 60 (15.8%) males and 321 (84.2%) females. The mean duration of migraine history before the first visit to the doctor was 7.7 (0-36) years. There was no concomitant disease in 50.5% of examinees. The most common concomitant diseases in the study population were: spondylosis (15.9%), head injury (12.9%), gynecological disorders (11.6% of female subgroup), hypotension (8.8%), hypertension (8.5%), allergy and asthma (5.8%), various cardiovascular diseases (4%) and epilepsy (3%). The incidence of the majority of diseases is in accordance with known epidemiological data for general population (except for head injury and epilepsy). In the subgroup of patients with comorbidity, almost 70% of patients reported more than one migraine attack per month, compared to 35% of patients without concomitant diseases, and about 60% of them had a higher intensity of headache in comparison with 35% of those without comorbidity. CONCLUSION: Present results indicate an increased severity of migraine attacks in patients with comorbidity. Therefore, it is necessary to assess how good management of comorbid diseases can alleviate the course and intensity of migraine headaches.

Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy.

AIM: To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. METHODS: An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years). All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD), Beck depression scale (BDI), and Hamilton anxiety scale (HMA) were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. RESULTS: Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01). Negative behavioral effects occurred in 10.7% of the patients. CONCLUSION: Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.