Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationship to temperamental dimensions measured by the Temperament and Character Inventory in healthy volunteers.

There is evidence for an association between polymorphisms of monoamine transporter genes and temperamental personality traits. Recent findings have shown that interaction of allelic variants of the different genes may contribute to the personality factors. We studied the association between temperamental personality dimensions measured with the Temperament and Character Inventory (TCI) and polymorphisms of the dopamine (DAT), norepinephrine (NET) and serotonin (5-HTT) transporter genes in 127 healthy Polish volunteers. There were no significant differences between means of TCI temperamental dimensions (novelty seeking, reward dependence, persistence and harm avoidance) and the transporter genes compared by ANOVA. There were some significant associations between genotypes and TCI subdimensions. Individuals carrying the A9/A9 DAT genotype have lower RD4 scores (dependence vs. independence) than A10/A10 individuals (3.0 +/- 1.4 vs. 3.5 +/- 1.3); p = 0.01. Examining 5-HTT gene promoter polymorphism, heterozygous individuals (l/s) and individuals with 44-bp deletion (s/s) scored significantly lower in the HA1 subdimension (anticipatory worry and pessimism vs. uninhibited optimism; 4.3 +/- 2.3 vs. 5.5 +/- 2.6) in comparison with individuals without deletion (l/l); p = 0.021. The NET transporter gene polymorphism showed no significant association with any of the temperamental TCI subdimensions.

[New implications for mental disorders treatment: pharmacogenetic studies of dopaminergic and serotonergic neurotransmission systems]. / Nowe perspektywy w leczeniu chorób psychicznych--badania farmakogenetyczne ukladów neuroprzekaznictwa dopaminergicznego i serotoninergicznego.

The aim of this article is to summarize the present state of pharmacogenetical knowledge compiled and based on various publications in this matter. Thanks to developing cloning and DNA-analysis techniques it is possible to analyze numerous proteins synthetized in the central nervous system. Several polymorphism sites in coding genes have already been located--first of all for some genes coding receptors linked to protein G, especially for dopamine and serotonine receptors. Some of mutations may influence the primary structure of receptor protein and in that way be responsible for alteration of receptors functioning. This is likely to be the reason for the difference in reaction to drugs in many patients. A couple of trials dealing with patient's response to neuroleptics in correlation with receptor genes polymorphism have already been completed. The results are promising. The assumption that inventing new drugs should be correlated with collecting DNA samples from patients to evaluate further pharmacogenetical linkage seems to be essential.

[The influence of genes on the development of personality]. / Wplyw genów na ksztaltowanie sie cech osobowosci.

Antisocial behavior and personality disorders are both heterogeneous and the product of interacting genetic and environmental factors acting at different levels of causation. Heritability studies show that individual differences in predisposition to antisocial behavior are transmitted by genetic mechanisms in families. Direct gene analysis and genetic linkage analysis have identified structural variants in genes involved in neurotransmitter function, and some progress has been made towards relating these genetic variants to antisocial personality and other behaviors. The monoamine oxidase-A variant leads to aggressive behavior in one family. Direct gene analyses have revealed amino acid substitutions and structural variants at DRD2, DRD3 and DRD4 dopamine receptors and 5-HT2A, 5-HT2C serotonin receptors, serotonin transporter gene, and genes for enzymes, metabolizing biogenic amines MAO-A, MAO-B. The stage is set to identify the phenotypic significance of these as well as genetic variants at other loci which may be relevant as candidate genes for antisocial behavior and related behavioral differences.

Effects of dopaminergic agonists and antagonists on the serum prolactin levels in alcoholized rats.

A single dose of ethanol (1 g/kg p.o.) significantly decreased, whereas higher doses of ethanol (2 or 3 g/kg p.o.) significantly increased the serum prolactin (PRL) concentration. Administration of ethanol at a dose of 2 g/kg p.o. for 4 weeks did not affect this parameter but the ethanol withdrawal syndrome caused a significant rise in the serum PRL level. Chronic studies showed that D1-dopaminergic agonist SKF 38390 (2.5 mg/kg) significantly raised serum PRL levels in rats. This effect was reversed by long-lasting treatment of rats with ethanol and ethanol withdrawal. Pimozide (1 mg/kg), D2 antagonist, increased PRL in those rats. On the other hand, D1-antagonist SCH 23390 (0.5 mg/kg) and D2-agonist PPHT (0.5 mg/kg) were without effect in rats administered ethanol for a long period of time. In rats with ethanol withdrawal syndrome, administration of D1-antagonist SCH 23390 (0.5 mg/kg) also did not affect the serum PRL concentrations. However, D1-agonist SKF 38393 (2.5 mg/kg) and D2-antagonist pimozide (1 mg/kg) increased the serum PRL level in rats with ethanol withdrawal syndrome, whereas D2 agonist PPHT (2 mg/kg) decreased PRL level in serum. Thus, the acute effect of ethanol on PRL level appears to be dose-dependent. It seems that chronic ethanol administration and its withdrawal especially affected D1 receptor.

[The effect of nifedipine and chlordiazepoxide on alcohol withdrawal syndrome]. / Ocena efektów dzialania nifedypiny i chlordiazepoksydu w alkoholowym zespole abstynencyjnym (AZA).

The aim this study was to evaluate the efficacy and tolerability of DHP calcium channel antagonist-nifedipine in human AWS in comparison to conventional treatment with chlordiazepoxide. Fifty nine hospitalized alcoholics of both sexes with diagnosis of AWS according to DSM-III-R criteria were treated for 2 weeks in monotherapy with nifedipine (Cordafen-Polfa)-60 mg/d. or with chlordiazepoxide (Elenium-Polfa)-150 mg/d. Evaluation of AWS symptoms was performed at baseline and after 3, 7, 14 days using Sandowal-Wang scale. Our original scales (37 items) were designed for measuring the depth of dependence (WGU) and the velocity of dependence syndrome appearance (WWO). The results show that both groups were similar regarding WGU and WWO before treatment. Both drugs caused an improvement of AWS symptoms after 3 and 7 days lasting till the end of hospitalization. Nifedipine was well tolerated and no side effects were observed or reported. The group and multidimensional analyses were performed using original computer program. The patients were divided into 3 subgroups. Comparison of mean values of improvement index between both drugs in those subgroups of patients according to WGU criteria, revealed that nifedipine was more effective on the 3-rd and 7-th day in 3 groups and 2 groups resp. According to WWO criteria the improvement index was significantly higher on the 3-rd and 7-th day in two groups whereas in one group chlordiazepoxide and nifedipine action was equal. The proposed method of group and multidimensional analysis enable us to compare the effectiveness of different kinds of AWS treatment. It is an useful aid of choosing the best drug treatment for a new patient.

[Mianserin efficacy in the treatment of depression]. / Skutecznosc mianseryny w leczeniu zespolów depresyjnych.

Fifty patients suffering from depression were treated wigh mianserin in monotherapy. ICD-9 and DSM-III criteria for depression were used. Patients were divided into four groups--with monopolar depression (28 patients), bipolar depression (8 patients), organic depression (10 patients), neurotic depression (4 patients). The intensity of psychopathological symptoms of depression was established using the Hamilton Depression Rating Scale (HDS) on the 7th, 14th and 28th day of the treatment. The antidepressant action of mainserin was evident already on the 14th day of treatment. Mianserin proved to be most effective in endogenous bipolar depression group and neurotic depression group (70% reduction in the score obtained on the HDRS). Mianserin was well tolerated by most patients. Most frequent side effects observed were: hypertension (8 patients), feeling of anxiety (10 patients), constipation (8 patients), tachycardia (6 patients), dry mouth (3 patients).

The role of dopamine neurotransmission in ethanol dependence development and ethanol withdrawal in rats.

This study was undertaken to evaluate the influence of acute doses of ethanol, chronic ethanol administration and the withdrawal syndrome on central dopaminergic neurotransmission in 700 rats. The ethanol effects were differentiated by their influence on D1 and D2 receptors using following dopaminergic ligands. SKF 38393 (2.5 mg/kg), SCH 23,390 (0.5 mg/kg), pimozide (1 mg/kg), PPHT (2 mg/kg). It was found that ethanol in a low single dose (1.0 g/kg p.o.) increased DA level in rats' brain. In chronic alcoholized rats SKF 38,393 increased the D1 receptor answer in biochemical and behavioural experiments. During the withdrawal period in rats D2 agonist PPHT reversed abstinence symptoms whereas other DA antagonists normalized only some parameters altered by ethanol removal from the diet.

[A new view of the evaluation of alcohol withdrawal and alcohol dependence]. / Nowa perspektywa oceny glebokosci zespolu zaleznosci alkoholowej i alkoholowego zespolu abstynencyjnego.

This study was designed to evaluate 21 alcohol dependent male individuals during withdrawal syndrome. The intensity of withdrawal symptoms was measured using Sandowal-Wang scale. The level of blood serum prolactin was measured twice a day (8 a.m. and 8 p.m.) on the lst, 3rd, 7th, 14th, 21st day of the study. Also the depth and the time of the development of dependence were evaluated using DSM-III-R criteria, alcohol dependence (WGU) and presence of dependence symptoms scale (WWO). It was establish that WGU, WWO and DSM-III-R criteria, separated similar groups of patients with the same depth of dependence clinical symptoms and prognosis. This study revealed a negative correlation between intensity of withdrawal symptoms and PRL levels in blood serum on the 1st day of abstinence. PRL levels increased from the 3rd to the 21st day of the study. Ethanol withdrawal symptoms intensity index was positively correlated with WGU.

[Psychopathologic picture of depression and the conduct of some hormone tests and the therapeutic response to thymoleptics]. / Psychopatologiczny obraz depresji i zachowanie sie niektórych testów hormonalnych a odpowiedz terapeutyczna na tymoleptyki.

Psychopathological picture of depression and the conduct of some hormone tests vs the therapeutic response to thymoleptics were examined. On the grounds of some diagnostic criteria, 84 patients with affective psychosis were divided into three diagnostic groups: unipolar (DJ, n = 54) and bipolar (DD, n = 20) endogenous depressions and non-endogenous depression (DN, n = 10). The control group (GK, n = 25) consisted of mentally healthy people. Hormone tests TRH and ITT were performed before and after the treatment. The hormones: TSH, T4, T3, PRL, GH, and CORT were marked by RIA methods. The findings of the examination, after being statistically described and thoroughly discussed, show that they could be useful in differential diagnosis of affective illnesses and in prognosis of therapeutic response.

[Further development of a computer program for supporting psychiatric diagnosis and choice of therapy]. / Dalsze rozwiniecie komputerowego programu wspomagania diagnozy psychiatrycznej i wyboru terapii.

The algorithm grouping the patients into natural subsets, according to their psychopathological features or results of laboratory examinations, was extended by a software enabling the allowance of a new patient to the nearest subset taking into account any features describing the representative set. Apart from that the system was extended by a software of multi-criterion assessment of drug usability in empirical subsets of patients. It was found out that the developed information system makes it possible to assess such relations between the features of the examined phenomenon that would not be noticeable without using the system.

[Evaluation of side effects and complications during the treatment of affective psychoses with thymoleptics]. / Ocena dzialan ubocznych i powiklan podczas leczenia psychoz afektywnych tymoleptykami.

Evaluation of effects of amitriptyline, imipramine, maprotiline, mianserin , clomipramine and citalopram was performed in 84 patients (49 females and 35 males) age on average 40 years with diagnosis of affective psychosis treated in the Department of Psychiatry Medical School of Szczecin. Antidepressants independently from their pharmacological profile cause in above 50% of patients side effects mainly from autonomous nervous system. Tricyclic antidepressants caused some cardiotoxic effects which were not observed during administration of antidepressant drugs of different chemical structure, especially of citalopram. No effects on the haemopoietic system and on parenchymatous organs were observed. Neither were affected hypothalamic mechanisms for basal secretion of thyrotropic hormone, prolactin , cortisol and so ACTH. Multifactorial analysis of positive and untoward effects observed during the treatment shows comparable clinical value of all six evaluated drugs. A choice of a drug for an individual should depend on particular clinical contraindications.

[Effect of delayed-action Mirenil (Polfa) on the hypothalamic function in patients with schizophrenia]. / Wpøyw mirenilu prolongatum (Polfa) na czynnosc podwzgórza u chorych z rozpoznaniem schizofrenii.

Hormonal tests--TRH, ITT and L-RH--were performed in 10 cases of paranoid schizophrenia before the paranoid deterioration and after--on average--ten months of treatment with fluphenazine depot injection. The drug did show a clear modulating effect on the mechanisms regulating secretion of gonadotrophins and prolactin --it did not effect the secretion of thyrotropin , thyroxine, triiodothyronine, cortisol, growth hormone or insulin .