Archives 1992-2013

2004, volume 13, suplement 3

Genetics

Association study of the 3 'UTR VNTR dopamine transporter (DAT) gene polymorphism in patients with early and late onset of schizophrenia

PIOTR M. CZERSKI, JOANNA HAUSER, PAWEŁ KAPELSKI, AGNIESZKA SŁOPIEŃ, MONIKA DMITRZAK-WĘGLARZ, MARIA SKIBIŃSKA, MACIEJ WILCZYŃSKI, ANNA MARZEC, JANUSZ K. RYBAKOWSKI
Postępy Psychiatrii i Neurologii, 200, ,13, suplement 3 (19), 3-15

Aim. The aim of this study was to specify the genotype and allele frequency of the 3'UTR VNTR DAT polymorphism in patients with schizophrenia and healthy controls. Both patients and healthy controls were divided into smaller subgroups based on the gender differences and the age of onset.

Method. The studied group comprised 362 unrelated patients with schizophrenia (205 males and 157 females) and 376 controls (150 males and 226 females). 69 patients developed schizophrenic symptoms at the age of 18 or earlier. All individuals participating in this study were Polish, mostly from the Wielkopolska region. For each patient, a consensus diagnosis was made by two psychiatrists using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Genotyping of the 3'UTR VNTR DAT polymorphism was performed using the PCR-VNTR method. Statistical analysis of genotype and allele frequencies was performed with the Pearson's x² and Fisher's exact tests, respectively. Additionally, an analysis of the power estimation as well as the concordance between the genotype distribution and the Hardy-Weinberg equilibrium was performed.

Results. The association between male schizophrenics and A9/A9 and A9/Al0 genotypes (p = 0,004) and A9 allele (p = 0,00l) was observed. Comparing patients with early onset of schizophrenia with controls, the association was also detected for genotypes A9/A9 and A9/A10 (p = 0,002) and for A9 allele (p = 0,003). Additionally, there was a statistically significant difference in the genotype frequency between patients with early and late onset of schizophrenia (p = 0,004).

Conclusions. The present results show a possible association between an increased susceptibility to early onset of schizophrenia in males and the A9 allele and genotypes containing this allele (A9/A9 and A9/A10).

Genetics

The search for the relationship between the paranoid schizophrenia occurrence and the COMT gene polymorphism and its influence on antipsychotic treatment efficacy

PIOTR TYBURA, Anna Grzywacz, GENOWEFA STEPIEŃ, MICHAŁ PARUS, Jerzy Samochowiec
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 3 (19), 17-23

Aim. A number of family, adoption, monozygotic and dizygotic twin's studies revealed the genetic background of schizophrenia. The estimated genetic risk of schizophrenia is about 40-50%. Based on the Carlsson's dopaminergic theory, linkage analysis and association studies, COMT gene was chosen as a candidate gene for schizophrenia.

Method. In our study alleles and genotypes frequency was evaluated in patients with schizophrenia (n = 41) and in the healthy population (n = 187).

Results. No association was found between schizophrenia and any genotype of the COMT gene polymorphism. In contrast, we found statistically significant differences in allele distribution: methionine alleles were more frequent in the schizophrenia group. Compared with the higher COMT activity patients, the homozygotic met/met patients with less active COMT, revealed significantly greater reduction in general psychopathological symptoms measured by the PANSS scale during the course of two and twelve week therapy.

Conclusions. Due to the small number of patients in this study, the obtained results should be treated as the preliminary ones.

Genetics

The association between the dopamine transporter and COMT gene polymorphisms and the personality traits measured by the Temperamental and Character Inventory (TCl) and NEO-FFI in healthy volunteers

JOLANTA KUCHARSKA-MAZUR, MICHAŁ PARUS, SZYMON SYREK, ANETA RYŻEWSKA, Justyna Pełka-Wysiecka, AGNIESZKA SAMOCHOWIEC, JERZY SAMOCHOWIECI
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 3 (19), 25-33

Aim. The association between the DAT1 and COMT gene polymorphisms and the temperament dimensions evaluated by the TCI and NEO-FFI inventories was studied.

Method. 181 healthy volunteers (without psychiatric disorders according to axis I of ICD-10), including 114 females (age 34,0 ± 12,4) and 67 males (age 35,1 ± 16,8), were recruited to represent a cross-section of the Szczecin's population in terms of sex, age, education, Caucasian race and Polish nationality.

Results. Statistically significant differences were obtained using the NEO-FFI inventory, i.e. the DAT1 genotype dependent Agreeableness and Conscientiousness and the COMT genotype dependent Neuroticism, Extraversion and Agreeableness. Probands carrying A9 allele of DAT1 gene polymorphism (males and the whole group) scored significantly lower in the Agreeableness scale (p < 0,05 and p ≤ 0,015 respectively) while males carrying A9 allele of DAT1 gene polymorphism scored significantly lower in the Conscientiousness scale (p < 0,05). Probands with G allele encoding the more active form COMT, scored significantly higher in Neuroticism (males: p = 0,001; the whole group: p < 0,05) and lower in Extraversion (p ≤ 0,015). Males carrying G allele scored significantly lower in Agreeableness (p < 0,05). Probands carrying A9 allele of DAT1 gene polymorphism scored significantly higher in the TCI's Novelty seeking scale (p < 0,05) and the NS4 subscale (p < 0,05). Probands carrying G allele of COMT gene polymorphism scored significantly higher in the NS2 subscale (p < 0,05). Conclusions. Our results do not support the hypothesis that there is a simple correlation between a single gene polymorphism and a personality trait measured by the TCI and NEO-FFI scales.

Genetics

Association study between the DRD2, DATl, 5HTT, MAO A and COMT gene polymorphisms and the anxiety and depression levels in alcoholics

Justyna Pełka-Wysiecka, Jerzy Samochowiec, JOLANTA KUCHARSKA-MAZUR, SZYMON SYREK, MICHAŁ PARUS, Anna Grzywacz, JAN HORODNICKI
Postępy Psychiatrii i Neurologii, 2004, 13 suplement 3 (19), 35-46

Aim. Alcoholics suffer from depressive and anxiety disorders three limes more often than a healthy population. Elevated levels of anxiety and depression are observed in the alcohol withdrawal syndrome. The aim of this study was to estimate the relationship between anxiety and depression levels in alcoholics (using psychometric scales: Zung's self-rating anxiety scale: SAS; Zung's self-rating depression scale: SDS) and the 5 candidate genes polymorphisms.

Method. 108 alcohol dependent patients, without other psychiatric illness than alcohol and/or nicotine dependence according to axis I of ICD-l0, were examined. Polymorphisms of DAT1, 5HTT, MAO A, COMT, DRD2 genes were tested.

Results. We found an association between some polymorphisms of tested genes and anxiety and depression levels estimated by the SAS and SDS scales.

Conclusions. The results of our study confirm the hypothesis about the biologically determined individual course of alcohol dependence.

Genetics

Association study between the serotonin transporter gene polymorphism (5-HTT_LPR) and the intensity of alcohol withdrawal

SZYMON SYREK, Justyna Pełka-Wysiecka, JOLANTA KUCHARSKA-MAZUR, GEORG ARENTOWICZ, Jerzy Samochowiec
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 3 (19), 47-52

Aim. Neurochemical, pharmacological and physiological studies indicate the important role of 5-HT in alcohol dependence and alcohol withdrawal syndrome. We tested the possible association between the serotonin transporter gene polymorphism and the intensity of alcohol withdrawal syndrome.

Method. The group of 96 alcohol dependent patients, diagnosed according to ICD-10 criteria were examined. The study included 187 healthy volunteers as control subjects. To assess the severity of withdrawal symptoms we used the CIWA-Ar scale.

Results. Based on the statistical analysis, we found the association between the 5-HTT_LPR gene polymorphism and the CIWA results. Individuals with low transcriptional activity of the 5-HTT gene promoter region proved to have significantly higher severity of withdrawal symptoms (p < 0,004). There were no significant differences in frequency of the genotypes and alleles between alcoholics and controls.

Conclusions. Presented results enable us to formulate the hypothesis that the 5-HTT gene polymorphism affects the severity of withdrawal syndrome.

Genetics

Candidate genes of the dopaminergic system in anorexia nervosa

MONIKA DMITRZAK-WĘGLARZ, FILIP RYBAKOWSKI, AGNIESZKA SŁOPIEŃ, PIOTR CZERSKI, ANDRZEJ RAJEWSKI, JOANNA HAUSER
Postępy Psychiatrii i Neurologii, 2004, 13 suplement 3 (19), 53-62

Aims. Anorexia nervosa (AN) is a disorder of complex etiopathogenesis. Both genetic and environmental factors are of great value. A significant genetic contribution to this disorder is marked by family and twin studies. Many clinical studies have shown that amphetamine, an indirect agonist of the dopaminergic system, is an anorectic agent, which means that it suppresses appetite and food intake. Thus, we studied candidate genes of the dopaminergic system (theoretically associated with the etiology of given disorder) with reference to anorexia nervosa. The aim of the present study was to assess the influence of genes polymorphisms coding dopamine receptors DRD 2 (polimorphisms-141C Ins/Dei), DRD 4 (polimorphisms-521 C/T), dopamine transporter DAT (polimorphisms VNTR w 3'UTR) and catechol-O-methyltransferase COMT (polimorphisms Val 158Met) on the risk of anorexia nervosa.

Method. The studied group comprised of 86-91 unrelated patients fulfilling the DSM-IV and ICD-10 criteria of anorexia nervosa (both restricted and bulimic type) and 77-135 controls. All individuals participating in this study were Polish, mostly from the Wielkopolska region. Genotyping of the DRD2, DRD4 and COMT polymorphisms was performed using the PCR-RPLF and of the DAT using the PCR-VNTR method. Statistical analysis of genotype and allele frequencies was performed with the Pearson's X² and Fisher's exact tests, respectively. An analysis of the power estimation as well as the concordance between the genotype distribution and the Hardy-Weinberg equilibrium was performed.

Review. No significant associations between the polymorphisms under study and anorexia nervosa of both type were proved.

Conclusions. Reported findings do not indicate a possible role of the dopaminergic system genes in predispositions to anorexia nervosa.

Genetics

Genetics of selected anxiety disorders

JOLANTA KUCHARSKA-MAZ, Anna Grzywacz, GEORG ARENTOWICZ, Jerzy Samochowiec
Postępy Psychiatrii i Neurologii, 2004, 13 suplement 3 (19), 63-69

Aim. The aim of the present paper was to review the literature on genetic factors in anxiety disorders.

Review. Numerous factors can contribute to the etiology of anxiety disorders. The population, association and linkage studies made so far show that the environmental factors influence 60-70% of the disorders' variability whereas the genetic factors influence up to 40%. The candidate genes are the ones encoding the central and peripheral nervous system receptors and transporters, including dopamine, serotonin and noradrenergic receptor's and transporters as well as GABA-A, GABA-B, adenosine and cholecystokinine receptors. They also encode enzymes metabolizing biogenic amines (e.g., monoaminooxidases and catechol-O-methyltransferase genes). According to the linkage studies, the loci for the specific anxiety disorders were found on human chromosome 1, 3, 9, 11, 14 and 16.

Conclusions. Further replication studies need to be done to confirm above data.

Pharmakotherapy

Studies on the role of the CYP2D6 activity in depressed patients

MONIKA SZEWCZUK-BOGUSŁAWSKA, KRYSTYNA ORZECHOWSKA-JUZWENKO, PIOTR MILEJSKI, Andrzej Kiejna, Jan Aleksander Beszłej, Magdalena Grzesiak
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 3 (19), 71-76

Aim. Cytochrome 2D6 is involved in oxidation processes of many antidepressant drugs. The CYP2D6 activity is characterized by genetically determined polymorphism. Four phenotypes can be distinguished: ultrarapid (UM), extensive (EM). intermediate (IM) and poor metabolism (PM). Clinical consequences of PM, IM and UM phenotypes may lead to therapeutic failure and the need for hospitalization. In contrast to the healthy population, there are data on the higher rate of PM in hospitalized psychiatric patients. Thus, the aim of this study was to compare the frequency of different CYP2D6 phenotypes in both hospitalized depressed patients and the healthy population.

Method. 52 patients diagnosed with depression according to the ICD-10 and DSM-IV criteria were included in the study. The healthy population consisted of 160 volunteers. CYP2D6 activity was assessed by the phenotyping method. Sparteine was used as a model drug. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Sparteine and its metabolites (2- and 5-dehydrosparteine) were measured in urine. The metabolic ratio was calculated as the percentage of the dose excreted as sparteine divided by the percentage of the dose excreted as 2- and 5-dehydrosparteine. Based on MR value, the CYP2D6 phenotype was estimated.

Results. There was no statistically significant difference between the frequency of CYP2D6 phenotypes in depressed patients and controls (Fisher exact test p = 0,502). A comparison of sparteine MR values in EM and IM shows statistically significant higher values (median 2,74) in depressed patients than in controls (median 1,75).

Conclusions. The frequency of different CYP2D6 phenotypes does not differ in hospitalized depressed patients in comparison with the healthy population. The CYP2D6 activity in EM and IM is lower in depressed patients than in controls.

Pharmakotherapy

The assessment of hypothalamo-pituitary-thyroid axis junction in depressed patients as a factor supporting the choice of antidepressant - the preliminary study

JUSTYNA ORZECHOWSKA, JAN M. HORODNICKI
Postępy Psychiatrii i Neurologii, 2004,13, suplement 3 (19), 77-85

Aim. The presented study is a follow-up to Prof Jan M. Horodnicki's scientific work and is aimed to assess the basal secretion of TSH and thyroid hormones, T3 and T4 in depressed patients as the predictive factors of choosing the most useful selective antidepressant.

Method. The study included 54 patients hospitalized in the PAM Department of Psychiatry, within 2000-2004, diagnosed with endogenous depression, according to ICD-10. Patients were randomly assigned to two groups: treated with maprotylin (antidepressant selectively acting on the noradrenergic system) and treated with citalopram (selective serotonin reuptake inhibitor). The intensity of depressive signs and symptoms was assessed with the diagnostic scales: by Hamilton (HDRS), by Montgomely-Asberg (MADRS) and Clinical Global Impression scale (CGI), before and after 4 weeks of pharmacotherapy. Simultaneously basal serum concentration of TSH and thyroid hormones (T3 and T4) was measured.

Results. Regarding the basal secretion of TSH, T3 and T4, before treatment, the group of patients treated with maprotylin with over 50-percent reduction of depressive symptoms (n1 = 24) was similar to the group of patients treated with citalopram with no improvement (n4 = 12). The group of patients treated with maprotylin without improvement (n2 = 6), was similar to the group of patients successfully treated with citalopram (n3 = 12).

Conclusions. The present results seem to confirm the hypothesis that the disturbed balance between the central noradrenergic and serotoninergic systems responsible for the therapeutic efficacy of the selective antidepressant can be assessed on the base of TSH and thyroid hormones secretion.

Outcome preduction

Follow-up studies of patients suffering from paranoid schizophrenia: individual and social consequences of the disease (part 1)

MAGDALENA LETKIEWICZ, SZYMON SYREK, JAN HORODNICKI
Postępy Psychiatrii i Neurologii, 2004, 13 suplement 3 (19), 87-94

Aim. About 1% of the population suffers from schizophrenia. Additionally, this disease affects indirectly a small percentage of people taking care of the schizophrenic patients. Thus, both individual and social consequences of paranoid schizophrenia seem to be an important issue in the modern society.

Method. 90 patients suffering from paranoid schizophrenia in the eighties and hospitalized at the Department of Psychiatry, Pomeranian School of Medicine in Szczecin, Poland, were the subjects alt his study. Only 41 out of 90 reported to the control examination. Clinical findings, including psychiatric history, the general physical examination, evaluation of mental status, laboratory findings, as well as the late complications of neuroleptic therapy were analyzed. Patient's social and professional status was also taken into consideration. The following diagnostic scales were employed: BPRS, PANSS, Simpson-Angus Extrapyramidal Signs Scale, Late Dyskinesia Scale and the MOS SF-36 Scale evaluating the subjective quality of life of the patients.

Results. For most patients, this catamnestic study revealed different than paranoid symptomatology of schizophrenia. Analysis of patient individual and social activity confirmed the negative influence of paranoid schizophrenia over family life, economic status and social activity. There's been a decline in the living standards of schizophrenic patients. However; the course of paranoid schizophrenia and the treatment history had no effects on patient s physical health.

Outcome preduction

Follow-up studies of patients suffering from paranoid schizophrenia: a fang-term prognosis (part 2)

MAGDALENA LETKIEWICZ, SZYMON SYREK, JAN HORODNICKI
Postępy Psychiatrii i Neurologii, 2004, 13 suplement 3 (19), 95-104

Aim. It's worth mentioning that Eugen Bleuler, known today for his introduction of the term schizophrenia, described a variety of psychopathological and neuropsychological symptom complexes characterizing the disorder previously known as dementia praecox. Since the beginning of 1970, there has been an attempt to describe prognostic factors for schizophrenia.

Method. Based on the access to the medical history of 41 patients, we made an attempt to describe predictive factors foretelling the course of paranoid schizophrenia. Employing the Horodnicki's software, patients with similar symptoms were divided into smaller subgroups using Steinhaus' algorithm for group and multidimensional analysis. This analysis enables us to select psychopathological and biological factors foretelling the course of paranoid schizophrenia.

Results. The basic and dynamic secretion of some hormones (i.e., TSH, FSH and cortisol) measured before the treatment may support the prospect of survival and recovery from individual and social consequences of paranoid schizophrenia. It turned out that the DSM-III diagnostic criteria for paranoid schizophrenia does not differentiate between patients with more and less negative consequences of the disease. On the contrary, the BPRS Overall diagnostic scale with its seven symptoms may be prognostic for the course of paranoid schizophrenia.

Conclusions. It is possible that the Steinhaus' algorithm for group analysis may be prognostic for the course of newly diagnosed paranoid schizophrenia.