[The influence of parents personality and DRD4 and 5HTT genes polymorphisms on predisposition to alcohol dependence in their sons]. / Wplyw cech osobowosci i polimorfizmów genów DRD4 i 5HTT rodziców na predyspozycje ich synów do uzaleinienia sie od alkoholu.

AIM: The aim of this work was to investigate differences in parents' personality and dopaminergic and serotoninergic gene polymorphisms which may affect certain predispositions to alcohol dependence as described in the typology developed by R. Cloninger and O.M. Lesch. Also the possibility of recognising their genotypes DRD4 (Gene ID: 1815A ) and 5HTT (Gene ID: 6532) could be helpful in predicting predisposition to addiction. METHODS: A total number of 213 individuals (71 Polish trios), Caucasian families were investigated. Fathers' mean age was: 61.7 +/- 10.8 and mothers were 59 +/- 10 years old. None of the parents fulfilled the criteria of alcohol dependence. The alcohol dependent probands were male, with confirmed biological descent, mean age: 35.2 +/- 9.7 years. In all the participants TCI was performed. Characterisation of alcohol dependence and the course of withdrawal were obtained by SSAGA. Specially designed questionnaires based on Cloninger and Lesch typologies were used. The essential data on both parents was collected and AUDIT was performed. DRD4 and 5HTT gene polymorphisms were determined by PCR and TDT test was calculated. RESULTS: TDT analysis showed no differences in the transmission of alleles of 5HTT and DRD4 genes in the investigated families. The analysis of TCI personality profiles confirmed no statistically significant relations between Cloninger 1 and 2 subtypes of alcoholics. A statistically significant difference was recorded between the scores for groups I and II classified according to Lesch's typology in dimensions NS, NS2 and NS4. Fathers of probands characterised as type I according to Cloninger had statistically lower scores in dimension C and C5 in comparison to type II fathers. Fathers of type II alcoholics according to Lesch's typology had higher NS2. Mothers of type I alcoholics according to Cloninger had statistically lower scores in dimension HA2 in comparison with type II mothers. CONCLUSIONS: On the basis of the above presented findings it can be stated that there might be specific interactions between personality traits in alcohol dependent probands and their parents. Nevertheless, further studies are needed to establish whether this relationship may have a predictive value, which may implicate therapeutic implications, as proposed by the clinical algorithm of O. M. Lesch.

Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence.

The paper focuses on such candidate gene polymorphisms that alter alcoholism-related intermediate phenotypes including: dopaminergic system polymorphic variants (DRD2 -141C Ins/Del in promoter region, exon 8 and DRD2 TaqI A and DAT 40bp VNTR genes polymorphisms) that cause predisposition to severe alcoholism (haplotype Ins/G/A2); COMT Val158Met gene polymorphism related to differences in executive cognitive function and 5-HTT gene promoter polymorphism, which alters stress response and affects anxiety and dysphoria. The transmission disequilibrium test (TDT) was used in the study. One hundred Polish families with alcohol dependence were recruited. The control subjects for the case-control study were 196 ethnically and gender matched healthy individuals. It was found that DRD2 TaqIA and DAT gene polymorphisms contained statistically significant differences in allele transmission. In the homogenous subgroups of patients with early onset and with withdrawal complications a statistically significant preferential A2 allele transmission was found in DRD2 TaqIA gene polymorphism. The alleles and genotypes distribution of the investigated polymorphisms did not differ significantly between the alcoholics and the controls in the case-control study. The results confirmed the fact that the candidate genes (DRD2 and DAT) are partially responsible for the development of alcohol dependence. The results are also in agreement with the hypothesis that there are various subtypes of alcohol dependence, which differ depending on their genetic background. Meanwhile, the currently available pharmacological therapies for alcoholism treatment are effective in some alcoholics but not for all of them. Some progress has been made in elucidating pharmacogenomic responses to drugs, particularly in the context of Clonninger and Lesch typology classification system for alcoholics.

Family-based and case-control association studies of glutamate receptor GRIK3 Ser310Ala polymorphism in Polish patients and families with alcohol dependence.

The aim of this study was to evaluate the role of the GRIK3 functional polymorphism (Ser310Ala) in the pathogenesis of alcoholism. This polymorphism was investigated in two types of studies: (1) the association study in a whole group of alcoholics (116 patients fulfilling ICD-10 alcohol dependence (AD) criteria and 255 controls, Polish descent) and homogenous overlapping subgroups of patients with: a history of delirium tremens and/or alcohol seizures, early age of onset of alcoholism (AOO<26 years), a co-occurrence of dissocial personality disorder, a history of familial alcoholism; (2) the family-based study (using Transmission Disequilibrium Test (TDT) in 100 Polish families with alcohol dependence). The history of alcoholism was obtained using SSAGA (Polish version). GRIK3 functional polymorphism was determined using PCR. TDT revealed an adequate transmission of both alleles to the affected offspring in the whole group of alcohol families (29 x Ser, 24 x Ala; chi2=0.472; d.f.=1; p=0.492) and in the homogenous subgroups of families. No significant associations between any of the above mentioned alcohol phenotypes and Ser310 allele were observed (the whole AD group: p=0.66 AD with delirium and/or seizures: p=0.521; early onset AD: p=0.868; AD with familial history of alcoholism: p=0.798 and AD with dissocial personality disorder: p=0.618). These findings do not seem to support the hypothesis of the role of this polymorphism in the pathogenesis of alcoholism.

[Anxiety and depression in patients with laryngeal and hypopharyngeal cancer (preliminary report)]. / Lek i depresja u pacjentów z rakiem krtani i gardla dolnego (doniesienie wstepne).

Occurrence of anxiety and depression was investigated in 76 patients with recognized larynx and/or hypopharynx cancer and with or without alcohol dependence. The patients were treated using total or partial laryngectomy or radiotherapy. Patients were examined three times using questionnaires: SCID, BDI, STAI. The greatest intensity of anxiety was observed before treatment, especially in patients qualified for surgery. After finishing the treatment, independently of the type of operation, intensity of anxiety was lower than in patients treated using radiotherapy In patients after total laryngectomy the greatest intensity of depression was observed 7 days after operation. The mood of these patients has improved significantly before discharge from hospital. In patients treated with partial laryngectomy such great changes of mood were not observed. In patients treated using radiotherapy were stated greater intensity of depression at the end of treatment - despite of initial mood improvement. Patients with alcohol dependence were stated greater intensity of anxiety and depression than in the other patients. Dynamics of the intensity of anxiety and depression in the different diagnostic and therapeutic groups of patients with laryngeal or hypopharyngeal cancer should be done under consideration of their prophylactic and rehabilitative effects.

[The endocrine mask of a developing process of schizophrenia--case study]. / Maska endokrynna rozwoju procesu schizofrenicznego--studium przypadku.

In this research psychic and somatic symptoms related to disturbances of hypothalamus-hypophysis-peripheral regulation which may occur in the schizophrenic process were analysed. Authors discussed the problem of relations between hypothalamus neuroregulation and pathogenesis of endocrine disturbances which suggest the organic cause of obesity, hirsutism and secondary amenorrhea among women diagnosed with paranoid schizophrenia. Actual antipsychotic pharmacological treatment, including some side-effects: the metabolic (obesity) and the endocrine (hyperprolactinemia) ones were considered. The authors conclude that endocrine disorders which are connected with hypothalamus disfunction (sleeping, eating and reproductive functions) may reach the psychotic symptoms and treating them influences at the same time some endocrine changes. The estimation of PRL release in a test of stimulation with metoclopramide can be a sensitive (though not specific) test of dopaminergic activity in tuberous--infundibulum pathway and may be used to control the treatment.

Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum.

Recent studies provide evidence that anxiety disorders may be linked to malfunction of serotonin neurotransmission or impaired activity of enzymes metabolising the catecholamines. Functional polymorphisms in the MAO-A uVNTR promoter gene, the COMT gene (Val158Met) exon 4, and the 5-HTT promoter gene (44 bp ins/del) were investigated in 101 patients with phobic disorders of the anxiety spectrum and 202 controls matched to the patients for sex, age and ethnicity. There were no significant differences between controls and patients in the allele and genotype frequencies of the 5-HTT and COMT gene polymorphisms. The frequency of >3 repeat alleles of the MAO-A gene polymorphism was significantly higher in female patients suffering from anxiety disorders, specifically panic attacks and generalized anxiety disorder. There was also a trend for the more frequent presence of >3 repeat alleles in female patients with agoraphobia and specific phobia, in contrast to female patients with social phobia, who did not differ from controls. The results support a possible role of the MAO-A gene in anxiety disorders.

Polymorphisms in the serotonin transporter and monoamine oxidase A genes and their relationship to personality traits measured by the Temperament and Character Inventory and NEO Five-Factor Inventory in healthy volunteers.

The associations between 5-HTT-linked polymorphic region (5-HTT-LPR), monoamine oxidase A (MAOA)-LPR and the dimensions of temperament evaluated using the Temperament and Character Inventory (TCI) and NEO Five-Factor Inventory (NEO-FFI) were studied. One hundred healthy volunteers (without psychiatric disorders) were recruited to represent a cross-section of the population of Szczecin (Poland) in terms of sex, age and education. No associations between 5-HTT-LPR and the TCI harm avoidance dimension and between 5-HTT-LPR and the NEO-FFI neuroticism dimension were found. Males carrying the 3-VNTR MAOA gene variant (209 bp) had significantly lower values on the NEO-FFI openness dimension (p = 0.039) and obtained higher scores on the subdimension 3 of the TCI reward dependence (RD3), i.e. attachment vs. detachment (p = 0.005). Individuals carrying the 'short' variant of 5-HTT-LPR had lower values on the reward dependence dimension and the RD4 subdimension (dependence vs. independence) than individuals not carrying the 'short' variant (p = 0.039 and p = 0.011, respectively). Females carrying the 'short' variant had lower values on NS1 (exploratory excitability vs. stoic rigidity) and RD4 (dependence vs. independence) than those not carrying the variant (p = 0.042 and 0.043, respectively). The obtained level of significance with respect to the observed associations between 5-HTT-LPR and the reward dependence scales and subscales and between 5-HTT-LPR and the NS1 subscale are too weak for further interpretation. Our results do not confirm the hypothesis that there is a simple correlation between single gene polymorphisms and a personality trait measured by the TCI and NEO-FFI scales.

Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are associated with alcoholism-related traits.

BACKGROUND: This study examined the hypothesis that allelic variants of the ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated with vulnerability to alcoholism and some related traits. METHODS: We investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the NMDAR2B genes, respectively. The case control study included 367 alcoholic and 335 control subjects of German origin. The family-based study comprised 81 Polish alcoholic patients and their parents using the transmission disequilibrium test. RESULTS: The genotype frequencies of the NMDAR1 polymorphism differed significantly between control and alcoholic subjects. This difference was also observed in more homogenous subgroups of alcoholic subjects with vegetative withdrawal syndrome and Cloninger type 1. Patients with a history of delirium tremens or seizures during withdrawal showed a significantly increased prevalence of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly reduced T allele in Cloninger type 2 alcoholics and in patients reporting an early onset compared with control subjects. Our family-based study for NMDAR2B, revealed a trend to a preferred transmission of the C allele by the fathers, and families with early-onset patients contributed most to this trend. CONCLUSIONS: These results suggest that variants in NMDAR genes are associated with alcoholism and related traits.

Association analysis of the insertion/deletion polymorphism in serotonin transporter gene in patients with affective disorder.

A polymorphism of serotonin transporter was studied in 226 patients with affective disorders (n = 132 for bipolar, n = 94 for unipolar affective disorder) and in 213 healthy subjects. Consensus diagnosis by at least two psychiatrists, according to the ICD-10 and DSM-IV criteria was made for each patient using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). A functional polymorphism in the promoter region of serotonin transporter gene, where 44 bp are either inserted (long allele) or deleted (short allele) was analysed. Genotype s/s was significantly more frequent in patients comparing to the control group (P = 0.011 for bipolar and P = 0.003 for unipolar affective disorder)--the most marked association was found in males with bipolar and unipolar illness. The allele frequencies also differ significantly between patients and controls (P = 0.003 for bipolar and P = 0.001 for unipolar affective disorder). The frequency of the low activity (short) allele was higher in patients than in controls (51.1% in bipolar, and 54.3 in unipolar vs 39.4% in controls). We suggest that the presence of allele s may increase the susceptibility to occurrence of affective disorder.

[Some hormones secretion and personality in anorexia nervosa syndrome]. / Wydzielanie niektórych hormonów a osobowosc w jadlowstrecie psychicznym.

The relationship between plasma leptin, some hormones (GH, IRI, IGF-1, DHEA-S, LH, FSH, T, E2, TSH, fT3, fT4), glucose level, personality dispositions and adipose tissue content in 22 women with anorexia nervosa were evaluated. Some personality features as: defensiveness, domination and aggression necessities, high self-control, bad self-estimation, retiring, expectation of custody--correlated with some hormones (LH, E2, IGF-1, fT3, F, T) and leptin level. The ascertained relationships suggest that still unexplained causes generate simultaneous disturbances in the endocrine and psychic processes in central nervous system of anorexia nervosa patients. Probably hormonal and neurotransmitter derangement are the adaptive changes allowing longer survival, as the low leptin secretion in the severest undernutrition states is.

[PAX-6 gene promoter polymorphism and other factors involved in brain atrophy in alcohol dependent patients]. / Polimorfizm genu promotora PAX-6 i inne czynniki zwiazane z atrofia mózgowia u osób uzaleznionych od alkoholu.

PAX-6 gene promoter polymorphism, alcohol dependence history and CT were determined in the group of 68 alcoholics. We found negative correlation between numbers of PAX-6 gene promoter B (AC)m (AG)n repeats and atrophy of the brain and the cerebellum. Occurrence of these lesions was correlated with a decrease of alcohol tolerance, withdrawal symptoms--especially delirium tremens.

Association of a CB1 cannabinoid receptor gene (CNR1) polymorphism with severe alcohol dependence.

Due to the involvement of the endogenous cannabinoid system in brain reward mechanisms a silent polymorphism (1359G/A; Thr453Thr) in the single coding exon of the CB1 human cannabinoid receptor gene (CNR1) was analysed in 121 severely affected Caucasian alcoholics and 136 most likely non-alcoholic controls. The observed frequency of the A allele was 31.2% for controls and 42.1% for alcoholics with severe withdrawal syndromes (P=0.010). Post-hoc exploration indicated that this allelic association resulted from an excess of the homozygous A/A genotype in patients with a history of alcohol delirium (P=0.031, DF 2), suggesting s an increased risk of delirium (OR=2.45, 95% CI 1.14--5.25). This finding suggests that the homozygous genotype CNR1 1359A/A confers vulnerability to alcohol withdrawal delirium.