Justyna Pełka-Wysiecka

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.

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.

Genetics of Lesch's typology of alcoholism

It is widely accepted that dopamine and serotonin (5-HT) neurotransmission can be critically involved in the development of alcohol abuse and alcohol dependence. Leschs typology of alcoholism has been gaining increasing popularity as it qualitatively differentiates patients into different treatment response subgroups. The aim of the present study was to evaluate a possible genetic background of Leschs typology with special emphasis placed on dopamine- and serotonin-related genes. 122 alcoholics (the mean age: 35+/-9 years) were investigated. According to Leschs typology, 58 patients were of type I, 36 patients of type II, 11 patients of type III, and 17 patients of type IV. Alcohol drinking and family history was assessed by means of a structured interview, based on the Semi-Structured Assessment for the Genetics of Alcoholism. 150 control subjects without psychiatric disorders were also recruited. The control group was ethnically-, age- and gender-matched to the patients. The DRD2 TaqIA, exon 8, and promoter -141C ins/del polymorphisms as well as COMT Val158Met, 5HTT 44 bp del in promoter, and DAT 40 bp VNTR polymorphisms were detected by means of PCR. No significant differences were observed when the whole group of alcoholics and the controls were compared. Similarly, there were no differences between either the Lesch type I or type II alcoholics and the control subjects. No significant differences were observed between type I and type II alcoholics. Alleles frequencies were not calculated for the Lesch type III and type IV alcoholics since the number of patients was too small. The present results argue against any major role of the investigated polymorphisms in either Lesch type I or type II alcoholism. More comprehensive studies are needed to define the role of the investigated polymorphisms in Lesch type III and type IV alcoholism.

Association of genetic polymorphisms with personality profile in individuals without psychiatric disorders.

OBJECTIVEnPopulation-based twin studies demonstrate that approximately 40-50% of the variability in personality dimensions results from genetic factors. This study assessed selected polymorphisms in the COMT Val158Met, MAOA 3VNTR, 5HTTLPR, 102T/C 5-HT2A, DAT 3VNTR and DRD2 exon 8 genes and evaluated their association with personality profiles, anxiety levels, and depressiveness in healthy subjects.nnnMETHODSnThis study included 406 unrelated (mean age 38.51 years), mentally and somatically healthy Caucasian subjects of Polish origin. The prevalence of the gene variants mentioned above and their association with personality profiles, anxiety levels, and depressiveness was assessed using the Temperament and Character Inventory, NEO Five-Factor Inventory, Spielbergers State-Trait Anxiety Inventory and Becks Depression Inventory.nnnRESULTSnThe effects of the 5HTTLPR gene on the s/s genotype and empathy (C2) were lowest in the entire group. The effects of gender, age and the HT2A gene for the T/T genotype and attachment (RD3) were highest in women. The effects of gender, age and the DAT gene on the 9/9 DAT genotype, compassion (C4) and cooperativeness (C) were lowest in women. The effects of gender, age and the COMT gene on the Met/Met genotype and neuroticism (NEU) NEO-FFI were also lowest in women.nnnCONCLUSIONSnOur results suggest considerable influence of individual genes on the formation of personality traits.

Psychosocial characteristics of benzodiazepine addicts compared to not addicted benzodiazepine users.

OBJECTIVEnAlthough the addictive potential of benzodiazepine drugs has been known for a long time, new cases of benzodiazepine addictions keep emerging in clinical practice. The etiology of benzodiazepine addiction seems to be multifactorial. The objective of this study was to investigate and measure psychological and situational factors differentiating benzodiazepine addicts from not addicted users.nnnMETHODSnA psychological profile and situational factors of patients with the diagnosis of benzodiazepine addiction and a carefully matched control group of not addicted former benzodiazepine users were defined and investigated.nnnRESULTSnThe investigated benzodiazepine addicts differed significantly from the control group in particular psychological dimensions, such as higher neuroticism and introversion, prevalence of emotional rather than task based coping mechanisms. There were also significant correlations between the addiction and situational factors such as BZD - treatment circumstances and adverse life events previous to the treatment.nnnCONCLUSIONSnThe results show psychological and situational factors which differentiate benzodiazepine addicts from not addicted benzodiazepine users. This data suggest that benzodiazepine addiction might be associated with higher neuroticism, introversion and less effective coping mechanisms as well as with previous accumulation of adverse life events and/or inadequate BZD treatment. The psychological and situational factors mentioned above might be considered as potential risk factors for benzodiazepine addiction.

Novel evidence for enhanced stem cell trafficking in antipsychotic-naïve subjects during their first psychotic episode

In this study, we tested the novel hypothesis that stem cells and those factors that modulate their trafficking may be biological markers for acute psychosis. Twenty-eight subjects during their first nonaffective psychotic episode were investigated before and after antipsychotic treatment and were compared with 35 healthy controls (CG); the psychotic group (PG) was divided into schizophrenic (SG) and non-schizophrenic (NG) subgroups. We examined the number of circulating Lin(-)/CD45(-)/CD34(+) and Lin(-)/CD45(-)/CD133(+) very small embryonic-like stem cells (VSELs), which express markers of the neural lineage, and also the plasma levels of factors that modulate their trafficking: the C3a, C5a, and C5b-9 activated complement cascade components, stromal-derived factor 1, and sphingosine-1-phosphate (S1P). We found that the mean numbers of Lin(-)/CD45(-)/CD34(+) VSELs and the plasma levels of S1P prior to treatment differ between the CG and PG and that these cells express markers of neural lineage. The number of Lin(-)/CD45(-)/CD133(+) VSELs in peripheral blood differed between the SG and NG prior to treatment. Using logistic regression analysis, we found that C3a and S1P are the best predictors of risk and are potential markers for the first psychotic episode. Furthermore, in the SG, the number of circulating Lin(-)/CD45(-)/CD34(+) VSELs and the S1P plasma level are the best predictors of risk and are proposed as novel markers for the first schizophrenic episode of psychosis.

BDNF rs 6265 polymorphism and COMT rs 4680 polymorphism in deficit schizophrenia in Polish sample

BACKGROUNDnDeficit schizophrenia (DS) is distinguished from the group of schizophrenic psychoses based on the presence of primary negative symptoms. It differs from nondeficit (NDS) forms of schizophrenia in dimensions such as risk factors, family history, course of illness and neurobiological differences. The aim of the study was assessment of a potential association of the investigated polymorphisms of the brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes with the deficit syndrome in schizophrenia.nnnMETHODSnA cohort of 200 patients with schizophrenia (81 DS and 119 NDS subjects) and a group of 100 control subjects matched for ethnicity, sex and age were recruited. Somatic and psychometric assessment were conducted as well as structured interview about the influence of adverse biological, family and social factors. Genetic analysis of the BDNF (Val66Met) rs6265 and the COMT (Val158Met) rs4680 polymorphisms was performed.nnnRESULTSnWe found significant differences between DS and NDS in rs4680 COMT genotype distribution: more homozygous Val/Val were found (31 vs. 17%) in the NDS compared to the DS subgroup. No associations were found between the investigated polymorphisms of the BDNF gene and the presence of schizophrenia either in DS and NDS subgroups.nnnCONCLUSIONnThe analysis of the COMT rs4680 polymorphism in the present DS and NDS study shows that some genetic factors may be relevant in analyzing the reasons for the differentiation of schizophrenic subtypes.

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.

Neuropsychological Characteristics of Verbal and Non-Verbal Fluency in Schizophrenia Patients

This review paper provides analyses confirming correlation between various brain regions activity, particularly its prefrontal portions, and schizophrenia patients performance in verbal fluency tests. Various factors modifying patients performance in the aforementioned tasks were singled out and discussed. Systematically we have reviewed the results of non-verbal fluency tests conducted in the schizophrenic patients. The authors also summarizes findings of earlier studies stressing the role of semantic fluency as a predictor of first-episode psychosis. Verbal and non-verbal fluency tests engage complex cognitive processes and executive functions in patients. As a result, the interpretation of their results is often complicated and requires special competences. The tests are popular neuropsychological tools used for assessment of verbal memory, executive functions, visual-spatial abilities and psychomotor speed in patients with mental and neurological disorders. The aim of this paper is to discuss diagnostic tools used for measuring both types of fluency (verbal and non-verbal), test interpretation methods, as well as their usefulness in clinical diagnostics and scientific research.

Odors identification differences in deficit and nondeficit schizophrenia

BACKGROUNDnThere is evidence that deficit schizophrenia (DS) is associated with neuroanatomical changes in structures including those involved in olfaction. Olfactory dysfunction, which includes impaired odor identification, is found in patients with schizophrenia and their family members.nnnMETHODSn82 patients with DS and 72 patients with NDS (nondeficit schizophrenia), somatically healthy and without acute psychotic symptoms undertook a smell identification test using the 16-item Sniffin Sticks ID test. Demographic and psychometric data were collected.nnnRESULTSnNo differences in the course of the illness, perinatal history and demographic data were found between the DS and NDS groups. No differences in the number of correctly identified odor samples were found. Some differences in the qualitative identification of samples between DS and NDS were found in the groups of female (fewer correct identifications of cinnamon and pineapple smells in DS) and male patients (fewer correct identifications of the smell of rose and more correct identifications of the smell of orange than in NDS).nnnCONCLUSIONSnNo overall differences between DS and NDS regarding odors identification have been found. The results seem to indicate some specific deficits in the identification of markers of rose, pineapple, orange and cinnamon.