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Lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of bipolar disorder (BD). The prophylactic efficacy of lithium can be determined by genetic factors, partially related to a predisposition to bipolar disorder. In the field of psychiatric genetics, the first decade of the 21st century was dominated by the "candidate gene" research. In this paper, the studies on candidate genes associated with lithium prophylaxis performed at the Poznan University of Medical Sciences in 2005-2018 are presented. During this time, the polymorphisms of multiple genes have been investigated, many of which are also associated with a predisposition to bipolar disorder. The associations with lithium prophylactic efficacy were found for the polymorphisms in 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1, and TIM genes, but not those in 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GRIN2B, GSK-3P, MMP-9, and NTRK2 genes. The polymorphism of the GSK-3P gene was found to be associated with the kidney side-effects occurring during lithium therapy. Possible roles for these genes in both the mechanism of lithium prophylactic efficacy and pathogenesis of bipolar disorder were discussed. [ABSTRACT FROM AUTHOR]

Aim. Suicide is an important clinical problem in psychiatric patients. The highest risk of suicide attempts is noted in affective disorders. In this study we tested 20 factors described in the literature (sociodemographic and clinical factors as well as family burden) in association with suicidal behavior and we analyzed whether the significance of those factors differs between males and females. Material. In the study we included patients with major depressive disorder (MDD; n = 249) and bipolar affective disorder (BP; n = 582). The Structured Clinical Interview for DSM-IV Axis I (SCID I), the Operational Criteria Diagnostic Checklist (OPCRIT) and a questionnaire of family history were used. Results. In the study population we observed an association between suicidal attempts and the following factors: family history of psychiatric disorders, affective disorders and psychoactive substance abuse/dependence; family history of attempted/completed suicide; occurrence of specific symptoms in the course of depressive episode (inappropriate guilt, sense of worthlessness, early morning awakening); and psychotic symptoms. Having children was also associated with suicide attempts. The risk factors of suicide attempt differ between males and females. The age of onset of MDD and coexistence of substance abuse/dependence with affective disorder were significant for lifetime risk of attempted suicide only in female group. Having children was associated with suicide attempts in the whole group and in the male subgroup, but not in the female subgroup. Conclusions. Suicide attempts are significantly associated with 10 out of 20 analyzed clinical factors in our group of affective patients, however, the significance (or lack of it) of these factors differed in female and male groups in half the cases. [ABSTRACT FROM AUTHOR]

Aim. Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. An etiopathological role for immunologic abnormalities in schizophrenia was hypothesized. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, antiinflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Transforming Growth Factor Beta 1 (TGFB1) signaling is critical for many biological processes, including proliferation, development, differentiation and regeneration. Multiple members of the TGFB1 superfamily play a role in the developing nervous system and are regulated by neuronal activity. We conducted family-based study to assess whether TGFB1 gene is associated with susceptibility to schizophrenia in Polish population. Methods. Two functional polymorphisms: rs1800469 (C-509T) and rs1800470 (T869C) of TGFB1 gene were analyzed within a group of 147 trios (patients diagnosed with schizophrenia and their healthy parents) using Transmission Disequilibrium Test (TDT). Results. No association of these polymorphisms with schizophrenia was found in Polish population. Conclusions. Further studies on larger groups along with correlation with circulating protein levels are needed. [ABSTRACT FROM AUTHOR]

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Psychiatria Polska is the property of Editorial Committee of Polish Psychiatric Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction of its resistance and to increase in its sensitivity to the glucocorticoid that regulate the functioning of the axis hypothalamus - pituitary - adrenal glands. Disturbances in the regulation of this axis are observed in patients with psychiatric disorders. The aim of this study was to demonstrate the association ER22/23EK polymorphism with bipolar disorder and major depressive disorders., Methods: In the study 144 patients with unipolar disorders and 479 patients with bipolar disorder were included. Patients were diagnosed by two psychiatrists on the basis of medical records and interview based on SCID criteria (Structured Clinical Interview for DSM Disorders). The control group comprised 595 healthy subjects. As the research material peripheral blood was used, from which DNA was obtained. Genotyping was performed using PCR - RFLP method., Results: No association of ER22/23EK polymorphism with unipolar disorder or with bipolar disorder was found. GA genotype was not observed in any of the subjects., Conclusion: ER22/23EK functional polymorphism of the glucocorticoid receptor gene is not associated with unipolar and bipolar disorder.

Aim: MMP-9 is a candidate gene related to the neurodevelopment hypothesis of schizophrenia. The aim of this research was TDT analysis of polymorphism -1562C>T MMP-9 gene in schizophrenia., Methods: Research was carried out on 147 trios (patient and his/hers both healthy parents). Genetic material was isolated from leukocytes using the salting out method. Polymorphism was studied with PCR-RFLP, statistic analysis was made using transmission disquilibrium test by Haploview 4.2., Results: There was no significant association between analyzed polymorphism of MMP-9 (-1562 C>T) and schizophrenia., Conclusions: Insignificant association doesn't exclude the possible contribution of MMP-9 to pathogenesis of schizophrenia. Further research is needed to be carried out on bigger groups and other populations.

Aim: The aim of the study was to estimate of the transmission of six candidate genes alleles (according to the dopaminergic hypothesis of schizophrenia) by parents to their children with schizophrenia. The genes under investigation were the following: DRD1 (polymorphism -48A/G), DRD2 (polymorphism -141C ins/del), DRD3 (polymorphism Ser9Gly), DRD4 (polymorphism -521C/T), DAT (polymorphism VNTR w 3'-UTR), COMT (polymorphism Val108(158)Met). Method. There were 116 families in the group under investigation (the ill person and his/her both parents). The patients and their parents were examined using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). No mental disturbances were found with all the patients' parents. The DNA was extracted from the peripheral blood leukocytes by the salting out method. Polymorphisms were studied by the PCR method (PCR-RFLP method for: DRDI, DRD2, DRD3, DRD4, COMT and PCR-VNTR method for: DAT). The statistical analysis of the frequency of transmission of alleles was carried out by the TDT (Transmission Disequilibrium Test) method. To analyse the transmission disequilibrium of alleles under examination, the Haploview v. 3.2. programme was used., Results: According to the results obtained, no connection between analysed polymorphism of genes: DRD2 (-141C ins/del), DRD3 (Ser9Gly), DRD4 (-521C/T), DAT (VNTR), COMT (Val108(158)Met) and schizophrenia was stated. In the case of polymorphism -48A/G of gene DRD1, a trend was observed towards a more frequent transmission of allele A of gene DRD1 by parents to their children with schizophrenia (p = 0.091)., Conclusions: This trend should be interpreted very carefully. There is also the possibility that other variant of gene in linkage disequilibrium with -48A/G polymorphism was responsible for the trend observed in this study.

Aim: The aim of the study was to estimate the transmission of two candidate genes' alleles (according to the serotonergic hypothesis of schizophrenia) by parents to their children with schizophrenia. The genes under investigation were the following: 5HTR2A (polymorphism T102C) and SLC6A4 (polymorphism 5-HTTLPR)., Method: There were 116 families in the group under investigation (patient and his/her both parents). Due to the missing genotypes or unlikely inheritance (other biological parent or genotyping error) the number of analysed trios differs for particular polymorphisms (these trios were not excluded from the study, however they were not analysed in the case of a given polymorphism). The patients and their parents were examined using the SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). No mental disorders were found with all the patients' parents. The DNA was extracted from the peripheral blood leukocytes by the salting out method. The polymorphisms were studied by the PCR method (PCR-RFLP method for: 5HTR2A and PCR-VNTR method for: SLC6A4). The statistical analysis of the frequency of transmission of alleles was carried out by the TDT (Transmission Disequilibrium Test) method. To analyse the transmission disequilibrium of alleles under examination, the Haploview v. 3.2. programme was used., Results: According to the results obtained, no association between the analysed polymorphism of genes: 5HTR2A (T102C), SLC6A4 (5-HTTLPR) and schizophrenia was found., Conclusions: Thus it seems advisable to carry out further examinations of the role of these polymorphisms in schizophrenia by means of TDT method and the classical association method.

Aim: Results from pharmacogenetic studies show importance of the relationship between response to treatment with antidepressants and polymorphisms within the genes involved in the neurotransmission and signal transduction. Changes in BDNF levels were reported in response to antidepressant treatment. The aim of study was to investigate a possible association of Val66Met polymorphism in the BDNF gene with response to antidepressants in patients with depression., Method: In the study, 90 patients (21 male and 69 females) were included, in the age range 19-68 years and suffering from a depressive disorder of at least moderate severity and meeting the research criteria of ICD-10 and DSM-IV for major depression. All patients were given the written consent for the study. The project was accepted by the local ethics committee. Patients were randomized into two groups: one was treated with the serotonergic drug - escitalopram (n=51) with therapeutic doses between 10-20 mg/day. The second group was treated with the noradrenergic drug--nortriptyline (n=39) with a dose range of 75-150 mg/day. The DNA was extracted from blood cells by the salting out method. The genotype for polymorphism of the Val66Met BDNF gene was established by the PCR-RFLP method in the Laboratory of Psychiatric Genetics of the Psychiatric Clinic. Statistical analysis was performed with the Statistica version 7.1 Results. We have not found any association between the Val66Met polymorphism of the BDNF gene with treatment response neither to escitalopram (p = 0.751 for genotypes, p = 0.798 for alleles) nor for nortryptyline (p = 0.607 for genotypes, p = 0.607 for alleles), Conclusions: The polymorphism of the BDNF gene is not likely to be associated with treatment response to escitalopram and nortriptyline in our group of patients with depression.

Aim: The role of the Serotonin receptor 5HT2A and Serotonin transporter 5HTTLPR polymorphisms was suggested in the pathogenesis of depression and the therapeutic response to serotonergic drugs. The aim of this study was to find a possible association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and drug response for escitalopram and nortriptyline in depressed patients., Method: We analysed 90 patients (21 male and 69 females), in the age range 19-68 years, suffering from depressive disorder of at least moderate severity meeting the research criteria of ICD-10 and DSM-IV for major depression. All patients were part of the GENDEP study and were given the written consent for the study. The project was accepted by the local ethics committee. The subjects were randomized to one of the 2 different treatment regimes: (1) patients who received the serotoninergic drug--escitalopram (n=51) with a specified dose range of 10-20 mg/day. (2) patients treated by a noradrenergic drug--nortriptyline (n=39) with the dose range of 75-150 mg/day. The efficacy of treatment was defined by a reduction > or =50% of the total score of the Hamilton scale in the 8th week of treatment. Genotypes for polymorphisms of the ins/del 5-HTT gene and T102C 5HTR2A gene were established by the PCR-RFLP method in the Laboratory of Psychiatric Genetics of the Psychiatric Clinic. Statistical analysis was performed with Statistica version 7.1., Results: The results of the pharmacogenetic analysis, showed no association between the effects of serotoninergic (escitalopram) or noradrenergic (noradrenaline) therapy and the genotypes or alleles polymorphisms of the 5HTT and 5HTR2A genes.

Aim: The authors analyzed the association between polymorphism of serotonin transporter gene and schizophrenia. This polymorphism is characterised by a 44-bp insertion or deletion in the promoter region of the gene which influences its transcriptional activity., Method: 349 not related patients with paranoid schizophrenia were included in this study. Using the SCID (Structured Clinical Interview for DSM-IV Axis I Disorders) a consensus diagnosis, according to the DSM-IV criteria was made by two independent psychiatrists for each patient. The control group consisted of 372 persons who have not been examined by psychiatrists. Genomic DNA was extracted from whole blood leukocytes using a salting out method. The polymorphism was amplified by the polymerase chain reaction (PCR). We received two products of PCR: 406 base pairs (short allele) and 450 base pairs (long allele)., Results: We analyzed genotypes and alleles of the 5-HTTLPR polymorphism in the group of patients and in the control group. We also divided our sample according to their gender and early onset of schizophrenia. The analysis did not show any significant differences between the studied groups., Conclusions: In the present study no association between 5-HTTLPR polymorphism and schizophrenia was found.

Recent studies have shown that in the aetiology of attention-deficit hyperactivity disorder (ADHD) genetic factors may be of importance. Biochemical and pharmacological studies reveal a connection between abnormalities of dopaminergic, adrenergic and serotonergic system and ADHD. Therefore genes for enzymes synthesizing or degrading proper neurotransmitters, genes for adequate transporters and receptors and genes for other substances, which altered the level of neurotransmitters, are studied. Many authors describe the connection between ADHD development and the synaptosomal-associated protein 25 (SNAP-25) gene. This protein plays a role in catecholamine secretion. Its higher expression is specific for neurones. SNAP-25 gene mutation may change this protein level, function of synapse and neurotransmitters storage. Acetylcholine receptor alpha4 subunit gene stimulation increases the dopamine level. Therefore this receptor gene may be important in the aetiology of ADHD studies. Other possible factors in ADHD background are substance influence on brain maturation, including N-methyl-D aspartate glutamate receptor 2A gene polymorphism (GRIN2A) and brain derived neurotrophic factor (BDNF) gene. One of the greatest challenges in studying the genetic basis of psychiatric disorders is to find appropriate ways to define the relevant endophenotype. ADHD often coexists with other psychiatric disorders, including specific developmental disorders, conduct disorders, obsessive-compulsive disorder and early onset of bipolar disorder.

Attention-deficit hyperactivity disorder (ADHD) begins in early childhood. In this article we review the studies supporting a genetic background of this disorder. ADHD occurs in 3-10% of the general population. Family studies reveal a 5 times more likely frequency of ADHD among first-degree relatives than in the general population. Monozygotic twin concordance rate for ADHD is 81%, whereas for dizygotic twins it is 29%. One of the ADHD predisposing factors is dopaminergic neurotransmission abnormality. According to other studies there is a relationship between polymorphism of dopamine transporter gene (DAT), dopamine receptors genes: DRD2, DRD3, DRD4, DRD5, dopamine-beta-hydroxylase gene (DBH) and catechol-O-methyltransferase gene (COMT) and ADHD. In other articles authors describe abnormalities of the serotonergic system, such as the polymorphism of the serotonin transporter gene (5HTT/SERT), serotonin receptors genes 5HT2A and 5HT1B in the development ofADHD. Another possible factor in ADHD background is the dysregulation of the adrenergic system. The most frequently studied is the connection between polymorphism of norepinephrine transporter gene (NET), adrenergic receptors genes: alpha 2A (ADRA2A), alpha 1C (ADRA1C), alpha 2C and monoamine oxidase A gene (MAO-A).

Unlabelled: THE AIM AND METHODS: The aim of this study was to assess the intensity and frequency of eye movement abnormalities measured with infrared reflectometry, and working memory disturbances assessed with the Wisconsin Card Sorting Test (WCST). The study was performed in 87 patients with bipolar affective illness, in 119 patients with schizophrenia and in 90 healthy persons. In patients, the assessment was done during a mild symptomatic period or in remission., Results: In patients with bipolar affective illness significant disturbances of eye movement and working memory compared with healthy subjects were found. Frequency and intensity of fixation abnormalities was less intense compared to schizophrenic patients, while smooth pursuit abnormalities had a similar degree. Working memory disturbances in bipolar patients were, as to the ability of formulation of logical conception, of similar degree as in schizophrenia. On the other hand, as to the effectiveness of thinking, no difference compared with healthy controls was found., Conclusions: The results obtained suggest that eye movement and working memory disturbances may constitute neurophysiological and neuropsychological endophenotypic markers of bipolar affective illness what makes possible using them in molecular genetic studies of this illness.

Aim: Anorexia nervosa (AN) is a disorder of complex etiopathogenesis including the genetic factors. The previous studies on the role of -1438 A/G promoter polymorphism in 5-HT2A receptor gene brought conflicting results, and it is possible that the analysed polymorphism increases the risk of AN only in some ethnic groups. The aim of the study was to assess the frequency of -1438 A/G polymorphism in Polish patients with AN and ethnically matched healthy controls., Method: The genotyping of 5-HT2A receptor polymorphism was performed in 67 AN patients and 114 healthy controls. The frequencies of alleles and genotypes were compared with Chi2 test., Results: The deviations from the Hardy-Weinberg equilibrium were not observed in any group. The frequencies of A/A, A/G and G/G genotypes in AN group were respectively: 37.3%, 50.7% and 11.9%; and in the control group: 40.4%; 47.4% and 12.3% (chi2 = 0.2; df = 2; p = 0.91). The prevalence of A and G alleles in the AN group was respectively 62.7% and 37.3%; and in the control group 64.0% and 36.0%; and did not show any statistically significant difference (chi2 = 0.67; df = 1; p = 0.79)., Conclusions: These results suggest that -1438 A/G polymorphism in the promotor region of the 5-HT2A receptor gene does not increase the risk of AN in the Polish population.

Results of family studies show the importance of genetic factors in etiopathogenesis of schizophrenia. Susceptibility to the disease is probably due to an interaction of many genes. This association study was conducted to investigate frequencies of alleles and genotypes in a group of patients with schizophrenia and in healthy controls. We examined DRD2 gene promoter polymorphism--insertion or deletion of the cytosine in the position -141 of 5'-flanking region of this gene. No relationship between the polymorphism under study and schizophrenia has been found.

The substantial importance of genetic factors in the etiology of schizophrenia was demonstrated in many studies. The complex model of disease inheritance seems to be the most probable, involving epistatic interaction of many genes. Association studies are based on the analysis of the so-called candidate genes, which are coding for neurotransmitter receptors, neurotransmitter transporters and enzymes involved in their metabolism. In the present work the results of an association study of VNTR polymorphism of dopamine transporter gene (DAT) in schizophrenia are presented. This polymorphism is characterised by a different number of tandem repeats (VNTR) within the 3'-untranslated region of gene. In Caucasians the 40 base pair motif has 3 to 11 repeats, the most common (about 90%) are alleles containing 9 and 10 repeats. In the present study no association between the polymorphism studied and schizophrenia was found.