Correlation of metabolic parameters, neurotrophin-3, and neurotrophin-4 serum levels in women with schizophrenia and first-onset depression.

BACKGROUND: Neurotrophin-3 (NTF3) and neurotrophin-4 (NTF4) play a crucial role in the neurodevelopment, differentiation, survival, and protection of neurons in different brain regions. Schizophrenia and depression are highly associated with metabolic abnormalities. Longitudinal and cross-sectional comparisons of NTF3 and NTF4 levels, as well as clinical and metabolic parameters, were studied in schizophrenia, first-episode depression, and control groups. MATERIALS AND METHODS: Serum NTF3 and NTF4 levels, body mass index (BMI), fasting serum glucose and lipid profile: cholesterol, triglyceride, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and week 8 in 133 women: 55 patients with schizophrenia (19 with first-episode and 36 chronic), 30 patients with a first-episode depression and 48 healthy controls. The severity of the symptoms was evaluated with the Positive and Negative Syndrome Scale, 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory. RESULTS: Longitudinal and cross-sectional comparisons did not detect any differences in the serum levels of NTF3 and NTF4 between studied groups. NTF3 and NTF4 levels were strongly correlated. Correlation of NTF3 and HDL-C levels at baseline was observed. Significant changes in cholesterol and fasting serum glucose levels in first-episode depression patients during 8 weeks of treatment were detected. Significant differences in BMI and LDL-C levels between schizophrenia and first-episode depression patients were discovered. CONCLUSIONS: To our knowledge, this is the first research which correlates NTF3 and NTF4 with metabolic parameters. Our study does not support the theory that the peripheral levels of NTF3 and NTF4 are disturbed in schizophrenia or first-episode depression.

Brain-derived neurotrophic factor (BDNF) serum level in women with first-episode depression, correlation with clinical and metabolic parameters.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development, as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of psychiatric disorders and its serum level is a potential biomarker for depression. The aim of this study was to examine serum levels of BDNF in first-episode depression and its correlation with clinical and metabolic parameters. MATERIALS AND METHODS: The study was performed on a group of 60 women: 30 diagnosed with a first-episode of depression and 30 healthy controls. 17-Item Hamilton Depression Rating Scale (HDRS-17) was used to assess the severity of depression. Patients were randomly chosen for treatment with sertraline or venlafaxine. BDNF serum levels and metabolic parameters: fasting serum glucose, cholesterol, triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured at baseline and week 8 of treatment. RESULTS: There were no differences between BDNF level in depressed patients compared with the healthy controls. Lack of differences in medication effect of sertraline or venlafaxine on HDRS-17 scores during 8 weeks of treatment was observed. Correlation of BDNF at baseline and fasting serum glucose at baseline and week 8 was detected. CONCLUSIONS: Correlations of BDNF serum levels with metabolic parameters were observed.

Pharmacy switch of antipsychotic medications: patient's perspective.

BACKGROUND AND AIM: Several studies have raised concerns over consequences of brand-to-generic and generic-to-generic pharmacy-generated medication substitutions in psychiatric and non-psychiatric patients. The purpose of this retrospective study was to assess behavioral and emotional responses of patients with schizophrenia to antipsychotic medication substitution performed by pharmacies. METHODS: A group of Polish ambulatory patients with schizophrenia (n = 196) chronically treated with antipsychotic medications were asked whether antipsychotic medication substitution had been proposed by a pharmacist in the last 12 months. Ninety-nine patients answering positively were administered more questions addressing the patient's emotional and behavioral response to the pharmacy proposal. RESULTS: The most important findings of the present study can be summarized as follows: (1) approximately half of the patients were confronted with a pharmacy proposal to switch their antipsychotic medications in the last 12 months, (2) one quarter of these patients did not accept the pharmacy switch, (3) a substantial proportion of patients (>40 %) did not receive any explanation from a pharmacist offering medication substitution, (4) pharmacy-generated substitution proposals were mainly associated with negative patient attitudes and negative emotional responses, (5) substitution proposals provoked an unscheduled psychiatric visit in approx. 10 % of patients, (6) despite the negative attitudes reported by patients, the pharmacy switch rarely led to treatment discontinuation, but did provoke a change in drug dosing in 7 % of patients accepting the switch. CONCLUSIONS: A pharmacy proposal to switch their antipsychotic medications is a relatively common experience of Polish ambulatory patients with schizophrenia. Pharmacy-generated substitution proposals are mainly associated with negative patient attitudes, but rarely lead to antipsychotic treatment discontinuation in this group of patients.

Effects of Age-Dependent Hormonal Changes and Estrogen Supplementation on Voice in Girls with Anorexia Nervosa-Preliminary Report.

INTRODUCTION: Human development includes lots of physical and emotional changes. The human voice depends on age. Voice production is a complex physiological and acoustic phenomenon that depends on many factors such as structure, hormone level, degree of fatigue or nutrition and hydration of the body, systemic diseases, and emotional state. All these factors can be present in anorexia nervosa (AN), such as excessive weight loss, generated hydro-electrolytic changes, nutritional deficiencies, hormonal disturbances in the function of the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-ovarian axis, and emotional distress. The prevalence of AN ranges between 0.3% and 3%, and it is the third most common chronic disease affecting adolescent girls. However, voice changes related to AN have not been fully investigated. OBJECTIVE: The purpose of this study was to evaluate the impact of AN on age-related changes in the voice of adolescent women-before and after puberty, particularly through acoustic analysis. An additional objective was to evaluate estrogen substitution in female patients with AN in order to investigate their effect on voice condition. MATERIALS AND METHODS: 126 girls diagnosed with AN (15.32 ± 2.12 years, range 12-19, BMI = 14.38 ± 1.67), were assessed for the condition of the voice such as perceptual voice evaluation on the GRBAS scale, maximal phonation time (MPT), laryngoscopy, with special attention to voice acoustic analysis-Multi-Dimensional Voice Program (MDVP). The control group (B) included 93 girls without eating disturbances (aged 12-19, mean age 15.52 ± 2.40, BMI = 21.50 ± 1.54). Perceptual voice assessment, aerodynamic test MPT, and acoustic parameters were analyzed in age groups (≤16 years and >16 years). The human vocal tract is sensitive to sex hormones, so the analysis was carried out in the group up to the age of 16 and above 16 to check possible effects. RESULTS: GRBAS scale was higher in girls with AN compared to the control group for breathiness (B) (P = 0.0002) and asthenia (A) (P < 0.05). The median GRBAS scale for the older group of anorexic women was the highest (2.0). The mean MPT for group A was significantly lower (15.40 ± 3.51 seconds). Comparing age subgroups there was a prolongation of MPT in the healthy group (in groups ≤16 years and >16 years respectively 21.13 seconds versus 25.40 seconds) and a shortening in the anorectic group (≤16 years versus >16 years: 17.06 seconds versus 14.17 seconds). There was no difference between groups A and C up to 16 years of age, but above 16 years of age appeared (14.17 seconds versus 25.40 seconds). Acoustic analysis revealed lower F0 values in group A and C in older subgroups (215,85 Hz versus 236,01 Hz-statistically significant), as well as between subgroups both groups (A: 251,38 Hz versus 215,85 Hz; C: 248,20 Hz versus 236,01 Hz). A narrowing of the vocal range in girls over 16 years in group A was observed. There were no statistically significant differences in F0 between subgroups ≤16 years in groups A and C (251.38 Hz versus 248.20 Hz). The ENT study found that more than half of the girls (54.55%) over the age of 16 who took hormone supplementation manifested laryngeal structure that was normal for their age, there was no effect of hormone supplementation on any of the MDVP parameters between the drug-taking and non-drug-taking groups. CONCLUSIONS: The acoustic results of the voice in MDVP measurements in adolescent women with AN are not within the normal range and do not mimic the normal developmental changes of the voice. The most important acoustic characteristics of the voice are changes in the fundamental frequency F0 and the range of the voice tended to be more severe in anorectic women >16 years of age and to increase with age, indicating a possible cumulative effect of malnutrition-related disorders as well as hormonal dysfunctions. MDVP can be considered a simple, non-invasive method of assessing the voice organ in AN. MPT differentiated the study groups well: statistically significant differences were noted both between the groups, as well as between age groups. There was no significant effect of oral hormone supplementation on any parameters of the voice. In conclusion, body mass and fat volume in AN may be related to voice production/physiology, affecting voice quality, voice acoustic parameters, voice aerodynamics, and phonatory range in an age-dependent manner. Future studies are needed to assess the long-term efficacy of estrogen treatment in AN.

[No association of glucocorticoid receptor gene polymorphism (rs6190) with unipolar and bipolar disorder]. / Brak zwiazku polimorfizmu (rs6190) genu receptora glikokortykoidowego z choroba afektywna jedno- i dwubiegunowa.

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.

Clinical assessment of impulsiveness and defence mechanisms in young patients with mood disorders in a two-year prospective study.

AIM: There have been limited prospective investigations of early clinical markers involved in mood regulation and diagnosis change in young patients. This study aimed to evaluate the changes in impulsivity and defence mechanisms in patients with major depressive disorder (MDD) and bipolar disorder (BD) with acute symptoms and remission compared to healthy controls (HC), and possible psychological predictors of diagnosis conversion. METHODS: Seventy-nine young MDD or BD patients and 40 HC were enrolled in a two-year prospective study. A comprehensive clinical interview focused on clinical and psychological evaluation during follow-up visits. The severity of depressive symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS-17), whilst the Young Mania Rating Scale (YMRS) was used for hypo/manic symptoms during each control visit. All patients completed the Defence Style Questionnaire (DSQ-40) and Barratt Impulsiveness Scale (BIS-11). RESULTS: Patients used more immature defences, and had significantly higher total impulsivity scores than controls. BD patients had elevated motor and non-planning impulsivity compared with HC and MDD subjects. Total and non-planning impulsiveness remained elevated in euthymia in BD and MDD compared to HC. There were no statistically significant differences in total defence styles and impulsiveness scores at baseline vs. euthymia in MDD or BD patients groups. Significantly higher dissociation scores at baseline discriminated depressive patients who convert to BD in their diagnosis. CONCLUSIONS: Patients with acute mood symptoms used more frequent immature defences and had significantly higher total impulsivity scores than healthy persons. A lack of differences in total defence styles and impulsiveness between patients with acute symptoms and after reaching euthymia in both MDD and BD groups indicates that they are independent of disease status. Dissociation defence mechanisms may be an early diagnostic indicator of BD.

Acoustics Features of Voice in Adolescent Females With Anorexia Nervosa.

INTRODUCTION: The process of human voice production is a complex physiological and acoustic phenomenon that depends on many structural, physical, and hormonal factors, systemic diseases as well as emotional states. All these factors can be present in eating disorders. However, studies on eating disorders and voice problems have usually been evaluated in terms of bulimia. Chronic starvation and emotional problems in the course of anorexia nervosa (AN) appear to be under-researched, despite various biochemical, metabolic, and hormonal changes. OBJECTIVE: The purpose of this study was to evaluate voice quality, specifically acoustic analysis, in adolescent female with AN from the point of view of the possible influence on the function and structure of the larynx, low body mass accompanying AN, as well as energy deficiency, hormonal and emotional disturbances. MATERIALS AND METHODS: A total of 84 girls diagnosed with AN (Gr.A) (15.32 years, SD = 2.12; range 12-19, BMI = 14.11 ± 1.72) were assessed for the condition of the voice such as perceptual voice evaluation on the GRBAS scale, maximal phonation time (MPT), laryngoscopy, with special attention to voice acoustic analysis - Multi-Dimensional Voice Program (MDVP). The control group (Gr.C) included 62 girls without eating disturbances (aged 12-19, mean age 15.41 ± 2.40, BMI = 21.60 ± 1.92). Perceptual voice assessment, aerodynamic test MPT, and acoustic parameters were analyzed according to girls' age. RESULTS: Total GRBAS scale was higher in girls with AN compared to the control group mainly for two parameters: breathiness (B) (P = 0.00015) and asthenia (A) (P < 0.05). The MPT for Gr.A was significantly shorter compared to Gr.C (15.40 ± 3.51 seconds vs. 23.19 ± 5.17 seconds) (P < 0.001), and a correlation of MPT values with the age of the adolescent female was observed: Spearman's coefficient for Gr.A = (-)0.5378, for Gr.C = 0.5516 (P = 0.0012). Acoustic analysis revealed the decrease in the basic frequency F0 in Gr.A compared to Gr.C (231.08 Hz vs. 242.30 Hz), and narrowing of the voice scale was observed, resulting mainly from a reduction in the upper limit. Significant differences were found for measures of frequency perturbations (Jita, Jitter, RPA, PPQ, sPPR), with Gr.A scoring significantly higher than Gr.C (P < 0.05 for all). Significant changes in voice acoustic analysis parameters were found with age. Negative correlations were found for measures of F0 for Gr.A to a much greater extent compared to Gr.C. Positive correlations were found with measures of tremor assessment (SPI, FTRI, ATRI) for Gr.A.

Dimensions of the Hamilton Depression Rating Scale Correlate with Impulsivity and Personality Traits among Youth Patients with Depression.

The heterogeneity of symptoms in young patients with major depression disorder makes it difficult to properly identify and diagnose. Therefore, the appropriate evaluation of mood symptoms is important in early intervention. The aim of this study was to (a) establish dimensions of the Hamilton Depression Rating Scale (HDRS-17) in adolescents and young adults and (b) perform correlations between the identified dimensions and psychological variables (impulsivity, personality traits). This study enrolled 52 young patients with major depression disorder (MDD). The severity of the depressive symptoms was established using the HDRS-17. The factor structure of the scale was studied using the principal component analysis (PCA) with varimax rotation. The patients completed the self-reported Barratt Impulsiveness Scale (BIS-11) and Temperament and Character Inventory (TCI). The three dimensions of the HDRS-17 identified as core in adolescent and young patients with MDD were (1) psychic depression/motor retardation, (2) disturbed thinking, and (3) sleep disturbances/anxiety. In our study, dimension 1 correlated with reward dependence and cooperativeness; dimension 2 correlated with non-planning impulsivity, harm avoidance, and self-directedness; and dimension 3 correlated with reward dependence. Conclusions: Our study supports the previous findings, which indicate that a certain set of clinical features (including the HDRS-17 dimensions, not only total score) may represent a vulnerability pattern that characterizes patients with depression.

Interleukin-8 and tumor necrosis factor-alpha in youth with mood disorders-A longitudinal study.

Bipolar disorder (BD) is one of the most disabling psychiatric illnesses. Over half of BD patients experienced early onset of the disease, and in most cases, it begins with a depressed mood episode. Up to 50% of adolescents initially diagnosed with major depressive disorder (MDD) convert to bipolar spectrum disorder. Diagnostic tools or biomarkers to facilitate the prediction of diagnosis conversion from MDD to BD are still lacking. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a 2-year follow-up study on 69 adolescent patients diagnosed with MDD or BD. The control group consisted of 31 healthy youths. We monitored diagnosis change from MDD to BD. Impulsiveness was assessed using Barratt Impulsiveness Scale (BIS-11) and defense mechanisms using Defense Style Questionnaire (DSQ-40). According to the immunological hypothesis of mood disorders, we investigated baseline cytokines levels either in depressive or hypomanic/manic episodes. We correlated interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-alpha) levels with clinical factors. We detected higher IL-8 and TNF-alpha in patients in hypomanic/manic compared to depressed episodes. We found correlations of cytokine levels with immature defense style. We did not discover predictors of diagnosis conversion from MDD to BD.

Temperament and character dimensions as psychological markers of mood disorders in Polish adolescents and young adults-A prospective study.

BACKGROUND: An increasing incidence of mood disorders in adolescents and young adults is being observed. The assessment of personality traits seems to be an interesting tool in identifying early markers of major depression (MD) or bipolar disorder (BD) as well as predictors of the course of the disease. The aim of this study was to compare the personality profiles in young patients with MD and BD in acute and remitted mood states. METHODS: Seventy-nine adolescents and young adults with mood disorder diagnoses (MD or BD) were included in the study. The participants were assessed based on structured diagnostic interviews and completed the Temperament and Character Inventory (TCI). The clinical evaluation was conducted during the acute episodes and after reaching the stabilized mood in the course of follow-up visits in a 2-year study observation. RESULTS: At baseline, MD patients had higher scores on the harm avoidance (HA) with more pronounced anticipatory worry and fatigability subscale than BD patients. Conversely, BD patients reached higher scores in the total self-directedness (SD) character dimension and its sub-dimensions. MD patients with acute depressive symptoms had higher scores in the HA dimension and its subscale: anticipatory worry, shyness, and fatigability compared with their euthymic states. No significant differences in TCI dimensions between baseline and euthymia in the BD subgroup were found, and no differences between euthymic MD and BD patients. CONCLUSIONS: Higher ST and SD sub-dimensions may constitute a personality profile specific to BD, while high HA seems to be related to major depression in both acute and remitted states in young patients.

Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders.

Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14-24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders-Longitudinal Study in Adolescent and Young Adult Patients.

Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.

Adverse reactions to antidepressants.

BACKGROUND: Adverse drug reactions are important determinants of non-adherence to antidepressant treatment, but their assessment is complicated by overlap with depressive symptoms and lack of reliable self-report measures. AIMS: To evaluate a simple self-report measure and describe adverse reactions to antidepressants in a large sample. METHOD: The newly developed self-report Antidepressant Side-Effect Checklist and the psychiatrist-rated UKU Side Effect Rating Scale were repeatedly administered to 811 adult participants with depression in a part-randomised multicentre open-label study comparing escitalopram and nortriptyline. RESULTS: There was good agreement between self-report and psychiatrists' ratings. Most complaints listed as adverse reactions in people with depression were more common when they were medication-free rather than during their treatment with antidepressants. Dry mouth (74%), constipation (33%) and weight gain (15%) were associated with nortriptyline treatment. Diarrhoea (9%), insomnia (36%) and yawning (16%) were more common during treatment with escitalopram. Problems with urination and drowsiness predicted discontinuation of nortriptyline. Diarrhoea and decreased appetite predicted discontinuation of escitalopram. CONCLUSIONS: Adverse reactions to antidepressants can be reliably assessed by self-report. Attention to specific adverse reactions may improve adherence to antidepressant treatment.

Elevated brain-derived neurotrophic factor (BDNF) serum levels in an acute episode of schizophrenia in polish women: Correlation with clinical and metabolic parameters.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders. Schizophrenia is associated with metabolic abnormalities and BDNF regulates energy homeostasis and glucose metabolism in peripheral tissues. The aim of this study was to examine serum levels of BDNF in schizophrenic women during 8 weeks of treatment and control group, and its correlation with clinical and metabolic parameters. The study was performed on a group of 96 women: 55 diagnosed with paranoid schizophrenia according to DSM-IV criteria, and 41 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of schizophrenia. BDNF serum levels and metabolic parameters: fasting serum glucose, total cholesterol, triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured at baseline and week 8 of treatment. BDNF serum levels were significantly elevated in medicated patients with schizophrenia comparing to controls. After 8 weeks of antipsychotic treatment, BDNF levels did not significantly change. Increase in TG and TG/HDL-C ratio and a decrease in HDL-C was detected in medicated patients. Correlation between BDNF and lipid profile as well as symptoms severity was found. In our study we detected abnormalities in BDNF levels and lipid profile in medicated schizophrenic women in Polish population.

[Association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and the drug response for escitalopram and nortriptyline in depressed patients]. / Polimorfizm ins/del genu 5-HTT oraz T102C genu 5-HTR2A a efekt terapii nortryptylina i escitalopramem u pacjentów z depresja.

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.

[Association between polymorphisms of Val66Met in the BDNF gene and the response to escitalopram and nortriptyline treatment in the light of the neurodevelopmental hypothesis of depression]. / Ocena zwiazku pomiedzy polimorfizmem Va166Met genu BDNF a odpowiedzia na leczenie escitalopramem i nortryptylina w swietle koncepcji neurorozwojowej depresji.

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.

Val66Met functional polymorphism and serum protein level of brain-derived neurotrophic factor (BDNF) in acute episode of schizophrenia and depression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of schizophrenia and depression. Val66Met polymorphism and BDNF serum level are potential biomarkers in neuropsychiatric disorders. The aim of this study was to determine the effect of BDNF gene Val66Met functional polymorphism on serum BDNF concentration in patients with schizophrenia, during depression episode and in healthy control group. METHODS: 183 participants were recruited (61 patients with depressive episode, 56 females with schizophrenia, 66 healthy controls) from Polish population. Serum BDNF levels were measured using ELISA method. Val66Met polymorphism was genotyped using PCR- RFLP method. RESULTS: Serum BDNF levels were not associated with Val66Met polymorphism in either of the groups. A significant increase of BDNF level in schizophrenia (p = 0.0005) and depression (p = 0.026) comparing to the control group has been observed. CONCLUSIONS: Our results suggest that the functional Val66Met BDNF polymorphism is not associated with BDNF serum levels, which is in line with previous findings. Replication studies on larger groups are needed.

Clock genes polymorphisms in male bipolar patients with comorbid alcohol abuse.

BACKGROUND: Psychiatric comorbidity affects 24-65% patients with bipolar disorder (BD), 45% of which have alcohol abuse/dependence (AAD). Despite the fact that BD has an equal incidence in both genders, AAD more often occurs in men. We hypothesized that the presence of BD and AAD, reported as a secondary diagnosis, may result from a common genetic background. However, specific genetic factors predispose to gender differences. METHODS: Based on the relationship between circadian clock genes pathway and BD/AAD we decided to test the connection of four core clock genes with common genetic background of both diseases. We analyzed 436 patients with BD, among which 17% were diagnosed with AAD. The control group consisted of 417 healthy subjects. We analyzed 44 SNPs of the previously described core molecular clock genes: CLOCK, ARNTL, TIMELESS and PER3. RESULT: We found association of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms with an increased risk of BD/AAD in a group of male patients. We also found that two other polymorphisms of PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. LIMITATIONS: Possible factors that could have influenced the results are: relatively small sample size, gender disproportion and unverifiable data form the patient interview. CONCLUSIONS: Our study confirms the existence of a link between clock genes and increased risk of alcohol abuse/dependence in male patients and the accumulation of risk genes in patients with a positive family history.

Are suicide risk factors gender specific? / Czy czynniki zwiazane z ryzykiem samobójstwa sa specyficzne dla plci?

OBJECTIVES: 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. METHODS: 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.

Suicidal behavior in the context of disrupted rhythmicity in bipolar disorder-Complementary research of clock genes with suicide risks factors and course of disease.

Former findings indicate that suicidal behavior in bipolar disorder is associated with clock genes. Additionally, numerous non-genetic risk factors are potentially associated with suicidal behavior. Therefore, we conducted an analysis of the relationship between clock genes (as distal risk factors) with clinical characteristics and the course of bipolar disorder. We also tried to obtain a predictive model for suicide attempts based on clinical and genetic data. We found associations between selected polymorphisms and.