Mario Ćurković

Association between brain-derived neurotrophic factor Val66Met and obesity in children and adolescents

Obesity in children and adolescents is a worldwide health problem, characterized by various somatic, psychosocial and psychiatric complications, and is often associated with adult obesity and related complications. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding behavior, food intake regulation, energy metabolism and weight control. A common polymorphism of the BDNF genotype (Val66Met) has been associated with various forms of eating disorders, alterations in body mass index (BMI) values and obesity in adult populations. The aim of this study was to determine the association between the gene variants of the BDNF Val66Met polymorphism and obesity in 300 healthy Caucasian children and adolescents of the same ethnic background of Croatian origin, subdivided according to the BMI percentile, but without any form of eating disorders. The frequency of the Met/Met, Met/Val and Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met and Met/Val genotypes versus the homozygous Val/Val genotype) differed significantly between underweight, normal weight, overweight and obese children, and the presence of one or two Met alleles contributed to this significant effect. These results showed for the first time the significant association between the presence of one or two Met alleles and obesity in ethnically homogenous groups of healthy Caucasian children and adolescents. These data confirmed the major role of BDNF in energy metabolism, food regulation and BMI.

The association between the catechol-O-methyltransferase Val108/158Met polymorphism and hyperactive–impulsive and inattentive symptoms in youth

RationaleHyperactivity, impulsivity, and inattention are major symptoms occurring in attention-deficit/hyperactivity disorder. This disorder is highly heritable, multifactorial, polygenic, and associated primarily with dysfunctions of dopaminergic, noradrenergic, and serotonergic systems.ObjectivesThe present study tested the possible association of the catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) polymorphism with hyperactive–impulsive and inattentive symptoms in male youth.MethodPolymorphism COMT Val108/158Met was analyzed in 807 male unrelated Caucasian young subjects: 231 healthy controls, 195 subjects with moderate hyperactive symptoms and 254 subjects with moderate inattentive symptoms, 111 subjects with severe hyperactive symptoms and 90 subjects with severe inattentive symptoms, all evaluated using Swanson, Nolan, and Pelham Questionnaire IV criteria.ResultsThe frequency of the COMT genotypes, alleles, and the homozygous Met/Met genotype versus Val carriers (χ2 test with standardized residuals) differed significantly between subjects without and subjects with hyperactive–impulsive and inattentive symptoms. In addition, significantly higher hyperactive–impulsive and inattentive scores were found in subjects with the Met/Met genotype compared to carriers of other COMT genotypes. These significant results were due to the more frequent occurrence of Met/Met genotype or the Met allele in subjects with moderate and severe hyperactive–impulsive and inattentive symptoms compared to matched controls.ConclusionThese results suggest that the Met/Met genotype or the Met allele of the COMT Val108/158Met, contributing to higher dopaminergic activity, are significantly overrepresented in subjects with moderate or severe hyperactive–impulsive and inattentive symptoms, and that this polymorphism is significantly associated with hyperactive–impulsive and inattentive symptoms in young boys and adolescents.

DETECTION OF THALLIUM AND URANIUM IN WELL WATER AND BIOLOGICAL SPECIMENS OF AN EASTERN CROATIAN POPULATION

Abstract Using inductively-coupled plasma mass spectrometry (ICP-MS), we measured the concentrations of thallium and uranium in local water resources from three villages (Ćelije, Draž, and Potnjani) in eastern Croatia, with the aim to determine if they were associated with the levels of these same elements in the serum, urine, and hair collected from the residents of this area. The exposure of the local population to thallium and uranium through drinking water was generally low. ICP-MS was capable of measuring the levels of both of the elements in almost all of the analysed samples. Although there were differences in the concentrations of both elements in water samples and biological specimens taken from the residents, they did not reach the maximum contaminant level in any of the four sample types studied. Although hair was previously reported as an excellent indicator of occupational and environmental exposure to various elements, our study did not confirm it as a reliable biological material for tracing thallium and uranium levels, mainly due to the very low concentrations of these elements, often well below the detection limit. However, our results have shown that the concentration of thallium and uranium in drinking water can be effectively traced in urine samples. Sažetak ODREĐIVANJE RAZINA TALIJA I URANA U BUNARSKOJ VODI I BIOLOŠKIM UZORCIMA STANOVNIŠTVA TRIJU ISTOČNOHRVATSKIH SELA Koristeći masenu spektrometriju induktivno spregnute plazme (ICP-MS), izmjerili smo koncentracije talija i urana u lokalnim izvorima vode triju istočnohrvatskih sela (Ćelije, Draž i Potnjani) radi određivanja jesu li povezane s razinama obaju elemenata u serumu, urinu i kosi stanovnika tih triju sela. Izloženost lokalnog stanovništva taliju i uranu preko pitke vode općenito je bila niska. ICP-MS uspješno je izmjerio razine obaju elemenata u gotovo svim analiziranim uzorcima. Iako je bilo razlika u razinama obaju elemenata u uzorcima vode i biološkim uzorcima stanovnika, nijedan nije prešao maksimalnu dopuštenu granicu. Kosa je prethodno opisana kao izvrstan pokazatelj profesionalne ili okolišne izloženosti različitim elementima, no rezultati našeg ispitivanja nisu potvrdili njenu pouzdanost pri mjerenju talija i urana uslijed vrlo niskih koncentracija obaju elemenata, koje su često bile i ispod razine detekcije. Međutim, pokazali su kako uzorci urina mogu poslužiti kao vrlo dobri indikatori prisutnosti talija i urana u pitkoj vodi.

Association between the polymorphisms of the selected genes encoding dopaminergic system with ADHD and autism

Attention-deficit hyperactivity disorder (ADHD) and autism are both heritable, polygenic neurodevelopmental disorders with similar symptoms. Both disorders have onset in childhood and occur more frequently in boys than in girls. Genetic studies have so far focused mostly on candidate genes involved in dopaminergic system, however more non-replications than positive associations were reported. The present study tested the possible association of the variants in dopamine system genes with these disorders in Croatian population. Polymorphisms of the dopamine receptor D4 (DRD4 variable number of tandem repeats), catechol-o-methyltransferase (COMT Val108/158Met), dopamine-beta-hydroxylase (DBH -1021C/T) and monoamine oxidase type B (MAO-B intron 13 polymorphism) were analyzed in unrelated male Caucasian subjects: 128 control subjects, 102 children with ADHD and 80 subjects with autism, diagnosed according to DSM-IV criteria. This study detected significantly reduced frequency of DRD4 L allele in autistic compared to other groups and increased frequency of the COMT Met/Met genotype in autistic and ADHD groups compared to control group. The frequency of the genotypes of DBH -1021C/T and MAO-B intron 13 polymorphisms was similar between subjects with ADHD or autism and healthy subjects. These results suggest that DRD4 L allele and the COMT Met/Met genotype might be associated with ADHD and autism.

Depression, Personality and Life Stress Among Women with Breast Cancer in Eastern Croatian Region

Breast cancer is the most common among women and representsthe overall leading cancer in mortality rates. There is more than million newlydiagnosed breast cancer in the world every year. Incidence of breast cancer inCroatia is 100/100 000 or 2300 women per year. Every year, in Croatia, 900women die due to this carcinoma. Breast carcinoma is mostly found in women ages45-60. As the depression rates grow higher every year it isimportant to address the fact that among women with breast cancer the depressivesymptomes or depressive disorder is three times higher. These symptomes areoften correlated with stress (various life events), personality traits, sociodemographics and course of the primary disease (breast cancer). We have conducted a research among eighty (N=80)premenopausal women (40-60 years) withdiagnosed breast cancer shortly (3-7 days) after surgical treatment. Exclusion criteria was any kind of earliermental illness or psychiatric treatment/therapy . This research was conductedon Clinic for Surgery, Department of Thoracic surgery in the Clinical HospitalCentre Osijek (Croatia) and following questionnaires were applied: Hamiltondepression rating scale; Temperament and Character Inventory and Life Change Index Scale – The Stress Test. The obtained results were showed new perspective in dealingwith this disease, especially in this eastern Croatian region, and need forinterdisciplinary approach since significantly high ratio of women showeddepressive simptomes due to negative results correlated with stress and poorsocial/family support and also with specific personality features.

EPA-1139 – Influence of personality traits on depression severity in adolescents

Introduction Recognizing the link between depression and personality traits in adolescents can alleviate identification of individual triggers for developing and diagnosing depression, treatment approach and plan as well as at-risk individuals for suicide ideation. Current studies suggest that depression is linked to several personality traits according to psychobiological model such as: harm avodiance, novelty seeking and self-directedness. Also, personality traits appear to contribute to the onest and course/severity ofdepression. Often, this is more pronounced if there are adverse social factors affectingthe overall family functioning of particular adolescent. Material and Methods Our study was conducted on the Clinical Department for Children and Adolescents during 6-month period. We included both female and male adolescentes (15 years and older) entering the psychatric treatment and diagnosed as depressive disorder according to criteria of ICD-10. Personality traits (temperament and character)were assesed with, Temperament and Character Inventory-revised’ (TCI, Cloninger) and depressive symptoms with, Beck Depression Inventory’ (BDI). The social factors were identified through the region-specific questionnaire. Conclusion Our study has shown that severity of depression correlates with specific temperament and character traits according to psychobiological model but also how adverse social factors have significant impact on presentation of depressive symptoms. It might be possible that such negative social enviroment could impact the development of specific personality traits which predispose individual for development of depression

EPA-0277 – Post-stroke depression and suicidality correlated with personality features among elderly patients

Introduction Depression may occur as a result of cerebrovascular disease in a significant subpopulation of elderly persons. Recent studies indicate a high frequency of depression in older patients with cardiovascular and cerebrovascular diseases, and the possibility of a bidirectional relationship between depression and vascular disease. Materials and methods Our research included 62 post-stroke patients above age 60 undergoing post-stroke treatment in department of Neurology and 30 elderly patients who had suffered stroke one year ago and underwent psychiatric treatment. Each patient were given scales for assessment of depressive symptomes (Hamilton depression rating scale HAM-D), suicidality (Columbia suicide severity rating scale CSSR-S) and the list for assessment of borderline personality symptoms (Borderline Symptom List BSL) with examination of mental state (MMSE). These scales were given prior to antidepressant treatment and two weeks following the treatment. Results The obtained results shown positive correlation of depressive symptoms, suidical ideation and cognitive impairment in the group of post-stroke patients in psychiatric (with higher positive correlation in women). While in the group of elderly patients in psychiatric treatment (> than 1 year) the depressive symptoms were highly correlated with positive bordeline personality features and these specific personality features were highly correlated with suicidal ideation. Conclusion Our research showed how depressive symptoms are variable and highly correlated with personality features along with cognitive functioning. However, suicidal ideation was more correlated with specific personality features than depression itself. We have also concluded that concept of suicidality in the elderly seems unjustifiable neglected and should be more vigorously identified.

The Medical Treatment of Autism Disorders

Autism is one of a group of pervasive developmental disorders and is characterised by qual‐ itative impairments in communication and social interactions and by stereotyped behav‐ iours and interests. Abnormal development is present before the age of 3 years. A quarter of affected children show developmental regression with loss of acquired skills. One third of children with autism have epilepsy and three quarters have mental retardation. Only 15 % of adults with autism lead independent live. Twin and family studies suggest that most cas‐ es of autism occur because of combination of genetics factors [1]. Concept of autism has been broadened the last few years from early infantile autism to an autistic spectrum and related communication disorders are grouped together under pervasive developmental disorders or autistic spectrum disorders. People with an autistic disorder have severe difficulties in the integration of perceived in social stimuli into a meaningful entity. More than two people with autistic disorder are also mentally retarded. Autism cannot be cured but adequate in‐ tervention can significantly improve the quality of life people with this disorder [2].

P.7.b.001 The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism in aggressive behaviour in adolescents

High rates of suicide among adolescents are a growing concern worldwide, while 8% of adolescents show high suicidal risk in Croatia. There are different psychiatric, psychological, environmental, biological and genetic factors for suicidal behavior that can lead to completed suicide. Aggression and agitation present risk factors for suicide. Gene for the enzyme catechol-o-methyl-transferase (COMT), that degrades dopamine, is frequently studied candidate gene for suicide risk. A functional polymorphism COMT Val108/158Met, consists of G to A transition, i.e. substitution of valine (Val) with methionine (Met). The Val/Val genotype has a 3-4 times higher COMT activity than the Met/Met genotype. This polymorphism was associated with suicidal behavior in adults. The hypothesis of this study was that COMT Val108/158Met polymorphism will be significantly associated with suicidal behavior and/or aggression in adolescents. The study included 187 female and 141 male adolescents (15.2 ± 2.4 years, range 7-19). The psychiatric diagnoses, suicidal behavior and aggression were established according to the SCID and DSM- IV criteria, and the Overt Aggression Symptom Checklist. DNA was isolated from the blood samples taken during regular laboratory check- ups. Genotyping was carried out on the ABI Prism 7000 Sequencing Detection System apparatus (ABI, Foster City, USA) with Taqman- based allele-specific PCR, according to the procedure described by Applied Biosystems (ABI, Foster City, USA). Statistical evaluation of the data was done using the Chi-square test, with p <0.05. All adolescents were subdivided into control subjects (without psychiatric diagnoses and without suicidal behavior), and suicidal and non-suicidal adolescents (with psychiatric diagnoses). COMT Val108/158Met genotypes were in the Hardy-Weinberg equilibrium, and no deviation was found in control (χ2 =0.490, p =0.484), suicidal (χ2 =0.070, p =0.703) or non-suicidal (χ2 =0.700, p = 0.402) groups. Control subjects and suicidal and non-suicidal adolescents had similar distribution of the Val/Val, Val/Met and Met/Met genotypes (χ2 = 5.629, df =4, p = 0.229), or Val and Met alleles (χ2 =4.376, df =2, p =0.0112). There were no significant differences in the distribution of the COMT Val108/158Met genotypes between adolescents with or without: verbal aggression (χ2 =2.867, df =2, p =0.238), physical aggression against self (χ2 =1.025, df =2, p =0.599), physical aggression against objects (χ2 =3.313, df =2, p =0.191), or physical aggression against other people (χ2 =0.225, df =2, p =0.893). The distribution of the COMT alleles did not differ significantly between adolescents with or without: verbal aggression (χ2 =2.856 , df =1, p =0.091), physical aggression against self (χ2 =0.166 , df =1, p =0.634), physical aggression against objects (χ2 =2.329, df =1, p =0.127), or physical aggression against other people (χ2 =0.081, df =1, p =0.776). Our preliminary results, showing similar distribution of the COMT Val108/158Met variants between suicidal and non-suicidal adolescents, or between non- aggressive and aggressive adolescents, did not confirm our hypothesis that suicidal behavior, and/or aggression, is significantly associated with the COMT Val108/158Met polymorphism in adolescents. The present findings suggest that further studies with larger samples should be included to evaluate the role of COMT Val108/158Met polymorphism in suicidal or aggressive behavior.