Yanki Yazgan

Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children

The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT χ2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT χ2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT χ2 = 2.38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT χ2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette’s syndrome, Sydenham’s chorea, and autoimmune disorders

BACKGROUND Some cases of Tourettes syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

No association between low- and high-activity catecholamine-methyl-transferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

Biochemical and genetic studies of attention deficit hyperactivity disorder (ADHD) suggest that regulation of catecholamine neurotransmission is a key factor in the aetiology of the disorder. In particular, it is postulated that an underactive dopamine system is associated with the disorder. In this study we have tested this hypothesis by screening a clinical sample of Turkish children with the combined subtype of ADHD with a functional variant of catecholamine-methyl-transferase (COMT) that codes for high- and low-activity variants of the enzyme. Using within-family tests of association and linkage in a sample of 72 children, we found no evidence for a genetic association or linkage. We conclude that altered regulation of catecholamines due to this polymorphism does not have a significant main effect on the risk for ADHD in this population. However, it remains feasible that more minor effects or interacting effects with other genes or environment exist.

Evidence for reduced hemispheric asymmetries in non-verbal functions in bilinguals

Abstract Hemispheric asymmetries in verbal and non-verbal visual half-field tasks were studied in highly proficient Turkish–German bilinguals. Besides a typical left-hemisphere advantage in word matching for both languages, a reduced right-hemisphere advantage in face discrimination in bilinguals was found as indicted by response times measures. In contrast, monolingual controls showed typical hemispheric asymmetries in both tasks. The results suggest that language experience affects the cerebral organization of non-language abilities which are known to show a right hemisphere advantage. It is conceivable that the acquisition of a second language leads to substantial modifications in various cortical areas, and thus affects cerebral organisation of other functional domains.

Association Among SNAP-25 Gene DdeI and MnlI Polymorphisms and Hemodynamic Changes During Methylphenidate Use A Functional Near-Infrared Spectroscopy Study

Objective: To investigate the interaction of treatment-related hemodynamic changes with genotype status for Synaptosomal associated protein 25 (SNAP-25) gene in participants with attention deficit hyperactivity disorder (ADHD) on and off single dose short-acting methylphenidate treatment with functional near-infrared spectroscopy (fNIRS). Method: A total of 15 right-handed adults and 16 right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten milligrams of short-acting methylphenidate was administered in a crossover design. Results: Participants with SNAP-25 DdeI T/T genotype had decreased right deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb] change. When the combinations of these genotypes were taken into account, the participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb]. Conclusions: These results suggested that SNAP-25 polymorphism might be associated with methylphenidate induced brain hemodynamic changes in ADHD participants.

Analysis of the dopamine beta hydroxylase gene in Gilles de la tourette syndrome

Numerous lines of evidence support the role of the catecholamines in the development of tics and Gilles de la Tourette syndrome (GTS). Dopamine‐β‐hydroxylase (DBH) is the key enzyme in the conversion of dopamine to norepinephrine and the alleles of several polymorphisms of the DBH gene are correlated with individual variation in serum levels of the enzyme. We investigated the genetic relationship of the gene for DBH to GTS in two samples, one collected in Canada and one collected in Turkey. In total 106 affected probands and siblings in 71 nuclear pedigrees and 40 affected individuals and 71 family members in five multi‐generational pedigrees were genotyped for three polymorphisms in the DBH locus. In the Canadian pedigrees we found no convincing evidence for linkage either in the multi‐generational pedigrees or association in the nuclear families. We found significant evidence for association in the Turkish pedigrees (n = 29) for the 19 bp insertion/deletion markers; however, there was no supporting evidence for association with the other two markers. Based on the small sample size and low number of informative transmissions, we conclude that the results from the 19 bp insertion/deletion markers may be a chance false positive finding. These findings, in total, suggest that the DBH locus is unlikely to be a major gene influencing the susceptibility to DBH.

Evaluation of the genes for the adrenergic receptors α2A and α1C and Gilles de la Tourette Syndrome

Gilles de la Tourette Syndrome (GTS) has long been known to be familial, and evidence from twin studies indicates that it has a substantial genetic component. Our genome scan of sibling pair families with GTS found evidence suggestive of linkage to several chromosomal locations. On the basis of these findings, we have begun to study additional markers in these regions, with some of the markers located in candidate genes. Two candidate genes stand out in these regions: the adrenergic receptor α1C(1A) (ADRA1C) located on chromosome 8p and the adrenergic receptor α2A (ADRA2A) located on chromosome 10q. The adrenergic system has been suggested to play a role in GTS based on the reduction of symptoms with the adrenergic receptor agonists, clonidine and guanfacine. We examined the inheritance of polymorphisms in the ADRA2A and ADRA1C genes in 113 nuclear families identified through a GTS proband. We found no significant evidence for linkage using the transmission disequilibrium test for these two genes. Based on our families, we conclude that these genes are not major genetic factors contributing to the susceptibility to GTS.

Prevalence of Peer Bullying in High School Students in Turkey and the Roles of Socio-Cultural and Demographic Factors in the Bullying Cycle

This research was conducted as a descriptive and relational study to determine the frequency of bullying among high school students and the relationships between some of their characteristics and their roles in the bullying cycle. The research data were obtained from 1670 students in the 9th and 10th grades of six high schools in Istanbul province. The data were analyzed with percentage distribution, Chi square, t test, correlation and Tukey test.The Determination of Peer Bullying Scale and a Personal Information Form were used for data collection in the research. According to the Determination of Peer Bullying Scale 17% of the students were in a bullying cycle (5.3% as bully, 5.9% as victim, and 5.8% as both bully and victim). The boys used more direct methods of bullying and girls more indirect methods of bullying. The rate of bullying behavior was also higher in boys and being a victim was higher in girls; the majority of the girls were bullied by girls and the majority of the boys were bullied by boys. More of those involved in bullying incidents had unexcused absenteeism from school and stated that they did not like school. The results obtained from this research show that the prevalence of bullying in high schools in Turkey is similar to the results in other countries. Determination of the causative factors that support and maintain bullying behavior for implementation of prevention programs is required.

Executive dysfunction in Turkish children at high risk for schizophrenia

AbstractObjectiveTo explore different aspects of executive function (i.e. sequencing, set shifting and mental flexibility) in children who are at high risk for schizophrenia by comparing them with normal controls.MethodThe high risk (HR) group consisted of 30 children whose parents were diagnosed as schizophrenia. As the control group (CG) 30 children, whose parents did not meet any DSM IV diagnostic criteria for any psychiatric disorder, participated. They were age and sex matched with the HR group. For the evaluation of different domains of cognitive functions Wechsler intelligence scale for children-revised (WISC-R), and a group of neuropsychological tests, including Trail Making A-B Tests, Color Form Test, and Progressive Figures Test were administered. Behavioral problems were assessed using Hacettepe Adjustment Scale.ResultsThe subjects in the high risk group had significantly lower scores on Trail Making A-B, Color Form, Progressive Figures Tests, as well as subtests and scores of WISC-R (Information, Comprehension, Similarities, Picture Completion, Block Design, Object Assembly and Coding subtests, Verbal, Performance and Full Scale IQ scores). There is no significant difference between the two groups in the frequency and severity of behavioral problems. ConclusionChildren of parents with schizophrenia displayed significantly greater number of difficulties in several areas of executive function, such as sequencing, set shifting, and mental flexibility, when compared to their controls.

Neurocognitive correlates of adult attention-deficit/hyperactivity disorder in a Turkish sample

We established a neuropsychological testing profile among Turkish adults presenting with ADHD controlling for general intelligence and comorbid psychiatric conditions. Adults with ADHD frequently present with comorbid conditions (e.g., mood and substance use/abuse disorders) that may have a detrimental impact on neurocognitive function. Hence, we excluded patients with ADHD meeting criteria for comorbid psychiatric syndromes. A comprehensive neuropsychological test battery was administered to adults with ADHD attending a general psychiatry clinic in Istanbul, Turkey, and healthy control participants. Adults with ADHD demonstrated performance deficits on tests of attention, information processing speed, and general and working memory. Patients with ADHD also reported a significantly greater number of symptoms associated with frontal lobe syndromes (i.e., dysexecutive symptoms and disinhibition). Patients with ADHD demonstrated rather striking deficits on tests of verbal and nonverbal memory. Once information was encoded, however, patients with ADHD do not demonstrate significant information loss. Patients with ADHD and healthy controls did not differ on tests of alternation learning, inhibitory control (error rates), and ToM skills. Findings support the contention that dorsal-prefrontal (rather than ventral-prefrontal) dysfunction is associated with adult ADHD. Unexpectedly, groups did not differ on executive control and fluency tasks. Yet patients with ADHD obtained substantially higher scores on a self-report measure of executive dysfunction. This suggests that dysexecutive symptoms among patients with ADHD in the current study do not reflect set-shifting or organizational deficits. Rather, symptoms may reflect attentional and working memory deficits as well as diminished information processing speed.