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Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 α subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a ∼3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND: A cross-sectional study was performed in a population-based German sample (n=13 318 children and adolescents aged 3-17) to replicate the recently reported independent association of atopic eczema (AE) and attention-deficit/hyperactivity disorder (ADHD) and to further investigate the role of environmental and behavioural factors. METHODS: The odds ratio (OR) was calculated with allergic comorbidity and various environmental factors considered as confounders and sleeping problems hypothesised to act as a potential effect modifier. RESULTS: The lifetime prevalence of AE and ADHD was 14.7% (male 14.4%; female 14.9%) and 4.9% (male 7.8%; female 2.0%), respectively. There was an association between ADHD and AE (OR 1.54; 95% CI 1.24 to 1.93; p<0.001), which was independent of sociodemographic factors, parental smoking, breastfeeding, number of siblings, perinatal health problems, and atopic comorbidity. Further analyses of a subgroup of 6484 children age 3-11 confirmed the hypothesis that the association between AE and ADHD was modified by sleeping problems (interaction effect AE*sleep problems OR 2.02 95% CI 1.03 to 3.97; p=0.04). There was a strong association between AE and ADHD in children with SP (OR 2.67 95% CI 1.51 to 4.71; p=0.001; n=1112), but not in children without SP (OR 1.24 95% CI 0.83 to 1.84; p=0.30; n=5796). CONCLUSIONS: ADHD and AE appear to be strongly and independently associated in children with sleeping problems, but not in children without sleeping problems. A substantial part of diagnoses met for ADHD might be engendered by the presence of AE and concomitant sleeping problems. [ABSTRACT FROM AUTHOR]

To cite this article: dos Santos RL, Pithon MM, Martins FO, Romanos MTV, de Oliveira Ruellas AC: Evaluation of the cytotoxicity of latex and non-latex orthodontic separating elastics Orthod Craniofac Res 2010; 13:28–33 Structured Abstract Authors – dos Santos RL, Pithon MM, Martins FO, Romanos MTV, de Oliveira Ruellas AC Objective – To test the hypothesis that a difference in cytotoxicity exists between latex and non-latex orthodontic separating elastics. Material and Methods – Five intra-oral separating elastics from different manufactures (four latex and one non-latex) were divided into five groups of 15 elastics each: Group MA (non-latex elastics, Masel), Group MO (natural latex, Morelli), Group DE (natural latex, Dentaurum), Group TP (natural latex, TP Orthodontics) and Group UN (natural latex, Unitek). The cytotoxicity assay was performed using cell cultures (epithelial HEp-2 cells originating from human laryngeal carcinoma) that were submitted to the cell viability test with neutral red (dye-uptake) at 24, 48, 72 and 168 h. Analysis of variance (anova) with multiple comparisons and Tukey's test were employed ( p < 0.05). Results – The results showed no statistically significant differences between groups MA, DE, TP and UN in relation to Group CC (cell control) for experimental times of 24, 48 and 168 h ( p > 0.05). Morelli, Dentaurum, TP Orthodontics and Unitek elastics induced a great amount of cell lyses at 72 h. Conclusion – One can demonstrate that the Masel elastic induced less cell lysis compared with other elastics, but all trademarks were found to be clinically biocompatible. Clinical relevance – Separating orthodontic elastics are used in the interdental subgingival region with the aim to separate the teeth for placement of orthodontic bands. However, latex has been known to cause allergy. As these materials are widely used in clinical orthodontics, care regarding the cytotoxicity of orthodontic elastics should be taken. Thus, clinically proven biocompatible materials should be acquired whenever possible. [ABSTRACT FROM AUTHOR]

Research on different subtypes of attention deficit hyperactivity disorder (ADHD) yielded inconsistent results regarding the nature of cognitive deficits. Whereas some studies report significant differences between subtypes, others fail to report these differences. In fact, the majority of studies in the field of ADHD does not differentiate between subtypes at all. The present study adopted the cognitive task of negating valence to compare the DSM-defined ADHD combined subtype (ADHD-C; n = 25), the inattentive subtype (ADHD-I; n = 25) and the control group ( n = 30). As a main result, children with ADHD-C showed significant impairments compared to children with ADHD-I and the control group on conscious responses—driven by executive function, as well as on unconscious associative tasks. Medical treatment with stimulants positively influenced cognitive performance, although to a different extent for subgroups. The results are discussed in the context of current theories of ADHD and imply indications for further research in this field. [ABSTRACT FROM AUTHOR]

Previous genome-wide linkage studies applied the affected sib-pair design; one investigated extended pedigrees of a genetic isolate. Here, results of a genome-wide high-density linkage scan of attention-deficit/hyperactivity disorder (ADHD) using an array-based genotyping of ∼50 K single nucleotide polymorphism (SNPs) markers are presented. We investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Our study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.Molecular Psychiatry (2008) 13, 522–530; doi:10.1038/mp.2008.12; published online 26 February 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To review the literature on the use of atypical antipsychotics in anorexia nervosa of children and adolescents and to present three case reports on quetiapine treatment of this subgroup. METHOD: Review of the literature and case report. RESULTS: Several case reports and two small open-label trials, mainly in adults, observed beneficial effects of olanzapine on anorexic psychopathology. Only 16 case reports have been published on children and adolescents. Because of its lower propensity to induce weight gain quetiapine might be favourable with regard to patients' compliance. Our case reports revealed positive psychopathological effects and good tolerability of quetiapine in minors with severe anorexia nervosa. Careful titration and intense drug monitoring are recommended. DISCUSSION: In a small subset of patients with severe, treatment- resistant anorexia nervosa, extreme weight phobia, delusional body image disturbances or severe hyperactivity might be considered as indications for atypical antipsychotics. However, controlled studies are needed. [ABSTRACT FROM AUTHOR]

Altered neurotransmission has been suggested to be a crucial factor in the pathophysiology of attention-deficit/hyperactivity disorder ADHD. Subsequently genes encoding for synaptic proteins have been investigated in candidate gene studies. These proteins mediate the release of neurotransmitters into the synaptic cleft in the process of signal transduction by forming a transient complex, enabling the junction of vesicle and synaptic membrane. One of the core proteins of this complex is the synaptosomal-associated protein 25 ( SNAP25). It is one of the most validated candidate genes in ADHD according to meta-analyses. However, differing results were observed in previous studies, some of which were not able to observe association with ADHD. In this study we aimed to investigate association of genetic variants of SNAP25 located in the putative promoter region of SNAP25 and a SNP in intron 8, previously reported to associated with ADHD. A family based design was applied to detect preferential transmission of genetic variants. In our German ADHD sample no preferential transmission of either variant could be observed. Further investigation considering sub-sample analysis regarding response to D-amphetamine could enlight the role of SNAP25 in ADHD. [ABSTRACT FROM AUTHOR]

Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5′ region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.Molecular Psychiatry (2007) 12, 923–933; doi:10.1038/sj.mp.4001986; published online 10 April 2007 [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable common neurodevelopmental disorder with onset in childhood. A coding SNP (rs6265, Val66Met) of the brain-derived neurotrophic factor gene ( BDNF) has recently been associated with ADHD. More specifically, paternal over-transmission of the common Val66 allele to affected children had been observed. We aimed to confirm these findings in a large, sufficiently powered, and well characterized German ADHD family sample. The Val66Met polymorphism of BDNF was genotyped in 294 families comprising one or more affected sibs (468 children). Contrary to previous reports, we did not observe over-transmission of the common Val66 allele, from either parent to affected children. We did not find support for an involvement of the Val66 allele of the Val66Met polymorphism of BDNF in the pathogenesis of ADHD in our sample. [ABSTRACT FROM AUTHOR]

Abstract: This paper''s main goal is to present the European Federation for all psychiatric Trainees. This organization is now twelve years old, and links psychiatric trainees from over twenty countries across Europe, whose delegates meet once a year at the annual forum. It represents over 12000 trainees. Through a description of the EFPT''s twelfth forum, we will introduce its main goals and means, as well as the achievements it has made so far. [Copyright &y& Elsevier]

Translational studies comparing imaging data of animals and humans have gained increasing scientific interests. With this upcoming translational approach, however, identifying harmonized statistical analysis as well as shared data acquisition protocols and/or combined statistical approaches is necessary. Following this idea, we applied Bayesian Adaptive Regression Splines (BARS), which have until now mainly been used to model neural responses of electrophysiological recordings from rodent data, on human hemodynamic responses as measured via fMRI. Forty-seven healthy subjects were investigated while performing the Attention Network Task in the MRI scanner. Fluctuations in the amplitude and timing of the BOLD response were determined and validated externally with brain activation using GLM and also ecologically with the influence of task performance (i.e. good vs. bad performers). In terms of brain activation, bad performers presented reduced activation bilaterally in the parietal lobules, right prefrontal cortex (PFC) and striatum. This was accompanied by an enhanced left PFC recruitment. With regard to the amplitude of the BOLD-signal, bad performers showed enhanced values in the left PFC. In addition, in the regions of reduced activation such as the parietal and striatal regions, the temporal dynamics were higher in bad performers. Based on the relation between BOLD response and neural firing with the amplitude of the BOLD signal reflecting gamma power and timing dynamics beta power, we argue that in bad performers, an enhanced left PFC recruitment hints towards an enhanced functioning of gamma-band activity in a compensatory manner. This was accompanied by reduced parieto-striatal activity, associated with increased and potentially conflicting beta-band activity.

A correction to this paper has been published: https://doi.org/10.1007/s00228-021-03159-0 [ABSTRACT FROM AUTHOR]

Preventive interventions, such as universal and targeted, i.e. selective and indicated, interventions can effectively reduce the incidence of anxiety disorders and thus lower the high individual and socioeconomic burden of anxiety disorders. This review article provides an overview of internationally established prevention programs for children, adolescents and adults. The efficacy and cost effectiveness of preventive interventions are discussed. Due to the large target group, universally implemented strategies are costly and organizationally complex but can prevent a large number of manifest anxiety disorders or reduce the clinical expression, despite only small effect sizes. Selective preventive measures are aimed at persons with a high risk for anxiety disorders (e.g. with high anxiety sensitivity, behavioral inhibition, harm avoidance, family history of anxiety disorders). The indicated preventive interventions in high-risk individuals with first subclinical anxiety symptoms are successful in preventing the manifestation of anxiety disorders and constitute the most cost-effective type of preventive measures. Biological, i.e. genetic, imaging or neurophysiological markers, or their combination, are discussed as promising future targets for selective or indicated prevention of anxiety disorders. [ABSTRACT FROM AUTHOR]