ORCID Profile
0000-0003-2667-2254
Current Organisation
King's College London
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Publisher: Wiley
Date: 03-02-2009
DOI: 10.1002/AJMG.B.30921
Publisher: SAGE Publications
Date: 12-02-2014
Abstract: Attention deficit hyperactivity disorder (ADHD) is a common condition with a high societal burden. The present guidelines summarise current literature, generating expert consensus recommendations for the treatment of ADHD in children and adults. These guidelines also provide a review of recent research in the fields of neuroimaging, neuropsychology and genetics of ADHD. Novel discoveries in these areas have informed physiological models for the disease. Since the publication of the previous British Association for Psychopharmacology guidelines in 2008, new drugs have been licensed and further compounds are being investigated. The publication of randomised controlled trials of psychological interventions has contributed to the range of treatment options for ADHD. As the disorder has been diagnosed more frequently there has been greater focus on comorbid conditions and how they impact treatment. Services have continued to develop for the treatment of ADHD in adults and care agreements have been introduced to facilitate access to treatment.
Publisher: Springer Science and Business Media LLC
Date: 05-05-2006
DOI: 10.1007/S00787-006-0549-0
Abstract: A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). In idual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.
Publisher: Wiley
Date: 24-08-2009
DOI: 10.1111/J.1469-7610.2009.02095.X
Abstract: Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT). Seven hundred and twenty-eight males between the ages of 5 and 17 with a DSM-IV research diagnosis of combined type ADHD were included in these analyses. Parents and teachers rated children's conduct and emotional problems. Positive maternal expressed emotion (PMEE) was coded by independent observers on comments made during a clinical assessment with the mother based on current or recent medication-free periods. Sensitivity to the effects of PMEE on CP was moderated by variants of the DAT1 and 5HTT genes. Only children who did not carry the DAT1 10R/10R or the 5HTT l/l genotypes showed altered levels of CP when exposed to PMEE. The effect was most marked where the child with ADHD had both these genotypes. For EMO, sensitivity to PMEE was found only with those who carried the DAT1 9R/9R. There was no effect of DRD4 on CP or EMO. The gene-environment interactions observed suggested that genetic make-up can alter the degree of sensitivity an ADHD patients has to their family environment. Further research should focus on distinguishing general sensitivity genotypes from those conferring risk or protective qualities.
Publisher: American Medical Association (AMA)
Date: 2021
Publisher: Elsevier BV
Date: 09-2010
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1086/381561
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent s les of probands and their parents, analyzed them in idually and, in the absence of heterogeneity, analyzed them as a joint s le. The joint analysis showed association with the DRD5 locus (P=.00005 odds ratio 1.24 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.
Publisher: Wiley
Date: 08-12-2001
DOI: 10.1002/AJMG.1553
Abstract: Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder of childhood that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD. First, nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers, and nonsmokers. Second, ADHD is a significant risk factor for early initiation of cigarette smoking in children and maternal cigarette smoking appears to be a risk factor for ADHD. Finally, animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity. The nicotinic system has previously been studied in schizophrenia where the neuronal nicotinic acetylcholine receptor alpha 7 subunit gene (CHRNA7) has been implicated in decreased P50 inhibition and attentional disturbances in patients with schizophrenia and in many of their nonschizophrenic relatives. Three known microsatellite markers (D15S165, D15S1043, and D15S1360) near the nicotinic acetylcholine alpha 7 receptor gene, CHRNA7, were studied in 206 ADHD parent-proband trios of children aged 5-16 with ADHD according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded from the study. Markers D15S165 and D15S1360 were in linkage disequilibrium. The extended Transmission Disequilibrium Test analyses demonstrated no evidence that variation at the microsatellite markers D15S1360, D15S1043, and D15S165 influences susceptibility to ADHD. However, it remains possible that the CHRNA7 gene and other nicotinic system genes may be involved in conferring susceptibility to ADHD.
Publisher: American Medical Association (AMA)
Date: 2006
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) is associated with ADHD in several studies, with an average 1.2 odds ratio and evidence of heterogeneity across data sets. To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy. Prospective study. Children with ADHD from child behavior clinics in the southeast of England and in the Taipei area of Taiwan. Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English s le. Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and low-exposure groups for the environmental variables. A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese s les. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy. The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.
Publisher: Elsevier BV
Date: 09-2010
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1038/S41398-021-01201-4
Abstract: Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult s les. The model trained on adult s les significantly predicted ADHD in the child s le, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.CHROMA.2011.03.036
Abstract: Hydrophilic interaction chromatography (HILIC) has emerged as a very useful separation method for polar analytes, including non-covalent metal species. Several types of stationary phases are available for HILIC applications, differing mainly in their chemical functionalities that supply additional interaction modes and alternative selectivities for the separation of special analytes. With regard to the separation of metal species only few of these stationary phases have been applied to date, and it is not completely clear what are their differences with respect to the chromatographic separation of metal species, but also with respect to species stability during chromatography. Here, a comparison of different column types for the HILIC separation of iron citrate and copper histidine species is presented and the results are discussed with respect to retention mechanisms and chromatographic stability of these metal species. It is shown that different stationary phases display very different separation patterns. In particular, three types of HILIC columns enable successful separation of iron citrates and copper histidine at pH 5.5, namely a crosslinked diol phase, a zwitterionic phase, and an amide phase. Two groups of iron-citrates are separated on all three columns, consisting of a species of 3:3 stoichiometry and another one of mainly 3:4 stoichiometry (plus 1:2 and 2:2 species). For copper-histidine only one stable species is found based on the 1:2 stoichiometry. Detection and unambiguous identification of the different species is possible by employing electrospray mass spectrometry in the negative ionization mode. Species found in standard solutions are consistent with species found in spiked plant s les. Also in unspiked solutions iron citrate of 3:4 stoichiometry (plus 1:2 and 2:2) is detectable, but no species of 3:3 stoichiometry. Significant differences of related species patterns are found in real plant s les.
Publisher: Wiley
Date: 22-11-1996
DOI: 10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P
Abstract: This paper investigates the spatial dimension of socioeconomic and demographic factors behind COVID-19 vaccine hesitancy. With a focus on a county with considerable sociodemographic ersity in the state of Texas, USA, we apply regression models to census-tract-level data of the unvaccinated population. In addition to disparities in accessing the vaccination service, particularly for residents in rural areas, empirical results confirm under-vaccination among lower socioeconomic neighborhoods and communities with signs of distrust in government. The spatial model regressions further underscore the impact that vaccine hesitancy among residents in one community spread to its nearby communities. This observed spatial spillover effect is attributable to the geographic interactions of similar socioeconomic groups.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 05-2008
Abstract: Hydrophilic interaction chromatography (HILIC) was applied for the separation of small, noncovalent metal species, and free ligands in plants, using two different zwitterionic stationary phases at pH 7.3. Ligands ranged from amino acids and phytosiderophores to organic acids and synthetic chelators like EDTA. Our results confirmed the suitability of zwitterionic stationary phases for the separation of such ligands and their metal complexes. In particular, the chromatographic behavior of phytosiderophore complexes of copper, nickel, and zinc on a sulfobetaine-type material was compared to that on a phosphorylcholine-type material under otherwise identical conditions. A compression of the usable retention range for phytosiderophore species on the latter phase was found, which can be traced back to the reversed charge orientation of the zwitterionic functionalities. Differences were also found for the integrity of more labile metal chelates during separation on the two columns. In particular, Ni-malate could only be analyzed on the sulfobetaine phase, and Cu-glutathione, Ni-aspartate, and Ni-citrate complexes were only stable on the phosphorylcholine stationary phase at pH 7.3. Ni-histidine species were only found after lowering the pH to 4-5. The identification of separated species is possible by online ESI-MS in the negative ionization mode.
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.05.077834
Abstract: Delineating age-related cortical trajectories in healthy in iduals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 in iduals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-in idual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-in idual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.
Publisher: Royal College of Psychiatrists
Date: 03-2009
DOI: 10.1192/BJP.BP.107.045245
Abstract: Symptoms of attention-deficit hyperactivity disorder (ADHD) are known to persist into adulthood in the majority of cases. To determine the prevalence of methylphenidate, dexamfetamine and atomoxetine prescribing and treatment discontinuation in adolescents and young adults. A descriptive cohort study using the UK General Practice Research Database included patients aged 15–21 years from 1999 to 2006 with a prescription for a study drug. Prevalence of prescribing averaged across all ages increased 6.23-fold over the study period. Overall, prevalence decreased with age: in 2006, prevalence in males dropped 95% from 12.77 per 1000 in 15-year-olds to 0.64 per 1000 in 21-year-olds. A longitudinal analysis of a cohort of 44 patients aged 15 years in 1999 demonstrated that no patient received treatment after the age of 21 years. The prevalence of prescribing by general practitioners to patients with ADHD drops significantly from age 15 to age 21 years. The fall in prescribing is greater than the reported age-related decrease in symptoms, raising the possibility that treatment is prematurely discontinued in some young adults in whom symptoms persist.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2006
Publisher: Wiley
Date: 16-12-2010
DOI: 10.1002/AJMG.B.31149
Publisher: Wiley
Date: 28-12-2007
DOI: 10.1002/AJMG.B.30659
Abstract: There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE s le (chi(1)(2) = 1.82, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD.
Publisher: Wiley
Date: 05-2008
DOI: 10.1002/AJMG.B.30737
Abstract: Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a s le of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the s le of ADHD cases.
Publisher: Wiley
Date: 02-2010
DOI: 10.1111/J.1469-7610.2010.02217.X
Abstract: The goal of this study was to investigate the occurrence, severity and clinical correlates of emotional lability (EL) in children with attention deficit/hyperactivity disorder (ADHD), and to examine factors contributing to EL and familiality of EL in youth with ADHD. One thousand, one hundred and eighty-six children with ADHD combined type and 1827 siblings (aged 6-18 years) were assessed for symptoms of EL, ADHD, associated psychopathology and comorbid psychiatric disorders with a structured diagnostic interview (PACS) as well as parent and teacher ratings of psychopathology (SDQ CPRS-R:L CTRS-R:L). Analyses of variance, regression analyses, chi(2)-tests or loglinear models were applied. Mean age and gender-standardized ratings of EL in children with ADHD were >1.5 SD above the mean in normative s les. Severe EL (>75th percentile) was associated with more severe ADHD core symptoms, primarily hyperactive-impulsive symptoms, and more comorbid oppositional defiant, affective and substance use disorders. Age, hyperactive-impulsive, oppositional, and emotional symptoms accounted for 30% of EL variance hyperactive-impulsive symptoms did not account for EL variance when coexisting oppositional and emotional problems were taken into account, but oppositional symptoms explained 12% of EL variance specifically. Severity of EL in probands increased the severity of EL in siblings, but not the prevalence rates of ADHD or ODD. EL and ADHD does not co-segregate within families. EL is a frequent clinical problem in children with ADHD. It is associated with increased severity of ADHD core symptoms, particularly hyperactivity-impulsivity, and more symptoms of comorbid psychopathology, primarily symptoms of oppositional defiant disorder (ODD), but also affective symptoms, and substance abuse. EL in ADHD seems to be more closely related to ODD than to ADHD core symptoms, and is only partly explainable by the severity of ADHD core symptoms and associated psychopathology. Although EL symptoms are transmitted within families, EL in children with ADHD does not increase the risk of ADHD and ODD in their siblings.
Publisher: Oxford University Press (OUP)
Date: 02-03-2007
Publisher: Elsevier BV
Date: 10-2008
Publisher: Elsevier BV
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 19-09-2008
Publisher: Springer Science and Business Media LLC
Date: 12-04-2020
DOI: 10.1038/S41386-020-0664-5
Abstract: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total s le of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent in iduals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2008
DOI: 10.1007/S10803-008-0621-3
Abstract: It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes Class 1(31%) had few autism symptoms and low comorbidity Classes 2-4 were intermediate Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.
Publisher: Wiley
Date: 07-10-2008
DOI: 10.1002/AJMG.B.30860
Abstract: Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-wide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent s les.
Publisher: Wiley
Date: 30-07-2008
DOI: 10.1002/AJMG.B.30782
Abstract: Multiple studies have reported an association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the dopamine transporter gene (DAT1). Yet, recent meta-analyses of available data find little or no evidence for this association although there is strong evidence for heterogeneity between datasets. This pattern of findings could arise for several reasons including the presence of relatively rare risk alleles on common haplotype backgrounds or the functional interaction of two or more loci within the gene. We previously described the importance of a specific haplotype at the 3' end of DAT1, as well as the identification of associated single nucleotide polymorphisms (SNPs) within or close to 5' regulatory sequences. In this study we replicate the association of SNPs at the 5' end of the gene and identify a specific risk haplotype spanning the 5' and 3' markers. These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD. Overall these data provide further evidence that genetic variants of the dopamine transporter gene confer an increased risk for ADHD.
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.CHROMA.2006.09.060
Abstract: A sensitive method for the separation of different phytosiderophores (PS) of the mugineic acid (MA) family, and the candidate ligand for intracellular metal transport in plants nicotianamine (NA), and respective metal complexes in plants by zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS) is described. Separation of mugineic acid, 2'-deoxymugineic acid (DMA), 3-epi-hydroxymugineic acid (epi-HMA), nicotianamine, Fe(III)-DMA, Fe(III)-NA, M(II)-DMA, and M(II)-NA complexes (M(II)=Zn(II), Cu(II), Ni(II), and Fe(II)), was achieved within 22 min on the ZIC-HILIC column by using a gradient elution with a mobile phase consisting of ammonium acetate and acetonitrile at pH 7.3, at a flow rate of 0.15 mL/min. The on-line coupling to ESI-MS in the negative ionization mode enables the detection of these compounds in the micromol/L range, which is the relevant concentration range in real plant s les. DMA-complexes of Fe(III), Zn, and Cu in wheat root, and an NA-complex of Ni in Arabidopsis were detected and identified by the proposed method. Even in the case of partial coelution of some alent metal complexes, the identification is possible by their distinct mass spectra. The stability of metal complexes during separation was checked by injecting ethylenediaminetetraacetic acid (EDTA) after each run of metal-phytosiderophore complexes. Good stability of alent-phytosiderophores, except for Fe(II)-complexes, was observed. During gradient separation, Fe(III)-complexes are partly dissociated (<20%), but a good sensitivity of Fe(III)-DMA in real plant s les is still achieved. In order to avoid instability problems with the separation of Fe-complexes, an isocratic separation is proposed, which allows the separation of ferrous and ferric complexes in 2 min.
Publisher: Wiley
Date: 31-05-2013
DOI: 10.1002/AJMG.B.32169
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Publisher: Wiley
Date: 16-05-2012
DOI: 10.1111/J.1469-8137.2012.04165.X
Abstract: • Retranslocation of iron (Fe) from source leaves to sinks requires soluble Fe binding forms. As much of the Fe is protein-bound and associated with the leaf nitrogen (N) status, we investigated the role of N in Fe mobilization and retranslocation under N deficiency- vs dark-induced leaf senescence. • By excluding Fe retranslocation from the apoplastic root pool, Fe concentrations in source and sink leaves from hydroponically grown barley (Hordeum vulgare) plants were determined in parallel with the concentrations of potential Fe chelators and the expression of genes involved in phytosiderophore biosynthesis. • N supply showed opposing effects on Fe pools in source leaves, inhibiting Fe export out of source leaves under N sufficiency but stimulating Fe export from source leaves under N deficiency, which partially alleviated Fe deficiency-induced chlorosis. Both triggers of leaf senescence, shading and N deficiency, enhanced NICOTIANAMINE SYNTHASE2 gene expression, soluble Fe pools in source leaves, and phytosiderophore and citrate rather than nicotianamine concentrations. • These results indicate that Fe mobilization within senescing leaves is independent of a concomitant N sink in young leaves and that phytosiderophores enhance Fe solubility in senescing source leaves, favoring subsequent Fe retranslocation.
Publisher: Wiley
Date: 03-11-2008
DOI: 10.1002/AJMG.B.30866
Publisher: Wiley
Date: 26-09-2008
DOI: 10.1002/AJMG.B.30867
Abstract: Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P-values with a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P-values lower than 0.01 and multiple association P-values at a magnitude of 10(-5) in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
Publisher: Wiley
Date: 20-10-2008
DOI: 10.1002/AJMG.B.30869
Publisher: American Psychiatric Association Publishing
Date: 07-2019
Publisher: Wiley
Date: 12-10-2020
DOI: 10.1002/HBM.25204
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta‐Analysis) Consortium presents the largest‐ever mega‐analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy in iduals 1‐90 years old (47% females). We observed significant patterns of greater male than female between‐subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene‐environment interaction mechanisms. The findings highlight the importance of in idual differences within the sexes, that may underpin sex‐specific vulnerability to disorders.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2013
Publisher: American Psychiatric Association Publishing
Date: 02-2012
Publisher: Cambridge University Press (CUP)
Date: 04-06-2010
DOI: 10.1017/S003329171000108X
Abstract: Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. Multivariate familial models were run on data from 1265 in iduals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). Significant familial association ( r F) was confirmed between cognitive performance and both ADHD ( r F=0.41–0.71) and IQ ( r F=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.
Publisher: Springer Science and Business Media LLC
Date: 04-12-2011
DOI: 10.1038/NG.1013
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.05.079475
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small s le sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalised on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine the age-related morphometric trajectories of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippoc us and amygdala using magnetic resonance imaging data obtained from 18,605 in iduals aged 3-90 years. All subcortical structure volumes were at their maximum early in life the volume of the basal ganglia showed a gradual monotonic decline thereafter while the volumes of the thalamus, amygdala and the hippoc us remained largely stable (with some degree of decline in thalamus) until the sixth decade of life followed by a steep decline thereafter. The lateral ventricles showed a trajectory of continuous enlargement throughout the lifespan. Significant age-related increase in inter-in idual variability was found for the hippoc us and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to derive risk predictions for the early identification of erse clinical phenotypes.
Publisher: Wiley
Date: 30-12-2010
Abstract: IEF is known as a powerful electrophoretic separation technique for hoteric molecules, in particular for proteins. The objective of the present work is to prove the suitability of IEF also for the separation of small, non‐covalent metal species. Investigations are performed with copper–glutathione complexes, with the synthetic ligand ethylenediamine‐ N , N ′‐bis( o ‐hydroxyphenyl)acetic acid (EDDHA) and respective metal complexes (Fe, Ga, Al, Ni, Zn), and with the phytosiderophore 2′‐deoxymugineic acid (DMA) and its ferric complex. It is shown that ethylenediamine‐ N , N ′‐bis( o ‐hydroxyphenyl)acetic acid and DMA species are stable during preparative scale IEF, whereas copper–glutathione dissociates considerably. It is also shown that preparative scale IEF can be applied successfully to isolate ferric DMA from real plant s les, and that multidimensional separations are possible by combining preparative scale IEF with subsequent HPLC‐MS analysis. Focusing of free ligands and respective metal complexes with di‐ and trivalent metals results in different p I s, but CIEF is usually needed for a reliable estimation of p I values. Limitations of the proposed methods (preparative IEF and CIEF) and consequences of the results with respect to metal speciation in plants are discussed.
Publisher: Wiley
Date: 10-2007
Abstract: Phytosiderophores (PS) and the closely related substance nicotianamine (NA) are key substances in metal uptake into graminaceous plants. Here, the CE separation of these substances and related metal species is demonstrated. In particular, the three PS 2'-deoxymugineic acid (DMA), mugineic acid (MA), and 3-epi-hydroxymugineic acid (epi-HMA), and NA, are separated using MES/Tris buffer at pH 7.3. Moreover, three Fe(III) species of the different PS are separated without any stability problems, which are often present in chromatographic analyses. Also alent metal species of Cu, Ni, and Zn with the ligands DMA and NA are separated with the same method. By using a special, zwitterionic CE capillary, even the separation of two isomeric Fe(III) chelates with the ligand ethylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid (EDDHA) is possible (i.e., meso-Fe(III)-EDDHA and rac-Fe(III)-EDDHA), and for fast separations of NA and respective alent and trivalent metal species, a polymer CE microchip with suppressed EOF is described. The proposed CE method is applicable to real plant s les, and enables to detect changes of metal species (Cu-DMA, Ni-NA), which are directly correlated to biological processes.
Publisher: Wiley
Date: 24-10-2008
DOI: 10.1002/AJMG.B.30871
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is typically characterized by inattention, excessive motor activity, impulsivity, and distractibility. In iduals with ADHD have significant impairment in family and peer relations, academic functioning, and show high co-morbidity with a wide range of psychiatric disorders including oppositional defiant disorder (ODD), conduct disorder (CD), anxiety disorder, depression, substance abuse, and pervasive developmental disorder (PDD). Family studies suggest that ADHD + CD represents a specific subtype of the ADHD disorder with familial risk factors only partly overlapping with those of ADHD alone. We performed a hypothesis-free analysis of the GAIN-ADHD s le to identify markers and genes important in the development of conduct problems in a European cohort of in iduals with ADHD. Using the Family-Based Association Test (FBAT) package we examined three measures of conduct problems in 1,043,963 autosomal markers. This study is part of a series of exploratory analyses to identify candidate genes that may be important in ADHD and ADHD-related traits, such as conduct problems. We did not find genome-wide statistical significance (P < 5 x 10(-7)) for any of the tested markers and the three conduct problem traits. Fifty-four markers reached strong GWA signals (P < 10(-5)). We discuss these findings in the context of putative candidate genes and the implications of these findings in the understanding of the etiology of ADHD + CD. We aimed to achieve insight into the genetic etiology of a trait using a hypothesis-free study design and were able to identify a number of biologically interesting markers and genes for follow-up studies.
Publisher: Wiley
Date: 19-11-2007
DOI: 10.1002/AJMG.B.30596
Abstract: A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify in idual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006) Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006) Arch Ger Psychiatry 63:462-469] findings in a clinical s le and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006) Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this s le were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed s le failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Wiley
Date: 17-02-2021
DOI: 10.1002/HBM.25364
Abstract: Delineating the association of age and cortical thickness in healthy in iduals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 in iduals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interin idual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association the slope was steeper up to the third decade of life and more gradual thereafter notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interin idual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
Publisher: Wiley
Date: 11-02-2021
DOI: 10.1002/HBM.25320
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small s le sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippoc us and amygdala using magnetic resonance imaging data obtained from 18,605 in iduals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter there was no significant association between age and the volumes of the thalamus, amygdala and the hippoc us (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐in idual variability in the hippoc us and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Wiley
Date: 20-10-2008
DOI: 10.1002/AJMG.B.30872
Publisher: Springer Science and Business Media LLC
Date: 06-03-2008
DOI: 10.1007/S10534-008-9137-8
Abstract: Phytosiderophores (PS) are strong iron chelators, produced by graminaceous plants under iron deficiency. The ability of released PS to chelate iron(III), and subsequent uptake of this chelate into roots by YS1-type transport proteins, are well-known. The mechanism of iron release from the stable chelate inside the plant cell, however, is unclear. One possibility involves the reduction of ferric PS in the presence of an iron(II) chelator via ternary complex formation. Here, the conversion of ferric PS species by ascorbate in the presence of the intracellular ligand nicotianamine (NA) has been investigated at cytosolic pH (pH 7.3), leading to the formation of a ferrous NA chelate. This reaction takes place when supplying Fe(III) as a chelate with 2'-deoxymugineic acid (DMA), mugineic acid (MA), and 3-epi-hydroxymugineic acid (epi-HMA), with the reaction rate decreasing in this order. The progress of the conversion of ferric DMA to ferrous NA was monitored in real-time by high resolution mass spectrometry (FTICR-MS), and the results are complemented by electrochemical measurements (cyclic voltammetry), which allows detecting reactive intermediates and their change with time at high sensitivity. Hence, the combined results of electrochemistry and mass spectrometry indicate an ascorbate-mediated mechanism for the iron release from ferric PS, which highlights the role of ascorbate as a simple, but effective plant reductant.
Publisher: Wiley
Date: 22-03-2021
DOI: 10.1111/JCPP.13396
Abstract: Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small s les. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total s le, to test exhaustively for potential associations of ADHD with structural brain asymmetries. There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls ( t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD ( t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing. Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
Publisher: Wiley
Date: 10-2008
Publisher: Wiley
Date: 28-07-2008
DOI: 10.1002/AJMG.B.30836
Publisher: Wiley
Date: 14-02-2006
DOI: 10.1002/RCM.2402
Abstract: Nano-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (nano-ESI-FTICRMS) was employed for the analysis of the phytosiderophore 2'-deoxymugineic acid (DMA) and the candidate ligand for the intracellular iron transport in plants nicotianamine (NA). Due to the zwitterionic nature of NA and DMA, complementary mass spectra were obtained in positive and negative ionization modes. The technique was also used for speciation of their complexes with Fe(II) and Fe(III), respectively. The species observed at pH 7.3 are the 1:1 Fe-ligand complexes and no evidence for the existence of dimeric complexes was observed. NA and DMA differ only by one mass unit. Consequently, in the system NA + DMA + Fe(II)/Fe(III), there are pairs of iron species (i.e. NA-Fe(II) and DMA-Fe(III)) with the same nominal mass, which differ only by approximately 0.02 mass units. It is shown that high-resolution MS accompanied by accurate mass data analysis allows the unequivocal identification of all four iron species (NA-Fe(II), NA-Fe(III), DMA-Fe(II), DMA-Fe(III)) in one solution without separation. We also addressed the possible alteration of the oxidation state of chelated iron under nano-ESI conditions, but no redox reactions were observed under optimized conditions.
Publisher: American Psychiatric Association Publishing
Date: 08-2013
Publisher: Springer Science and Business Media LLC
Date: 08-2002
Abstract: Attention deficit hyperactivity disorder (ADHD) is a highly heritable and heterogeneous disorder, which usually becomes apparent during the first few years of childhood. Imbalance in dopamine neurotransmission has been suggested as a factor predisposing to ADHD. However, evidence has suggested an interaction between dopamine and serotonin systems in the pathophysiology of the disorder. Studies using selective agonists of the different 5-HT receptors microinjected into selected brain structures have shown a positive modulating effect on the functional activities of the mesotelencephalic dopaminergic system. This suggests that some of the genetic predisposition to ADHD might be due to DNA variation at serotonin system genes. In this study, we investigated polymorphisms in HTR(1B) and HTR(2A) (which encode the serotonin receptors 5-HT(1B) and 5-HT(2A) respectively) in a European ADHD s le. Using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) analyses, we observed significant preferential transmission of the allele 861G of the HTR(1B) in the total s le (for HHRR chi(2) = 7.4, P = 0.0065 and TDT (chi(2) = 6.4, P = 0.014). Analysis of HTR(2A) failed to reveal evidence of association or linkage between the His452Tyr polymorphism and ADHD in the total s le. However, a significantly increased transmission of the allele 452His was observed in the Irish s le alone (chi(2) = 4.9, P = 0.026). These preliminary data suggest an important role for the serotonin system in the development of ADHD. Further studies, preferentially including different ethnic groups are required to substantiate these findings.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.BIOPSYCH.2006.06.029
Abstract: Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.
Publisher: American Medical Association (AMA)
Date: 11-2010
Publisher: Wiley
Date: 08-03-2002
DOI: 10.1002/AJMG.10149
Abstract: Recent family and twin study findings suggest that ADHD when comorbid with conduct problems may represent a particularly familial and heritable form of ADHD. Although several independent groups have shown association between the DRD4 7 repeat allele and ADHD, others have failed to replicate this finding. Previous TDT analyses of UK and Eire s les had also been negative. We set out to further examine the role of DRD4 but selecting a subgroup of children with ADHD and comorbid conduct problems. Families were recruited from Manchester, Ireland, Birmingham and London clinics. From these, 67 children who fulfilled diagnostic criteria for ADHD and who displayed conduct disorder symptoms were selected. TDT analysis, which had previously yielded negative results for the total s le, showed evidence of association between DRD4 and "ADHD with conduct problems" (7 repeat allele-24 transmissions, 13 non-transmissions one-tailed P=0.05). These results provide further support for the role of DRD4 in ADHD. Furthermore, these results when considered together with family and twin study findings, suggest that those children with ADHD and comorbid conduct problems may be particularly informative for molecular genetic studies of ADHD. Further work is needed to examine these phenotype issues.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2008
Abstract: As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13) both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 08-2011
Publisher: Wiley
Date: 24-05-2007
DOI: 10.1002/AJMG.B.30562
Abstract: Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent s les collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. We conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2021
DOI: 10.1186/S12888-021-03070-Z
Abstract: ADHD is neurodevelopmental disorder which persists into adulthood. Presently, therapeutic approaches are mainly pharmacological and psychological whilst the role, scope and approaches of occupational therapists have not been adequately described. In this consensus statement we propose that by assessing specific aspects of a person’s occupation, occupational therapists can deploy their unique skills in providing specialist interventions for adults with ADHD. We also propose a framework with areas where occupational therapists can focus their assessments and give practice ex les of specific interventions. Occupational therapists have much to offer in providing interventions for adults with ADHD. A unified and flexible approach when working with adults with ADHD is most appropriate and further research on occupational therapy interventions is needed.
Publisher: Wiley
Date: 21-12-2009
DOI: 10.1002/AJMG.B.30960
Abstract: We [Hawi et al. (2005) Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new s le comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE s le, the largest of the three-replication s les, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller s les although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.
Location: Germany
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Philip Asherson.