ORCID Profile
0000-0002-6336-0092
Current Organisation
Monash University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: SAGE Publications
Date: 30-07-2016
Abstract: Objective: The aim of the study was to investigate motor performance in children with ADHD using a size-scaling handwriting task. Method: In all, 14 male children with ADHD and 14 typically developing (TD) children (age 7-15) wrote 10-mm and 40-mm cursive letter “ l.” Results: Children with ADHD were unable to maintain their writing accurately at 40 mm, falling short by several millimeters this was not evident in the TD children. Children with ADHD also had slightly faster and more fluent writing than TD children. Conclusion: It was concluded that children with ADHD have difficulties scaling handwriting movement in the larger 40-mm condition that may reflect poor planning and modulation of movement, despite having faster and more fluent movements.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.NEUROSCIENCE.2016.07.013
Abstract: Although there is little overlap in core diagnostic criteria for ADHD and Autism Spectrum Disorder (ASD), ASD symptoms are estimated to co-occur in children with ADHD in 20-50% of cases. As motor control deficits are common to both disorders, we investigated the impact of ASD symptoms on ocular motor control in children with Attention Deficit Hyperactivity Disorder-Combined Type (ADHD-CT), using a cued saccade paradigm sensitive to cerebellar ocular motor impairment in ASD. Basic saccade metrics (latency, velocity and accuracy), trial-to-trial variability, and main sequences relationships (saccade velocity for a given litude) were assessed, for 14 males with ADHD-CT and 14 typically developing (TD) males (aged 8-14, IQ>80). Our results revealed that saccade profiles of the ADHD-CT group showed a pattern of hypermetria and altered main sequence. As the cerebellum is crucially involved in the regulation of saccade parameters, we propose that this pattern of deficit in ADHD-CT is consistent with the widely reported morphological abnormalities in ocular motor vermis (cerebellar lobules VI-VII) in ADHD-CT and ASD.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2015.03.015
Abstract: Within-subject, or intra-in idual, variability in reaction time (RT) is increasingly recognised as an important indicator of the efficiency of attentional control, yet there have been few investigations of the neural correlates of trial-to-trial RT variability in healthy adults. We sought to determine the neural correlates of intra-in idual RT variability during a go/no-go response inhibition task in 27 healthy, male participants. We found that reduced trial-to-trial RT variability (i.e. greater response stability) was significantly associated with greater activation in the left pregenual anterior cingulate. These results support the role of the left anterior cingulate in the dynamic control of attention and efficient response selection. Greater understanding of intra-in idual RT variability and top-down attentional control in healthy adults may help to inform disorders that impact executive/attentional control, such as attention deficit hyperactivity disorder and schizophrenia.
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2018
DOI: 10.1101/437376
Abstract: Psychotic symptoms are proposed lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in non-clinical populations to frank disorder. Here, we investigate neurobiological correlates of this symptomatologic continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in patients and high-risk in iduals, is associated with the severity of subclinical PLEs. A community s le of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis (PCA) estimated major dimensions of PLEs from the questionnaires. PCA dimension scores were then correlated with whole-brain voxelwise functional connectivity (FC) maps of the striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol. PCA identified two dimensions of PLEs accounting for 62.57% of variance in the measures, corresponding to positive and negative PLEs. Reduced FC between the dorsal striatum and prefrontal cortex correlated with higher positive PLEs. Negative PLEs correlated with increased FC between the dorsal striatum and visual and sensorimotor areas. In the ventral corticostriatal system, positive and negative PLEs were both associated with FC between the ventro-rostral putamen and sensorimotor cortices. Consistent with past findings in patients and high-risk in iduals, subthreshold positive symptomatology is associated with reduced FC of the dorsal circuit. These findings suggest that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.JNS.2014.05.057
Abstract: The dentate nucleus (DN) is the major relay station for neural connection between the cerebellum and cerebrum via the thalamus, and is a significant component of the neuropathological profile of Friedreich ataxia (FRDA). We have previously shown that the size of the superior cerebellar peduncle (SCP), which links the DN to cortical and subcortical structures via the thalamus, is significantly reduced in in iduals with FRDA compared to control participants. This study used magnetization transfer imaging (MTI) to examine and contrast the integrity of white matter (WM) in the SCP and the corpus callosum (CC) (control region) in ten in iduals with FRDA and ten controls. In iduals with FRDA demonstrated a significant reduction in the magnetization transfer ratio (MTR) in the SCP compared to control participants. However, there was no significant difference between groups in MTR in the CC. When comparing regions within groups, there was a significant reduction in MTR in the SCP compared to CC in participants with FRDA only. We suggest that the reduction in MTR in the SCP may be indicative of lack of myelin secondary to axonal loss and oligodendroglial dysfunction in WM tracts in in iduals with FRDA.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2016
DOI: 10.1038/MP.2016.117
Abstract: Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.
Publisher: Mary Ann Liebert Inc
Date: 07-2016
Publisher: Informa UK Limited
Date: 15-05-2015
DOI: 10.3109/15622975.2015.1036771
Abstract: Dysregulation in neurotransmitter signalling has been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Polymorphisms of the gene encoding dopamine beta hydroxylase (DBH) have been reported to be associated with ADHD however, small s le sizes have led to inconsistency. We conducted transmission disequilibrium test analysis in 794 nuclear families to examine the relationship between DBH and ADHD. The effects of the ADHD-associated polymorphisms on gene expression were assessed by luciferase reporter assays in a human neuroblastoma cell line, SH-SY5Y. A SNP within the 3' untranslated region of DBH rs129882 showed a significant association with ADHD (χ(2) = 9.71, p = 0.0018, OR = 1.37). This association remained significant after Bonferroni correction for multiple testing (p = 0.02). Further, allelic variation in rs129882 significantly impacted luciferase expression. Specifically, the C allele of the ADHD-associated rs129882 SNP produced a 2-fold decrease (p < 0.001) in luciferase activity. These data demonstrate for the first time that a DBH gene variant, rs129882, which confers risk to ADHD is also associated with reduced in vitro gene expression. Reduced DBH expression would be consistent with decreased conversion of dopamine to noradrenaline and thus with a relative hypo-noradrenergic state in ADHD.
Publisher: Informa UK Limited
Date: 20-08-2018
DOI: 10.1080/87565641.2018.1504948
Abstract: The primary aim of this study was to kinematically assess how children with autism spectrum disorder (ASD) plan and control their handwriting actions. Forty-three boys aged between 8 to 12 years were included in the present analysis 23 with ASD and 20 typically developing (TD) controls. Sophisticated objective and quantifiable assessment of movement metrics and dynamics was applied across a series of basic cursive handwriting sequences. Children with ASD demonstrated atypical control of handwriting metrics and dynamics, as well as significantly greater neuromotor noise relative to age-matched peers. They also engaged in less regular monitoring and regulation of their movement during the handwriting task. This study provides new insights into the way children with ASD plan and sequence their handwriting movements. Overall, results revealed that even at a basic level, children with ASD appear to have a breakdown in their ability to control and regulate their handwriting movements. This has important implications for the school-aged child who constantly engages in handwriting tasks within the classroom environment and provides insight into possible directions for future intervention.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2018
DOI: 10.1038/S41398-018-0329-X
Abstract: It is well-established that there is a strong genetic contribution to the aetiology of attention deficit hyperactivity disorder (ADHD). Here, we employed a hypothesis-free genome-wide association study (GWAS) design in a s le of 480 clinical childhood ADHD cases and 1208 controls to search for novel genetic risk loci for ADHD. DNA was genotyped using Illumina’s Human Infinium PsychArray-24v1.2., and the data were subsequently imputed to the 1000 Genomes reference panel. Rigorous quality control and pruning of genotypes at both in idual subject and single nucleotide polymorphism (SNP) levels was performed. Polygenic risk score (PGRS) analysis revealed that ADHD case–control status was explained by genetic risk for ADHD, but no other major psychiatric disorders. Logistic regression analysis was performed genome-wide to test the association between SNPs and ADHD case–control status. We observed a genome-wide significant association ( p = 3.15E−08) between ADHD and rs6686722, mapped to the Tenascin R ( TNR ) gene. Members of this gene family are extracellular matrix glycoproteins that play a role in neural cell adhesion and neurite outgrowth. Suggestive evidence of associations with ADHD was observed for an additional 111 SNPs (⩽9.91E−05). Although intriguing, the association between DNA variation in the TNR gene and ADHD should be viewed as preliminary given the small s le size of this discovery dataset.
Publisher: SAGE Publications
Date: 22-05-2014
Abstract: Objective: Children with ADHD–combined type (ADHD-CT) display fine and gross motor problems, often expressed as handwriting difficulties. This study aimed to kinematically characterize the handwriting of children with ADHD using a cursive letter l’s task. Method: In all, 28 boys (7-12 years), 14 ADHD-CT and 14 typically developing (TD), without developmental coordination disorder (DCD) or comorbid autism, wrote a series of four cursive letter l’s using a graphics tablet and stylus. Results: Children with ADHD-CT had more inconsistent writing size than did TD controls. In addition, ADHD-CT symptom severity, specifically inattention, predicted poorer handwriting outcomes. Conclusion: In a s le of children with ADHD-CT who do not have DCD or autism, subtle handwriting differences were evident. It was concluded that handwriting might be impaired in children with ADHD in a manner dependent on symptom severity. This may reflect reports of underlying motor impairment in ADHD.
Publisher: Frontiers Media SA
Date: 27-06-2022
DOI: 10.3389/FPSYT.2022.914668
Abstract: Attention deficit hyperactivity disorder (ADHD) frequently co-occurs with other neurodevelopmental diagnoses, such as autism spectrum disorder (autism), which can make clinical decision making around symptom management challenging for clinicians. There is a paucity of research examining pharmacotherapeutic management of children who have ADHD with co-occurring diagnoses. We aimed to report on the co-occurring diagnoses and symptom profile of children, and report on medication use, stratified by ADHD, autism and ADHD + autism diagnoses. Caregivers of 505 children (2–18 years) with ADHD ( n = 239), autism ( n = 117), and co-occurring ADHD + autism ( n = 149) completed a questionnaire on current medication use and clinical rating scales about their child's symptoms, as part of a broader project investigating diagnosis and management of symptoms in children with ADHD or autism. The parents of the ADHD group reported a higher proportion of their children had learning disorders (17.15%) and speech and language disorders (4.60%) compared to the parents of the autism and ADHD + autism groups. Parents of the ADHD + autism group reported higher proportions of intellectual disability (5.37%), oppositional defiant disorder (20.13%), anxiety (38.93%), depression (6.71%) and genetic conditions (3.36%) in their children, in comparison to the parents of the ADHD and autism groups. Children with ADHD were reported to be taking a higher proportion of psychotropic medication (90%), followed by ADHD + autism (86%) and autism (39%). The parents of children with ADHD + autism reported a higher proportion of non-stimulant ADHD medication (25.5%), antipsychotic (18.79%), antidepressant (22.15%) and melatonin (31.54%) use by their children, compared to the parents of the ADHD and autism groups. A similar proportion of children with ADHD + autism and ADHD were reported to be taking medication. However, the types of medication taken were different, as expected with reported co-occurring diagnoses. The complexity of symptoms and diagnoses in ADHD + autism warrants targeted research to optimize management and therapeutic outcomes.
Publisher: Wiley
Date: 18-09-2018
DOI: 10.1002/AJMG.B.32592
Abstract: Converging evidence from candidate gene, genome-wide linkage, and association studies support a role of cadherins in the pathophysiology of five major psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). These molecules are transmembrane proteins which act as cell adhesives by forming adherens junctions (AJs) to bind cells within tissues. Members of the cadherin superfamily are also involved in biological processes such as signal transduction and plasticity that have been implicated in the etiology of major psychiatric conditions. Although there are over 110 genes mapped to the cadherin superfamily, our literature survey showed that evidence of association with psychiatric disorders is strongest for CDH7, CHD11, and CDH13. Gene enrichment analysis showed that those cadherin genes implicated in psychiatric disorders were overrepresented in biological processes such as in cell-cell adhesion (GO:0007156 & GO:0098742) and adherens junction organization (GO:0034332). Further, cadherin genes were also mapped to processes that have been linked to the development of psychiatric disorders such as nervous system development (GO:0007399). To further understand the role of cadherin SNPs implicated in psychiatric disorders, we utilized an in silico computational pipeline to functionally annotate associated variants. This analysis yielded eight variants mapped to PCDH1-13, CDH7, CDH11, and CDH13 that are predicted to be biologically functional. Functional genomic evaluation is now required to understand the molecular mechanism by which these variants might confer susceptibility to psychiatric disorders.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 05-2017
Publisher: Elsevier BV
Date: 03-2015
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.NEUROSCIENCE.2013.03.051
Abstract: Autism and Asperger's disorder (AD) are neurodevelopmental disorders primarily characterized by deficits in social interaction and communication, however motor coordination deficits are increasingly recognized as a prevalent feature of these conditions. Although it has been proposed that children with autism and AD may have difficulty utilizing visual feedback during motor learning tasks, this has not been directly examined. Significantly, changes within the cerebellum, which is implicated in motor learning, are known to be more pronounced in autism compared to AD. We used the classic double-step saccade adaptation paradigm, known to depend on cerebellar integrity, to investigate differences in motor learning and the use of visual feedback in children aged 9-14 years with high-functioning autism (HFA IQ>80 n=10) and AD (n=13). Performance was compared to age and IQ matched typically developing children (n=12). Both HFA and AD groups successfully adapted the gain of their saccades in response to perceived visual error, however the time course for adaptation was prolonged in the HFA group. While a shift in saccade dynamics typically occurs during adaptation, we revealed aberrant changes in both HFA and AD groups. This study contributes to a growing body of evidence centrally implicating the cerebellum in ocular motor dysfunction in autism. Specifically, these findings collectively imply functional impairment of the cerebellar network and its inflow and outflow tracts that underpin saccade adaptation, with greater disturbance in HFA compared to AD.
Publisher: Cold Spring Harbor Laboratory
Date: 22-06-2020
DOI: 10.1101/2020.06.21.163915
Abstract: Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.NEUBIOREV.2016.08.007
Abstract: There has been considerable focus placed on how in iduals with autism spectrum disorder (ASD) visually perceive and attend to social information, such as facial expressions or social gaze. The role of eye movements is inextricable from visual perception, however this aspect is often overlooked. We performed a series of meta-analyses based on data from 28 studies of eye movements in ASD to determine whether there is evidence for ocular motor dysfunction in ASD. Tasks assessed included visually-guided saccade tasks, gap/overlap, anti-saccade, pursuit tasks and ocular fixation. These analyses revealed evidence for ocular motor dysfunction in ASD, specifically relating to saccade dysmetria, difficulty inhibiting saccades and impaired tracking of moving targets. However there was no evidence for deficits relating to initiating eye movements, or engaging and disengaging from simple visual targets. Characterizing ocular motor abnormalities in ASD may provide insight into the functional integrity of brain networks in ASD across development, and assist our understanding of visual and social attention in ASD.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2016
DOI: 10.1038/MP.2016.2
Abstract: Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition with negative lifetime outcomes. Uncovering its genetic architecture should yield important insights into the neurobiology of ADHD and assist development of novel treatment strategies. Twenty years of candidate gene investigations and more recently genome-wide association studies have identified an array of potential association signals. In this context, separating the likely true from false associations ('the wheat' from 'the chaff') will be crucial for uncovering the functional biology of ADHD. Here, we defined a set of 2070 DNA variants that showed evidence of association with ADHD (or were in linkage disequilibrium). More than 97% of these variants were noncoding, and were prioritised for further exploration using two tools-genome-wide annotation of variants (GWAVA) and Combined Annotation-Dependent Depletion (CADD)-that were recently developed to rank variants based upon their likely pathogenicity. Capitalising on recent efforts such as the Encyclopaedia of DNA Elements and US National Institutes of Health Roadmap Epigenomics Projects to improve understanding of the noncoding genome, we subsequently identified 65 variants to which we assigned functional annotations, based upon their likely impact on alternative splicing, transcription factor binding and translational regulation. We propose that these 65 variants, which possess not only a high likelihood of pathogenicity but also readily testable functional hypotheses, represent a tractable shortlist for future experimental validation in ADHD. Taken together, this study brings into sharp focus the likely relevance of noncoding variants for the genetic risk associated with ADHD, and more broadly suggests a bioinformatics approach that should be relevant to other psychiatric disorders.
Publisher: Frontiers Media SA
Date: 18-12-2015
Publisher: BMJ
Date: 06-12-2012
Publisher: Elsevier BV
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 12-01-2017
DOI: 10.1007/S10803-016-3019-7
Abstract: Handwriting is commonly identified as an area of weakness in children with autism spectrum disorder (ASD), but precise deficits have not been fully characterised. Boys with ASD (n = 23) and matched controls (n = 20) aged 8-12 years completed a simple, digitised task to objectively assess handwriting performance using advanced descriptive measures. Moderate to large associations were identified between handwriting performance and attention, ASD symptoms and motor proficiency. The ASD group demonstrated significantly less smooth movements and significantly greater sizing variability and peak velocity relative to controls. These findings provide a clearer indication of the specific nature of handwriting impairments in children with ASD, and suggest a relationship with core clinical symptom severity, attention and motor behaviours.
Publisher: Frontiers Media SA
Date: 2012
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.RIDD.2013.06.003
Abstract: It has been consistently reported that children with autism spectrum disorders (ASD) show considerable handwriting difficulties, specifically relating to accurate and consistent letter formation, and maintaining appropriate letter size. The aim of this study was to investigate the underlying factors that contribute to these difficulties, specifically relating to motor control. We examined the integrity of fundamental handwriting movements and contributions of neuromotor noise in 26 children with ASD aged 8-13 years (IQ>75), and 17 typically developing controls. Children wrote a series of four cursive letter l's using a graphics tablet and stylus. Children with ASD had significantly larger stroke height and width, more variable movement trajectory, and higher movement velocities. The absolute level of neuromotor noise in the velocity profiles, as measured by power spectral density analysis, was significantly higher in children with ASD relatively higher neuromotor noise was found in bands >3 Hz. Our findings suggest that significant instability of fundamental handwriting movements, in combination with atypical biomechanical strategies, contribute to larger and less consistent handwriting in children with ASD.
Publisher: Springer Science and Business Media LLC
Date: 09-07-2021
DOI: 10.1038/S41467-021-24306-2
Abstract: Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2015
DOI: 10.1038/MP.2014.183
Abstract: Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition which affects 2-10% of school age children worldwide. Although the underlying molecular mechanism for the disorder is poorly understood, familial, twin and adoption studies suggest a strong genetic component. Here we provide a state-of-the-art review of the molecular genetics of ADHD incorporating evidence from candidate gene and linkage designs, as well as genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs) and rare copy number variations (CNVs). Bioinformatic methods such as functional enrichment analysis and protein-protein network analysis are used to highlight biological processes of likely relevance to the aetiology of ADHD. Candidate gene associations of minor effect size have been replicated across a number of genes including SLC6A3, DRD5, DRD4, SLC6A4, LPHN3, SNAP-25, HTR1B, NOS1 and GIT1. Although case-control SNP-GWAS have had limited success in identifying common genetic variants for ADHD that surpass critical significance thresholds, quantitative trait designs suggest promising associations with Cadherin13 and glucose-fructose oxidoreductase domain 1 genes. Further, CNVs mapped to glutamate receptor genes (GRM1, GRM5, GRM7 and GRM8) have been implicated in the aetiology of the disorder and overlap with bioinformatic predictions based on ADHD GWAS SNP data regarding enriched pathways. Although increases in s le size across multi-center cohorts will likely yield important new results, we advocate that this must occur in parallel with a shift away from categorical case-control approaches that view ADHD as a unitary construct, towards dimensional approaches that incorporate endophenotypes and statistical classification methods.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2018
DOI: 10.1038/S41398-018-0262-Z
Abstract: Intra-in idual response time variability (IIRTV) is proposed as a viable endophenotype for many psychiatric disorders, particularly attention-deficit hyperactivity disorder (ADHD). Here we assessed whether IIRTV was associated with common DNA variation genome-wide and whether IIRTV mediated the relationship between any associated loci and self-reported ADHD symptoms. A final data set from 857 Australian young adults (489 females and 368 males M age = 22.14 years, SD age = 4.82 years) who completed five response time tasks and self-reported symptoms of ADHD using the Conners’ Adult ADHD Rating Scale was used. Principal components analysis (PCA) on these response time measures (standard deviation of reaction times and the intra-in idual coefficient of variation) produced two variability factors (labelled response selection and selective attention). To understand the genetic drivers of IIRTV we performed a genome-wide association analysis (GWAS) on these PCA-derived indices of IIRTV. For the selective attention variability factor, we identified one single-nucleotide polymorphism (SNP) attaining genome-wide significance rs62182100 in the HDAC4 gene located on chromosome 2q37. A bootstrapping mediation analysis demonstrated that the selective attention variability factor mediated the relationship between rs62182100 and self-reported ADHD symptoms. Our findings provide the first evidence of a genome-wide significant SNP association with IIRTV and support the potential utility of IIRTV as a valid endophenotype for ADHD symptoms. However, limitations of this study suggest that these observations should be interpreted with caution until replication s les become available.
Publisher: CRC Press
Date: 25-09-2017
Publisher: Wiley
Date: 05-02-2015
DOI: 10.1002/AJMG.B.32283
Abstract: Previous genetic studies have postulated that attention deficit hyperactivity disorder (ADHD) should be regarded as the extreme end of a set of behavioural traits that can be continuously measured in the general population. The current study adopted a quantitative trait approach to examine the relationship between dopamine gene variants and self-reported ADHD symptoms in 517 nonclinical adults. Although genetic associations with variants of both the dopamine transporter (DAT1 SLC6A3) and D4 receptor (DRD4) genes have been reliably reported in children, results in adults are less consistent. We probed two potentially functional variable number of tandem repeat (VNTR) polymorphisms in the 3'UTR and intron 8 of DAT1, the 10-repeat and 6-repeat alleles of which respectively form a haplotype (10/6 DAT1 haplotype) that is associated with childhood ADHD. We also genotyped the exon 3 VNTR of DRD4, the 7-repeat allele of which is also an established risk factor for childhood ADHD. Permutation analysis showed an influence of the 10/6 DAT1 haplotype on both CAARS-G and CAARS-H (DSM-IV ADHD Symptoms Total and ADHD Index respectively), such that ADHD symptom scores increased with each additional copy of the 10/6 DAT1 haplotype. This result survived corrections for multiple comparisons both at the level of genotype and phenotype. A nominal association with CAARS-G was also found for the 7-repeat allele of the DRD4 VNTR however this did not survive multiple comparison correction. Our results provide further support for the influence of variation in the 10/6 DAT1 haplotype and in idual differences in ADHD symptoms in adults.
Publisher: Mary Ann Liebert Inc
Date: 06-2022
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental conditions among school-age children. Early intervention and ongoing evaluation of treatment effectiveness are essential to minimize the life-long negative impact of ADHD. Neurocognitive functions have been reported to improve with pharmacological and cognitive training interventions for children with ADHD. We evaluated the value of measuring change in neurocognitive functions following ADHD interventions as a treatment outcome. We systematically reviewed randomized control trials of two distinctive types of ADHD interventions-pharmacological treatments and cognitive training-and summarized the changes in neurocognitive and clinical outcomes using a series of meta-analyses. Both pharmacological and cognitive training interventions showed positive effects on some aspects of neurocognitive functions. However, there were no significant correlations between changes in neurocognitive function (e.g., inhibition) and changes in ADHD behavioral symptoms (e.g., impulsive behavior). Although the associations between changes in neurocognitive function and clinical outcomes are not well studied, based on current findings, it is not suitable to use change in neurocognitive outcomes as a proxy for change in ADHD clinical symptom-based outcomes. There is, however, notable value in monitoring changes in neurocognitive function associated with ADHD interventions to achieve the following aims: (1) understanding full treatment effect on children with ADHD, (2) identifying ancillary indicators of subclinical changes, and (3) provision of objective and less biased measures of treatment effects. These findings are important evidence that changes in neurocognitive function could be a co-occurring objective indication that parallels the clinical effects of ADHD treatments.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.BIOPSYCH.2019.02.013
Abstract: Psychotic symptoms are proposed to lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in nonclinical populations to frank disorder. Here, we investigated the neurobiological correlates of this continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in psychosis patients and in iduals at high risk for psychosis, is associated with the severity of subclinical PLEs. A community s le of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis of 12 subscales taken from seven questionnaires was used to estimate major dimensions of PLEs. Dimension scores from principal component analysis were then correlated with whole-brain voxelwise functional connectivity maps of the dorsal striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol. Principal component analysis identified two dimensions of PLEs that accounted for 62.57% of variance in the measures, corresponding to positive (i.e., subthreshold delusions and hallucinations) and negative (i.e., subthreshold social and physical anhedonia) symptom-like PLEs. Reduced functional connectivity between the dorsal striatum and prefrontal and motor cortices correlated with more severe positive PLEs. Increased functional connectivity between the dorsal striatum and motor cortex was associated with more severe negative PLEs. Consistent with past findings in patients and in iduals at high risk for psychosis, subthreshold positive symptomatology is associated with reduced functional connectivity of the dorsal circuit. This finding suggests that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1007/S10803-021-05091-9
Abstract: Parents of children with ASD who had attended an Australian emergency department (ED n = 421) completed a questionnaire relating to their experiences in the ED, including (1) child's reason for presentation and existing comorbidities, (2) quality of care during the visit (3) child's behaviour during visit, e.g. sensory responses to the ED environment, and disruptive behaviours. Children with comorbid ASD and intellectual disability were more likely to present with gastrointestinal issues and seizures, while those with comorbid ASD and oppositional defiant disorder were more likely to present with self-injury. ED staff awareness of ASD-related issues, including communication and expression of pain, were common difficulties for parents. The ED environment (e.g. lights, sounds, waiting areas), exacerbated child anxiety and led to disruptive behaviour.
Publisher: Society for Neuroscience
Date: 19-11-2014
DOI: 10.1523/JNEUROSCI.2327-14.2014
Abstract: Although lateral asymmetries in orienting behavior are evident across species and have been linked to interhemispheric asymmetries in dopamine signaling, the relative contribution of attentional versus motoric processes remains unclear. Here we took a cognitive genetic approach to adjudicate between roles for dopamine in attentional versus response selection. A s le of nonclinical adult humans ( N = 518) performed three cognitive tasks (spatial attentional competition, spatial cueing, and flanker tasks) that varied in the degree to which they required participants to resolve attentional or response competition. All participants were genotyped for two putatively functional tandem repeat polymorphisms of the dopamine transporter gene (DAT1 SLC6A3 ), which are argued to influence the level of available synaptic dopamine and confer risk to disorders of inattention. DAT1 genotype modulated the task-specific effects of the various task-irrelevant stimuli across both the spatial competition and spatial cueing but not flanker tasks. Specifically, compared with in iduals carrying one or two copies of the 10-repeat DAT1 allele, in iduals without this allele demonstrated an immunity to distraction, such that response times were unaffected by increases in the number of distractor stimuli, particularly when these were presented predominantly in the left hemifield. All three genotype groups exhibited uniform costs of resolving leftward response selection in a standard flanker task. None of these significant effects could be explained by speed–accuracy trade-offs, suggesting that participants without the 10-repeat allele of the DAT1 tandem repeat polymorphism possess an enhanced attentional ability to suppress task-irrelevant stimuli in the left hemifield.
Publisher: Informa UK Limited
Date: 20-01-2018
DOI: 10.1080/15622975.2016.1273549
Abstract: Previous studies have postulated that noradrenergic and/or dopaminergic gene variations are likely to underlie in idual differences in impulsiveness, however, few have shown this. The current study examined the relationship between catecholamine gene variants and self-reported impulsivity, as measured by the Barratt Impulsiveness Scale (Version 11 BIS-11) Methods: Six hundred and seventy-seven non-clinical adults completed the Barratt Impulsiveness Scale (BIS-11). DNA was analysed for a set of 142 single-nucleotide polymorphisms (SNPs) across 20 autosomal catecholamine genes. Association was tested using an additive regression model with permutation testing used to control for the influence of multiple comparison. Analysis revealed an influence of rs4245146 of the dopamine D2 receptor (DRD2) gene on the BIS-11 attention first-order factor, such that self-reported attentional impulsiveness increased in an additive fashion with each copy of the T allele. These findings provide preliminary evidence that allelic variation in DRD2 may influence impulsiveness by increasing the propensity for attentional lapses.
Publisher: Research Square Platform LLC
Date: 18-02-2021
DOI: 10.21203/RS.3.RS-207275/V1
Abstract: Background ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has h ered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD Genetics and Neurodevelopment (MAGNET) Project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET Project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. Methods The MAGNET Project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. Conclusion The MAGNET Project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2021
DOI: 10.1186/S13229-021-00457-3
Abstract: ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has h ered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures.
Start Date: 2014
End Date: 2014
Funder: University of Southern California
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2020
End Date: 2024
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2019
Funder: Monash University
View Funded ActivityStart Date: 2015
End Date: 2020
Funder: National Health and Medical Research Council
View Funded Activity