@article{pmid42698352,

title = {Comprehensive Treatment and Monthly 2 Year Follow-Up in Children With ADHD: Randomized Controlled Prospective Study},

author = {Lily Hechtman and Natalie Grizenko and Ridha Joober and Jens Kreitewolf and Mariam Ter-Stepanian and Marie-Ève Fortier and Kayla Eisenberg and Joy Etcovitch and William J Harvey},

doi = {10.1177/10870547261478344},

issn = {1557-1246},

year  = {2026},

date = {2026-11-01},

journal = {J Atten Disord},

volume = {30},

number = {11},

pages = {1438--1451},

abstract = {ObjectivesTo evaluate the efficacy of regular monthly follow up in maintaining treatment gains versus follow up as needed in the community for children ages 6 to 12 years with ADHD.MethodsOne hundred and eighty six children, age 6 to 13 with DSM-IV diagnosed Attention Deficit Hyperactivity Disorder (ADHD) (combined presentation) received 3 months of comprehensive treatment which included long-acting stimulant medication titrated to optimal dose (via parent and teacher reports) and weekly parent training groups and child social skills and academic training. After the 3 months of treatment, children were randomized to either monthly follow up by the research team (treatment group) or follow up as usual in the community (control group). Comprehensive evaluations occurred at 3 months at the end of the comprehensive treatment, and at 6, 12, 18, and 24 month follow-up.ResultsChildren in both groups improved significantly in all domains after the 3 months of intensive comprehensive treatment. Treatment gains were maintained during the 2 year follow up period in both groups. However, the Hyperactive/Impulsive rating in Conners scale by parent report and some teacher reports were worse in the community group during the follow-up period.ConclusionThe importance of the initial intensive comprehensive 3 month treatment cannot be underestimated as these treatments resulted in significant improvements which were maintained for 2 years in both groups. Factors such as social economic status and available community treatment which may have influenced these results are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41417862,

title = {Top ten priorities identified by healthcare professionals to support the clinical care of individuals with attention-deficit/hyperactivity disorder: A Canadian Delphi study},

author = {Ariana Walji and Debra A Butt and Emma A Climie and Penny Corkum and Lily Hechtman and Anne-Claude V Bedard and Yuanyuan Jiang and Natalie Grizenko and Stacey D Espinet and Carlin J Miller and Maria A Rogers and Maggie E Toplak and Brandy L Callahan},

doi = {10.1371/journal.pone.0339378},

issn = {1932-6203},

year  = {2025},

date = {2025-01-01},

journal = {PLoS One},

volume = {20},

number = {12},

pages = {e0339378},

abstract = {BACKGROUND: Limited research exists on key issues that healthcare professionals perceive as important for optimizing Attention-Deficit/Hyperactivity Disorder (ADHD) care. This study identified the top ten priorities that healthcare professionals consider vital to support ADHD care in Canada.nnMETHODS: A three-round online Delphi study was conducted using electronic surveys from 2022-2024 across Canada. In Round 1, healthcare professionals were asked to rate 21 predetermined items using a 5-point Likert scale and re-evaluated those rankings in Round 2. In Round 2, a new set of 34 items identified from Round 1 were rated and the rankings re-evaluated in Round 3. Consensus was determined by percentage agreement ≥ 90% with a Likert score ≥ 4. For each priority item, the mean Likert score, standard deviation, 95% confidence interval (CI), and the minimum and maximum Likert scores were calculated.nnRESULTS: 96 Canadian healthcare professionals completed Round 1. 82 (85% response rate) completed Round 2 and 73 (89% response rate) completed Round 3. The two highest ranked priorities that achieved 100% consensus agreement were: providing access to well-trained healthcare providers in ADHD (mean score 4.74, 95% CI 4.65-4.84) and access to ADHD-related services (mean score 4.50, 95% CI 4.39-4.61). Among the top ten consensus-derived items, the highest frequency pertained to providing access to healthcare experts in ADHD and related-services (50%) followed by research into ADHD on socio-emotional functioning, co-existing conditions and in diagnosing ADHD in females (30%). Increasing knowledge and educating healthcare professionals and school systems on ADHD was also identified among the top ten priorities (20%).nnCONCLUSIONS: Healthcare professionals identified ten top priorities by consensus where most focused on providing access to trained healthcare providers and services to support ADHD care in Canada. Implementing strategies to improve access on a national level will improve the quality of life for individuals living with ADHD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38367455,

title = {Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder},

author = {Nellie H Fotopoulos and Boris Chaumette and Gabriel A Devenyi and Sherif Karama and Mallar Chakravarty and Aurelie Labbe and Natalie Grizenko and Norbert Schmitz and Weam Fageera and Ridha Joober},

doi = {10.1016/j.psychres.2024.115791},

issn = {1872-7123},

year  = {2024},

date = {2024-04-01},

journal = {Psychiatry Res},

volume = {334},

pages = {115791},

abstract = {Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37857414,

title = {Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD},

author = {Boris Chaumette and Natalie Grizenko and Weam Fageera and Marie-Ève Fortier and Marina Ter-Stepanian and Aurelie Labbe and Ridha Joober},

doi = {10.1503/jpn.230062},

issn = {1488-2434},

year  = {2023},

date = {2023-01-01},

journal = {J Psychiatry Neurosci},

volume = {48},

number = {5},

pages = {E390--E399},

abstract = {BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD.nnMETHODS: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively.nnRESULTS: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in  were positively correlated with the CBCL scores, and DNA methylation in  correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in  correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of  methylation levels with the CBCL score.nnLIMITATIONS: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models.nnCONCLUSION: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36075963,

title = {The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder},

author = {Sami Ben Hamida and Sarojini M Sengupta and Ellie Clarke and Michael McNicholas and Eleonora Moroncini and Emmanuel Darcq and Marina Ter-Stepanian and Marie-Ève Fortier and Natalie Grizenko and Ridha Joober and Brigitte L Kieffer},

doi = {10.1038/s41380-022-01738-w},

issn = {1476-5578},

year  = {2022},

date = {2022-11-01},

journal = {Mol Psychiatry},

volume = {27},

number = {11},

pages = {4662--4672},

abstract = {The neural orphan G protein coupled receptor GPR88 is predominant in the striatum and cortex of both rodents and humans, and considered a potential target for brain disorders. Previous studies have shown multiple behavioral phenotypes in Gpr88 knockout mice, and human genetic studies have reported association with psychosis. Here we tested the possibility that GPR88 contributes to Attention Deficit Hyperactivity Disorder (ADHD). In the mouse, we tested Gpr88 knockout mice in three behavioral paradigms, best translatable between rodents and humans, and found higher motor impulsivity and reduced attention together with the reported hyperactivity. Atomoxetine, a typical ADHD drug, reduced impulsivity in mutant mice. Conditional Gpr88 knockout mice in either D1R-type or D2R-type medium spiny neurons revealed distinct implications of the two receptor populations in waiting and stopping impulsivity. Thus, animal data demonstrate that deficient GPR88 activity causally promotes ADHD-like behaviors, and identify circuit mechanisms underlying GPR88-regulated impulsivity. In humans, we performed a family-based genetic study including 567 nuclear families with DSM-IV diagnosis of ADHD. There was a minor association for SNP rs2036212 with diagnosis, treatment response and cognition. A stronger association was found for SNP rs2809817 upon patient stratification, suggesting that the T allele is a risk factor when prenatal stress is involved. Human data therefore identify GPR88 variants associated with the disease, and highlight a potential role of life trajectories to modulate GPR88 function. Overall, animal and human data concur to suggest that GPR88 signaling should be considered a key factor for diagnostic and treatment of ADHD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32564645,

title = { by  Epistatic Interaction in Modulating Behaviors in Children with ADHD: A Pharmaco-Dynamic Behavioral Approach},

author = {Weam Fageera and Natalie Grizenko and Sarojini M Sengupta and Norbert Schmitz and Ridha Joober},

doi = {10.1177/1087054720934191},

issn = {1557-1246},

year  = {2021},

date = {2021-10-01},

journal = {J Atten Disord},

volume = {25},

number = {12},

pages = {1720--1730},

abstract = {OBJECTIVE: Examining the joint effect of two functional variants in two dopamine-related genes ( and ) on ADHD-relevant behaviors under three experimental conditions (EC).nnMETHOD: 362 children with ADHD were assessed by parents and teachers during a week of baseline evaluation, followed by 1 week of MPH and placebo, administered in a double-blind crossover design.nnRESULTS: Statistically significant 3-way (-by--by-EC;  = .004) and 2-way interactions ( by EC;  = .002) were observed on Conners'-Teachers scores. Children with the  Met/Met genotype had lower scores at baseline and on placebo compared to the other genotype groups. Furthermore, stratifying the children according to their  genotypes helped to detect statistically significant and biologically meaningful effects of  genotype.nnCONCLUSIONS: These findings suggest that  and  genetic variants may together play a role in ADHD symptomatology and response to treatment through gene-gene interaction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33677046,

title = {Sex-dependent complex association of TPH2 with multiple dimensions of ADHD},

author = {Weam Fageera and Sarojini M Sengupta and Marie-Ève Fortier and Natalie Grizenko and Svetlana Babienco and Aurelie Labbe and Ridha Joober},

doi = {10.1016/j.pnpbp.2021.110296},

issn = {1878-4216},

year  = {2021},

date = {2021-08-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {110},

pages = {110296},

abstract = {BACKGROUND: Tryptophan hydroxylase 2 (TPH2) is a key enzyme in the biosynthesis of serotonin in the brain. This study aims to investigate the role of a functional variant in TPH2 (rs17110747) in the pathophysiology of ADHD. This variant has been implicated in mood disorders in recent meta-analysis. This study uses a comprehensive approach that combines association testing and pharmaco-dynamic evaluation of behaviour, in a large sample of children with ADHD (n = 570).nnMETHODS: The association between various ADHD relevant traits and rs17110747 was analyzed using family-based association tests (FBAT). Children were assessed by parents, teachers and research staff under three experimental conditions (EC): baseline, placebo, and methylphenidate using a double-blind placebo-controlled crossover trial.nnOUTCOMES: FBAT analysis conducted in a sample stratified based on sex of the proband, showed that there was a highly significant overtransmission of the G allele from parents to affected girls. In addition, significant association with several behavioral and cognitive dimensions of ADHD was observed only when the proband was female. Further, girls with the G/G genotype (rs17110747) had greater response to placebo when evaluated by parents.nnINTERPRETATION: These results suggest that there may be a complex association of TPH2 in the etiology of ADHD, with a sex-specific effect.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33453563,

title = {Association between COMT methylation and response to treatment in children with ADHD},

author = {Weam Fageera and Boris Chaumette and Marie-Ève Fortier and Natalie Grizenko and Aurelie Labbe and Sarojini M Sengupta and Ridha Joober},

doi = {10.1016/j.jpsychires.2021.01.008},

issn = {1879-1379},

year  = {2021},

date = {2021-03-01},

journal = {J Psychiatr Res},

volume = {135},

pages = {86--93},

abstract = {BACKGROUND: COMT had been considered a promising candidate gene in pharmacogenetic studies in ADHD; yet the findings from these studies have been inconsistent. Part of these inconsistencies could be related to epigenetic mechanisms (including DNA methylation). Here we investigated the role of genetic variants of the COMT gene on the methylation levels of CpG sites in the same gene and explored the effect of methylation on methylphenidate (MPH) and placebo (PBO) response in children with ADHD.nnMETHODS: Two hundred and thirty children with ADHD (6-12 years) participated in a randomized, double-blind, placebo-controlled crossover trial with MPH. Univariate analysis was performed to examine the associations between genotypes in the COMT gene and DNA methylation in the same genetic loci. Association between the DNA methylation of 11 CpG sites and PBO/MPH responses were then assessed using spearman's correlation analysis in 212 children. Multiple linear regression analyses were performed to test the interaction between these factors while accounting for sex.nnRESULTS: Associations were observed between specific genetic variants and methylation level of cg20709110. Homozygous genotypes of GG (rs6269), CC (rs4633), GG (rs4818), Val/Val (rs4680) and the haplotype (ACCVal/GCGVal) were significantly associated with higher level of methylation. This CpG showed a significant correlation with placebo response (r = -0.15, P = 0.045) according to the teachers' evaluation, and a close-to significance correlation with response to MPH according to parents' evaluation (r = -0.134, p = 0.051). Regression analysis showed that in the model including rs4818, sex and DNA methylation of cg20709110 contributed significantly to treatment response.nnCONCLUSIONS: These preliminary results could provide evidence for the effect of genetic variations on methylation level and the involvement of the epigenetic variation of COMT loci in modulating the response to treatment in ADHD.nnTRIAL REGISTRATION: clinicaltrials.gov, number NCT00483106.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34015673,

title = {Cumulative exposure to ADHD medication is inversely related to hippocampus subregional volume in children},

author = {Nellie H Fotopoulos and Gabriel A Devenyi and Stephanie Guay and Sarojini M Sengupta and M Mallar Chakravarty and Natalie Grizenko and Sherif Karama and Ridha Joober},

doi = {10.1016/j.nicl.2021.102695},

issn = {2213-1582},

year  = {2021},

date = {2021-01-01},

journal = {Neuroimage Clin},

volume = {31},

pages = {102695},

abstract = {BACKGROUND: Although there is some evidence for a normalization of brain structure following exposure to ADHD medication, literature on the effects of duration and dose of continued use on the brain is scarce. Here, we investigated the association between cumulative exposure to medication (range 1 week to 4.69 years) and cortical structures and subcortical volumes in a clinical sample of children with ADHD taking medication (n = 109). To the best of our knowledge, this is the first structural MRI study investigating the effects of cumulative exposure to medication on subregional volumes in children treated for ADHD.nnMETHODS: Cumulative exposure to ADHD medication (CEM) was defined as the product of duration on medication (days) and dose (mg/day), yielding the area under the curve (total mg). Cortical thickness and surface area measurements (CIVET-1.1.12), and subcortical volumes in 51 regions (MAGeT-Brain) were analyzed using general linear modelling.nnRESULTS: Significant effects of CEM were found in two subregions of the left hippocampus, the CA1 (df = 95; q = 0.003) and the strata radiatum/lacunosum/moleculare (df = 95; q = 0.003). Specifically, higher CEM was associated with smaller volumes within these subregions. No effects of medication exposure were detected on cortical thickness or surface area.nnCONCLUSIONS: Although this study is cross-sectional, the results found within this sample of children show that prolonged ADHD medication use at higher doses is significantly associated with smaller hippocampus volumes in specific subregions. More research is required to determine whether these results are reproduced in other samples of children of ADHD, and further, whether these are beneficial or off-target effects of the medication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32774401,

title = {Facing the Methodological Challenge in Dissecting the Genetics of ADHD: A Case for Deep Phenotyping and Heterogeneity Reduction},

author = {Sarojini M Sengupta and Natalie Grizenko and Marie-Ève Fortier and Marina Ter-Stepanian and Ridha Joober},

issn = {1719-8429},

year  = {2020},

date = {2020-08-01},

journal = {J Can Acad Child Adolesc Psychiatry},

volume = {29},

number = {3},

pages = {188--201},

abstract = {OBJECTIVE: The aetiology of ADHD is complex, with genetic and environmental factors both implicated in the disorder. The most recent ADHD genome-wide association study identified 12 loci that showed significant association with the disorder. However, as highlighted by the authors, these loci "only capture a tiny fraction" of the risk for ADHD. It has been suggested that it may be important to disentangle: (1) the clinical complexity of the disorder, and (2) the complex interaction between genetic and environmental factors, in order to better dissect the aetiology of the disorder.nnMETHOD: We have conducted a clinically-relevant Pharmaco-Behavioural Genetic study in a large group of children with ADHD (~850 families) over the last 15 years. The study includes detailed evaluation of quantitative behavioural and neuropsychological phenotypes, as well as short-term response of these phenotypes to treatment with a fixed dose of methylphenidate (0.5mg/kg in a b.i.d. dose). Specific genetic markers and environmental factors were examined for their association with these dimensions.nnRESULTS: Here we present results that highlight the importance of examining genetic association with quantitative traits, including those constructs having relevance to Research Domain Criteria (RDoC). Further, we demonstrate that by conducting association analysis in groups of children stratified based on exposure to key environmental exposure (maternal smoking or stress during pregnancy), we are able to increase the sensitivity for finding genes involved in the disorder.nnCONCLUSION: These results suggest that deep phenotyping and heterogeneity reduction may be imperative in order to uncover the "missing heritability" of the disorder.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31965445,

title = {Therapeutic response in children with ADHD: role of observers and settings},

author = {Venkat Bhat and Sarojini M Sengupta and Natalie Grizenko and Ridha Joober},

doi = {10.1007/s12519-019-00332-5},

issn = {1867-0687},

year  = {2020},

date = {2020-06-01},

journal = {World J Pediatr},

volume = {16},

number = {3},

pages = {314--321},

abstract = {BACKGROUND: This study aims at characterizing the extent of correlation of treatment response (TR) obtained in various observation settings (home, school, clinic) by different observers (parents, teachers, clinicians).nnMETHODS: Children with attention deficit hyperactivity disorder (ADHD) underwent a 2-week double-blind, randomized, cross-over clinical trial with methylphenidate and placebo, and various measures were obtained during the 2 weeks. Interrelationships of TR were examined using Pearson's correlation coefficients.nnRESULTS: The study included 526 children (420 male, 106 female) with ADHD. TR between different observers shows a variable correlation between parents and teachers. No correlation is seen between parents/teacher evaluation of TR and laboratory-based measures (Continuous Performance Task; Restricted Academic Situation Scale).nnCONCLUSION: The results firmly support the need to synthesize information from many sources in evaluating TR in ADHD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32194651,

title = {Therapeutic Response to Methylphenidate in ADHD: Role of Child and Observer Gender},

author = {Venkat Bhat and Sarojini M Sengupta and Natalie Grizenko and Ridha Joober},

issn = {1719-8429},

year  = {2020},

date = {2020-03-01},

journal = {J Can Acad Child Adolesc Psychiatry},

volume = {29},

number = {1},

pages = {44--52},

abstract = {OBJECTIVE: This study aims to examine the interaction between the gender of the child and the gender of the observers (teachers, parents) on the therapeutic response (TR) noted with methylphenidate (MPH) in children with ADHD.nnMETHOD: Children with ADHD participated in a two week double-blind, randomized, cross-over clinical trial with MPH and placebo, and the difference between the week of treatment with MPH and placebo was calculated for each measure to obtain the treatment response (TR) with MPH. The TR for differences based on the gender of child and the observer was examined by using a univariate analysis of covariance (ANCOVA).nnRESULTS: 299 children (269-male, 30-female; average age 8.9±1.8 years) were evaluated by 52 male teachers, 212 female teachers; 269 female parents and 30 male parents. For the baseline week, the ANCOVA analysis for teachers yielded a significant teacher's gender x child's gender interaction. For the evaluation of TR, the ANCOVA analysis revealed a significant teacher's gender x child's gender interaction whereas no parent's gender x child's gender interactions were noted, all noted interactions were of a small effect size (eta squared <0.02).nnCONCLUSIONS: These results suggest that there are differences in symptom assessment between parents and teachers at baseline and with TR based on the gender of the observer and the child. While clinicians need to be aware of these interactions, it remains unclear if these interactions will be clinically useful due to the small effect sizes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31415825,

title = {Acute blood pressure change with methylphenidate is associated with improvement in attention performance in children with ADHD},

author = {Alexandru Traicu and Natalie Grizenko and Marie-Ève Fortier and Weam Fageera and Sarojini M Sengupta and Ridha Joober},

doi = {10.1016/j.pnpbp.2019.109732},

issn = {1878-4216},

year  = {2020},

date = {2020-01-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {96},

pages = {109732},

abstract = {This exploratory study aims to determine whether the change in systolic blood pressure (sBP) after acute methylphenidate (MPH) administration (ΔBP) is associated with the neurocognitive response to MPH in the Conners Continuous Performance Test (CPT) in 513 children with ADHD (aged 6 to 12 years old). We noted that higher increases in sBP were associated with larger improvement in CPT performance with MPH. In the univariate regression model, the ΔBP accounted for an additional 2% of the variance in the change in CPT-Overall Index (OI) after controlling for covariates (p < .001). Linear regression analysis also indicated that ΔBP significantly contributed to predict a change in omission errors, reaction time, and reaction time variability (p < .001, p < .01, p = .001, respectively), but not in commission errors or detectability index (d`). Participants with a clinically meaningful sBP increase of at least 5 mmHg (n = 191) improved by 4.8 points on the CPT-OI score (p < .001), compared to an improvement of only 0.6 points for participants whose sBP declined by at least 5 mmHg (n = 121). In conclusion, larger sBP increases after MPH administration were associated with greater enhancement in CPT performance. These results could be useful in informing MPH dosing in clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29182037,

title = { exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate},

author = {Darya Naumova and Natalie Grizenko and Sarojini M Sengupta and Ridha Joober},

doi = {10.1080/15622975.2017.1410221},

issn = {1814-1412},

year  = {2019},

date = {2019-07-01},

journal = {World J Biol Psychiatry},

volume = {20},

number = {6},

pages = {486--495},

abstract = { Dopamine plays an important role in modulating attention and motor behaviours, dimensions altered in attention deficit/hyperactivity disorder (ADHD). Numerous association studies have linked dopamine receptor 4 () to increased risk of ADHD. This study investigated the effect of  exon 3 polymorphism on child behaviours in response to treatment with methylphenidate.  A total of 374 children diagnosed with ADHD (ages 6-12 years) were evaluated under three experimental conditions: baseline, placebo and MPH (0.5 mg/kg/day). This was a 2-week prospective within-subject, placebo-controlled, crossover trial. The Conners' Global Index for parents and for teachers was used to evaluate the behaviours of the children. One-way repeated measures analysis of variance was used to test the effect of the interaction between  genotype and experimental conditions.  A significant interaction between  genotype and treatment was detected when the child's behaviour was evaluated by the parents ( = 0.035, effect size of 0.014), driven by a better treatment response in children homozygous for long 7-repeat allele.  According to the parent assessment, children homozygous for the long 7-repeat allele were more responsive to experimental condition. This is the largest pharmacogenetic investigation of the effect of  exon 3 polymorphism in childhood ADHD.  clinicaltrials.gov, identifier NCT00483106.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30051166,

title = {DRD3 Gene and ADHD: A Pharmaco-Behavioural Genetic Study},

author = {Weam Fageera and Sarojini M Sengupta and Aurelie Labbe and Natalie Grizenko and Ridha Joober},

doi = {10.1007/s12017-018-8504-z},

issn = {1559-1174},

year  = {2018},

date = {2018-12-01},

journal = {Neuromolecular Med},

volume = {20},

number = {4},

pages = {515--524},

abstract = {Results of candidate gene investigations in ADHD have been difficult to replicate. The complexity of the phenotypes and their underlying determinants, and the relatively small effect sizes of genetic variants may, in part, be contributing to these inconsistencies. The objective of this study is to conduct an exploratory analysis using a comprehensive approach to investigate the role of candidate genes. This approach combines a dimensional behavioural approach akin to Research Domain Criteria (RDoC), a pharmaco-dynamic evaluation of behaviours relevant to ADHD, together with association and linkage testing in a large sample of children with ADHD. Parents, teachers, and research staff evaluated children with ADHD under three experimental conditions (EC): 1 week of baseline observation, followed by 1 week of methylphenidate (MPH) and 1 week of placebo, administered in a double-blind crossover order. Several quantitative behavioural and cognitive dimensions relevant for ADHD were also assessed. We combined family-based (FBAT) and quantitative trait genetic analyses (n = 575 probands with members of their nuclear families) to investigate the role of DRD3 (Ser-9-Gly) in ADHD and its relevant behavioural dimensions. Comparing the behaviours of children with different genotypes under the three EC showed a nominal association between the T allele and poorer behavioural scores during the MPH week (as assessed by teachers), particularly in boys. With the family-based analysis, the T allele showed a nominal association with increased risk for ADHD, response to placebo and MPH as assessed by research staff, and the modulation of other behavioural and cognitive dimensions. These results provide convergent, albeit preliminary evidence for the implication of the DRD3 (Ser-9-Gly) polymorphism in the aetiology of ADHD and the modulation of its various behavioural dimensions, including RDoC cognitive constructs and response to pharmacological probes. This illustrative example suggests that this research paradigm might help to reliably uncover the role of other candidate genes in ADHD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30216917,

title = {Dissecting genetic cross-talk between ADHD and other neurodevelopmental disorders: Evidence from behavioural, pharmacological and brain imaging investigations},

author = {Sarojini M Sengupta and Nellie Fotopoulos and Gabriel A Devenyi and Marie-Ève Fortier and Marina Ter-Stepanian and Saba Sagliker and Sherif Karama and M Mallar Chakravarty and Aurelie Labbe and Natalie Grizenko and Ridha Joober},

doi = {10.1016/j.psychres.2018.08.080},

issn = {1872-7123},

year  = {2018},

date = {2018-11-01},

journal = {Psychiatry Res},

volume = {269},

pages = {652--657},

abstract = {Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatment with a fixed dose of methylphenidate, in a relatively large sample of children with ADHD. Family-based association tests were conducted with nine tag SNPs with 602 nuclear families. In addition, structural magnetic resonance imaging (sMRI) was conducted in a subset of children with ADHD (n = 76). Of the 9 tag SNPs examined, rs1602565 showed a significant association with ADHD, several dimensional measures and response to treatment. An association was also observed between rs1006737 (CACNA1C) and performance IQ. In addition, significant reductions in cortical thickness measurements were observed with the risk allele in rs1006737. These results provide preliminary evidence for putative shared genetic vulnerability between childhood ADHD and other neurodevelopmental disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}