@article{pmid41820538,

title = {Comprehensive large-scale analyses reveal association between brain structure and cognitive ability during adolescence},

author = {Jiadong Yan and Yasser Iturria-Medina and Gleb Bezgin and Paule Joanne Toussaint and Ke Xie and Liang He and Judy Chen and Kirsten Hilger and Erhan Genç and Alan C Evans and Sherif Karama},

doi = {10.1038/s42003-026-09831-4},

issn = {2399-3642},

year  = {2026},

date = {2026-03-01},

journal = {Commun Biol},

volume = {9},

number = {1},

abstract = {Significant changes occur in brain structure and cognition during adolescence. Investigating their association can provide insight into brain-based cognitive development, yet previous studies are limited by narrow measures, small samples, and lacking focus on age-dependence. Using a large cohort (n = 8534, age 9-15) with structural MRI and diffusion imaging, we derive 16 regional metrics and integrate them via morphometric similarity networks to characterize 16,563 brain features. We apply large-scale models to investigate their associations with seven cognitive subtests and general intelligence (g), as well as age-dependence. Brain areas most strongly associated with cognition also show the greatest age-dependence of the associations, primarily in the frontal, temporal, and occipital lobes. Stronger and more age-dependent associations with cognition are observed for structural MRI measures and global hub measures, compared with diffusion-derived metrics and local measures, respectively. Overall, our study provides a comprehensive and reliable characterization of adolescent brain structure-cognition associations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40909731,

title = {Association between Brain Structure and Cognitive Ability during Adolescence: Insights from a Comprehensive Large-Scale Analysis of 9 to 15 Year-Olds},

author = {Jiadong Yan and Yasser Iturria-Medina and Gleb Bezgin and Paule Joanne Toussaint and Ke Xie and Liang He and Judy Chen and Kirsten Hilger and Erhan Genç and Alan Evans and Sherif Karama},

doi = {10.1101/2024.06.18.599653},

issn = {2692-8205},

year  = {2025},

date = {2025-08-01},

journal = {bioRxiv},

abstract = {Significant changes occur in brain structure and cognitive abilities during adolescence. Investigating their association can provide insight into brain-based cognitive development, yet previous studies were limited by narrow brain measures, small samples, and lacking focus on age-related variation. Here, we analyzed a large cohort ( = 8,534, age 9-15) from the Adolescent Brain Cognitive Development dataset. Using structural MRI and diffusion imaging, we derived 16 regional structural measures and integrated them via morphometric similarity networks to characterize 16,563 regional, connectivity, and hub features. We applied large-scale computational models to investigate their associations with performance on seven cognitive subtests and general intelligence (), as well as age-related changes. Brain areas most strongly associated with cognitive ability also showed the greatest age-related variability in these associations, located primarily in the frontal, temporal, and occipital lobes. Structural MRI measures exhibited stronger associations with cognition and greater age-related variability than diffusion-derived metrics, while global hub measures showed stronger and more variable associations than local measures. Overall, our study provides a comprehensive and reliable understanding of brain structure-cognition associations during adolescence.},

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{pmid38569724,

title = {Making use of N-of-1 trials to treat ADHD in people with psychosis: a hypothetical case},

author = {Kathryn Dalton and Ridha Joober and Sherif Karama and Lena Palaniyappan},

doi = {10.1503/jpn.240010},

issn = {1488-2434},

year  = {2024},

date = {2024-01-01},

journal = {J Psychiatry Neurosci},

volume = {49},

number = {2},

pages = {E133--E134},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33766753,

title = {Maturational trajectories of pericortical contrast in typical brain development},

author = {Stefan Drakulich and Anne-Charlotte Thiffault and Emily Olafson and Olivier Parent and Aurelie Labbe and Matthew D Albaugh and Budhachandra Khundrakpam and Simon Ducharme and Alan Evans and Mallar M Chakravarty and Sherif Karama},

doi = {10.1016/j.neuroimage.2021.117974},

issn = {1095-9572},

year  = {2021},

date = {2021-07-01},

journal = {Neuroimage},

volume = {235},

pages = {117974},

abstract = {In the last few years, a significant amount of work has aimed to characterize maturational trajectories of cortical development. The role of pericortical microstructure putatively characterized as the gray-white matter contrast (GWC) at the pericortical gray-white matter boundary and its relationship to more traditional morphological measures of cortical morphometry has emerged as a means to examine finer grained neuroanatomical underpinnings of cortical changes. In this work, we characterize the GWC developmental trajectories in a representative sample (n = 394) of children and adolescents (~4 to ~22 years of age), with repeated scans (1-3 scans per subject, total scans n = 819). We tested whether linear, quadratic, or cubic trajectories of contrast development best described changes in GWC. A best-fit model was identified vertex-wise across the whole cortex via the Akaike Information Criterion (AIC). GWC across nearly the whole brain was found to significantly change with age. Cubic trajectories were likeliest for 63% of vertices, quadratic trajectories were likeliest for 20% of vertices, and linear trajectories were likeliest for 16% of vertices. A main effect of sex was observed in some regions, where males had a higher GWC than females. However, no sex by age interactions were found on GWC. In summary, our results suggest a progressive decrease in GWC at the pericortical boundary throughout childhood and adolescence. This work contributes to efforts seeking to characterize typical, healthy brain development and, by extension, can help elucidate aberrant developmental trajectories.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33414497,

title = {Genome-wide analysis of gene dosage in 24,092 individuals estimates that 10,000 genes modulate cognitive ability},

author = {Guillaume Huguet and Catherine Schramm and Elise Douard and Petra Tamer and Antoine Main and Pauline Monin and Jade England and Khadije Jizi and Thomas Renne and Myriam Poirier and Sabrina Nowak and Charles-Olivier Martin and Nadine Younis and Inga Sophia Knoth and Martineau Jean-Louis and Zohra Saci and Maude Auger and Frédérique Tihy and Géraldine Mathonnet and Catalina Maftei and France Léveillé and David Porteous and Gail Davies and Paul Redmond and Sarah E Harris and W David Hill and Emmanuelle Lemyre and Gunter Schumann and Thomas Bourgeron and Zdenka Pausova and Tomas Paus and Sherif Karama and Sarah Lippe and Ian J Deary and Laura Almasy and Aurélie Labbe and David Glahn and Celia M T Greenwood and Sébastien Jacquemont},

doi = {10.1038/s41380-020-00985-z},

issn = {1476-5578},

year  = {2021},

date = {2021-06-01},

journal = {Mol Psychiatry},

volume = {26},

number = {6},

pages = {2663--2676},

abstract = {Genomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways.},

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{pmid33403948,

title = {Using a simulation centre to evaluate preliminary acceptability and impact of an artificial intelligence-powered clinical decision support system for depression treatment on the physician-patient interaction},

author = {David Benrimoh and Myriam Tanguay-Sela and Kelly Perlman and Sonia Israel and Joseph Mehltretter and Caitrin Armstrong and Robert Fratila and Sagar V Parikh and Jordan F Karp and Katherine Heller and Ipsit V Vahia and Daniel M Blumberger and Sherif Karama and Simone N Vigod and Gail Myhr and Ruben Martins and Colleen Rollins and Christina Popescu and Eryn Lundrigan and Emily Snook and Marina Wakid and Jérôme Williams and Ghassen Soufi and Tamara Perez and Jingla-Fri Tunteng and Katherine Rosenfeld and Marc Miresco and Gustavo Turecki and Liliana Gomez Cardona and Outi Linnaranta and Howard C Margolese},

doi = {10.1192/bjo.2020.127},

issn = {2056-4724},

year  = {2021},

date = {2021-01-01},

journal = {BJPsych Open},

volume = {7},

number = {1},

pages = {e22},

abstract = {BACKGROUND: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.nnAIMS: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician-patient interaction.nnMETHOD: Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback.nnRESULTS: All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician-patient interaction.nnCONCLUSIONS: The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician-patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33427178,

title = {Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder},

author = {Lawrence M Chen and Marieke S Tollenaar and Shantala A Hari Dass and Andrée-Anne Bouvette-Turcot and Irina Pokhvisneva and Hélène Gaudreau and Carine Parent and Josie Diorio and Lisa M McEwen and Julia L MacIsaac and Michael S Kobor and Roseriet Beijers and Carolina de Weerth and Patricia P Silveira and Sherif Karama and Michael J Meaney and Kieran J O'Donnell and },

doi = {10.1017/S0954579420001418},

issn = {1469-2198},

year  = {2020},

date = {2020-12-01},

journal = {Dev Psychopathol},

volume = {32},

number = {5},

pages = {1810--1821},

abstract = {Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10-4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10-9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30121549,

title = {Role of DHEA and cortisol in prefrontal-amygdalar development and working memory},

author = {Nasr A I Farooqi and Martina Scotti and Ji Min Lew and Kelly N Botteron and Sherif Karama and James T McCracken and Tuong-Vi Nguyen},

doi = {10.1016/j.psyneuen.2018.08.010},

issn = {1873-3360},

year  = {2018},

date = {2018-12-01},

journal = {Psychoneuroendocrinology},

volume = {98},

pages = {86--94},

abstract = {There is accumulating evidence that both dehydroepiandrosterone (DHEA) and cortisol play an important role in regulating physical maturation and brain development. High DHEA levels tend to be associated with neuroprotective and indirect anabolic effects, while high cortisol levels tend to be associated with catabolic and neurotoxic properties. Previous literature has linked the ratio between DHEA and cortisol levels (DC ratio) to disorders of attention, emotional regulation and conduct, but little is known as to the relationship between this ratio and brain development. Due to the extensive links between the amygdala and the cortex as well as the known amygdalar involvement in emotional regulation, we examined associations between DC ratio, structural covariance of the amygdala with whole-brain cortical thickness, and validated report-based measures of attention, working memory, internalizing and externalizing symptoms, in a longitudinal sample of typically developing children and adolescents 6-22 years of age. We found that DC ratio predicted covariance between amygdalar volume and the medial anterior cingulate cortex, particularly in the right hemisphere. DC ratio had a significant indirect effect on working memory through its impact on prefrontal-amygdalar covariance, with higher DC ratios associated with a prefrontal-amygdalar covariance pattern predictive of higher scores on a measure of working memory. Taken together, these findings support the notion, as suggested by animal and in vitro studies, that there are opposing effects of DHEA and cortisol on brain development in humans, and that these effects may especially target prefrontal-amygdalar development and working memory, in a lateralized fashion.},

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}

}

@article{pmid30179274,

title = {Association between carotid atheroma and cerebral cortex structure at age 73 years},

author = {Saud Alhusaini and Sherif Karama and Tuong-Vi Nguyen and Alexander Thiel and Boris C Bernhardt and Simon R Cox and Janie Corley and Adele Taylor and Alan C Evans and John M Star and Mark E Bastin and Joanna M Wardlaw and Ian J Deary and Simon Ducharme},

doi = {10.1002/ana.25324},

issn = {1531-8249},

year  = {2018},

date = {2018-10-01},

journal = {Ann Neurol},

volume = {84},

number = {4},

pages = {576--587},

abstract = {OBJECTIVE: To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline.nnMETHODS: We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function.nnRESULTS: A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex.nnINTERPRETATION: The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29665419,

title = {Widespread associations between trait conscientiousness and thickness of brain cortical regions},

author = {Gary J Lewis and David Alexander Dickie and Simon R Cox and Sherif Karama and Alan C Evans and John M Starr and Mark E Bastin and Joanna M Wardlaw and Ian J Deary},

doi = {10.1016/j.neuroimage.2018.04.033},

issn = {1095-9572},

year  = {2018},

date = {2018-08-01},

journal = {Neuroimage},

volume = {176},

pages = {22--28},

abstract = {The neural correlates of human personality have been of longstanding interest; however, most studies in the field have relied on modest sample sizes and few replicable results have been reported to date. We investigated relationships between personality and brain gray matter in a sample of generally healthy, older (mean age 73 years) adults from Scotland drawn from the Lothian Birth Cohort 1936. Participants (N = 578) completed a brain MRI scan and self-reported Big Five personality trait measures. Conscientiousness trait scores were positively related to brain cortical thickness in a range of regions, including bilateral parahippocampal gyrus, bilateral fusiform gyrus, left cingulate gyrus, right medial orbitofrontal cortex, and left dorsomedial prefrontal cortex. These associations - most notably in frontal regions - were modestly-to-moderately attenuated by the inclusion of biomarker variables assessing allostatic load and smoking status. None of the other personality traits showed robust associations with brain cortical thickness, nor did we observe any personality trait associations with cortical surface area and gray matter volume. These findings indicate that brain cortical thickness is associated with conscientiousness, perhaps partly accounted for by allostatic load and smoking status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}