Biology subjects

Dickie, E.

Publications and source records attributed to Dickie, E..

3 recordsLinked to original sources

bioRxiv2020

Greater male than female variability in regional brain structure across the lifespan

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

neuroscience↗

bioRxiv2020

Integration of Brain and Behavior Measures for Identification of Data-Driven Groups Cutting Across Children with ASD, ADHD, or OCD

Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders (NDDs). The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders. A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments was used. Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control. Normalized mutual information (NMI) was used to determine top contributing model features. Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups. Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups. Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences. Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning. Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group. Such new groups can be evaluated longitudinally for prognostic utility and could be stratified for clinical trials targeted toward each groups unique brain and behavioral profiles.

neuroscience↗

bioRxiv2019

White Matter Microstructure and its Relation to Clinical Features of Obsessive-Compulsive Disorder: Findings from the ENIGMA OCD Working Group

ImportanceMicrostructural alterations in cortico-subcortical connections are thought to be present in Obsessive-Compulsive Disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. ObjectiveTo investigate microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. Design, Setting, and ParticipantsIn this cross-sectional case-control magnetic resonance study, we investigated diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA-OCD Working Group. Main Outcomes and MeasuresWe extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohens d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. ResultsAdult OCD patients showed significant FA reduction in the sagittal stratum (d=-0.21, z=-3.21, p=0.001) and posterior thalamic radiation (d=-0.26, z=-4.57, p<0.0001). In the sagittal stratum only, lower FA was associated with a younger age of onset (z=2.71, p=0.006), longer duration of illness (z=-2.086, p=0.036) and a higher percentage of medicated patients in the cohorts studied (z=-1.98, p=0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to matched controls. Conclusions and RelevanceMicrostructural alterations in projection and association fibers to posterior brain regions were found in adult OCD, and related to disease course and medication status. Such results are relevant to models positing deficits in connectivity as a crucial mechanism in OCD. KEY POINTSO_ST_ABSQuestionC_ST_ABSDo patients with Obsessive-Compulsive Disorder (OCD) show white matter microstructural alterations, and are these alterations related to clinical features? FindingsData from 19 sites of the ENIGMA-OCD Consortium were included, involving 700 adult patients and 645 adult controls, 174 pediatric patients and 144 pediatric controls. Diffusion tensor imaging data were meta-analyzed using a harmonized data processing and analysis protocol. Adult, but not pediatric, patients showed alterations in the sagittal stratum and posterior thalamic radiation; sagittal stratum differences were associated with clinical features. MeaningMicrostructural abnormalities found in adult but not in the pediatric cohort, are related to illness duration and medication status.

neuroscience↗