Biology subjects

Karama, S.

Publications and source records attributed to Karama, S..

7 recordsLinked to original sources

bioRxiv2026

Separable Brain Maturation Patterns Mediate Exposome Influences on Cognitive Development: A Longitudinal Study

Adolescent cognitive ability develops within a complex landscape of environmental exposures, yet the patterns of brain maturation through which these exposures relate to cognitive development remain poorly understood. Resolving this requires an integrated longitudinal view of the multidimensional exposome, multimodal brain change, and cognitive growth. Here, we examined whether brain maturation mediates the relationship between the exposome and cognitive development in a large longitudinal cohort of 1,112 adolescents, using 4,882 multimodal brain features and 112 exposome variables spanning six domains. Brain maturation patterns associated with cognitive development showed moderate yet consistent spatial correspondence with those associated with the exposome, with the family environment domain showing the strongest correspondence. We identified four latent brain patterns associated with distinct components of the exposome-cognition relationship. Collectively, these results indicate that distinct exposome domains relate to cognitive development through distinct brain maturation pathways, which also exhibit different molecular annotation profiles.

neuroscience↗

bioRxiv2025

Modeling Individualized Adolescent Mental Health through a Multifactorial Causal Framework to Identify Potential Intervention Strategies

Associations between psychopathology, cognition, and personality are well established. However, these associations unfold within a broader developmental context shaped by brain maturation, environmental exposures and pubertal transitions, whose influences remain poorly understood. Here, we characterized how cognition and personality relate to adolescent mental health within this developmental context. Using data from the Adolescent Brain Cognitive Development Study (N = 4501), we simultaneously modeled 16610 brain structural, environmental, and pubertal measures to examine 165 behavioral pairs comprising cognitive and personality traits with mental health symptoms. Using an integrated analytic pipeline combining multifactorial mediation and longitudinal interaction-inclusive models, we evaluated whether developmental changes in cognition and personality relate to mental health at the individual level, and whether these associations vary across brain, environmental, and pubertal profiles. Most behavioral pairs showing significant mediation effects likewise exhibited significant longitudinal effects. These pairs were primarily influenced by neurobiological and environmental measures; cortical frontal and temporal regions relevant for cognitive control and emotional regulation as well as family and lifestyle contexts were most prominently implicated. Finally, after accounting for inter-individual heterogeneity, personality traits emerged as the main behavior associated with mental health. These findings characterize developmental associations linking cognition and personality with adolescent mental health, and show that these associations vary across brain, environmental, and pubertal profiles. The study advances understanding of behavioral development and provides a framework for identifying targets for psychopathology prevention.

neuroscience↗

bioRxiv2024

Association between Adolescent Brain Morphometry and Cognitive Function: Insights from a Cross-Sectional Analysis of ABCD Data from 9 to 15 Years Old

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 (N = 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 (g), 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.

neuroscience↗

bioRxiv2020

Estimating the effect-size of gene dosage on cognitive ability across the coding genome

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 IQ 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.

genetics↗

bioRxiv2018

Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/{beta}-catenin, TGF-{beta} and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

genetics↗

bioRxiv2018

Planar cell polarity pathway and development of the human visual cortex

The radial unit hypothesis provides a framework for global (proliferation) and regional (distribution) expansion of the primate cerebral cortex. Using principal component analysis (PCA), we have identified cortical regions with shared variance in their surface area and cortical thickness, respectively, segmented from magnetic resonance images obtained in 23,800 participants. We then carried out meta-analyses of genome-wide association studies of the first two principal components for each phenotype. For surface area (but not cortical thickness), we have detected strong associations between each of the components and single nucleotide polymorphisms in a number of gene loci. The first (global) component was associated mainly with loci on chromosome 17 (9.5e-32 [≤] p [≤] 2.8e-10), including those detected previously as linked with intracranial volume and/or general cognitive function. The second (regional) component captured shared variation in the surface area of the primary and adjacent secondary visual cortices and showed a robust association with polymorphisms in a locus on chromosome 14 containing Disheveled Associated Activator of Morphogenesis 1 (DAAM1; p=2.4e-34). DAAM1 is a key component in the planar-cell-polarity signaling pathway. In follow-up studies, we have focused on the latter finding and established that: (1) DAAM1 is highly expressed between 12th and 22nd post-conception weeks in the human cerebral cortex; (2) genes co-expressed with DAAM1 in the primary visual cortex are enriched in mitochondria-related pathways; and (3) volume of the lateral geniculate nucleus, which projects to regions of the visual cortex staining for cytochrome oxidase (a mitochondrial enzyme), correlates with the surface area of the visual cortex in major-allele homozygotes but not in carriers of the minor allele. Altogether, we speculate that, in concert with thalamocortical input to cortical subplate, DAAM1 enables migration of neurons to cytochrome-oxidase rich regions of the visual cortex, and, in turn, facilitates regional expansion of this set of cortical regions during development.

neuroscience↗

bioRxiv2017

Brain Structural Differences Between 73- And 92-Year Olds Matched For Childhood Intelligence, Social Background, And Intracranial Volume

Fully characterizing age differences in the brain is a key task for combatting ageing-related cognitive decline. Using propensity score matching on two independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age 92 years (n = 42) to very similar participants at mean age 73 (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in grey and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural ageing, in which brains from the eighth and tenth decades of life differ widely despite the same cognitive, socio-economic, and brain-volumetric starting points.

neuroscience↗