Section on Developmental Neurogenomics

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

This work is conducted under protocol 89-M-0006 (NCT00001246), and falls into two broad research themes: Theme 1: Studies of behavior and brain organization in typically-developing groups Work in this theme uses large-scale neuroimaging studies in health to advance our basic understanding of human brain organization, and guide the selection and application of imaging phenotypes for disease studies. We have so far emphasized structural magnetic resonance imaging (sMRI) because it offers intermediate in vivo phenotypes that can be reliably measured at scale, and are highly heritable, developmentally dynamic, sensitive to disease states, and amenable to translational study in mice. During the last year, we have published work in three main areas. First, we have used brain scans from groups of related individuals to better understand genetic control of brain development and how these influences overlap with genetic determinants of cognitive ability. Second, in a large sample of typically-developing individuals, we have identified reproducible patterns of sex-biased brain anatomy and identified gene sets, cell types and cognitive domains that these sex-biases might most closely relate to. Third, we have used large neuroimaging datasets to mine correlations between different measures of brain anatomy for insights into how brain proportions vary as a function of brain size, age, the in utero environment and cognition. Theme 2: Deep phenotypic studies of participants with sex chromosome aneuploidy syndromes (SCAs) Work in this theme seeks to understand brain and behavioral changes in individuals with genetically defined neurodevelopmental disorders focusing on sex chromosome aneuploidy syndromes (SCAs) in particular. Collectively, these studies are designed to expand on past work in SCA by gathering more comprehensive measures of brain structure and function, as well as providing more fine-grained information regarding the cognitive and behavioral variations that can be seen in SCA. These data will ultimately help to better define the developmental risks and resiliencies associated with X- and Y-chromosome dosage variation in humans, and identify neurobiological systems that might underpin these associations. We hope these insights will (i) improve accurate public and professional awareness of SCAs, (ii) help clinicians provide more targeted assessment and counseling to patients and families with SCA, and (iii) begin to identify biological markers with the potential to ultimately improve assessment, prediction and treatment of neurodevelopmental issues in SCA. More broadly, this work in the specific case of SCA will shed light on (i) the principles that organize genetic influences on brain and behavior in the context of neuropsychiatric impairment, and (ii) genetic contributions to sex-differences in the brain, which are relevant for understanding the well-documented male-bias in risk for neurodevelopmental disorders more generally. During the last year, we have published work in two main areas. First, we have detailed how SCA can impact structural and functional connectivity in the human brain. Secondly, we have harnessed family-based measures of behavior and cognition to try and better-predict how severely a given SCA carrier is likely to be impacted.