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Principal Investigator: Tonya White
Organization: NATIONAL INSTITUTE OF MENTAL HEALTH
Fiscal Year: 2024
Award: $2,106,102
Funding agency: National Institute of Mental Health
We have focused on four primary projects in the past year comprised of i). evaluating the best practices for analyzing longitudinal data; ii). evaluating a large cohort of twins from Virginia Commonwealth University's Mid-Atlantic Twin Registry with the goal to assess genetic and environmental characteristics of autism spectrum disorder (ASD) and importantly, co-occurring disorders along the continuum within the population; iii). parsing the etiologic contributions from genetics, shared and non-shared environment, and stochastic processes in children and adolescents with autism spectrum disorder; and iv). a review of neuroimaging findings in autism spectrum disorders.
For the first project, we coordinated an international effort aimed at investigating the longitudinal interplay between brain, behavior, cognition and condition (ASD vs. neurotypicals) from childhood into young adulthood. One of the challenges of longitudinal studies is the lack of a gold standard related to the nature of the underlying relationship between brain and behavior. Thus, applying different statistical models to longitudinal data, considering that different models have different underlying assumptions, will allow us to test which models work best with specific underlying assumptions. By working together with one additional internal NIH site and six external sites, we have created large simulated longitudinal datasets, which have been shared with the wider research community. Research groups are invited to explore statistical models that capture the associations between brain and behavior in the simulated datasets. The project proposal was announced during the Organization for Human Brain Mapping (OHBM) meeting in 2023, the data was made available during OHBM 2024, and we plan to present lessons learned and host an educational session and symposium during the 2025 OHBM meeting. A preprint of the manuscript detailing the design of the study and dataset characteristics has been submitted to PsyArXiv, and both the simulated longitudinal data and the paper can be accessed on the Open Science Framework.
The second project, through collaboration with the Virginia Commonwealth University (VCU), has utilized a twin registry, the Mid-Atlantic Twin Registry (MATR) to screen a large sample of twins from the general population for autistic traits and co-occurring mental health symptoms. In the past year, we have collected data from 676 twin pairs, and have begun to analyze these data. We plan to examine how comorbid symptom domains of anxiety, depression, hyperactivity, attention, conduct problems, and sleep covary with autistic symptom domains to investigate the potential role of environmental or stochastic mechanisms in the development of ASD.
The third project will utilize the results from the MATR project to recruit a subgroup of monozygotic twins with ASD and matched controls. These twins and their parents will come to the National Institutes of Health for in-depth clinical, cognitive, and social-cognitive assessments. In addition, we will apply high-field neuroimaging approaches to measure brain structure, function, and neurochemistry. In the past year, we have written the protocol for this project and gotten approval from the scientific review committee. In addition, we have created the infrastructure necessary to implement this project through the programming and testing of questionnaires, interviews, tracking systems, and neuropsychological assessments. We have also started to implement neuroimaging protocols using 7T magnetic resonance imaging (MRI) and magnetoencephalography (MEG).
The fourth project consisted of an extensive literature review of neuroimaging studies investigating ASD youth that have been published in the past decade. The aim was to examine structural, functional, and chemical differences between autistic and neurotypical youth, and to compare findings across neuroimaging modalities to identify converging patterns. A total of 172 studies were included in the review, including structural and functional MRI, diffusion tensor imaging (DTI), functional Near Infrared Spectroscopy (fNIRS), magnetoencephalography (MEG), electroencephalography (EEG) and magnetic resonance spectroscopy (MRS) neuroimaging methods. Across modalities, we found consistent differences between ASD and typically developing neuroimaging profiles, in addition to substantial heterogeneity. Specific brain regions appeared consistently across neuroimaging modalities, including the anterior cingulate cortex, insula, prefrontal cortex, amygdala, thalamus, cerebellum, corpus callosum, and default mode network. The manuscript resulting from this literature review has recently been submitted for publication.
In addition to these projects, we have simultaneously been utilizing large datasets, including the Adolescent Brain Cognitive Development (ABCD) study and the Generation R study to examine several research questions. These studies include i). maternal viral infection risk and development of autistic traits; ii). sexual dimorphisms in trajectories of global brain growth over the lifespan, iii). functional connectome fingerprinting in early brain development, iv). the role of plasticizers in the environment and downstream brain development; v). neuroimaging approaches to differentiate the course of anorexia nervosa in adolescent girls; vi). social responsiveness in children with and without a diagnosis of ASD: cognitive and behavioral correlates; and vii.) mental health issues in gender diverse youth.
We also studied the effects of the COVID-19 pandemic on girls and young women with anorexia nervosa, evaluating both the severity of symptoms and comorbid psychopathology. Interestingly, we found lower severity of symptoms of anorexia nervosa and comorbid psychopathology during the peri-pandemic compared to during the pandemic. These findings may be related to less social pressure and more family contact and more protective parenting during the pandemic.
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Tomography><National Institutes of Health><Nature><Neurobiology><Neurodevelopmental Disorder><Neurological Development Disorder><Neurophysiology / Electrophysiology><Neuropsychologies><Neuropsychology><Neurosciences><Nuclear Magnetic Resonance Imaging><Paper><Parenting><Parenting behavior><Parents><Pattern><Plasticizers><Population><Prefrontal Cortex><Printing><Probabilistic Models><Probability Models><Protocol><Protocols documentation><Psychological Health><Psychopathology><Publications><Publishing><Questionnaires><Registries><Reporting><Research><Review Committee><Review Literature><Role><Sampling><Scientific Publication><Severities><Site><Sleep><Statistical Models><Stochastic Processes><Structure><Subgroup><Symptoms><System><Techniques><Testing><Thalamic structure><Thalamus><Twin Multiple Birth><Twins><United States><United States Centers for Disease Control><United States Centers for Disease Control and Prevention><United States National Institutes of Health><Universities><Viral Diseases><Virginia><Virus Diseases><Work><Writing><Youth><Youth 10-21><Zeugmatography><abnormal psychology><adolescent girl><adolescent with ASD><adolescent with autism><adolescent with autism spectrum disorder><adolescents on the autism spectrum><adult youth><amygdaloid nuclear complex><analyzing longitudinal><associated symptom><autism attributes><autism indicator><autism spectral disorder><autism spectrum disorder><autism spectrum disorder features><autism spectrum disorder indicator><autism spectrum disorder symptoms><autism symptomology><autism symptoms><autism-like symptoms><autism-related attributes><autistic><autistic adolescent><autistic children><autistic features><autistic spectrum disorder><autistic symptoms><autistic traits><autistic youth><autistic-like symptoms><brain overgrowth><causation><childrearing><children on the autism spectrum><children with ASD><children with autism><children with autism spectrum disorder><cingulate cortex><co-morbid><co-morbid symptom><co-morbidity><co-occuring symptom><co-occurring disorders><cognitive assessment><cognitive development><cognitive testing><cohort><comorbid symptom><comorbidity><concurrent symptom><conduct problem><conference><connectome><convention><cooccuring symptom><coronavirus disease 2019 pandemic consequence><coronavirus disease 2019 pandemic impact><dMRI><depression><design><designing><developmental><diffusion tensor imaging><disease causation><dual diagnosis><effects following the COVID-19 pandemic><electrophysiological><eye tracking><fMRI><fNIRS><functional near infrared spectroscopy><gender diverse><girls><impact of the SARS-CoV-2 pandemic><infection risk><juvenile><juvenile human><kids><large data sets><large datasets><life span><lifespan><long-term study><longitudinal analysis><longitudinal data set><longitudinal dataset><longitudinal outcome studies><longterm study><magnetoencephalogram><magnetoencephalographic imaging><meeting><meetings><neural imaging><neuro-imaging><neurobiological><neurochemical><neurochemistry><neurodevelopmental disease><neuroimaging><neurological imaging><neuropsychologic><non-genetic><nongenetic><open data><open science><open-source data><pandemic><pandemic disease><parent><pediatric><pressure><recruit><sex dimorphism><sexual dimorphism><sexually dimorphic><social><social role><statistical linear mixed models><statistical linear models><stochastic method><summit><symposia><symposium><symptom association><symptom comorbidity><symptomatology><thalamic><viral infection><virus infection><virus-induced disease><visual tracking><young adult><young adulthood><young woman><youngster><youth on the autism spectrum><youth with ASD><youth with autism><youth with autism spectrum disorder>