Schmitt Lab
Projects

Understanding the Underlying Mechanisms in Neurodevelopmental Disorders

The overall mission of the Schmitt lab is use translational neuroscientific approaches to better understand underlying mechanisms in neurodevelopmental disorders in order to guide individualized and tailored treatment development. Our current projects cover a diverse range of research from establishing the clinical utility of the molecular assays in FXS to conducting focus groups and qualitative analysis to develop a new parent-report measure of behavioral flexibility in FXS to conducting in-person trainings for first responders and autistic individuals to enhance community safety.

Lab Projects

Electrophysiological Biomarkers of Neurocognitive Deficits in Fragile X Syndrome

Speech production deficits and behavioral inflexibility are among the most functionally disabling behavioral features of Fragile X Syndrome (FXS), but continue to lack effective treatments due to limited mechanistic understanding. This study examines speech production and behavioral flexibility deficits in FXS using performance-based tasks during high-density electroencephalography (EEG) to investigate fronto-temporal and fronto-parietal circuits in individuals with FXS, respectively. This is the first study of its kind to use performance-based tasks of EEG in FXS, and has the potential to elucidate atypical local neural circuity and its integration in widely distributed brain networks underlying these behavioral features, thus this work will provide critical insight into underlying neurophysiological mechanisms and will assist in the identification of disorder-relevant biomarkers. This study is funded by NICHD K23 Mentored Patient-Oriented Research Career Development Award.

Molecular Phenotyping in Fragile X Syndrome to Predict Disease Outcome and Severity

In collaboration with Craig Erickson, MD (Psychiatry) and Christina Gross, PhD (Neurology), this study tests our highly sensitive and optimized molecular assays of FMR1 mRNA and Fragile X Protein (FMRP) and evaluate their potential as predictors of disease severity and outcomes in FXS. Our preliminary work suggests that nearly half of “full mutation” males with FXS demonstrate previously undetected mRNA and protein expression in very low concentrations. Furthermore, we show that increased mRNA and FMRP levels relate to higher IQ levels, suggesting a dose-dependent effect of underlying molecular biomarkers on IQ. This study aims to determine whether FMR1 mRNA and FMRP levels relate to other hallmark clinical phenotypes in FXS. This study received initial support through the Cincinnati Children’s Research Innovation Pilot Funding Program (RIP).

HOme-based Molecular and Electrophysiological (HOME) Biomarker Study

Current research studies conducted at the Cincinnati Fragile X Center have been limited to individuals who can participate in traditional research visits at the hospital. However, numerous factors, including those directly related to the Fragile X phenotype (e.g., clinically significant anxiety, irritability, challenging behaviors) and those associated with marginalized backgrounds (e.g., low SES, rurality), often prevent many families from participating in traditional research visits. Thus, conducting research visits in the participant’s home (“home visits”) is necessary to include the most representative sample of FXS. No FXS research study, to date, has conducted at-home blood draws and/or EEG testing. The initial aims of this study are to determine the feasibility and test-retest reliability of conducting research visits at home, with the long-term aim of including home visits as an option for all future research studies, including clinical trials!

Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability – Fragile X Syndrome (RIGID-FX)

The Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability –Fragile X Syndrome (RIGID-FX) was recently developed to be used to rate the type, severity, and impact of behaviors associated with rigid and inflexible behaviors in individuals diagnosed with Fragile X Syndrome (FXS) across the lifespan. RIGID-FX was developed via focus groups with key stakeholders, predominantly caregivers of individuals with FXS, and subsequent thematic analysis. Currently, we are conducting initial feasibility, acceptability, and validation studies for the measure. This study received initial support through the Jack H Rubinstein Foundation.

Creating a Safer Community: A Culturally-Responsive Training for First Responders and Autistic Individuals and Their Families

In collaboration with Meg Stone-Heaberlin, PsyD (BMCP) and our community partners (Autism and We, Autism Connections, Deon Mack), we have created a training curriculum for first responders and autistic individuals. Currently, the training includes a first responder module that has didactic information about ASD and prepares officers for real-life contact with autistic individuals and an autism module that provides autistic individuals across the spectrum using multimodal learning opportunities via video modeling, experiential activities, and engagement with first responders. We also are working on developing a stand-alone caregiver curriculum to provide caregivers with how-to's during a crisis situation.

Key Collaborations

The Schmitt Lab is a strong believer in team science! Dr. Schmitt is a key member of the Neurobehavioral Treatment Discovery Team, which was awarded the Cincinnati Children’s Hospital Medical Center Research Team Award for 2021!

Dr. Schmitt is co-Investigator on several ongoing NIH-funded translational studies focused on understanding the underlying mechanisms using EEG in FXS. These multi-site translational studies also include collaborations with basic scientists Carlos Portera-Cailliau, MD, PhD from the University of California-Los Angelos (UCLA) and Mike Ragozzino from the University of Illinois-Chicago (UIC). These partnerships have allowed the Schmitt Lab to conduct human studies in FXS in direct parallel with studies using mouse models of FXS.

Dr. Schmitt serves as co-Investigator in the Shaffer Lab. Specifically, Dr. Schmitt has helped Rebecca C. Shaffer, PsyD, HSPP with the curriculum development of Regulating Together, a group-based intervention targeting emotion dysregulation in autistic youth. In addition, Dr. Schmitt’s performance-based computer paradigm of cognitive flexibility serves as a secondary outcome measure for ongoing randomized-controlled trials of Regulating Together.

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