University of Vermont

College of Medicine

Althoff Laboratory


Clinical neuroscience has struggled to adequately characterize children who have profound problems regulating their affect, behavior, and cognition but who do not meet the criteria for the most severe form of mood dysregulation - pediatric bipolar disorder. These children are best described as having dysregulation (or impaired self-regulation). Twin studies have revealed significant roles of both genetic and shared environment components to childhood dysregulation. This phenotype has a different genetic architecture and different life course than children with ADHD, oppositional defiant disorder, or depression. Work in our lab has demonstrated that children with problems in self-regulation go on to have severe problems in adulthood.

By characterizing these children as having profound problems with attention, mood swings, and aggression, work in the Althoff laboratory strives to identify modifiable genetic and environmental factors to reduce depression, personality disorders and substance use in adolescence and adulthood. The most fundamental questions about these children remain. How are these children different from children with bipolar disorder? What are the neuroscientific pathways associated with the development of self-regulation? How does dysregulation look throughout the lifespan? How can we characterize these children in a developmentally sensitive and specific way? What are underlying genetic and environmental influences on self-regulation and how do they interact?

The Althoff lab uses a multi-method approach to answering these questions. This work is done in close collaboration with Drs. Hudziak and Rettew in the Vermont Center for Children, Youth, and Families at UVM. We have additional collaborators in Amsterdam, Rotterdam, Washington University in St. Louis, and McGill University. There are studies specifically designed towards phenotypic definition using statistical models of dimensional and categorical approaches (latent class and latent profile models). Psychophysiological studies are being performed in a cohort of children with and without dysregulation using eye movement and heart rate variability monitoring. Genetic and environmental contributions to this phenotype are being investigated using behavioral genetic (twin and family studies) and statistical/molecular genetic (pedigree-based association of candidate genes and whole genome/copy number variation) approaches. Neuroimaging (structural and functional connectivity) is being performed with our colleagues at McGill and Washington University in St. Louis. Epigenetic studies (whole genome methylation) are being performed with our colleagues in Amsterdam and New York. Examination of early precursors, longitudinal outcome, and associations with suicidality are being performed with colleagues at UVM and in The Netherlands. Intervention and prevention studies are currently being planned.

Last modified November 12 2015 01:33 PM