We are interested in understanding atypical development. What causes it? How do these causes change brain development? How do these changes in brain development alter the development of psychological functions? Which altered psychological functions underlie the patterns of abnormal behaviors that distinguish different developmental disorders? What does atypical development tell us about normal development?
Answering these questions about a disorder will provide an integrated scientific explanation for that disorder. Achieving such explanations will have profound consequences for both basic developmental science and clinical practice. For instance, understanding the different ways that language development goes wrong in dyslexia, autism, Down syndrome, and fragile X syndrome will help us understand how it goes right in typical language development. The same is true for other domains like executive control, social cognition, and emotion regulation. As for clinical practice, having an integrated scientific explanation of a disorder almost inevitably leads to revolutionary changes in diagnosis, early identification, and preventive treatment.
For over 30 years, my colleagues and I have been pursuing such integrated explanations of several developmental disorders: dyslexia, ADHD, autism spectrum disorder, and intellectual disability. Our lab includes a Developmental Neuropsychology Clinic, and we have had clinical experience with all these disorders. To understand the developmental pathways that lead to the different neuropsychological phenotypes found in these disorders, my colleagues and I have pursued two strategies: working forward from genotype to phenotype, and backward from phenotype to genotype.
If the genetic etiology of a syndrome is known, one can work forward from genotype to phenotype. This is the approach we have taken with phenylketonuria, fragile X syndrome, and Down syndrome. In some of these disorders, we have been able to demonstrate a dose-response relation between an aspect of the disorder's biology and the severity of the neurocognitive phenotype. In the Down syndrome work, we have collaborated with other scientists who have developed mouse models of Down syndrome. Yet, even with a known mutation, there is variability in the neuropsychological phenotype.
But most developmental disorders are behaviorally-defined and etiologically complex: They are caused by the interaction of multiple genetic and environmental risk factors. Because they are behaviorally-defined, one must work backward from phenotype to etiology. This is the approach we have taken to understand the development of several related, complex behavioral disorders: dyslexia, other speech and language disorders, and ADHD. In addition, since these disorders are comorbid with each other, we can use genetic and neuropsychological methods to test hypotheses to explain their comorbidity. We now know that each of these disorders is familial and heritable and that some pairs of them are co-familial and co-heritable, which means that comorbidity is likely due in part to shared genes. We have demonstrated this genetic overlap using molecular methods for the comorbidities between dyslexia and ADHD and dyslexia and speech sound disorder. We have also demonstrated that each of these pairs shares a different cognitive risk factor.
In sum, it now appears that comorbidity is often due to partly shared etiological and cognitive risk factors. Working out which risk factors are shared and not shared across these developmental disorders is an important goal for our future research.
Our clinical experience with all of these disorders has helped focus our research, and our research results have led to improvements in their diagnosis and treatment. My research and clinical work informs the courses I regularly teach on cognitive assessment, developmental neuropsychology and psychopathology.
Bruce F. Pennington, Ph.D.
Director, Developmental Neuropsychology Lab