MAILMAN RESEARCH CENTER
Laboratory of Developmental Neuropharmacology
Sue Andersen of the LDN
With a bench to bedside (and back again) approach, the Laboratory of Developmental Neuropharmacology (LDN) has a long-standing interest in understanding the neural basis of childhood and developmentally-based psychiatric disorders. Such disorders include Attention Deficit Hyperactivity Disorder (ADHD), Tourette's Syndrome, schizophrenia, and depression. These disorders are apparent during brain development during childhood (ADHD and Tourette's Syndrome) or appear as the brain matures into adulthood (most cases of schizophrenia and depression). Abnormal development of the brain chemicals dopamine and serotonin, which are vital for their treatment, play important roles in the emergence of these disorders. Despite its significance, developmentally-based research has received little attention. We know that genetic risk sets the stage for increased vulnerability, but an additional factor (a "second hit") is often needed for symptoms to reach clinical significance. The research aims of the laboratory are to determine what these factors are and how they influence the expression and course of these disorders.
The mission of the laboratory is to determine how medication and environmental factors can pathologically alter brain development, and conversely, how abnormal development can be redirected back onto a normal course with proper intervention. Our primary area of interest is to determine how psychotropic agents, including stimulants and antidepressants, affect an immature brain during the short- and long-term. For example, preclinical research by Andersen and colleagues suggest that exposure to stimulants during sensitive periods of development reduces reward function. This reduction in ability to enjoy pleasurable activities is supported by clinical epidemiological research demonstrating that stimulant exposure in ADHD children reduces substance abuse relative to a non-treated ADHD population. Studies suggest that the timing of exposure to stimulants during childhood is vital to this process. Through the use of animal models, we strive to determine how stimulants affect development at the physiological and biochemical level. Questions that cannot be answered ethically in normal or children with ADHD, including:
- how much stimulant exposure is necessary?
- does a window of opportunity exist to maximize effective treatment?
- are there sex differences in this process?
can be investigated in animals quite readily. Conversely, the preclinical answers from these questions can be redirected back to the clinic to determine how these factors relate to behavior and brain function in medication-exposed children and adults with ADHD. A similar situation and tactic also exists in the laboratory for understanding early childhood antidepressant exposure, but these studies and their results are just emerging. Our approach is rare and encompassing: these issues can be investigated with magnetic resonance imaging and genetic analyses in both species, with further characterization at a biochemical level in the animal model.
Additional detrimental factors of interest that are known to affect psychiatric function are stress and birth insults. Both of these are known risk factors for the expression of schizophrenia and depression, but how they affect the process of brain development has not been adequately investigated. Ongoing neuroanatomical and neurochemical studies hope to determine whether novel treatment interventions based on maturational processes might provide an important strategy to reduce symptoms or alter the course of these disorders by adulthood.
- Susan L. Andersen, Ph.D. - Director, and Associate Professor of Psychiatry
- Heather Brenhouse, Ph.D. - Post-Doctoral Fellow (e-mail)
- Melanie Leussis, Ph.D. - Post-Doctoral Fellow (617-855-2037 or e-mail)
- Lucinda Kussmaul - Research Associate (617-855-3202 or e-mail)
- Lee Napierata - Research Associate (617-855-3213 or e-mail)
- National Institute of Drug Abuse (NIDA)
- National Alliance for Research On Schizophrenia and Depression (NARSAD)
- Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr. Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat Neurosci. 2002 Jan;5(1):13-4.
- Andersen SL. Stimulants and the developing brain. Trends Pharmacol Sci. 2005 May;26(5):237-43. Review.
- Andersen SL, Teicher MH. Delayed effects of early stress on hippocampal development. Neuropsychopharmacology. 2004 Nov;29(11):1988-93.
- Andersen SL, Navalta CP. Altering the course of neurodevelopment: a framework for understanding the enduring effects of psychotropic drugs. Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):423-40. Review.