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Children's Hospital, DCRI specialize in adolescence
by Heather Woolwine
MUSC Public Relations
Jan. 13, 2006
As many of us remember, adolescence spans years marked by uncertainty, peer pressure, major hormonal changes, and
feelings of insecurity linked to the voyage from child to adult.
Because of so many major changes, including physical maturity and sexuality, cognitive processes, emotional feelings, and
relationships with others, this age group represents a distinct challenge for health professionals in the MUSC Children's Hospital.
These changes often intersect with developmental modifications of health care needs, effectiveness of treatment, health education, and health promotion.
"These patients are halfway between being an adult and a child," said Janice Key, M.D., Adolescent Medicine director. "You have to treat them uniquely.
They often look like adults... but they're not."
In keeping with the combined mission of the Children’s Hospital and the Darby Children’s Research Institute (DCRI), both groups realize that
adolescents face challenges during this developmental stage unparalleled to almost any other stage in life.
"Adolescence is a key period. It's when many of us first initiate behaviors that will affect the rest of our lives," Key said. "For
instance, many people start smoking in their preteen or teen years, or begin having sex. We call these risk-taking behaviors, and it's critical to
prevent or intervene and address these behaviors at this point in a patient’s life. We are determined to help adolescents get through this challenging transition."
Genetic and environmental factors each contribute to occurrence of stress and various disorders, with life stress paramount to other
outside influences. Life stress means everything from an infection while still in the womb and its implications, to child abuse and malnutrition.
But as the age old argument of nature versus nurture suggests, you simply can’t have one without the other; so, researchers at the DCRI and those
involved with Key's research in school-based settings remain determined to study the interplay among genetic factors and life stress.
Key's projects include teen pregnancy and primary and secondary intervention, abstinence education, smoking cessation, and pregnancy prevention. The division also initiated a community intervention in the Sea Island area of rural southern Charleston County funded through the New Morning Foundation.
While Key and her collaborators study the challenge of life stress for adolescents, DCRI scientists strive to understand the delicate balance between genetics and this stress to better understand adolescent addiction and development of disorders.
With that in mind, the need to study disorders such as depression, bipolar disorder, generalized stress disorder, drug addiction, obsessive compulsive disorder and attention deficit hyperactivity disorder (ADHD) in relation to adolescence has become a priority for basic scientists in the lab.
In studies conducted in the DCRI, rodents are exposed to either enriched or impoverished environments beginning as soon as the animals are weaned at 21 days after birth, and continue until sexual maturity at 60 days after birth. In the enriched environment, animals live in groups of eight to10 in a large environment where objects (toys) are traded in and out everyday. An investigator handles the subjects for 20 minutes each day. On the other end of the spectrum, the impoverished rats live alone in a relatively small environment with no interesting objects and are never handled by the investigator. Roberto Melendez, Ph.D., Neurosciences / Neuroscience Research, and graduate student Mary Lee Gregory showed that animals reared in the impoverished environment show a number of deficits in the development of their brains, ranging from molecular changes in cell signaling to poor performance in memory tasks.
Peter Kalivas, Ph.D., and his team focus on changes produced in the prefrontal cortex, a brain region implicated in a number of neuropsychiatric disorders. Their work indicates that signaling through glutamate receptors in this area is defective in the impoverished animals, and thus reduces the ability to perform memory tasks. Poor attention to the task, similar to ADHD in humans, may cause this behavior.
Another graduate student, Jamie Peters, Neurosciences/Neuroscience Research, demonstrated that rats reared in an impoverished environment also show greater sensitivity to psycho stimulant drugs of abuse, such as cocaine.
While at MUSC, Karen Szumlinski, Ph.D., University of California- Santa Barbara, used genetic mouse models of deficits in glutamate transmission in the prefrontal cortex. In these studies, a family of genes called the Homers, which encode proteins critical for glutamate receptor signaling, were deleted. These mice showed deficits in cell signaling and behavior akin to the rats reared in an impoverished environment, including memory deficits and increased addiction to cocaine. Research also suggests a mutation in the Homer gene is associated with the development of schizophrenia, a disease with typical onset in late adolescence.
Finally, Alejandra Pacchioni, M.D., College of Medicine-Physiology/Neuroscience, and collaborators at the University of Pennsylvania showed that a mutant mouse deficient in a gene called Nac-1 is unresponsive to an acute injection of cocaine in both behavior and neurotransmission. Haowei Shen, Ph.D., and Ryan LaLumiere, Ph.D., both of Neurosciences/Neuroscience Research, discovered it possible for Nac-1 to transport protein degrading machinery in response to cellular activation.
Given the ability of the Homer and Nac-1 genes to regulate psychostimulant effects or learning and memory, the next step decides if rearing environments can intensify or improve these genetic vulnerabilities.
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