Breakdown of myelin insulation in brain's wiring implicated in childhood developmental disorders
Evidence of myelination as neural Achilles’ heel grows
New evidence points to production of myelin, a fatty insulation coating the brain's internal wiring, as a neural Achilles' heel early in life.
An upcoming application of a novel model of human brain development and degeneration pioneered by a UCLA neuroscientist identifies disruption of myelination as a key neurobiological component behind childhood developmental disorders and addictive behaviors.
Detailed in an article in press with the upcoming annual peer-reviewed publication Adolescent Psychiatry (Hillsdale, N.J.; The Analytic Press Inc.; 2005) the analysis suggests that many factors can disrupt myelination and contribute to or worsen disorders such as autism, attention deficit/hyperactivity disorder and schizophrenia.
In addition, the analysis suggests that alcohol and other drugs of abuse have toxic effects on the myelination process in some adolescents, contributing to poor treatment outcomes and exacerbating co-existing psychiatric disorders.
Author Dr. George Bartzokis, a professor of neurology at UCLA's David Geffen School of Medicine, concludes that the high incidence of impulsive behaviors that characterize the teen years as well as many psychiatric disorders that occur in the teens and 20s are related to incomplete myelination of inhibitory "stop" brain circuits, while the "go" circuits become fully functional earlier in development. These inhibitory circuits are not on line to quickly interrupt high-risk behaviors that are so prevalent in teens and young adults.
"Myelination, a process uniquely elaborated in humans, arguably is the most important and most vulnerable process of brain development as we mature and age," said Bartzokis, who directs the UCLA Memory Disorders and Alzheimer's Disease Clinic and the Clinical Core of the UCLA Alzheimer's Disease Research Center.
"Environmental toxins, genetic predispositions and even diet appear to influence and sometimes disrupt this process," he added. "By shifting our research focus to medications that act on brain metabolism and development, as opposed to brain neurotransmitter chemistry, neuroscientists will likely find a wealth of novel opportunities for addressing the cause of brain disease rather than simply the symptoms."
Myelin is a sheet of lipid, or fat, with very high cholesterol content -- the highest of any brain tissue. The high cholesterol content allows myelin to wrap tightly around axons, speeding messages through the brain by insulating these neural "wire" connections.
Bartzokis' analysis of magnetic resonance images and post-mortem tissue data suggests that the production of myelin is a key component of brain development through childhood and well into middle age, when development peaks and deterioration begins (Neurobiology of Aging, January 2004). He also identifies the midlife breakdown of myelin as a key to onset of Alzheimer's disease later in life (Archives of Neurology, March 2003; Neurobiology of Aging, August 2004).
"This model of a lifelong trajectory of brain development and degeneration embraces the human brain as a high-speed Internet rather than a computer," Bartzokis said. "The speed, quality, and bandwidth of the connections determine the brain's ability to process information, and all these depend in large part on the insulation that coats the brain's connecting wires."
Funders for the research include the National Institute of Mental Health, the Research and Psychiatry Services of the Department of Veterans Affairs, the National Institute of Aging Alzheimer's Disease Center, and the Alzheimer's Disease Research Center of California.
The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks No. 2 among its peers nationwide in National Institutes of Health funding.
The Alzheimer Disease Research Center (ADRC) at UCLA, directed by Dr. Jeffrey L. Cummings, was established in 1991 by a grant from the National Institute on Aging. Together with grants from the Alzheimer's Disease Research Center of California grant and the Sidell Kagan Foundation, the center provides a mechanism for integrating, coordinating and supporting new and on-going research by established investigators in Alzheimer's disease and aging. The Memory Disorders and Alzheimer's Disease Clinic of the ADRC is an evaluation clinic for individuals over the age of 45 who are experiencing mild but gradually progressing cognitive or memory declines that are not related to other brain diseases such as strokes, tumors, infection, metabolic abnormalities, psychiatric disease or trauma.
Additional online resources:
David Geffen School of Medicine at UCLA: http://www.medsch.ucla.edu/
UCLA Department of Neurology: http://neurology.medsch.ucla.edu/
Alzheimer's Disease Research Center at UCLA: http://www.adc.ucla.edu/