Brain's Wiring Stunted, Lopsided In Childhood Onset Schizophrenia
Growth of the brain's long distance connections, called white matter, is stunted and lopsided in children who develop psychosis before puberty, NIMH researchers have discovered. The yearly growth rate of this brain tissue was up to 2.2 percent slower-than-normal in such childhood onset schizophrenia (COS). The slower the rate, the worse the outcome - suggesting that this Magnetic Resonance Imaging (MRI) measure could someday lead to development of a biomarker that could aid treatment. Nitin Gogtay, M.D., and colleagues in the NIMH Child Psychiatry Branch and UCLA's Laboratory of Neuromaging report on their findings online in the Proceedings of the National Academy of Sciences during the week of October 13, 2008.
Previous studies of COS by the NIMH/UCLA team had found a back-to-front wave of accelerated loss of the brain's working tissue - neurons and their immediate connections -- called gray matter. White matter is so-named because these long-distance nerve fibers are protected by a white sheath of insulation. To measure white matter growth, the researchers scanned 12 children with COS and 12 healthy controls over five years. Superimposing one MRI scan onto another as they grew up grew up revealed how fast a child's white matter was growing in different brain areas. This was the first time this technique developed by UCLA's Paul Thompson, Ph.D., and colleagues, called tensor-based morphometry, had been used to study COS.
Results of This Study
In contrast to gray matter, the wave of stunted white matter growth spread from front-to-back as the child grew up. The up to 2.2 percent slower than normal yearly growth rate was seen on the right side of the brain in COS. Even on the left side of the brain, the annual rate of white matter growth was only 1.3 percent in children with COS, compared 2.6 percent per year throughout the brain in controls. Children with COS who had higher white matter growth rates performed better on tests of brain function and had better prognoses.
Because the waves of net tissue reductions encroach from opposite directions, the findings put to rest earlier speculation that the gray matter loss might have resulted from white matter encroachment, say the researchers. Much like insulation makes an electrical wire more efficient, the white matter sheath on nerve fiber tracts normally thickens as we grow up, making for more efficient conduction of neural signals. The better functional outcomes in children with COS who had higher white matter growth rates may be attributable to this increased processing capacity, suggest the researchers.
The researchers cite as cause for hope the fact that the progressive deterioration in both gray and white matter is not yet complete at onset of psychosis in children with COS - perhaps leaving open "a window of opportunity" for future treatment interventions that might nip it in the bud. Imaging-based biomarkers of disease that could emerge from this line of studies hold promise for use in testing the efficacy of new treatments, said Gogtay. Tensor-based morphometry might also illuminate other neurodevelopmental conditions, such as certain forms of autism, in which white matter deficits have been implicated.
Average rates of white matter tissue growth (red) and tissue loss (blue) for healthy controls and childhood onset schizophrenia (COS) patients. COS patients' brains developed an asymmetrical pattern, with white matter growing at up to a 2.2 percent slower-than-normal yearly rate in the right hemisphere. 3-D tensor based morphometry MRI maps created from MRI scans of 12 patients and 12 matched controls over a 5-year period.