Science Update
August 28, 2007
Bipolar Youth Show Distinct Pattern of Brain Development
The first picturess of the brain changing before-and-after the onset of pediatric bipolar disorder reveal a distinct pattern of development, when compared to that seen in healthy youth or in childhood onset schizophrenia. Repeated magnetic resonance imaging (MRI) brain scans of youth, ages 7-22, followed prospectively as they developed symptoms of mania and depression, showed asymmetrical gains and losses of the brain's working tissue, or gray matter, report scientists at the National Institute of Mental Health (NIMH) and the University of California at Los Angeles (UCLA).
Nitin Gogtay, M.D., Judith Rapoport, M.D., NIMH Child Psychiatry Branch, and colleagues, report on their discovery in the September, 2007 issue of the Journal of Child Psychology and Psychiatry.
"Our findings should help put to rest speculation that pediatric bipolar disorder and childhood onset schizophrenia might stem from the same underlying illness process, despite overlapping symptoms and genetics," said Gogtay.
Some pruning of gray matter, neurons and their connections, is normal as the brain matures and circuitry is streamlined for efficiency. Cases of childhood onset schizophrenia, which are very rare, show an exaggeration of this normal pattern of pervasive gray matter loss — with affected teens losing gray matter in the prefrontal cortex at four times the normal rate.
By contrast, Gogtay's team found that children with bipolar disorder showed a more complicated pattern of gray matter gains in certain areas in the left hemisphere and losses in the right hemisphere, and in mood regulating circuitry in the mid-front part of the brain.
A pattern similar to that seen in bipolar youth was shared by youth diagnosed as "multi-dimensionally impaired" (MDI). These children had neither bipolar disorder nor schizophrenia, but experienced short psychotic episodes, attention problems, and — like their bipolar peers — unstable moods. The latter suggested that the developmental pattern might reflect a tendency toward mood instability in general.
The new pictures (see movie below) emerged from long-term, prospective studies in which children were scanned every two years to learn how the brain develops normally, and how it develops in childhood psychiatric disorders. Nine children who were initially suspected of having schizophrenia, but ultimately diagnosed with bipolar disorder, were included in the current study, along with 8 children with MDI.
MOVIE
The brain developing in pediatric bipolar disorder
Time-lapse MRI movie shows the brain developing from ages 7 to 22 years in nine youth who developed pediatric bipolar disorder. Blue indicates areas with smaller-than-normal, green normal, and yellow, orange and red larger-than normal gray matter volumes. The researchers found a pattern of gray matter gains in certain areas in the left hemisphere and prominent gray matter loss on the right and in mood regulating circuitry in the anterior cingulate, near the front of the brain. This differed from the pattern seen in children with childhood onset schizophrenia (below), suggesting a different underlying illness process, despite overlapping symptoms.
Source: Gogtay N, Ordonez A, Herman DH, Hayashi KM, Greenstein D, Vaituzis C, Lenane M, Clasen L, Sharp W, Giedd JN, Jung D, Nugent Iii TF, Toga AW, Leibenluft E, Thompson PM, Rapoport JL. Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. J Child Psychol Psychiatry. 2007 Sep;48(9):852-62. PMID: 17714370
MOVIE
The brain developing in childhood onset schizophrenia
Time-Lapse MRI movie shows the brain developing in 12 teens with childhood onset schizophrenia. Areas of gray matter loss - red and yellow — spread from back-to-front over 5 years. These teens lost gray matter in the prefrontal cortex at 4 times the rate of normal health teens (see below).
Source: Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11650-5. PMID: 11573002
MOVIE
The brain developing in normal healthy youth
Time-lapse "movie" compresses 15 years of normal brain development (ages 5-20) into just a few seconds. Red indicates more gray matter, blue less gray matter. Gray matter wanes in a back-to-front wave as the brain matures and neural connections are pruned. Areas performing more basic functions mature earlier; areas for higher order functions mature later. The prefrontal cortex, which handles reasoning and other "executive" functions, emerged late in evolution and is among the last to mature.
Source: Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8174-9. Epub 2004 May 17. PMID: 15148381
Jules Asher
