Evidence of progressive abnormal brain development in schizophreniahas emerged from the first longitudinal brain imaging study ever conductedin adolescents for any illness.
MRI(magnetic resonance imaging) scans revealed ventricles (fluid-filled cavitiesin the middle of the brain) enlarging between ages 14 and 16 in teens witha rare, severe, childhood onset form of the disorder, reportJudith Rapoport, M.D., and colleagues of the National Institute of MentalHealth, in the October issue of the Archives of General Psychiatry.
Also in this issue, NIMH's Theodore Zahn, Ph.D., Rapoport and colleaguesreportthat the same adolescents, all of whom had experienced psychosis priorto age 12, showed autonomic nervous system abnormalities characteristicof adult schizophrenia.
"These and other studies add to mounting evidencethat the childhood and adult forms are the same illness," said Rapoport,Chief of the NIMH Child Psychiatry Branch. "Understanding what's happeningin these young people during this period of highly volatile brain developmentmay provide clues about risk factors and neurodevelopmental abnormalitiesinvolved in the much more common adult onset schizophrenia. Adults withthe disorder may well have experienced the same kind of abnormal brainchanges during their teens."
Affecting about 1 percent of adults, but only about .005 percent ofchildren, schizophreniais the most chronic and disabling mental illness. It typically begins asa psychotic episode in young adulthood, with devastating hallucinations,delusions, social withdrawal, blunted emotionality and loss of social andpersonal care skills. A new generation of antipsychoticmedications, such as clozapine, has helped many patients manage theirsymptoms with fewer side effects.
In the MRI study, the researchers compared scans of 16 ill teenagersparticipating in a clozapine trial with those of 24 age-matched controls.At the initial scan, the youths with schizophrenia tended to show enlargedventricles, reduced total cerebral volume, and other structural anomalies.After two years, a series of re-scans revealed "highly significant"increases in the size of ventricles among those with schizophrenia. Thecontrols showed no significant changes.
Although adult schizophrenia patients tend to have enlarged ventricles,evidence for progressive brain changes in adults has been more equivocal.Absent signs of an ongoing illness process, one prevailing theory has heldthat schizophrenia likely stems from damage caused by a prenatal event– such as a viral infection in the womb, or some other environmental insultto the developing brain -- that interacts with normal brain developmentand life stresses, in genetically vulnerable individuals, to produce thedisorder in young adulthood. While not one of its original tenets, thefindings of progressive brain changes in adolescence are not inconsistentwith this "neurodevelopmental" hypothesis, say the researchers.
Unlike in adults, schizophrenia usually emerges gradually in children,and is often preceded by developmental disturbances, such as lags in motorand speech development. Adolescents in the study who had histories of suchautistic-like behavior tended to show greater ventricular enlargement.Childhood onset schizophrenia also tends to be harder to treat and to havea worse prognosis than the adult onset form. However, in a series of studiesover the past few years, Rapoport's group has shown that affected childrenshare with adults a similar pattern of brain structure abnormalities andphysiological features. For example, in the study led by Zahn, the researchersreport that the ill children had skin conductance and heart rate anomaliessimilar to those seen in affected adults.
In interpreting the imaging findings, Rapoport and colleagues suggestthat the scans captured changes in the brain during a critical period indevelopment when it is "uniquely sensitive" to effects of theillness. It's unlikely that the ventricles would continue enlarging atsuch a high rate, "as that would produce improbably large ventricularvolume later in life," they note. Also, the "possibility thatclozapine treatment accelerates adolescent brain change can not be ruledout," they add. The 16 affected adolescents in the study were thefirst to be re-scanned from a total of 30 patients in the clozapine trial.Their MRI scans were compared with scans from an ongoing NIMH study designedto provide data on normal brain development during childhood and adolescence.
"The study of childhood onset cases presents a unique approachto schizophrenia," said Rapoport. "If we can understand whatturns on the illness in these rare cases, it may provide clues about howto turn it off for others."
Also participating in the studies were: Drs. Jay Giedd, Sanji Kumra,Leslie Jacobsen, and Amy Smith, Paul Lee, Jean Nelson and Susan Hamburgerof NIMH; and Dr. Charles Gordon, University of Maryland; Dr. Kathleen McKenna,Northwestern University; and Dr. Jean Frazier, Harvard University.
NIMH is a component of the National Institutes of Health, an agencyof the U.S. Department of Health and Human Services.
Materials provided by NIH-National Institute of Mental Health. Note: Content may be edited for style and length.
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