Evidence of progressive abnormal brain development in schizophrenia has
emerged from the first longitudinal brain imaging study ever conducted in
adolescents for any illness. MRI (magnetic resonance imaging) scans
revealed ventricles (fluid-filled cavities in the middle of the brain)
enlarging between ages 14 and 16 in teens with a rare, severe, childhood
onset form of the disorder, report Judith Rapoport, M.D., and colleagues of
the National Institute of Mental Health, in the October issue of the
Archives of General Psychiatry.
Also in this issue, NIMH's Theodore Zahn, Ph.D., Rapoport and colleagues
report that the same adolescents, all of whom had experienced psychosis
prior to age 12, showed autonomic nervous system abnormalities
characteristic of adult schizophrenia.
"These and other studies add to mounting evidence that the childhood and
adult forms are the same illness," said Rapoport, Chief of the NIMH Child
Psychiatry Branch. "Understanding what's happening in these young people
during this period of highly volatile brain development may provide clues
about risk factors and neurodevelopmental abnormalities involved in the much
more common adult onset schizophrenia. Adults with the disorder may well
have experienced the same kind of abnormal brain changes during their teens."
Affecting about 1 percent of adults, but only about .005 percent of
children, schizophrenia is the most chronic and disabling mental illness.
It typically begins as a psychotic episode in young adulthood, with
devastating hallucinations, delusions, social withdrawal, blunted
emotionality and loss of social and personal care skills. A new generation
of antipsychotic medications, such as clozapine, has helped many patients
manage their symptoms with fewer side effects.
In the MRI study, the researchers compared scans of 16 ill teenagers
participating in a clozapine trial with those of 24 age-matched controls.
At the initial scan, the youths with schizophrenia tended to show enlarged
ventricles, 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. The
controls 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 held
that schizophrenia likely stems from damage caused by a prenatal event -
such as a viral infection in the womb, or some other environmental insult
to the developing brain -- that interacts with normal brain development and
life stresses, in genetically vulnerable individuals, to produce the
disorder in young adulthood. While not one of its original tenets, the
findings of progressive brain changes in adolescence are not inconsistent
with 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 motor and
speech development. Adolescents in the study who had histories of such
autistic-like behavior tended to show greater ventricular enlargement.
Childhood onset schizophrenia also tends to be harder to treat and to have a
worse prognosis than the adult onset form. However, in a series of studies
over the past few years, Rapoport's group has shown that affected children
share with adults a similar pattern of brain structure abnormalities and
physiological features. For example, in the study led by Zahn, the
researchers report that the ill children had skin conductance and heart rate
anomalies similar to those seen in affected adults.
In interpreting the imaging findings, Rapoport and colleagues suggest that
the scans captured changes in the brain during a critical period in
development when it is "uniquely sensitive" to effects of the illness. It's
unlikely that the ventricles would continue enlarging at such a high rate,
"as that would produce improbably large ventricular volume later in life,"
they note. Also, the "possibility that clozapine treatment accelerates
adolescent brain change can not be ruled out," they add.
The 16 affected adolescents in the study were the first 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 designed to provide data on
normal brain development during childhood and adolescence.
"The study of childhood onset cases presents a unique approach to
schizophrenia," said Rapoport. "If we can understand what turns on the
illness in these rare cases, it may provide clues about how to turn it off
Also participating in the study were Drs. Jay Giedd, Sanji Kumra, Leslie
Jacobsen, and Amy Smith, Paul Lee, Jean Nelson and Susan Hamburger.
NIMH is a component of the National Institutes of Health, an agency of the
U.S. Department of Health and Human Services.