A region of the hippocampus appears to be uniquely activated during
functional magnetic resonance imaging (MRI) among individuals who later go on
to develop psychosis.
Using cerebral blood volume mapping, the region—known as the CA1
subfield of the hippocampus—was found to be hyperactive among those
individuals who were at high risk of psychosis and who later developed a
first-episode psychotic disorder. Moreover, hyperactivity in the CA1 subfield
also tracked positively with increasing severity of delusional symptoms and
with avolition and social withdrawal—two "negative" symptoms
associated with worsening
The report appeared in the September Archives of General
Psychiatry. The lead author is Scott Small, M.D., the Herbert Irving
Associate Professor of Neurology in the Sergievsky Center and in the Taub
Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia
University Medical Center.
"Functional imaging can tell you where in the brain something is
happening, not what is happening," said first author Scott Schobel,
M.D., an assistant professor of clinical psychiatry at Columbia University
College of Physicians and Surgeons, in an interview with Psychiatric
News. "But what this hyperactive state strongly suggests is an
increase in metabolism that is plausibly linked to dysfunction in the
Though far from conclusive, the finding points to the possibility in the
future of a screen for determining which high-risk (or"
prodromal") patients are likely to go on to develop a
first-episode psychosis. Using clinical criteria today, clinicians can
reliably predict approximately 50 percent to 60 percent of high-risk
individuals who will go on to develop a psychotic disorder.
"The idea would be that one could use brain imaging as a snapshot of
illness severity within the CA1 subfield," Schobel said. "It could
potentially be used to identify those within the high-risk population who have
abnormal activity above a certain threshold to selectively target this group
with clinical treatments aimed at preventing illness progression, including
potentially a glutamate-modulating therapy and/or cognitive
Schobel said the study relied on a new high-resolution MRI technique
developed by Small. In the study, cerebral blood volume mapping with the new
technique was used on 18 patients with schizophrenia, 18 age-matched, healthy
control subjects, and 18 individuals with prodromal psychosis.
In a first between-group analysis comparing patients with schizophrenia and
controls, abnormal cerebral blood volume (CBV) was found in the CA1 subfield
and in the orbitofrontal cortex; abnormal decreases in CBV were found in the
dorsolateral prefrontal cortex. In a second longitudinal analysis, abnormal
CBV increases in the CA1 subfield predicted clinical progression to psychosis
among the 18 prodromal individuals.
Finally, a third analysis showed that CBV levels in the CA1 subfield
correlated with severity of symptoms of psychosis.
"Progressive hyperfunctionality of the CA1 subfield was positively
associated with worsening delusional severity," Schobel told
Psychiatric News. "That was also found in the groups when you
looked at them separately—in both [the prodromal and schizophrenia]
groups, worsening delusions were associated with greater hyperactivity.
"Moreover, in the prodromal group, hyperactivity also tracked
positively with avolition and social withdrawal," Schobel said. The
latter are negative symptoms associated with worsening outcome.
The findings are an important first step in the effort to prevent
schizophrenia or to more rapidly treat those who do experience a first-episode
In a statement released by Columbia University announcing the study,
Jeffrey Lieberman, M.D., who is leading a new effort at the National Institute
of Mental Health to develop optimal treatments for first-episode psychosis,
cited the benefits of early intervention.
"Research has shown that early intervention and treatment can prevent
the debilitating effects of schizophrenia by dramatically slowing progression,
reducing mortality and disability, and increasing recovery of one of mankind's
most costly mental disorders," said Lieberman, who is Lawrence E. Kolb
Professor and chair of the Department of Psychiatry at Columbia University and
director of the New York State Psychiatric Institute.
An abstract of "Differential Targeting of the CA1 Subfield of
the Hippocampal Formation by Schizophrenia and Related Disorders" is