Where in the dark depths of the human brain do things go awry to create the
positive symptoms of schizophrenia and related disorders?
So far, auditory hallucinations have been linked with a small left temporal
gyrus, which is on the upper part of the left temporal lobe.
And now small left and right entorhinal cortexes have been associated with
delusions. These cortexes are located in the inner parts of the left and right
The study was led by Konasale Prasad, M.D., a research fellow at the
University of Pittsburgh, and findings appear in the September American
Journal of Psychiatry.
The entorhinal cortex functions as a relay station between the prefrontal
cortex and the hippocampus. It holds real sensory information while the
hippocampus compares such information with internal representations to detect
familiarity versus novelty. Because findings regarding the entorhinal cortex
and schizophrenia are conflicting, Prasad and his coworkers wanted to see
whether the size of the entorhinal cortex in psychosis subjects differs from
that in mentally healthy subjects.
Prasad and his colleagues used high-resolution structural MRI scans and a
previously validated method of defining the entorhinal cortex to examine
entorhinal cortex volume in 44 subjects who were experiencing their first
episode of psychosis and who had not yet been put on antipsychotic
medications. They then used the same methods to examine entorhinal cortex
volume in 43 mentally healthy subjects.
All subjects were rated on the Scale for the Assessment of Positive
Symptoms and the Scale for the Assessment of Negative Symptoms.
The left entorhinal cortex was about 10 percent smaller in the subjects
with psychosis than in the mentally healthy subjects, they found, and the
right entorhinal cortex was about 6 percent smaller in the former. This
finding implicates both the left and the right entorhinal cortexes in the
The researchers then attempted to determine whether entorhinal cortex size
in the psychotic subjects correlated with delusions, hallucinations, or
negative symptoms. They found that it was linked only with delusions, implying
that the entorhinal cortex plays some role in delusions.
The scientists then compared entorhinal cortex size in the mentally healthy
subjects with that in the 35 psychosis subjects who were delusional and in the
five psychosis subjects who were not delusional. The subjects who were
delusional had somewhat larger left and right entorhinal cortexes than the
subjects with psychosis who were not delusional, yet their entorhinal cortexes
were still not as large as those of the mentally healthy subjects.
The researchers said that they did not expect this result. They had
anticipated that psychotic subjects with delusions would have even smaller
left and right entorhinal cortexes than psychotic subjects without delusions.
The investigators aren't sure how to interpret this finding. But as Prasad
told Psychiatric News, the fact that "we found that the
entorhinal cortex volume of delusional subjects was not very different from
that of healthy subjects, whereas that of nondelusional subjects was
significantly smaller suggests that either normal function or near-normal
function of the entorhinal cortex is required for delusion
But how might an almost normally sized entorhinal cortex be associated with
delusions? Prasad suggests that since his team found a smaller parahippocampal
gyrus in delusional psychotic subjects than in nondelusional psychotic
subjects, and the parahippocampal gyrus feeds information from the prefrontal
cortex to the entorhinal cortex, it's possible that an abnormally small
parahippocampal gyrus might present corrupted information to the entorhinal
cortex. This corrupted information may then be kept as a sensory template in
the entorhinal cortex for the hippocampus to compare and retrieve information
from the neocortex.
The hippocampus, he suggested, might then retrieve old, irrelevant
memories; the amygdala might then add emotional salience to the memories; and
the old, irrelevant, emotionally charged memories might then crystallize into
Matcheri Keshavan, M.D., a professor of psychiatry at the University of
Pittsburgh and one of the study authors, suggested how the study's findings
could play a role in clinical practice. "If these findings are
confirmed," he told Psychiatric News, "it may eventually
help psychiatrists to identify brain-imaging markers that can help monitor the
nature, course, and treatment response of delusions in schizophrenia and other
The study was financed by the National Institutes of Health.
The study, "The Entorhinal Cortex in First-Episode Psychotic
Disorders: A Structural Magnetic Resonance Imaging Study," is posted
Am J Psychiatry20041611612