Delusions Linked to Brain Region, But Why?

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 temporal lobes.

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 psychotic process.

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 formation.”

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 delusions.

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 psychiatric disorders.”

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 online at<http://ajp.psychiatryonline.org/cgi/content/full/161/9/1612>.▪