November 26, 2001

About five years ago, I was diagnosed with schizophrenia. Fortunately, medication works well to manage the illness. Occasionally, I experience a flare-up of symptoms, but my wife and I are very good about detecting the early warning signs. Please explain, without too many technical terms, the structural differences between the brains of persons with schizophrenia and those without the illness.

Of all the methods used to investigate biological abnormalities in psychiatric illnesses, structural neuroimaging studies such as CAT (computed axial tomography) and MRI (magnetic resonance imaging) measurements have provided some of the most consistent evidence for brain abnormalities in people with schizophrenia. However, these studies show subtle rather than dramatic changes, and the findings are not seen in all cases of schizophrenia, so they are not useful as clinical tests for making the diagnosis of the disorder.
The first report by Eve Johnstone and Tim Crow from England in 1976, using CAT scans, showed enlargement in the brains in schizophrenic patients of the fluid-filled spaces normally found in the brain.

The entire cortex (gray matter) of the brain in schizophrenia is, on average, smaller in volume by only about 5 percent than in healthy people without the disorder. However, this loss is not equally distributed in all brain regions. Recent MRI methods generally show specific deficits in gray matter volumes of around 20 percent in frontal and temporal regions of the brain. Such studies suggest the most notable brain changes in schizophrenia occur in a very organized and interconnected brain system that includes areas that normally help us to process speech and language, make complicated decisions and learn rules.

These regions are most developed in humans, (which may explain why schizophrenia only occurs in humans) and they may be especially vulnerable to disruptions in nerve cell function or in making connections during brain development in the fetus. These areas mature more slowly than other brain regions. Therefore, a process occurring during a particular brain development
phase might affect these regions but spare others. Secondly, th e development of these brain regions is lengthy, extending into early adult life. These frontal and temporal lobe regions only fully "come on line" in late adolescence, (which may explain why schizophrenia typically begins during this period of life).

The normal brain is asymmetrical; some regions are larger on the left or right side. These asymmetries appear disturbed in schizophrenia. For example, some research has found a reversal of the normal left-right relationship of temporal lobe speech areas in the brain. This abnormality seems to be connected with the tendency of people with schizophrenia to "hear voices" and to show speech disturbances when acutely ill. There is also evidence for disturbed connections between different brain regions in schizophrenia.

However, the cause and mechanism of all of these brain abnormalities remains unknown. Ongoing advances in structural neuroimaging technology promise that more fine-tuned approaches for investigating the brain in schizophrenia become available, allowing researchers to match up the anatomical findings with clinical, cognitive, postmortem, functional neuroimaging and EEG (electro encephalogram) data.

Godfrey Pearlson, MD
Johns Hopkins Medicine Institute
Baltimore