Imaging clues to schizophrenia.

Schizophrenia unhinges mental life with an array of tools that includes hallucinations and delusions, incoherent trains of thought, inappropriate or blunted emotions, and a deepseated sense of apathy. The search for schizophrenia's roots has yet to yield any clear-cut cerebral culprits.

However, a study in the Oct. 14 SCIENCE suggests that this debilitating condition may spring from abnormalities in the thalamus and areas throughout the brain with anatomical links to that structure. Prior evidence suggests that the thalamus -- located deep within the brain -- helps to focus attention, filter sensations, and process other types of information.

Troubles in the thalamus and its related structures, which extend from above the spinal cord to behind the forehead, can create the full range of symptoms observed in schizophrenia, suggest psychiatrist Nancy C. Andreasen and her colleagues at the University of Iowa Hospitals and Clinics in Iowa City.

Andreasen's team took magnetic resonance imaging (MRI) scans of the brains of 47 healthy men and 39 men diagnosed with schizophrenia. They then transformed each brain image onto the same three-dimensional space. The average intensity of the magnetic signal in each unit of those images was computed for men in the two groups, yielding an average schizophrenic brain and an average healthy brain.

Then the team subtracted the average schizophrenic brain from its healthy counterpart to identify areas in which the two differed most. The greatest contrast in signal strength emerged for the thalamus and adjacent tissue that lead to the front of the cortex. Schizophrenic men also displayed a substantially smaller thalamus than the comparison men.

Most abnormalities appeared in the brain's right hemisphere, a finding that contrasts with many previous studies that have emphasized left-hemisphere problems in schizophrenia.

Impairment of the brain circuitry that runs through the thalamus, which perhaps occurs before or shortly after birth, may represent a "core disturbance" that underlies the various manifestations of schizophrenia, Andreasen proposes.

However, it remains unclear whether the deficits noted in her study apply only to schizophrenia or to other severe psychiatric disorders as well. Researchers must also clarify whether these abnormalities primarily cause schizophrenia or result from years of antipsychotic drug use.

"This new study is a novel, interesting approach, but what it means about brain pathology in schizophrenia is difficult to interpret," asserts Daniel R. Weinberger, a psychiatrist at the National Institute of Mental Health in Bethesda, Md.

For example, the implication of differences in MRI-produced images for actual brain function remains unknown, Weinberger holds. Andreasen's group also replicated prior findings that schizophrenic men have smaller brains with larger fluid-filled spaces, a trait that may play a greater role in this condition than thalamic abnormalities, he adds.