Neurologists and psychiatrists at Columbia University believe activity in the hippocampus may help predict the onset of the disease, offering opportunities for earlier diagnosis and for the development of drugs for schizophrenia prevention.
In the study, the researchers scanned the brains of 18 high-risk individuals with “prodromal” symptoms, and followed them for two years. Of those individuals who went on to develop first-episode psychotic disorders such as schizophrenia, 70 percent had unusually high activity in this region of the hippocampus, known as the CA1 subfield.
Although earlier studies have identified a more general increase in activity in the hippocampus in chronic schizophrenia, this research suggests that in the early stages of the illness, before symptoms are fully manifest, increased activity is evident only in this one sub-region and can distinguish who among high-risk individuals will go on to develop these disorders.
Brain scans accomplished by functional magnetic resonance imaging can measure brain metabolism, thereby indicating what parts of the brain are active during which activities. Mapping cerebral blood volume (CBV) is a method used in fMRI to measure this activity and it indicates increases or decreases in metabolism.
Using a novel high-resolution application of fMRI, pioneered by lead study investigator Scott A. Small, M.D., the researchers first compared 18 patients with schizophrenia to 18 healthy controls and observed abnormalities in multiple areas of the brains of the patients with schizophrenia.
Next, to learn which of those regions of the brain were targeted first in patients with first-episode psychotic disorders, like schizophrenia, the investigators imaged young people identified as being at high risk for psychosis, who were then followed for two years to determine diagnostic outcome.
“By applying this imaging technology to a population of high-risk individuals, we wanted to see if we could find an area of the brain that is selectively targeted,” said first author Scott A. Schobel, M.D., assistant professor of clinical psychiatry at Columbia and the New York State Psychiatric Institute.
“In comparing those high-risk individuals who developed psychosis with those who did not, we found that only the CA1 subfield was abnormal in those young people who went on to develop schizophrenia. We believe that this may give us an early snapshot of disease.”
“What many brain disorders have in common is that they are all relatively invisible to conventional imaging techniques,” said Dr. Small, 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.
“It is crucial to be able to visualize the most affected area of the brain and to pinpoint the region that is most vulnerable. This will give us clues into the causes of the disease.
“Our findings could help us improve diagnosis in the preclinical stage, which is most important because it is this stage of the disease that will be most amenable to treatment,” said Dr. Small.
Currently, no tests are available to diagnose schizophrenia. Diagnosis is mostly based on clinical symptoms after tests to rule out other possible causes. “Right now, the odds of knowing who will go on to develop schizophrenia from the prodromal stage is only a little better than a coin toss,” said Dr. Schobel.
Despite the strength of the findings in this small population of patients, imaging of a larger group and replication of the findings are necessary to clarify how accurate and specific this is for diagnosing preclinical schizophrenia.
“A larger study will determine if this is really a true biomarker that can be used as a diagnostic tool for identifying risk for schizophrenia on an individual basis,” said Dr. Small.
Details of the findings were published in the current issue of Archives of General Psychiatry.
Source: Columbia University