UI Study Ties Drugs to Brain Tissue Loss in Schizophrenia
February 7, 2011
Using magnetic resonance imaging (MRI) to track how brain volumes change over time, University of Iowa researchers have found that antipsychotic medications commonly used to treat schizophrenia appear to contribute to the loss of brain tissue that sometimes occurs in patients with this condition.
The findings, which are published in the February issue of the Archives of General Psychiatry, suggest that physicians should consider using the lowest effective dose of antipsychotics when treating patients with schizophrenia. However, lead study author Beng-Choon Ho, MD, associate professor of psychiatry in the UI Carver College of Medicine, notes that the study does not mean that patients with schizophrenia should not be treated with antipsychotic medications.
"Antipsychotic medications are still the most important and effective form of treatment for schizophrenia patients," Ho said. "These medications reduce psychiatric symptoms and prevent relapse in patients. What our study suggests is that careful review of risks and benefits of dosage and duration is very important."
Schizophrenia affects 1 percent of the world's population and is a leading cause of chronic disability among young adults. On average, progressive loss of brain tissue occurs at a faster rate in patients with schizophrenia than in normal comparison groups.
It has been assumed that brain volume reduction in schizophrenia is mostly a consequence of the disease process. However, animal studies have shown that antipsychotic treatment can reduce brain volume.
To investigate what factors may contribute to progressive brain volume reductions after illness onset, the UI team obtained serial MRI brain scans of 211 patients with schizophrenia starting soon after the patients were diagnosed. Each patient had, on average, three scans and was followed for an average of seven years. The study examined the relationships between changes in the volume of gray matter and white matter in the patients' brains and four potential contributing factors -- illness duration, the amount of antipsychotic treatment, illness severity and alcohol or illicit drug use.
"The main finding is that more antipsychotic treatment is associated with smaller volumes of gray matter and with greater reductions in white matter volume over time," Ho said.
The researchers also found that these relationships between more antipsychotic treatment and reduced brain volume were still present even after the effects of the other three factors were taken into account.
In addition to their use in schizophrenia, antipsychotic medications also are increasingly used to treat other conditions, including depression and bipolar disorder, and in managing behavioral disorders in children and elderly individuals. The study findings raise the possibility that reduction in brain volume could be a potential effect when antipsychotic drugs are used to treat these conditions.
"We do not know if antipsychotics are related to brain volume reductions in other patients receiving antipsychotic treatment," Ho said. "Clinicians and patients with other mental conditions should review the benefits and potential risks of antipsychotic treatment."
In addition to Ho, the UI research team included Nancy Andreasen, MD, PhD, professor of psychiatry who holds the Andrew H. Woods Chair of Psychiatry; Steven Ziebell; Ronald Pierson; and Vincent Magnotta, PhD, associate professor of radiology.
The study was funded in part by grants from the National Institute of Mental Health.