Philadelphia, PA, May 8, 2012 It is increasingly recognized that chronic psychotropic drug treatment may lead to structural remodeling of the brain. Indeed, clinical studies in humans present an intriguing picture: antipsychotics, used for the treatment of schizophrenia and psychosis, may contribute to cortical gray matter loss in patients, whereas lithium, used for the treatment of bipolar disorder and mania, may preserve gray matter in patients.
However, the clinical significance of these structural changes is not yet clear. There are many challenges in executing longitudinal, controlled, and randomized studies to evaluate this issue in humans, particularly because there are also many confounding factors, including illness severity, illness duration, and other medications, when studying patients.
It is therefore critical to develop animal models to inform the clinical research. To accomplish this, a group of researchers at King's College London, led by Dr. Shitij Kapur, developed a rat model using clinically relevant drug exposure and matched clinical dosing in combination with longitudinal magnetic resonance imaging. They administered either lithium or haloperidol (a common antipsychotic) to rats in doses equivalent to those received by humans. The rats received this treatment daily for eight weeks, equivalent to 5 human years, and underwent brain scans both before and after treatment.
Dr. Kapur explained their findings, "Using this approach, we observed that chronic treatment with haloperidol leads to decreases in cortical gray matter, whilst lithium induced an increase, effects that were reversible after drug withdrawal." Gray matter was decreased by 6% after haloperidol treatment, but increased by 3% after lithium treatment.
"These important observations clarify conflicting findings from clinical trials by removing many of the confounding effects," commented Dr. John Krystal, Editor of Biological Psychiatry. "
|Contact: Rhiannon Bugno|