Atypical Antipsychotics Affect Brain Structures Differently

New research is furthering the abandonment of the casual moniker of “atypical antipsychotic,” casual because it loosely groups together as a class medications that are very different.

A report by University of North Carolina (UNC) at Chapel Hill researchers in Neuropsychopharmacology, posted online June 24, details changes in the volume of specific brain structures following administration of various antipsychotic medications to rats. At first pass, the results appear confounding, but after some analysis, they could actually explain varying clinical observations of patients taking different antipsychotic medications, according to the study’s lead author.

“I think that what this is saying, and is really becoming recognized,” Candace Andersson, Ph.D., a research assistant professor of psychiatry at UNC, told Psychiatric News, “is that the basal ganglia are going to be a very plastic area of the brain, and that is important for a number of reasons.”

Andersson noted that the field’s knowledge of what the basal ganglia do is expanding, moving from an early view that their function primarily involved movement to a view of the basal ganglia as a center not only for movement, but also as playing a significant role in cognition, learning, and memory. In addition, the basal ganglia have been shown in numerous studies, she said, to be an area of the brain that structurally reacts to changing levels of neurotransmitters, resulting in changes in the volume of the basal ganglia.

“Our study very much clarifies the human studies that have shown that this area is responsive to drug treatment,” Andersson said.

She and her colleagues administered either haloperidol, clozapine, olanzapine, or risperidone to young adult male rats for four to eight months through their drinking water. The researchers compared changes in the volume of the basal ganglia structures from baseline to the conclusion of medication administration in the study groups and matched controls.

“We saw specific increases in volume in animals that received either haloperidol or clozapine, compared with the control animals,” Andersson noted. “In animals receiving olanzapine, volume decreased significantly compared with the controls, and in the risperidone-treated animals, no significant difference was seen compared with the control animals.”

The group of researchers had set out to determine whether changes usually seen in human patients with schizophrenia were pathological in origin, a true drug effect, or perhaps a combination.

“We know that in schizophrenia, you see structural abnormalities in the brain, an increase in the lateral ventricles, and a decrease in the size of both the hippocampus and thalamus,” she explained. “So you have a brain that has already had some significant structural insults to it, and then you add a medication, and you see additional changes. One would think that this would not necessarily be a good thing to do.”

But, she said, the drug effects could well signify compensatory changes.

“We simply don’t have enough supporting information yet [from human studies] to separate out the drugs within the classes and say that these results are conflicting. This may actually completely explain what is going on clinically.”

What is clear, Andersson stressed, is that these drugs are very different from each other, not only in what receptors they interact with in the brain, but also in differences between low and high doses of the same drug affecting different receptor targets.

There are many more questions to answer, Andersson said.

“The thing to try to address once you really break out the individual drugs and look at the volumetric changes correlated with clinical observations. . .is by what cellular mechanism are you getting the varied volumetric changes and associated clinical response?”

“Striatal Volume Changes in the Rat Following Long-Term Administration of Typical and Atypical Antipsychotic Drugs” is posted on the Web at www.acnp.org/citations/Npp011402225. ▪