Tardive Dyskinesia Etiology May Lie In Dearth of Key Brain Chemical

A paucity of a brain chemical known as brain-derived neurotrophic factor may play a role in the development of tardive dyskinesia, a new study suggests.

The study was conducted by Yun Long Tan, M.D., a Ph.D. candidate at Peking University in Beijing, China; Dong Feng Zhou, M.D., a professor of psychiatry at Peking University and chair of the Chinese Psychiatric Association; and Xiang Yang Zhang, M.D., Ph.D., associate research scientist at Yale University. Results are in press with Schizophrenia Research.

Brain-derived neurotrophic factor is the most abundant nerve-nourishing chemical in the brain. It is known to exert numerous effects on the central nervous system, such as regulating neuronal growth, bolstering the action of neurons that deploy various types of neurotransmitters, and assisting neurons that have been stressed and injured. Various lines of research have also suggested that the factor might be implicated in tardive dyskinesia. For example, tardive dyskinesia is linked with neuronal degeneration, and the factor can protect neurons from degeneration.

Tan and his coworkers set out to determine whether a deficiency of brain-derived neurotrophic factor might be involved in tardive dyskinesia. They selected as their subjects 80 schizophrenia patients with tardive dyskinesia, 45 schizophrenia patients without the disorder, and 45 mentally healthy individuals. All subjects lived in Beijing, and all three subject groups were comparable in age and gender.

While brain-derived neurotrophic factor is highly concentrated in the nervous system, it is also present in blood. Further, when the factor is present in blood, it can cross the blood-brain barrier into the brain, implying that levels of the factor in blood reflect levels in the brain. Thus, Tan and his colleagues measured levels of brain-derived neurotrophic factor in the blood of each of their subjects, then compared blood levels of the factor among the three groups.

Blood levels of the factor were significantly lower in the schizophrenia subjects with tardive dyskinesia than in schizophrenia subjects without it, and also significantly lower in the former than in the healthy control group, the researchers found. Moreover, subjects with more severe tardive dyskinesia had even lower blood levels of the factor than did subjects with less severe tardive dyskinesia.

“Our results suggest that decreased brain-derived neurotrophic factor may play an important role in the pathophysiology of tardive dyskinesia,” Tan and his group concluded.

One question raised by these results, Zhang told Psychiatric News, is whether giving brain-derived neurotrophic factor to patients with tardive dyskinesia might counter their tardive dyskinesia. He and his team will now conduct a double-blind, randomized, placebo-controlled trial to determine whether adding therapeutic amounts of brain-derived neurotrophic factor to antipsychotic therapy might subdue tardive dyskinesia in schizophrenia patients. To date, there is no standard treatment for the disorder.

The study was funded by the Chinese National Science Foundation, the Capital Medical Development Scientific Foundation of Beijing, and the Beijing Scientific and Technological New Stars Fund.

An abstract of “Decreased Plasma Brain-Derived Neurotrophic Factor Levels in Schizophrenia Patients With Tardive Dyskinesia: Association With Dyskinetic Movements” can be accessed online at<www.sciencedirect.com> by clicking on “Browse A-Z of journals,” “S,” and“ Schizophrenia Research” and searching on title.▪