NEW YORK, NEW YORK — The inability to hear subtle changes in pitch, a common problem for people with schizophrenia, is due to dysfunctional N-methyl-D-aspartate (NMDA) brain receptors, according to a study by researchers at Columbia University Medical Center. The study also found that this particular hearing issue can be improved by combining auditory training exercises with a drug that targets the brain’s NMDA receptors.
The results of the study were published last week in the journal Brain.
“Slight variations in our tone of voice are an important way of communicating emotions, such as happiness or sadness. This inability to detect subtle changes in pitch can also make it difficult to sound out words while reading, with over 70 percent of patients meeting criteria for dyslexia and further exacerbating communication problems in social and work situations. But while psychiatrists have recommended medications for symptom control, these treatments have not addressed the underlying auditory deficits.” –Joshua T. Kantrowitz, MD
Lead study author Dr. Joshua Kantrowitz, and his colleagues, compared the results of 40 stabilized schizophrenia patients and 42 healthy controls. As part of the study, each subject listened to a series of tone pairs and was asked to indicate which tone was higher. Based on a subject’s performance, the difficulty of the task was changed for the next pair of tones. When subjects correctly identified the higher tone, the pitch difference in subsequent tone pairs decreased; when subjects failed to identify the higher tone, the tones were moved further apart.
As expected, the healthy controls performed better at discriminating between the two tones as the study progressed. On average, the control group was able to distinguish between tones with a difference in pitch of as little as 3 percent. In contrast, the patients with schizophrenia did not improve as much, detecting an average 16 percent difference in pitch.
While undergoing the auditory exercises, EEG recordings were taken on both groups. The recordings revealed that the schizophrenia patients had lower brainwave activity than the controls, which suggests impaired auditory sensory cortex functioning and a reduced response to training exercises.
Schizophrenia: NMDA Receptors Causing Auditory Deficit?
Dr. Kantrowitz and his colleagues suspect that schizophrenia patients’ inability to improve their pitch discrimination is caused by dysfunction in their NMDA receptors, which are critical for learning and memory. Thus, if true, improving NMDA activity would improve the ability to discriminate between pitches.
In order to test the hypothesis, some schizophrenia patients in the study were given D-serine, which is an amino acid that activates NMDA receptors. The D-serine would be given once a week for up to three weeks, while others were given a placebo.
The patients saw a significant improvement in pitch detection with auditory training but only when D-serine was taken for two consecutive weeks. There was no improvement seen in patients who took D-serine only once or in those that took only a placebo.
“What’s important is that we now know that people with schizophrenia can improve their pitch detection with a combination of auditory training exercises and repeated doses of a learning-enhancing drug that affects the NMDA receptor,” said Dr. Kantrowitz. He added further that “it remains to be seen whether D-serine or another NMDA-activating drug is best suited for this purpose.”