A lesser-known but common and debilitating symptom in schizophrenia patients is the inability to hear subtle changes in pitch. Now a new study by researchers at Columbia University Medical Center (CUMC) shows that this condition may be due to dysfunctional N-methyl-D-aspartate (NMDA) brain receptors. The researchers say this hearing issue may be improved by combining auditory training exercises with a drug that targets NMDA receptors.
“Slight variations in our tone of voice are an important way of communicating emotions, such as happiness or sadness,” said lead author Joshua T. Kantrowitz, MD, assistant professor of clinical psychiatry at CUMC.
“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.”
For the study, the researchers compared auditory plasticity (the ability to learn from hearing tasks) in 40 stabilized schizophrenia patients and 42 healthy controls. Each participant listened to a series of tone pairs and was asked to indicate which tone was higher. Depending on the participant’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 were incorrect, the tones were moved further apart.
In the first tone sample, there was a 50 percent difference in the pitch of the tones (e.g., 1,000 Hz and 1,500 Hz). On average, the healthy controls were able to discern between tones with a difference in pitch as little as 3 percent, while patients with schizophrenia did not improve as much, detecting an average 16 percent difference in pitch.
“People with normal auditory plasticity usually get better at discriminating between the two tones as the test progresses, reflecting the ability to learn,” said Kantrowitz. “And that was the case with the healthy controls in our study.”
EEG recordings taken during the exercises also revealed that the schizophrenia patients had lower brainwave activity than the controls. Lower brainwave activity is connected to impaired auditory sensory cortex functioning and a reduced response to the training exercises.
The research team suspected that the schizophrenia patients’ inability to improve their pitch discrimination was due to dysfunction in the NMDA receptors, which are critical for learning and memory. If their hypothesis was true, then improving NMDA activity would also enhance their ability to detect variation in pitch.
To test this theory, some schizophrenia patients in the study were given D-serine, an amino acid that activates NMDA receptors, once a week for up to three weeks, while others were given a placebo. In patients who took D-serine for two consecutive weeks, their ability to detect pitch significantly improved. No improvement was seen in patients who took D-serine only once or in those who took a placebo.
“It remains to be seen whether D-serine or another NMDA-activating drug is best suited for this purpose,” said Kantrowitz. “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 effects the NMDA receptor.”
The findings are published online in the journal Brain.
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