New York, NY (February 16, 2018)-Researchers at Columbia University Irving Medical Center (CUIMC) and New York State Psychiatric Institute (NYSPI) found that people with schizophrenia who experience auditory hallucinations tend to hear what they expect, an exaggerated version of a perceptual distortion that is common among other people without hallucinations. Those with hallucinations and other psychotic symptoms are known to have elevated dopamine, the main area of focus for available treatments for psychosis, but it was unclear how this could lead to hallucinations. The researchers found that elevated dopamine could make some patients rely more on expectations, which could then result in hallucinations.
The findings, published recently in Current Biology, explain why treatments targeting the production of dopamine could help alleviate this condition.
"Our brain uses prior experiences to generate sensory expectations that help fill in the gaps when sounds or images are distorted or unclear," said Guillermo Horga, MD, PhD, assistant professor of clinical psychiatry at CUIMC and a research psychiatrist at NYSPI. "In individuals with schizophrenia, this process appears to be altered, leading to extreme perceptual distortions, such as hearing voices that are not there. Furthermore, while such hallucinations are often successfully treated by antipsychotic drugs that block the neurotransmitter dopamine in a brain structure known as the striatum, the reason for this has been a mystery since this neurotransmitter and brain region are not typically associated with sensory processing."
The researchers designed an experiment that induces an auditory illusion in both healthy participants and participants with schizophrenia. They examined how building up or breaking down sensory expectations can modify the strength of this illusion. They also measured dopamine release before and after administering a drug that stimulates the release of dopamine.
Patients with hallucinations tended to perceive sounds in a way that was more similar to what they had been cued to expect, even when sensory expectations were less reliable and illusions weakened in healthy participants. This tendency to inflexibly hear what was expected was worsened after giving a dopamine-releasing drug, and more pronounced in participants with elevated dopamine release, and more apparent in participants with a smaller dorsal anterior cingulate (a brain region previously shown to track reliability of environmental cues).
"All people have some perceptual distortions, but these results suggest that excess dopamine can exacerbate our distorted perceptions," said Dr. Horga. "Novel therapies should aim to improve the processing of contextual information by targeting the dopamine system or downstream pathways associated with modulation of perceptual processing, which likely include the dorsal anterior cingulate cortex."
The study is titled "A perceptual inference mechanism for hallucinations linked to striatal dopamine."
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Funding for this study was provided by grants K23-MH101637 (PI: Horga), P50-MH086404 (PI: Abi-Dargham), R21-MH099509 (PI: Abi-Dargham), and R01MH068073 (PI: Balsam) from the National Institute of Mental Health. Dr. Cassidy was supported by a post-doctoral fellowship from the Fonds de Recherche du Québec, Santé. Dr. Horga was additionally supported by a grant from the Sidney R. Baer Jr. Foundation. The authors declare no competing financial interests.
The other contributors from CUIMC and NYSPI are Clifford M. Cassidy, PhD, Peter D Balsam, PhD, Jodi J. Weinstein, MD, Rachel J. Rosengard, BA, and Anissa Abi-Dargham, MD.
Columbia University Department of Psychiatry/New York State Psychiatric Institute
New York State Psychiatric Institute was founded in 1896 and has been closely affiliated with the Columbia University Department of Psychiatry since 1925. NYSPI/Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. It is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders and childhood psychiatric disorders. Their combined expertise provides state of the art clinical care for patients, and training for the next generation of psychiatrists and psychiatric researchers.
Columbia University Irving Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Irving Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.
Journal
Current Biology