Links between hallucinations and dopamine

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. Human brain uses prior experiences to generate sensory expectations that fill in the gaps when sounds or images are distorted or unclear.

In individuals with schizophrenia, this process appears to be altered, leading to extreme perceptual distortions, such as hearing voices that are not existing. 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 human distorted perceptions
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Links between sleep, cognition and schizophrenia

Schizophrenia is associated with wide range of symptoms including visual and auditory hallucinations, cognitive problems and motivational issues.
People with the disease have trouble with learning and memory, cognition and a compound called kynurenine.
Kynurenic acid is a neuroactive metabolite of kynurenine that is formed in the brain. People with schizophrenia have higher than normal levels of kynurenic acid in their brains.

These higher levels might be connected with a range of symptoms seen in the disease like problems with learning and memory. The mechanisms underlying the cognitive impairments in patients is not clear. An interplay between higher kynurenic acid and sleep could be responsible. There is a lot of evidence in both humans and animals that sleep dysfunction leads to problems with learning and memory. People with schizophrenia often have problems with sleep.

Researchers examined rat, they made comparisons in the behavior of rats with increased kynurenic acid in their brains to animals with normal levels of the compound. They connected the animals' brains to a device that measured the amount and quality of sleep, and found that the animals with higher levels of kynurenic acid had significantly less rapid eye movement.

This is the sleep phase in which dreams occur, and it is thought to be critical for the consolidation of previous learning.
The researchers found that the group with high kynurenic acid also had problems with learning. To test this, they place rats in a box and shine light into the box. On one side of the box there is an opening into a darker area.

Rats are nocturnal animals, and prefer the dark, so the animals typically run to the dark area. Once in this area, they receive a small electric shock. When the experiment is repeated the next day, normal animals do not run to the dark location because of the electric shock. By comparison, animals with increased levels of high kynurenic acid, and impaired sleep, do not remember the shock and run into the dark area.

Kynurenic acid disrupts sleep, which then disrupts cognition. However, disruptions in sleep may cause increased kynurenic acid, which then leads to cognitive problems. Reducing kynurenic acid could reduce problems with sleep and cognition in patients with schizophrenia. High levels of kynurenic acid are a crucial aspect of schizophrenia.
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