Mail & Guardian

Mice give new clues into mental illness

- Boitumelo Kgobotlo

Scientists had presumed that a mouse brain was too different from a human brain to be used for psychiatri­c research. But the link between the two can be used to understand the neurobiolo­gical roots of mental illness and help develop psychiatri­c therapies.

This was found by the Washington University of Medicine in St Louis after they developed a computer game that will assist in finding the cause of schizophre­nia in both people and mice. The research is premised on the fact that there has not been enough progress in understand­ing the basic mechanisms underlying psychosis. Studying psychotic disorders in animal models is difficult because the diagnosis relies on selfreport­ed symptoms that can only be assessed in humans.

The study was released this month in the journal Science and was titled Striatal Dopamine Mediates Hallucinat­ionlike Perception in Mice.

According to the National Institute for Mental Health, schizophre­nia is a mental illness affecting behaviour, emotions and thinking abilities – it makes people feel they have lost touch with reality, resulting in distress.

The mental illness can cause the individual to lose touch with close relatives and friends or have troubles engaging in personal relationsh­ips, while also finding it challengin­g to focus on daily activities such as work or exercises – but treatment is available and most effective when delivered on time.

Both humans and the lab mouse had to participat­e in the game by listening to different sounds. Tone signals were embedded in a noisy background on half of the trials. Humans pressed one of two buttons to report whether or not they heard a signal, whereas mice poked into one of two choice ports. Humans indicated how confident they were in their report by positionin­g a cursor on a slider. Mice expressed their confidence by waiting to earn rewards.

In humans, hallucinat­ion-like percepts, defined as high-confidence false alarms, were correlated with the tendency to experience spontaneou­s hallucinat­ions, as quantified by a self-report questionna­ire.

In mice, hallucinat­ionlike percepts increased with two manipulati­ons known to induce hallucinat­ions in humans: administra­tion of ketamine and the heightened expectatio­n of hearing a signal.

It was found that expecting to hear the sound made the subjects confidentl­y believe that they heard it even when it was not playing.

The research found that dopamine, the happy neurochemi­cal messenger, affected triggering hallucinat­ions, but how it changes the brain to produce these hallucinat­ions is still a mystery. According to the research, these findings support the idea that hallucinat­ions arise as faulty perceptual inferences due to elevated dopamine, producing a bias favouring prior expectatio­ns against current sensory evidence. “Our results also yield circuit-level insights into the long-standing dopamine hypothesis of psychosis and provide a rigorous framework for dissecting the neural circuit mechanisms involved in hallucinat­ions. We propose that this approach can guide the developmen­t of novel treatments for schizophre­nia and other psychotic disorders.”

The study’s senior author, neuroscien­ce professor Adam Kepecs, said the prognosis for psychotic patients hadn’t improved as the neurobiolo­gy of the illness was still unknown.

“We think that hallucinat­ions occur when these neural circuits get unbalanced, and antipsycho­tics rebalance them. Our computer game probably engages this same circuit, so hallucinat­ion-like events reflect this circuit imbalance,” he said.

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