Text: By Erik Freudenreich
Photo: DR

Daniel Javitt: “We should pay more attention to how patients perceive their environment”

Professor Daniel Javitt has been studying how the brain functions for many years. The unit that he oversees at Columbia University in New York studies the effects of glycine in treating certain disorders of perception.

IN VIVO Is it accurate to say that perception is one of the main focuses of your research?

DANIEL JAVITT I’m especially interested in perception from the point of view of schizophrenia. My work is based on what are called N-methyl-D-aspartate (NMDA) receptors, which can be found in the visual and auditory cortex. Our studies have revealed a link between NMDA dysfunction and perception disorders such as schizophrenia. Schizophrenia patients often explain that the world feels like it’s been shattered into a thousand pieces, that things go too fast.

Scientists, such as psychiatrists, long ignored these remarks, because they believed that the schizophrenia psychosis only involved the frontal cortex and dopamine receptors. But once we establish the relationship between the pathology and NMDA receptors, the patients’ description sounds more logical. We generally don’t pay enough attention to the way mentally ill patients perceive their environment.

IV Why did you decide to study schizophrenia?

DJ When I was finishing medical school, the United States had a serious problem with PCP, a synthetic drug that became the subject of my dissertation. Curiously, people under the influence of PCP display the same symptoms as patients with schizophrenia. The fact that the effects of the disease could be reproduced by taking a chemical substance meant that there was a very basic problem behind the illness. We were then able to identify a dysfunction in the NMDA receptors, which are essential for memory and neural connections. That’s where the idea came up that we could stimulate these receptors with glycine to treat schizophrenia.

Daniel Javitt is at the forefront of global research on new treatments for serious mental disorders.

IV Patients with schizophrenia can suffer from auditory hallucinations. What causes them?

DJ You should turn that question around. Why don’t healthy people normally have hallucinations? If you take a subject who do not have schizophrenia and place them in an airtight container that cuts out all sound, they too will begin hearing things. Actually, it’s the constant flow of information from the outside world that keeps us from going deep into our thoughts and hearing those voices. Interestingly, if you analyse the brain images while someone with schizophrenia is experiencing an auditory hallucination, you can see that the areas of the brain that process language are activated. It’s not merely a cognitive problem, but also a sensory one. The patient’s brain reacts as if it’s truly perceiving the voices.

IV What about optical illusions?

DJ We’ve been studying the phenomenon for a long time. These illusions cause different reactions in the brain. Some of our patients react normally, while others are extremely sensitive to certain optical effects. The Hermann grid illusion is one that causes them the most problems. You are normally supposed to see grey patches at the intersections of the lines on the grid because your brain is trying to stick the pieces of the puzzle back together. That’s not what happens in schizophrenia, as the neural interconnections used to see these patches are not operational. In fact, you could say that their perception of the grid corresponds to reality.

IV How many years until we have a good understanding of our brain?

DJ We will never be able to completely understand how it works. But today we have many tools that we can use to analyse and measure a number of major functions. Take my work or that of my colleague in Lausanne, Micah Murray, on what is called mismatch negativity. This phenomenon occurs when the brain processes an infrequent change in a repetitive sequence of stimuli in the brain. For example, if you live in the country, you automatically notice when the birds suddenly stop singing.

It’s a very important function encoded in our brain for survival in a hostile environment. We’ve been able to show that this function is produced by the NMDA receptors in the auditory cortex. What we try to do is help patients to activate the reflexes that they don’t currently have. Schizophrenia patients often lose the ability to read passages of information fluently, both because of difficulty in controlling taking in visual information and in sounding out complex words. These are important process that involves NMDA receptors. If we manage to repair this dysfunction, for example with the glycine-based treatments that we are currently studying, we will make a huge leap forward in rebuilding patients’ social and professional lives.



​Specialising in schizophrenia

With degrees in neuroscience and psychiatry, American scientist Daniel C. Javitt is at the forefront of global research on new treatments for serious mental disorders. He is the director of the Division of Experimental Therapeutics in the Department of Psychiatry at Columbia University in New York and the director of schizophrenia research at the Nathan Kline Institute, also based in New York.