Martin Osugo, PhD

I became interested in psychosis in my first year studying undergraduate medicine. Like many people of that age, I began to think more philosophically than I had when younger. Questions such as “Do you perceive things the same way I do?”, “What is reality?”, “What makes us who we are?” and “Why do we behave the way we do?” were the subject of many debates between my friends and I at the time. If I’d been studying something other than medicine, my interest may have found a totally different outlet, but as a medical student, this most naturally aligned with schizophrenia, where perceptions, reality and identity are dramatically altered. I found learning about how the brain finds meaning much more profound and interesting than learning about medical diseases like heart failure.

I was initially attracted to the ideas of people like the psychotherapist and philosopher Carl Jung as I searched for answers to these questions.  Later, as I read more about current schizophrenia research, I was excited to hear that modern brain imaging techniques were now being used to gain further insights. My desire to work in the field of schizophrenia was confirmed when I moved to London and began practicing as a doctor. Part of this was seeing first-hand that psychosis disproportionately affected young black men like myself, and the feedback I received from several patients that they valued having a peer as their doctor and felt more able to relate to me as a result.

Soon after qualifying, I got the opportunity to work with Professor Oliver Howes, a world expert on schizophrenia. I worked clinically as a psychiatrist in our outpatient service for people with treatment resistant schizophrenia (TREAT), based at the Maudsley hospital. I also started my PhD (“The neurobiology of negative and cognitive symptoms of schizophrenia”) at King’s College London, which aimed to understand the reasons that people with schizophrenia don’t recover full functioning even after the psychosis is successfully treated.

In my work presented at SIRS 2024, I showed that healthy volunteers who received amisulpride (a dopamine blocking antipsychotic) for 7 days at a dose used to treat schizophrenia developed negative symptoms (reduced motivation, emotional expression and enjoyment of activities) that we often see in schizophrenia. I also found a mechanism in the brain which might explain this, showing that amisulpride reduced the activation of an important part of the brain’s reward centre (the caudate) during an MRI task where people could win money whilst in the scanner, and that these two things were related to each other – so people who had more severe negative symptoms after receiving amisulpride also had greater reduction in their brain’s reward response to winning money. I showed that this was not a general effect of all antipsychotics; I found that another antipsychotic, aripiprazole, did not have these effects in healthy volunteers who also received it for 7 days. We included this experiment with aripiprazole because amisulpride blocks dopamine receptors to a greater extent than aripiprazole. Aripiprazole is a more flexible drug which acts in a similar way to amisulpride when dopamine levels are high, but can also have the opposite effect when dopamine levels are low. I like to think of it as a bit like the difference between a dimmer switch (aripiprazole) and a standard light switch (amisulpride).

Our study was designed to show cause and effect clearly, in that we compared both drugs to placebo (sugar pills), and neither the people taking the medications or us as the investigators knew who was taking what (double-blind). We chose to do our study in healthy volunteers, because there can be other factors which might confuse the interpretation of cause and effect on motivation after taking antipsychotics in people with schizophrenia. The most important thing to consider is that they usually reduce the distressing symptoms of psychosis, and so people are likely to be able to take part in activities more just because of this. But we screened the healthy volunteers in our study to be sure that they didn’t have any impairments at the start of the study for any reason, so we could be confident that any effects we saw were because of the drug.

This means that our results show quite clearly what many people with schizophrenia know first-hand, which is that receiving dopamine blocking drugs like amisulpride for a prolonged period can cause problems with motivation, emotional expression and enjoyment of activities. It’s important to note that negative symptoms are common in schizophrenia even in people not taking an antipsychotic, and that the evidence overall shows that antipsychotics improve negative symptoms in schizophrenia (probably because of the effect on improving psychosis). However, our work suggests that people who are experiencing negative symptoms caused by a drug like amisulpride might benefit from switching to a drug more like aripiprazole and also guides researchers towards developing future treatments for schizophrenia which don’t cause these problems with processing reward or motivation. If interested, you can find more information in the published article.

I was able to address some of the questions I had as a student, looking specifically at how the dopamine system relates to determining human behaviour. In future, I look forward to trying to answer more questions about how other neurotransmitters relate to changes in perception and understanding of reality. I am very grateful for the Early Career Award from SIRS that supported my conference attendance to present my work, as this gives me a great platform to address these and other questions, such as why black men are disproportionately affected by psychotic disorders, and how to improve outcomes for them and all people with schizophrenia.