Exploring the gut-brain connection in treatment-resistant schizophrenia


Building on the growing interest in the role that the gut microbiome plays in influencing a range of health conditions, a team of researchers from Mater Research and The University of Queensland have asked the question: “Does the gut microbiome play a role in how people diagnosed with schizophrenia respond to treatment?”.

The gut is home to billions of bacteria and over two million microbial genes that influence many aspects of human health, potentially including brain functions such as cognition, mood and psychiatric disorders—such as schizophrenia.

In the first study to investigate the possible link between the gut microbiome and treatment-resistant schizophrenia, a research team led by Queensland Brain Institute (QBI) PhD student Svetlina Vasileva, in collaboration with Mater Research Cognitive Health Genomics Group Leader Professor Jake Gratten, explored the associations between the composition of the gut microbiome, schizophrenia and its treatment.

Treatment-resistant schizophrenia refers to the persistence of symptoms despite two or more trials of antipsychotic medications. Once a person receives a diagnosis of treatment-resistant schizophrenia, a trial of a medication called clozapine is recommended.

Ms Vasileva said that the team found strong gut microbiome differences between people with schizophrenia and individuals without a diagnosis, consistent with findings from previous studies.

“However, we found that the strong gut microbiome associations with schizophrenia were mainly driven by participants with treatment-resistant schizophrenia, all of whom were taking clozapine,” Ms Vasileva said.

Corresponding author Professor Gratten said that although numerous prior studies have reported links between the gut microbiome and schizophrenia, many haven’t accounted for comorbidities such as constipation, and lifestyle factors like diet, that are associated with both schizophrenia and the microbiome. Published studies also have not explored the role of antipsychotic medications.

“Our study aimed to address these gaps in the research. By using powerful statistical analyses that consider all microbiome features and confounding factors concurrently, we showed that microbiome changes in schizophrenia are most likely a consequence of lifestyle and health factors associated with the condition, as opposed to the popular view that a particular gut microbiome leads to schizophrenia,” Professor Gratten said.

Ms Vasileva said that it was important to note that further work will be needed to confirm this.

“Only longitudinal studies involving analysis of the microbiome before and after starting clozapine use will be able to establish this.”

Ms Vasileva also emphasised that it is still not understood whether gut microbiome differences in the treatment resistant population are beneficial or detrimental, which is another area of future research.

The study was published in JAMA Psychiatry.

/Public Release. View in full here.