Researchers Find Brain Patterns that Could Improve Mental Health Disorder Diagnosis

 By Jim Windell

            Clinicians treating clients with a range of mental health disorders are always on the lookout for ways of better matching clients and treatment plans.

            A new study that comes from researchers at The University of Texas Health Science Center at Houston (UTHealth) may have found clues that could help in the more accurate diagnosis and treatment of several major mental health disorders.

           Recently published in Molecular Psychiatry, the study may have found a pattern in howthe brain breaks down tryptophan, a common amino acid consumed through food.  

           Tryptophan can be metabolized to either a route where serotonin is produced, or to the kynurenine pathway. As the tryptophan breaks down in the brain, it can use the kynurenine pathway to turn into quinolinic acid, which is considered neurotoxic, or kynurenic acid, which is considered neuroprotective.

           "The research shows that people with mood disorders and schizophrenia not only have decreased levels of tryptophan overall, but the tryptophan they do have is being broken down more often in the kynurenine pathway, shifting away from the production of serotonin, the chemical made from tryptophan that is thought to regulate anxiety and improve mood," said Brisa Fernandes, MD, MSc, PhD, a postdoctoral research fellow with the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth and co-senior author of the paper.

           The researchers, led by Fernandes and colleagues, conducted a systematic review of more than 100 peer-reviewed studies assessing kynurenine metabolites, which are the tryptophan amino acids being broken down in the kynurenine pathway, in people with major depressive disorder, schizophrenia, or bipolar disorder, compared to healthy controls. Within those studies, which included more than 10,000 study participants, they examined the difference in metabolite concentrations between each group.

           “We chose these disorders because they share several biological pathways, meaning the same root causes and pathophysiology,” Fernandes says. “We tried to find biomarkers that are common among these disorders, but most importantly, biomarkers that distinguish them. This is essential to help clinicians guide treatment and implement personalized medicine in psychiatry – not the 'one-size-fits-all' approach that is so prevalent today.”

           In this study the researchers identified several patterns that occur as tryptophan breaks down. Taken together, these patterns suggest there is a shift from serotonin production to the kynurenine pathway, which could lead to increased neurotoxicity from the quinolinic acid.

           "This can help us to develop new tests for diagnosing these disorders and, more importantly, of discovering and selecting new treatments for people with mood disorders and schizophrenia that will be more personalized," Fernandes says.

           “The major challenge that we have in psychiatry is having biomarkers to differentiate one diagnostic from the other, as our diagnoses are 100% clinical,” noted João de Quevedo, MD, PhD, professor of psychiatry and behavioral sciences and co-author of the study. De Quevedo went on to say that this type of research is needed to identify those biomarkers and that the next step is to see if these findings can be validated in patients.

  To read the original journal article, find it at:

Wolfgang Marx, Amelia J. McGuinness, Tetyana Rocks, Anu Ruusunen, Jasmine Cleminson, Adam J. Walker, Susana Gomes-da-Costa, Melissa Lane, Marsal Sanches, Alexandre P. Diaz, Ping-Tao Tseng, Pao-Yen Lin, Michael Berk, Gerard Clarke, Adrienne O’Neil, Felice Jacka, Brendon Stubbs, André F. Carvalho, João Quevedo, Jair C. Soares, & Brisa S. Fernandes. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Molecular Psychiatry, 2020; DOI: 10.1038/s41380-020-00951-9