A new study in Molecular Psychiatry has brought forward two new biomarkers of schizophrenia and opened up the potential for more tailored approaches to managing the psychiatric condition.
Schizophrenia is notoriously difficult to diagnose, given that it's an incredibly complex disease involving multiple intersecting neurobiological pathways and that the symptoms of the condition vary widely.
In search of deeper insights on how to diagnose and treat the disorder, a team led by psychiatric neuroscience expert Kim Do went about investigating the molecular pathways involved in the metabolism of parvalbumin neurons, brain cells directly involved in several cognitive functions.
The brain churns out large amounts of free radicals, cleared via cellular antioxidant reactions. Disruptions to these chemical reactions (as commonly observed in individuals with schizophrenia) can lead to marked cognitive changes.
In schizophrenia, levels of the antioxidant glutathione are usually low. To investigate how these dips in glutathione affect neurons, Do and colleagues used a specialized animal model of genetically-engineered mice to produce significantly lower glutathione levels. Interestingly, they found that these mice had a build-up of impaired mitochondria in the prefrontal cortex region of the brain. These dysfunctional mitochondria are swiftly eliminated or recycled in the brain in healthy tissues, leading the authors to hypothesize that this cellular "cleaning system" does not work as effectively in brains with schizophrenia.
The study's first author, Inès Khadimallah, said that the team also identified two key markers linked to the accumulation of impaired mitochondria. "In other words, the mitochondria of parvalbumin neurons are dysfunctional following the increase in oxidative stress, and it can be shown through analyzing the levels of miR-137 and COX6A2 in the blood".
Additionally, the team analyzed blood samples from a cohort of patients diagnosed with psychosis and identified two clear groups: patients with and without the build-up of abnormal mitochondria (as measured via miR-137 and COX6A2 levels). The authors said that individuals with mitochondrial deficiencies tended to experience more severe clinical symptoms of schizophrenia.
On a positive note, the mice's fluctuations in miR-137 and COX6A2 levels could be corrected by administering an antioxidant compound called MitoQ. Upon receiving MitoQ, parvalbumin neurons in the prefrontal cortex of the animals regained their function.