Mental disorders are generally characterized by heterogeneous phenotypes but there is a lack of evidence for biologic markers,1 said Professor Gregor Hasler, University of Fribourg, Switzerland. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnoses2 therefore lack biological validity.
Biomarkers need to have the power to predict treatment response
Characteristics of promising biomarkers
A variety of promising biomarkers have been identified by magnetic resonance imaging (MRI), in the blood and from smartphone and sensor digital data, explained Professor Hasler, and need to
- be associated with a DSM disease
- related to the pathogenetic processes
- have the power to predict treatment response and enable translational research
Prefrontal glutamine is increased in the early phases of mood and anxiety disorders
Professor Hasler described his own research using a magnetic resonance spectroscopy technique to compare glutamate-related biomarkers in unmedicated adults with major depressive disorder (MDD) and controls.3
It demonstrated abnormal reductions in glutamate/glutamine and gamma-aminobutyric acid (GABA) in dorsomedial/dorsal anterolateral prefrontal brain regions compatible with findings from postmortem histopathologic studies.3,4
Prefrontal glutamine is increased in the early phases of mood and anxiety disorders,5 said Professor Hasler, and further understanding of glutamate–glutamine dysfunction in stress-related disorders may lead to new therapeutic strategies.
High levels of extracellular glutamate damage neural dendrites and spines
In terms of the pathogenetic process, Professor Hasler described research showing that prolonged MDD alters prefrontal glutamate release and reduces glutamate uptake. The resulting high levels of extracellular glutamate damage neural dendrites and lead to decreased spine density and synaptic strength.6
Serum brain-derived neurotrophic factor increases in patients who respond to antidepressants
Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), and stress-related, inflammatory and epigenetic biomarkers can all be measured in the blood, said Professor Hasler. He highlighted a 2020 systematic review and meta-analysis demonstrating that serum BDNF levels
- are decreased in patients with MDD
- increase in patients who respond to antidepressants7
Digital biomarkers are showing promise as biomarkers of mental illness
Digital biomarkers obtained from smartphones and sensors, for instance phone usage, activity and voice characteristics may be associated with specific psychiatric behaviors,8,9 said Professor Hasler. They are likely to play a more prominent role as biomarkers of mental illness in the future.
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