UC Berkeley researchers have identified biomarkers linked with reduced motivation, a common symptom of depression.
The findings, published in Neuron, could help refine the process of diagnosis as well as help develop treatment methods. According to the National Institute of Mental Health, depression affected approximately 17.3 million American adults, or around 7.1% of the U.S. population over the age of 18, in 2017. It is also the leading cause of disability worldwide, according to the World Health Organization.
“No one treatment works for everyone and no one has objective data on how to differentiate the enormous variability of depression symptoms and subtypes,” said Stephan Lammel, researcher and campus professor of neurobiology, in an email.
The researchers developed a multidisciplinary platform where they analyzed genes, synapses, cells and circuits to identify biological markers associated with specific symptoms related to depression. In order to develop the platform, the researchers used mice as models — when under constant stress, they produce three or more common symptoms of human depression, including anxiety, lack of motivation and loss of pleasure.
For example, in order to better understand loss of motivation, researchers focused on the distinct brain nucleus lateral habenula, or LHb, that becomes increasingly active when an animal is depressed. The researchers were able to ameliorate this specific behavior by reducing the activity of the LHb.
“We hope that the combination of anatomical, physiological and molecular biomarkers described in our study may be useful in the development of the next generation of antidepressants that are tailored to specific depression symptoms,” Lammel said in the email.
Even if two people have the same diagnosis of depression, their symptoms can differ greatly, which is the main reason why current treatments are often ineffective and involve many side effects, according to Lammel.
Lammel added that this is exacerbated by the simplicity of research in the past, when researchers did not account for how symptoms could vary, sorting all mice into the binary of “depressed” or “not depressed.” Instead, the researchers’ work focused on identifying all the specific changes in the brain relating to each symptom.
Ignas Cerniauskas, the study’s first author and a neuroscience graduate student, also hopes these findings will help the process of treating depression among humans.
“Even though our study was performed in mice, LHb hyperactivity has also been observed in humans with depression, suggesting that there may be –at least in part—a translational aspect of our findings,” Lammel said in an email. “As such, we hope our results may serve as a foundation for the development of symptom-specific therapeutic interventions as well as predictive biomarkers, both of which are severely lacking in current treatment of depression.”