U.S. researchers have revealed a neurobiological marker to identify and treat major depressive disorder, after finding that the condition is associated with unusual brain activity.
Altered signaling in the anterior cingulate cortex (ACC) of the brain, which has previously been linked with the processing of emotions, correlated with major depressive disorder.
Transcranial magnetic stimulation caused shifts in this signaling, which in turn predicted an improvement in symptoms.
“In sum, our results offer a pathway for identifying and treating mechanisms of neuropsychiatric diseases,” report Anish Mitra, PhD, from Stanford University, and co-workers in the Proceedings of the National Academy of Sciences.
Major depressive disorder is one of the most significant causes of morbidity in the world, the team says.
Although widely believed to result from disordered communication across brain-wide networks, its biological signatures remain poorly understood despite decades of neuroimaging research.
To investigate further, the team studied magnetic resonance imaging (MRI) data from clinical trials of the Stanford neuromodulation therapy, which has been cleared by U.S regulators.
The neuromodulation approach involves daily administration of 10 neurostimulation sessions applied through a repetitive transcranial magnetic stimulation device each day for five days.
The protocol involves a spaced intermittent theta burst pulse design applied to individual targets in the left dorsolateral prefrontal cortex of the brain.
While the protocol has proven effective in the acute clinical treatment of treatment-resistant major depressive disorder, the researchers acknowledge that the biological basis behind its effects remain unknown.
Seeking further insight, they analyzed directed signaling patterns in resting-state-functional (rs-f)MRI data obtained immediately before and after treatment in two clinical trials of the approach.
Brain-wide directed signaling patterns among individuals without major depressive disorder were also assessed.
Mitra et al found that the Stanford neuromodulation therapy modulated the directional flow of rs-fMRI activity between the dorsal ACC and the salience network of the brain.
They report that it caused specific directed-signaling shifts in the left dorsolateral prefrontal cortex (DLPFC) and bilateral ACC.
The treatment protocol corrected baseline alterations in directed rs-fMRI signals, with baseline rs-fMRI temporal structure predicting both individual depression severity and treatment response.
The temporal shift in the ACC relating to brain regions of the salience network—including the anterior insula, lateral prefrontal cortex, and temporoparietal junction—correlated with symptomatic improvements in the disorder. However, the temporal shift of the left DLPFC did not relate to the effectiveness of treatment.
“Our results highlight the key functional role of a major hub in the salience network, the dorsal ACC,” the researchers report.
They add: “On the basis of our findings, we propose a model of an [major depressive disorder] biotype in which the pathophysiology is marked by aberrantly early signaling by the dorsal ACC within the salience network.”