Conor Liston, M.D., Ph.D., a Robert Michels Professor of Psychiatry at Weill Cornell Medical College, has focused his research on understanding the mechanisms underlying mood changes in depression. Depression is characterized by episodic low mood, and much of the existing research compares the brain activity of depressed individuals to that of never-depressed individuals at one point in time. However, it remains unclear why mood can fluctuate in an individual and how treatment can initiate and maintain recovery from depression.
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Liston’s lab utilizes functional MRI (fMRI) to track brain changes in individuals with depression and conducts similar studies in mice. His team investigates the impact of chronic stress and antidepressant treatments, particularly ketamine, on dendritic spines—tiny protrusions on neurons that represent synaptic connections. Chronic stress is known to reduce these spines, leading to fewer connections in the brain, whereas ketamine appears to promote the formation of new connections.
By employing advanced imaging techniques, Liston’s lab observed that chronic stress led to both a loss of existing spines and an increase in new spines in various brain regions. This suggests targeted pruning of connections due to stress, raising the hypothesis that antidepressants like ketamine could restore lost connections. Their findings indicated that, while ketamine treatment results in both restored and new connections, the critical changes in mood and behavior occur before the formation of these new connections, challenging previous assumptions regarding the treatment’s mechanism.
Further studies showed that deleting new connections formed after ketamine leads to a rapid loss of mood improvement, implying the importance of these connections in sustaining the antidepressant effects over time. This underscores the challenge faced in maintaining recovery from depression after initial treatment, leading to considerations for repeated dosing or additional therapies to boost connection formation.
Liston’s team is also exploring the impacts of ketamine on neural networks associated with reward processing—a critical aspect of understanding depressive symptoms such as anhedonia, or reduced pleasure in activities. Their research in humans demonstrates that specific brain networks exhibit changes correlated with mood fluctuations, with an expanded salience network in individuals with depression.
Interestingly, this salience network's expansion does not fluctuate with mood states but may signify a predisposition to depression. Analysis of data from the ABCD study suggests that the salience network size may predict future depressive episodes, highlighting a potential target for interventions.
Overall, Liston’s work aims to develop more effective treatments for depression by enhancing understanding of the neural mechanisms involved. This could lead to tailored approaches that consider individual differences in brain connectivity and responses to various treatments.