How Depression Treatment Boosts Brain Flexibility

In this Q&A, Jonathan Repple, MD, professor of predictive psychiatry at the University of Frankfurt, Germany, discussed his most recent study presented on a poster at the 35th annual European College of Neuropsychopharmacology (ECNP) Congress. The study found depression treatment changes brain structure and can increase brain flexibility after just 6 weeks. Through email with Psych Congress Network, Dr Repple explores what the study's findings mean for clinicians, treatment, and future research. 

This interview has been edited for clarity.

Psych Congress Network: What led you and your colleagues to investigate brain structure and its connection to depression treatment? 

Jonathan Repple, MD: We studied the foundations of MRI-based brain alterations in depression for years. However, as we only ever studied it in a cross-sectional manner, meaning a scan at only 1 time-point, it was challenging to disentangle trait from state aspects in regard to the observed alterations. Therefore, we were motivated to scan the same subject twice, once before treatment and once after. 

PCN: Please briefly describe the study method and your most significant finding(s). 

Repple: We studied 109 patients with severe depression (major depressive disorder) and compared them with 55 healthy controls. Their brains were scanned using an MRI scanner that had been set up to identify which parts of the brain were communicating with other parts, determining the level of connections within the brain. The patients were then treated for depression, some with electroconvulsive therapy (ECT), some with psychological therapy or medication, some with a combination of all therapies. After treatment, they were then rescanned and the number of connections recounted. They were also retested for symptoms of depression.
 
PCN: Were there any outcomes that were different than you expected? 
 
Repple: We found that treatment for depression changed the infrastructure of the brain, which goes against previous expectations. Treated patients showed a greater number of connections than they had shown before treatment. Moreover, those who showed the most response to treatment had developed a greater number of new connections than those who showed little response. We found these changes took place over only 6 weeks; we were surprised at the speed of response. We don’t have an explanation as to how these changes take place or why they should happen with such different forms of treatment.
 
PCN: What do these results mean for patients with depression?
 
Repple: This gives hope to patients who believe nothing can change and that they have to live with a disease forever because it is “set in stone” in their brain.
 
PCN: What practical applications of your findings exist for clinicians treating depression? 
 
Repple: None yet. We now want to figure out why some patients show more clinical improvement than others and why some patients show more brain changes after treatment than others. Moreover, we want to further disentangle which treatments lead to what changes in the brain in which subset of patients. 

PCN: Is there anything else health care professionals should know about these findings? 
 
Repple: The results align very much with our current belief that the brain has more flexibility in adaptation over time than was previously thought—even a short time. Indeed, a major idea of what treatment of depression (and other psychiatric illnesses) invoke is plastic changes over time. This has been proposed as a common mechanism for antidepressants, psychotherapy, and ECT. However, the amount of research to elucidate which changes are necessary or specific for response to treatment or remission of the depression is limited. Moreover, the next question is whether different treatments have the possibility to specifically change targeted brain networks or, vice versa, whether we can use the disturbances in brain-networks as measured in the present study to choose which therapy will be helpful.

Jonathan Repple, MD, is a professor of predictive psychiatry at University of Frankfurt, Germany, and senior physician in the department of psychiatry, University Hospital Frankfurt, Germany. He completed his residency in the psychiatry department at the University of Muenster, Germany.