Pretreatment Brain Connectome Fingerprint Predicts Treatment Response in Major Depressive Disorder.

BACKGROUND

Major depressive disorder (MDD) treatment is characterized by low remission rate and often involves weeks to months of treatment. Identification of pretreatment biomarkers of response may play a critical role in novel drug development, in enhanced prognostic predictions, and perhaps in providing more personalized medicine. Using a network restricted strength predictive modeling (NRS-PM) approach, the goal of the current study was to identify pretreatment functional connectome fingerprints (CFPs) that (1) predict symptom improvement regardless of treatment modality and (2) predict treatment specific improvement.

METHODS

Functional magnetic resonance imaging and behavioral data from unmedicated patients with MDD (n = 200) were investigated. Participants were randomized to daily treatment of sertraline or placebo for 8 weeks. NRS-PM with 1000 iterations of 10 cross-validation were implemented to identify brain connectivity signatures that predict percent improvement in depression severity at week-8.

RESULTS

The study identified a pretreatment CFP that significantly predicts symptom improvement independent of treatment modality but failed to identify a treatment specific CFP. Regardless of treatment modality, improved antidepressant response was predicted by high pretreatment connectivity between modules in the default mode network and the rest of the brain, but low external connectivity in the executive network. Moreover, high pretreatment internal nodal connectivity in the bilateral caudate predicted better response.

CONCLUSIONS

The identified CFP may contribute to drug development and ultimately to enhanced prognostic predictions. However, the results do not assist with providing personalized medicine, as pretreatment functional connectivity failed to predict treatment specific response.

Informations de copyright

© The Author(s) 2020.

Déclaration de conflit d'intérêts

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Abdallah has served as a consultant and speaker and/or on advisory boards for Genentech, Janssen, Lundbeck, Psilocybin Labs, and FSV7 and editor of Chronic Stress for Sage Publications, Inc. and filed a patent for using mTORC1 inhibitors to augment the effects of antidepressants (filed on Aug 2,02,018). All other co-authors declare no conflict of interest.