Functional Connectome Fingerprints Provide Clues to Major Depressive Disorder

The goals of this study were to identify functional connectome fingerprints that predict symptom improvement with any treatment and with specific treatment.

Functional connectome fingerprints (CFPs) derived from functional magnetic resonance imaging (fMRI) data predicted improvement of depressive symptoms, not response to antidepressant therapy, among patients with major depressive disorder (MDD). These findings, from a randomized trial conducted by researchers at Yale University, were published in Chronic Stress.

Unmedicated patients (N=200) with MDD were randomized to receive sertraline (up to 200 mg daily) or placebo for 8 weeks. Patients were assessed by the 17-item Hamilton Depression Rating Scale (HAMD) and fMRI. The A424 atlas was used for gray matter whole-brain parcellation into 424 nodes to construct the patient-specific network. The full network comprised information about pairwise connectivity of functional networks, nodal strength, and nodal internal and external network-restricted strength.

Symptom improvement at 8 weeks was associated with CFP, regardless of receiving sertraline or placebo (r, 0.19; P =.03), in which patients who had lower connectivity between executive and sensorimotor, and salience modules with increased connectivity between default mode modules and the rest of the brain, were more likely to have decreased symptoms of depression.

Stratified by CFP resolution, those with higher resolution (full connectome with 424 nodes) predicted percent change of MDD symptoms (r, 0.19; P =.02) but not among patients with lower resolution (r, 0.14; P =.08).

Similarly, the nodal fingerprint (NFP) was significantly associated with symptom improvement at 8 weeks independent of receiving sertraline or placebo (r, 0.18; P =.03). This association was driven by nodal internal (r, 0.19; P =.02) but not nodal external (r, 0.15; P =.08) network-restricted strength.

No CFP or NFP patterns were associated with sertraline treatment (all P <.05).

This study was limited by its sample size and some group differences were likely missed due to lack of statistical power.

The study authors concluded MDD symptom improvement was more likely to occur among patients who had reduced functional connectivity in the central-executive region of the brain. Longitudinal studies are needed to assess whether connectivity changes correlated with symptom alterations.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Fan S, Nemati S, Akiki TJ, et al. Pretreatment brain connectome fingerprint predicts treatment response in major depressive disorder. Published online December 29, 2020. Chronic Stress (Thousand Oaks). doi:10.1177/2470547020984726