Macroeconomics

Precuneus

Neuroscience

Prefrontal cortex

Biology

Dorsolateral prefrontal cortex

Default mode network

Depression (economics)

Cognition

Anterior cingulate cortex

Melancholia

Psychiatry

Economics

Biochemistry

Functional magnetic resonance imaging

Antidepressant

Major depressive disorder

Resting state fMRI

Biomarker

Melancholic depression

Psychology

Hippocampus

Medicine

Chemistry

Scientific Reports

The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.

Primary functional brain connections associated with melancholic major depressive disorder and modulation by antidepressants