Alterations in Cerebral Intrinsic Activity in First-Episode, Drug-Naive Patients With Major Depressive Disorder.

Background: The amplitude of low-frequency fluctuation (ALFF) obtained by resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to measure cerebral intrinsic neural activity in major depressive disorder (MDD). The primary objective is to investigate alterations in cerebral intrinsic activity, as measured by ALFF, in first-episode, drug-naive patients with MDD of relatively short illness duration, and to examine correlations between ALFF and clinical measures.

Methodology: This cross-sectional observational study was conducted at the University of Health Sciences, Lahore, from June 2024 to January 2025. Thirty first-episode, drug-naive patients with MDD of relatively short illness duration (mean = 14 weeks), along with 52 healthy controls (HCs), were scanned with rs-fMRI to obtain ALFF across the whole brain. Voxel-based analysis of ALFF maps was performed to compare MDD and HC groups using a two-sample -test. Correlations between ALFF and symptom severity measured by the Hamilton Rating Scale for Depression (HAMD) score or illness duration were conducted using simple regression.

Results: Compared with HC, patients with MDD had increased ALFF in the dorsal anterior cingulate cortex (dACC) and vermal sub-regions V3 of the cerebellum; no areas of significantly decreased ALFF were found. There was no correlation between the elevated ALFF value and clinical parameters; only the ALFF value in the right dorsolateral prefrontal cortex (DLPFC) was found to correlate negatively with the HAMD score in patients with MDD.

Conclusions: Our study demonstrates that alterations of cerebral intrinsic activity may occur in the early course of MDD without interference from antidepressants. As these regions are crucial for the regulation of cognition, we speculate that these changes may subserve the disturbances of cognitive function in early MDD.