Integrative intrinsic brain activity and molecular analyses of the interaction between first-episode depression and age

Abstract

Background: Numerous studies have underscored the presence of abnormal intrinsic neural activity (INA) in individuals with depression. However, recognizing that the age stage may influence the pathophysiology of depression, our study sought to delve into the interplay of depression and age on INA and molecular architecture. Methods: One hundred and thirty-eight first-episode depression patients and 120 healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging. The participants were stratified into four groups based on age. Utilizing amplitude of low-frequency fluctuation (ALFF) analyses, we employed an ANCOVA to compare INA patterns in four groups. Additionally, we conducted correlation analyses between ALFF and neurotransmitter maps to elucidate molecular underpinnings of INA abnormalities. Results: In comparison to adolescents with early-onset depression and adult HC, adult-onset depression exhibited increased ALFF in the right paracentral lobule. Conversely, early-onset depression, when contrasted with adolescent HC, displayed reduced ALFF in the right paracentral lobule. The interactive brain regions affected by ALFF alterations were associated with serotonergic, GABAergic, and opioid neurotransmitter systems. Limitations: The present study was limited to its cross-sectional design. Conclusions: This study illuminates an antagonistic effect of depression and age on brain activity in paracentral lobule and provides molecular underpinnings of the corresponding INA abnormalities related to key neurotransmitter systems. These insights may prove valuable in the development of neuromarkers for clinical intervention and treatment of depression.