Integrative Molecular and Structural Neuroimaging Analyses of the Interaction Between Depression and Age of Onset: A Multimodal Magnetic Resonance Imaging Study

Depression is a neurodevelopmental disorder that exhibits progressive gray matter volume (GMV) atrophy. Research indicates that brain development is influential in depression-induced GMV alterations. However, the interaction between depression and age of onset is not well understood by the underlying molecular and neuropathological mechanisms. Thus, 152 first-episode depression individuals and matched 130 healthy controls (HCs) were recruited to undergo T1-weighted high-resolution magnetic resonance imaging for this study. By two-way ANOVA, age and diagnosis were used as factors when analyzing the interaction of GMV in the participants. Then, spatial correlations between neurotransmitter maps and factor-related volume maps are established. Results illustrate a pronounced antagonistic interaction between depression and age of onset in the right insula, superior temporal gyrus, anterior cingulate gyrus, and orbitofrontal gyrus. Depression-caused reductions in GMV are mainly distributed in thalamic-limbic-cortical regions, regardless of age. For the main effect of age, adults exhibit brain atrophy in frontal, cerebellum, parietal, and temporal lobe structures. Cross-modal correlations showed that GMV changes in the interactive regions were linked with the serotonergic system and dopaminergic systems. Summarily, our results reveal the interaction between depression and age of onset in neurobiological mechanisms, which provide hints for future treatment of different ages of depression.