Age-related abnormalities in brain functional and molecular neuroimaging signatures in first-episode depression

Abnormalities in resting-state brain activity have been demonstrated in depression patients with different ages, yet the age-related changes in dynamics of brain activity in depression are still limited. Here, we investigated the impacts of age on dynamics of brain activity and the molecular architecture. Resting-state functional magnetic resonance images were obtained from 138 first-episode depression patients and 120 healthy volunteers. All the participants were classified into two age cohorts, including adolescents and adults. Two-way analysis of variance was performed to examine the effect of age on dynamic amplitude of low-frequency fluctuations (ALFF) in depression. Then, cross-modal correlation analyses between dynamic ALFF and neurotransmitter maps were established. Significant diagnosis-by-age interaction of dynamic ALFF was located in medial frontal gyrus, supplementary motor area, postcentral gyrus, paracentral lobule and rolandic operculum. Dynamic ALFF alterations in the diagnosis-by-age interaction effect were associated with serotonergic, dopaminergic, noradrenergic, and GABAergic systems. These findings highlight the interaction between depression and age in brain functional and molecular neuroimaging signatures, which may be useful for future treatment strategies of different ages of depression.