Modulation of default-mode network activity by acute tryptophan depletion is associated with mood change: A resting state functional magnetic resonance imaging study

Recently, resting-state fMRI (R-fMRI) has attracted interest based on its ability to detect the default mode network. We examined the effect of acute tryptophan depletion (ATD) on the fractional amplitude of low-frequency fluctuation (fALFF) during the resting state, and the correlation between changes of mood and fALFF following ATD. We manipulated the central serotonergic levels of 21 right-handed healthy males (mean age = 21.57 ± 1.83 years) following ATD. A within-subjects, double-blind, placebo-controlled, and counter-balanced design was employed. Following ATD or sham depletion, subjects completed the Profile of Mood States (POMS) and underwent 5-min R-fMRI scans. Our findings show that the fALFF of the middle orbitofrontal cortex and precuneus was significantly decreased and the fALFF of the superior parietal lobule, paracentral lobule and precentral gyrus was significantly increased after ATD. The fALFF of the orbitofrontal cortex was negatively correlated with depressive mood. The fALFF of the superior parietal lobule was positively correlated with anger–hostility and the fALFF of the paracentral lobule was negatively correlated with vigor–activity. The middle orbitofrontal cortex plays a key role in serotonin depletion-induced brain changes and individual differences in depressive mood change. These results serve to further elucidate the mechanism of ATD-induced relapse in remitted MDD patients.

Research highlights▶ Serotonin depletion decreased the activity in orbitofrontal cortex and precuneus. ▶ Serotonin depletion increased the activity in the sensory-motor areas. ▶ Decreased orbitofrontal activity was correlated with the increased depressive mood. ▶ Increased superior parietal activity was correlated with the increased anger. ▶ Increased paracentral cortex activity was correlated with the decreased vigor.