The serotonergic neurotransmitter system is thought to play a substantial role in modulating the default mode network (DMN). For example, antidepressants (SSRIs) have consistently shown to decrease DMN connectivity. However, it is unclear whether SSRIs also dose-dependently affect DMN connectivity. Therefore, we investigated the association between SERT occupancy by SSRIs (SPECT) and DMN functional connectivity (rs-fMRI). We confirm a dose-dependent effect of SSRIs on connectivity with the DMN; higher SERT occupancy by the SSRI in the thalamus was significantly associated with decreased DMN connectivity. This suggests that DMN connectivity might be interesting biomarker, e.g. for treatment monitoring.