Based on previous studies implicating increased functional connectivity within the self-referential brain network in major depressive disorder (MDD), and considering the functional roles of three distinct modules of such brain net (responsible for three-dimensional components of Selfhood) together with the documented abnormalities of self-related processing in MDD, we tested the hypothesis that patients with depression would exhibit increased connectivity within each module of the self-referential brain network and that the strength of these connections would correlate positively with depression severity. Applying (...) the electroencephalogram (EEG) operational synchrony analysis to extract three modules of the self-referential brain network in 12 medication-free depressive outpatients and 10 control subjects we have found an increase in the strength of EEG synchrony within all three modules in depressive patients (though non-significant for the right module). Furthermore, multiple regression analysis that used 3 factors (values of synchrony strength for all three modules) as input indicated that combined increase in the strength of synchrony in all three modules was positively associated with severity of depression. Taken together the findings of this study suggest that depression is primarily associated with hypersynchrony in all three modules of the brain self-referential network (the anterior module been responsible for “witnessing observation and first–person perspective”, the left posterior module been responsible for “reflective agency and narration” and the right posterior module been responsible for “bodily representational-emotional agency”), thus contributing to excessive self-focus, rumination, and body tension. (shrink)