Despite different treatments and courses of illness, depressive symptoms appear similar in bipolar disorder (BD) and major depressive disorder (MDD), causing BD with an onset of depressive episode being frequently misdiagnosed as MDD, and leading to inappropriate treatment and poor clinical outcomes. Therefore, there is an urgent need to explore underlying neural basis to distinguish BD from MDD. The medical records of 80 first-episode, drug-naïve depressive patients with an initial diagnosis of MDD and illness duration of at least 5 years were reviewed retrospectively for this study. Fourteen bipolar depressed patients with a diagnosis conversion from MDD to BD, 14 patients with diagnosis of MDD, and 14 healthy subjects demographically matched with the BD group, were selected to participate in the study. Firstly, we examined whether there were differences among the three groups in whole brain fALFF during resting state. Secondly, clusters showing group differences in fALFF in any two groups were chosen as regions of interest (ROI) and then correlation between clinical features and fALFF values of ROIs were calculated. The BD group showed increased fALFF in bilateral putamen relative to both the MDD group and controls, while the MDD group exhibited decreased fALFF in left superior frontal gyrus (SFG) relative to both the BD group and controls (p < 0.05, corrected). Positive correlations between abnormality in the putamen and symptom severity were observed (significant for the MDD group, p = 0.043; marginally significant for the BD group, p = 0.060/0.076). These results implicate that abnormalities of key regions in the striatum and prefrontal areas may be trait markers for BD and MDD.