Frequency-Specific Changes in the Fractional Amplitude of the Low-Frequency Fluctuations in the Default Mode Network in Medication-Free Patients With Bipolar II Depression: A Longitudinal Functional MRI Study

Objective: This study aimed to examine the treatment-related changes of the fractional amplitude of low-frequency fluctuations (fALFF) in the default mode network (DMN) across different bands after the medication-free patients with bipolar II depression received a 16-week treatment of escitalopram and lithium. Methods: A total of 23 medication-free patients with bipolar II depression and 29 healthy controls (HCs) were recruited. We evaluated the fALFF values of slow 4 (0.027-0.073 Hz) band and slow 5 (0.01-0.027 Hz) band of the patients and compared the results with those of the 29 HCs at baseline. After 16-week treatment of escitalopram with lithium, the slow 4 and slow 5 fALFF values of the patients were assessed and compared with the baselines of patients and HCs. The depressive symptoms of bipolar II depression in patients were assessed with a 17-item Hamilton Depression Rating Scale (HDRS) before and after treatment. Results: Treatment-related effects showed increased slow 5 fALFF in cluster D (bilateral medial superior frontal gyrus, bilateral superior frontal gyrus, right middle frontal gyrus, and bilateral anterior cingulate), cluster E (bilateral precuneus/posterior cingulate, left cuneus), and cluster F (left angular, left middle temporal gyrus, left superior temporal gyrus, and left supramarginal gyrus) in comparison with the baseline of the patients. Moreover, a positive association was found between the increase in slow 5 fALFF values (follow-up value minus the baseline values) in cluster D and the decrease in HDRS scores (baseline HDRS scores minus follow-up HDRS scores) at follow-up, and the same association between the increase in slow 5 fALFF values and the decrease in HDRS scores was found in cluster E. Conclusions: The study reveals that the hypoactivity of slow 5 fALFF in the DMN is related to depression symptoms and might be corrected by the administration of escitalopram with lithium, implying that slow 5 fALFF of the DMN plays a key role in bipolar depression.