Antidepressants normalize brain flexibility associated with multi-dimensional symptoms in major depressive patients.

Abstract Background The fundamental pathophysiology of major depressive disorder (MDD) could be characterized by functional brain networks which tightly and dynamically connect into groups as communities, making the flexible brain possible to external multifarious demands. We aim to scrutinize what brain dynamics go awry in MDD and antidepressants effects on multi-dimensional symptoms. Methods Thirty-five patients and thirty-five controls underwent resting-state functional magnetic resonance imaging (MRI). Patients were scanned before and after 8 or 12 weeks of pharmacotherapy. Group independent component analysis decomposed resting-state images to instinct networks and networks' integrated flexibility was calculated. Network flexibility between patients at baseline and after therapy were compared. Results All patients completed the clinical trial and MRI scans. Following antidepressants treatment, we found significant normalization of reduced network flexibility in default mode network (DMN) and cognitive control network (CCN) of MDD patients. Selectively significant correlations between network flexibility and multi-dimensional symptoms such as anxiety/somatization and hysteresis factor were also found. Conclusions “Hypoflexible” CCN may involve in anxiety syndrome. Low flexibility in DMN may be indicative of hysteresis. These suggest an important pathophysiology of depressive manifestation of MDD. The antidepressant-induced normalization of the “hypoflexibility” suggests a selective pathway through which antidepressants may alleviate symptoms in depression.