Spontaneous thought-related network connectivity predicts sertraline effect on major depressive disorder

Li Ming Hsu, Timothy Joseph Lane, Changwei W. Wu, Chien Yuan Lin, Chi Bin Yeh, Hung Wen Kao, Ching Po Lin

Research output: Contribution to journalArticlepeer-review


Sertraline is one of the most commonly prescribed antidepressants. Major depressive disorder (MDD) is characterized by spontaneous thoughts that are laden with negative affect—a “malignant sadness”. Prior neuroimaging studies have identified abnormal resting-state functional connectivity (rsFC) in the spontaneous brain networks of MDD patients. But how antidepressant medication acts to relieve the experience of depression as well as adjust its associated spontaneous networks and mood-regulation circuits remains an open question. In this study, we recruited 22 drug-naïve MDD patients along with 35 normal controls and investigated whether the functional integrity of cortical networks associated with spontaneous thoughts is modulated by sertraline treatment. We attempted to predict post-treatment effects based upon what we observed in the pre-treatment rsFC of drug-naïve MDD patients. In the result, we demonstrated that (1) after the sertraline treatment, the medial temporal lobe of default network (DNMTL) and mood regulation pathway—the fronto-parietal control network (FPCN), the thalamus, and the salience network (SN)—were restored to normal connectivity, relative to the pre-treatment condition; however, the altered connections of FPCN-core DN (DNCORE), FPCN-SN, and intra-FPCN among MDD patients remained impaired; (2) thalamo-prefrontal connectivity provides moderate predictive power (r2 = 0.63) for the effectiveness of sertraline treatment. In summary, our findings contribute to a body of evidence that suggests salubrious effects of sertraline treatment primarily involve the FPCN-thalamus-SN pathway. The pre-treatment rsFC in this pathway could serve as a predictor of sertraline treatment outcome.

Original languageEnglish
Pages (from-to)1705-1717
Number of pages13
JournalBrain Imaging and Behavior
Issue number4
Publication statusPublished - Aug 2021


  • Antidepressants
  • Depression
  • fMRI
  • Functional connectivity
  • Neuroimaging
  • Sertraline
  • Treatment

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Cognitive Neuroscience
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience


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