Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression

Int J Neuropsychopharmacol. 2020 Dec 29;23(12):791-798. doi: 10.1093/ijnp/pyaa056.

Abstract

Background: Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown.

Methods: In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls.

Results: Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion.

Conclusion: Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

Keywords: frontostriatal network; low-dose ketamine infusion; treatment response; treatment-resistant depression.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Connectome*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / physiopathology*
  • Depressive Disorder, Treatment-Resistant / diagnostic imaging
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / physiopathology*
  • Female
  • Follow-Up Studies
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology*
  • Humans
  • Infusions, Intravenous
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Outcome Assessment, Health Care
  • Prognosis

Substances

  • Antidepressive Agents
  • Ketamine