Inflammatory cytokines derived from peripheral blood contribute to the modified electroconvulsive therapy-induced cognitive deficits in major depressive disorder

Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):475-485. doi: 10.1007/s00406-020-01128-9. Epub 2020 May 2.

Abstract

Little is known about the pathophysiology of memory deficits in patients with major depressive disorder (MDD) treated with modified electroconvulsive therapy (MECT). This study examined the profiles of cytokines, the memory function, and their association in MECT-treated MDD patients. Forty first-episode, drug-free MDD patients and 40 healthy controls were recruited. MECT was started with antidepressant treatment at a stable initial dose. The Wechsler Memory Scale (WMS) and Hamilton Rating Scale for Depression 17 (HRSD-17) were used to assess the cognitive function. MDD patients were divided into the memory impairment group (WMS < 50) and the non-memory impairment group (WMS ≥ 50) based on the total WMS scores after MECT. The levels of NOD-like receptor 3 (NLRP3) inflammasome, interleukin-18 (IL-18) and nuclear factor kappa-B (NF-κB) in the serum were measured. MDD patients showed significantly higher levels of NLRP3 inflammasome, IL-18 and NF-κB than that in the controls prior to MECT, and the levels also significantly increased after MECT. In MDD patients, the serum levels of these inflammatory cytokines were negatively associated with the total WMS scores and likely contributed to the scores independently. The receiver operating characteristic curve showed that the serum levels of these inflammatory cytokines may predict the cognitive impairment risk in MDD patients receiving MECT. Abnormal levels of NLRP3 inflammasome, IL-18 and NF-κB reflecting the disturbed balance of pro-inflammatory and anti-inflammatory mechanisms likely contribute to the MECT-induced cognitive deficits in MDD patients.

Keywords: Cognitive impairment; IL-18; MDD; MECT; NF-κb; NLRP3.

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Case-Control Studies
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / immunology
  • Cognitive Dysfunction* / physiopathology
  • Combined Modality Therapy
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Depressive Disorder, Major* / blood
  • Depressive Disorder, Major* / complications
  • Depressive Disorder, Major* / immunology
  • Depressive Disorder, Major* / therapy
  • Electroconvulsive Therapy / adverse effects*
  • Female
  • Humans
  • Inflammasomes / blood*
  • Interleukin-18 / blood*
  • Male
  • Memory Disorders* / blood
  • Memory Disorders* / etiology
  • Memory Disorders* / immunology
  • Memory Disorders* / physiopathology
  • Middle Aged
  • NF-kappaB-Inducing Kinase
  • NLR Family, Pyrin Domain-Containing 3 Protein / blood*
  • Outcome Assessment, Health Care
  • Protein Serine-Threonine Kinases / blood*

Substances

  • Antidepressive Agents
  • Cytokines
  • IL18 protein, human
  • Inflammasomes
  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Protein Serine-Threonine Kinases