Association between the loudness dependence of auditory evoked potential, serotonergic neurotransmission and treatment outcome in patients with depression

Eur Neuropsychopharmacol. 2023 May:70:32-44. doi: 10.1016/j.euroneuro.2023.02.008. Epub 2023 Feb 28.

Abstract

Previous studies have suggested that the loudness dependence of auditory evoked potential (LDAEP) is associated with the effectiveness of antidepressant treatment in patients with major depressive disorders (MDD). Furthermore, both LDAEP and the cerebral serotonin 4 receptor (5-HT4R) density is inversely related to brain serotonin levels. We included 84 patients with MDD and 22 healthy controls to examined the association between LDAEP and treatment response and its association with cerebral 5-HT4R density. Participants underwent both EEG and 5-HT4R neuroimaging with [11C]SB207145 PET. Thirty-nine patients with MDD were re-examined after 8 weeks of treatment with selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitor (SSRI/SNRI). We found that the cortical source of LDAEP was higher in untreated patients with MDD compared to healthy controls (p=0.03). Prior to SSRI/SNRI treatment, subsequent treatment responders had a negative association between LDAEP and depressive symptoms and a positive association between scalp LDAEP and symptom improvement at week 8. This was not found in source LDAEP. In healthy controls, we found a positive correlation between both scalp and source LDAEP and cerebral 5-HT4R binding but that was not observed in patients with MDD. We did not see any changes in scalp and source LDAEP in response to SSRI/SNRI treatment. These results support a theoretical framework where both LDAEP and cerebral 5-HT4R are indices of cerebral 5-HT levels in healthy individuals while this association seems to be disrupted in MDD. The combination of the two biomarkers may be useful for stratifying patients with MDD. Clinical Trials Registration:https://clinicaltrials.gov/ct2/show/NCT02869035?draw=1Registration number: NCT0286903.

Keywords: 5-HT(4) receptor (5-HT(4)R); Biomarker; Electroencephalogram (EEG); Loudness dependence of auditory evoked potential (LDAEP); Major depressive disorders (MDD); Selective serotonin reuptake inhibitors (SSRI).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Depression
  • Depressive Disorder, Major* / diagnostic imaging
  • Depressive Disorder, Major* / drug therapy
  • Electroencephalography
  • Evoked Potentials, Auditory / physiology
  • Humans
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / metabolism
  • Serotonin and Noradrenaline Reuptake Inhibitors* / therapeutic use
  • Synaptic Transmission
  • Treatment Outcome

Substances

  • Serotonin
  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Selective Serotonin Reuptake Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02869035