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

• Published in: European neuropsychopharmacology Vol. 70; pp. 32 - 44
• Main Authors: Ip, Cheng-Teng, Ganz, Melanie, Ozenne, Brice, Olbrich, Sebastian, Beliveau, Vincent, Dam, Vibeke H., Köhler-Forsberg, Kristin, Jørgensen, Martin B., Frøkjær, Vibe G., Knudsen, Gitte M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: 5-HT4 receptor (5-HT4R); Biomarker; Depression; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; Electroencephalogram (EEG); Electroencephalography; Evoked Potentials, Auditory - physiology; Humans; Loudness dependence of auditory evoked potential (LDAEP); Major depressive disorders (MDD); Selective serotonin reuptake inhibitors (SSRI); Selective Serotonin Reuptake Inhibitors - therapeutic use; Serotonin - metabolism; Serotonin and Noradrenaline Reuptake Inhibitors - therapeutic use; Synaptic Transmission; Treatment Outcome; Selective serotonin reuptake inhibitors (SSRI); Biomarker; Electroencephalogram (EEG); 5-HT4 receptor (5-HT4R); Major depressive disorders (MDD); Loudness dependence of auditory evoked potential (LDAEP); 5-HT receptor (5-HTR)
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2023.02.008

•Patients with MDD show a higher source LDAEP compared to healthy control.•Patients with higher pretreatment scalp LDAEP profit more from escitalopram and duloxetine.•LDAEP correlates positively with cerebral 5-HT4R binding in healthy controls but not in patients with MDD.•No modulation effect was observed on LDAEP after 8 weeks of SSRI/SNRI treatment in patients with MDD. 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.