Biological Psychiatry, 2018; 83:S383-S384. [Paper to be presented at the 57th Annual Meeting of the Society of Psychophysiological Research (SPR) in Vienna, Austria, October 11 Â 15, 2017.]
Loudness dependency of auditory evoked potentials (LDAEP) as a differential predictor of antidepressant treatment response in major depressive disorder (MDD): results from the sertraline/placebo-controlled EMBARC study
Jürgen Kaysera, Craig E. Tenkea, Eva Petkovab, Lidia Y.X. Wonga, Priya Wickramaratnea, Daniel M. Alschulera, Jorge E. Alvarengaa, Karen Abrahama, Pia Pechtelc, Christian A. Webbc, Daniel G. Dillona, Patricia Deldine, Crystal Cooperf, Joseph Trombellof, Patrick J. McGratha, Maurizio Favac,d, Maria A. Oquendog, Madhukar H. Trivedif, Myrna M. Weissmana, Diego A. Pizzagallic, Gerard E. Brudera
aNew York State Psychiatric Institute and Columbia University, New York, NY, USA; bNew York University, New York, NY, USA; cHarvard Medical School and McLean Hospital, Belmont, MA, USA; dMassachusetts General Hospital, Boston, MA, USA; eUniversity of Michigan Health System, Ann Arbor, MI, USA; fUT Southwestern Medical Center, Dallas, TX, USA; gUniversity of Pennsylvania, PA, USA
Abstract
Background: Loudness-dependent auditory evoked potentials (LDAEP), a monotonic increase of N1/P2 amplitude with increasing tone intensity, has promise as a predictor of clinical treatment response with serotonin agonists in MDD. LDAEP was therefore included in a comprehensive array of putative clinical and biological moderators of treatment effect (rate of change in depressive symptoms across randomized SSRI or placebo treatment [Tx]) in the multisite project Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC).
Methods: MDD patients (baseline HAMD17 $15, 78 sertraline, 86 placebo) who completed Stage 1 (8-wk) provided baseline 72-channel ERPs to 1000-Hz tones at five intensities (60-100 dB). N1 activity attributable to primary auditory cortex (tangential dipole) was quantified using scalp current source density and temporal PCA. Multilevel analysis examined the association of N1 dipole amplitude, Tx, intensity, and rate of symptom change (slope of HAMD scores).
Results: A significant Tx*intensity*symptom change interaction (p = .006) originated from an increasingly stronger association between larger N1 and better clinical response with increasing tone intensity for sertraline only, whereas this association was lower for placebo and did not vary with intensity. At the same time, a significant intensity*symptom change interaction (p = .003) confirmed that a steeper LDAEP N1 slope was linked to symptom improvement, independent of Tx. These effects remained after adding gender, age, and baseline HAMD as covariates to the regression model.
Conclusions: Results confirm and extend prior findings, suggesting that LDAEP as a neurobiological marker may function both as a predictor of MDD treatment response and as a moderator of treatment effect.
Key Words: antidepressant response; predictive biomarkers; sertraline; ERPs; N100
[Supported by NIMH grant U01MH092250].