Loudness dependent auditory evoked potentials and suicidality in depression – A meta-analysis with replication in unmedicated patients

Objective: Major Depressive Disorder (MDD) is a risk factor for suicide. Loudness-Dependent Auditory Evoked Potentials (LDAEP) is an electroencephalographic biomarker of central serotonergic activity associated with MDD and suicidality. Yet, studies on the matter are conflicting. We therefore: 1) Conducted a meta-analysis to clarify the relation between LDAEP, past suicide attempts and current suicidality in MDD, and 2) replicated the findings in independent data of unmedicated patients with MDD. Methodology: 1) 10 studies were included in the meta-analysis. The difference in scalp LDAEP between patients with and without past suicide attempts was estimated using Hedge's g. The correlation between scalp LDAEP and suicidality was estimated using Fisher's Zr. The Newcastle-Ottawa Scale was used to assess methodological differences. The review was preregistered (PROSPERO). 2) We examined the associations above within an independent cohort of 88 unmedicated patients with MDD. The analyses were preregistered (AsPredicted.org) and used to update the meta-analysis. Results: In the initial meta-analysis, scalp LDAEP was not associated with past suicide attempts (g = 0.11 [−0.23, 0.46], p = 0.53) or correlated with suicidality (Zr = 0.06 [−0.15, 0.27], p = 0.60). In the independent cohort, scalp LDAEP was also not associated with past suicide attempts (g = 0.05 [−0.56, 0.65] t(86) = 0.15, p = 0.88) or correlated with suicidality (Zr = 0.11 [−0.1, 0.33] r = 0.11 [−0.10, 0.32], p = 0.30). In the updated meta-analysis, scalp LDAEP continued not to be associated with suicide attempts (g = 0.10 [−0.19, 0.39], p = 0.51) or suicidality (Zr = 0.06 [−0.12, 0.24], p = 0.50). Conclusion: LDAEP is not associated with past suicide attempts or suicidality in MDD, and LDAEP's usefulness in suicide prevention seems limited.