Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

Oct 19, 2020Journal of affective disorders

Ketamine changes brain responses to emotional faces in major depression

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Abstract

MDD participants showed larger calcarine M100 amplitudes post-placebo compared to healthy volunteers, which became more similar after ketamine administration.

Individuals with major depressive disorder (MDD) exhibited higher accuracy for sad-angry faces compared to happy-neutral faces during baseline evaluations.
Healthy volunteers responded faster to happy-neutral faces than to sad-angry faces in baseline analyses.
Post-infusion, MDD participants' calcarine M100 amplitudes were larger following placebo treatment than those of healthy volunteers.
After ketamine infusion, calcarine M100 amplitudes in MDD participants became more similar to those of healthy volunteers.
Fusiform M170 amplitudes in MDD participants were associated with their response to antidepressant treatment.

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BACKGROUND: The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD). However, ketamine's effects on emotional processing biases remain largely unknown, and understanding these processes may help elucidate ketamine's mechanism of action.

METHODS: Magnetoencephalography (MEG) was used to investigate ketamine's effects on early visual responses to affective stimuli in individuals with MDD (n=31) and healthy volunteers (HVs; n=24). Participants were enrolled in a double-blind, placebo-controlled, crossover clinical trial and were assessed at baseline and after subanesthetic-dose ketamine and placebo-saline infusions. During MEG recording, participants completed an emotional evaluation task in which they indicated the sex or emotional valence (happy-neutral or sad-angry) of facial stimuli. Source-localized event-related field (ERF) M100 and M170 amplitudes and latencies were extracted from regions of interest. Linear fixed effects models examined interactions between diagnosis, stimulus valence, and drug session for behavioral and MEG data.

RESULTS: In baseline behavioral analyses, MDD participants exhibited higher accuracy for sad-angry than happy-neutral faces, and HVs responded faster to happy-neutral than sad-angry faces. In the MEG post-infusion analyses, calcarine M100 amplitudes were larger in MDD than HV participants post-placebo but became more similar post-ketamine. Finally, fusiform M170 amplitudes were associated with antidepressant response in MDD participants.

LIMITATIONS: The modest sample size and the need to collapse across responses to happy and neutral faces to increase statistical power limit the generalizability of the findings.

CONCLUSIONS: Ketamine rapidly altered emotional stimulus processing in MDD, laying the groundwork for future investigations of biomarkers of antidepressant treatment response.

CLINICAL TRIAL: Clinicaltrials.gov, NCT#00088699.

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Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

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