Studies have found evidence of dichotic listening, electrophysiologic (EEG/ERP), and neurocognitive abnormalities in depressed patients, which are related to clinical response to antidepressants. Measures of hemispheric asymmetry, quantitative EEG in alpha/theta bands and intensity-dependence of auditory event-related potentials (ERPs) show particular promise of being predictive of response to a selective serotonin reuptake inhibitor (SSRI). Sample size in most studies has, however, been small and little is known about the specificity of predictors to SSRI antidepressants. An upcoming dual therapy clinical trial offers an ideal opportunity to conduct a prospective study to assess the value of these electrophysiologic and cognitive measures as predictors of therapeutic response to the SSRI escitalopram (ESC) as opposed to the noradrenaline/dopamine reuptake inhibitor (NDRI) bupropion (BUP). Patients are randomly assigned to 12 weeks of treatment with ESC, BUP or a combination of these antidepressants (ESC + BUP). Unmedicated depressed patients and healthy controls will be tested at baseline on a battery of tests, including resting EEG, intensity-dependence of auditory ERPs, novelty oddball task, dichotic listening, and neurocognitive tests. Patients are retested on the EEG and auditory ERP measures after 1 week of treatment and again after 12 weeks, and controls are retested at the same intervals. This will enable us to examine whether these electrophysiologic measures change during treatment or are stable, state-independent markers. A preclinical study found that firing rates of serotonin neurons in the dorsal raphi nucleus were markedly increased after combined administration of ESC + BUP, but not after either drug alone, which could account for the more rapid and increased benefit of this dual treatment. If this translates to humans, ESC + BUP would be predicted to have acute and chronic effects on EEG and auditory ERP measures not seen for either antidepressant alone. Moreover, we will examine whether acute changes in EEG and auditory ERPs predict which patients will show remission of symptoms with combined treatment. The long-range goal of this project is to contribute toward the development of electrophysiologic and behavioral tests that could aid the clinician in choosing antidepressants that will most benefit a depressed patient.

Public Health Relevance

A clinical trial comparing treatment with an SSRI, bupropion or combined therapy offers an ideal opportunity to do a prospective study of the value of electrophysiologic and neurocognitive tests as predictors of therapeutic response to these antidepressants. This research could translate into development of clinical aides for selecting treatments for individual depressed patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH036295-27
Application #
8209198
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Muehrer, Peter R
Project Start
1982-09-28
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
27
Fiscal Year
2012
Total Cost
$370,668
Indirect Cost
$147,918
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Tenke, Craig E; Kayser, Jürgen; Pechtel, Pia et al. (2017) Demonstrating test-retest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response. Psychophysiology 54:34-50
Bruder, Gerard E; Stewart, Jonathan W; McGrath, Patrick J (2017) Right brain, left brain in depressive disorders: Clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings. Neurosci Biobehav Rev 78:178-191
Tenke, Craig E; Kayser, Jürgen; Svob, Connie et al. (2017) Association of posterior EEG alpha with prioritization of religion or spirituality: A replication and extension at 20-year follow-up. Biol Psychol 124:79-86
Kayser, Jürgen; Tenke, Craig E (2015) On the benefits of using surface Laplacian (current source density) methodology in electrophysiology. Int J Psychophysiol 97:171-3
Kishon, Ronit; Abraham, Karen; Alschuler, Daniel M et al. (2015) Lateralization for speech predicts therapeutic response to cognitive behavioral therapy for depression. Psychiatry Res 228:606-11
Kayser, Jürgen; Tenke, Craig E (2015) Issues and considerations for using the scalp surface Laplacian in EEG/ERP research: A tutorial review. Int J Psychophysiol 97:189-209
Tenke, Craig E; Kayser, Jürgen (2015) Surface Laplacians (SL) and phase properties of EEG rhythms: Simulated generators in a volume-conduction model. Int J Psychophysiol 97:285-98
Tenke, Craig E; Kayser, Jürgen; Abraham, Karen et al. (2015) Posterior EEG alpha at rest and during task performance: Comparison of current source density and field potential measures. Int J Psychophysiol 97:299-309
Bruder, Gerard E; Alvarenga, Jorge E; Alschuler, Daniel et al. (2014) Neurocognitive predictors of antidepressant clinical response. J Affect Disord 166:108-14
Miller, Lisa; Bansal, Ravi; Wickramaratne, Priya et al. (2014) Neuroanatomical correlates of religiosity and spirituality: a study in adults at high and low familial risk for depression. JAMA Psychiatry 71:128-35

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