Skip to main content
SpringerLink
Log in

Loudness Dependence of Auditory Evoked Potentials: A Promising Pre-treatment Predictor of Selective Serotonin Reuptake Inhibitor Response

  • Protocol
  • First Online:
Translational Methods for PTSD Research

Part of the book series: Neuromethods ((NM,volume 198))

  • 219 Accesses

Abstract

Selective serotonin reuptake inhibitors are the most commonly prescribed class of medications for patients with PTSD. However, many patients are not responsive to SSRIs and there is no rapid, uncomplicated way to determine who will benefit from this family of medications. Loudness dependence of auditory evoked potentials, a measure derived from auditory event-related potentials to a series of increasingly loud tones, appears to be strongly influenced by brain serotonin level and thereby holds considerable promise as an indicator of the brain’s potential responsiveness to SSRIs. The overarching goal of this chapter is to (a) describe the scientific rationale supporting the use of the LDAEP task in research advancing precision medicine approaches to the treatment of PTSD and (b) provide specific guidance to enable readers to administer this task in their own labs. Information regarding the requisite equipment is provided, as well as detailed instructions regarding the procedures for data collection, cleaning, and scoring.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Cz:

Electrode placement at the central region of the cap on the midline

EBA:

Electro-Based Adapter

EEG:

Electroencephalogram

ERP:

Event-Related Potentials

Fz:

Electrode placement at the frontal region of the cap on the midline

HEOR/HEOL:

Horizontal Electro Oculogram Right/Left

LDAEP:

Loudness Dependence of Auditory Evoked Potentials

M1/M2:

Left Mastoid/Right Mastoid

Pz:

Electrode placement at the posterior region of the cap on the midline

REF:

Reference

SNRI:

Selective Norepinephrine Reuptake Inhibitor

SSRI:

Selective Serotonin Reuptake Inhibitor

VEOU/VEOL:

Vertical Electro Oculogram Upper/Lower

References

  1. Grohol J (2016) Top 25 psychiatric medication prescriptions for 2013. Psych Central. http://psychcentral.com/lib/top-25-psychiatric-medication-prescriptions-for-2013/. Accessed 23 Sept 2016

  2. Brady K, Pearlstein T, Asnis GM et al (2000) Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 283(14):1837–1844

    Article  CAS  PubMed  Google Scholar 

  3. Davidson JR, Rothbaum BO, van der Kolk BA et al (2001) Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 58(5):485–492

    Article  CAS  PubMed  Google Scholar 

  4. Metzger LJ, Carson MA, Paulus LA et al (2002) Event-related potentials to auditory stimuli in female Vietnam nurse veterans with posttraumatic stress disorder. Psychophysiology 39(1):49–63

    Article  PubMed  Google Scholar 

  5. Buchsbaum M, Stevens S (1971) Neural events and psychophysical law. Science 172(3982):502–502

    Article  CAS  PubMed  Google Scholar 

  6. Carrillo-De-La-Pena MT (2001) One-year test–retest reliability of auditory evoked potentials (AEPs) to tones of increasing intensity. Psychophysiology 38(03):417–424

    Article  CAS  PubMed  Google Scholar 

  7. Hensch T, Herold U, Diers K et al (2008) Reliability of intensity dependence of auditory-evoked potentials. Clin Neurophysiol 119(1):224–236

    Article  CAS  PubMed  Google Scholar 

  8. Tenke CE, Kayser J, Pechtel P 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(1):34–50

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hegerl U, Juckel G (1993) Intensity dependence of auditory evoked potentials as an indicator of central serotonergic neurotransmission: a new hypothesis. Biol Psychiatry 33(3):173–187

    Article  CAS  PubMed  Google Scholar 

  10. Davis LL, Suris A, Lambert MT et al (1997) Post-traumatic stress disorder and serotonin: new directions for research and treatment. J Psychiatry Neurosci 22(5):318–326

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Eison MS (1990) Serotonin: a common neurobiologic substrate in anxiety and depression. J Clin Psychopharmacol 10(3):26S–30S

    Article  CAS  PubMed  Google Scholar 

  12. Juckel G, Molnár M, Hegerl U et al (1997) Auditory-evoked potentials as indicator of brain serotonergic activity first evidence in behaving cats. Biol Psychiatry 41(12):1181–1195

    Article  CAS  PubMed  Google Scholar 

  13. Juckel G, Hegerl U, Molnár M et al (1999) Auditory evoked potentials reflect serotonergic neuronal activity—a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus. Neuropsychopharmacology 21(6):710–716

    Article  CAS  PubMed  Google Scholar 

  14. Brocke B, Beauducel A, John R et al (2000) Sensation seeking and affective disorders: characteristics in the intensity dependence of acoustic evoked potentials. Neuropsychobiology 41(1):24–30

    Article  CAS  PubMed  Google Scholar 

  15. Wang W, Wang Y, Fu X et al (2006) Cerebral information processing in personality disorders: I. intensity dependence of auditory evoked potentials. Psychiatry Res 141(2):173–183

    Article  PubMed  Google Scholar 

  16. Carrillo-de-la-Pena M, Vallet M, Perez MI et al (2006) Intensity dependence of auditory-evoked cortical potentials in fibromyalgia patients: a test of the generalized hypervigilance hypothesis. J Pain 7(7):480–487

    Article  CAS  PubMed  Google Scholar 

  17. Siniatchkin M, Kropp P, Neumann M et al (2000) Intensity dependence of auditory evoked cortical potentials in migraine families. Pain 85(1):247–254

    Article  CAS  PubMed  Google Scholar 

  18. Croft RJ, Klugman A, Baldeweg T et al (2001) Electrophysiological evidence of serotonergic impairment in long-term MDMA (“ecstasy”) users. Am J Psychiatr 158(10):1687–1692

    Article  CAS  PubMed  Google Scholar 

  19. Tuchtenhagen F, Daumann J, Norra C et al (2000) High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users. Neuropsychopharmacology 22(6):608–617

    Article  CAS  PubMed  Google Scholar 

  20. Senkowski D, Linden M, Zubrägel D et al (2003) Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder. Biol Psychiatry 53(4):304–314

    Article  CAS  PubMed  Google Scholar 

  21. Jaworska N, Protzner A (2013) Electrocortical features of depression and their clinical utility in assessing antidepressant treatment outcome. Can J Psychiatry 58(9):509–514

    Article  PubMed  Google Scholar 

  22. McPherson WB, Newton JE, Ackerman P et al (1997) An event-related brain potential investigation of PTSD and PTSD symptoms in abused children. Integr Physiol Behav Sci 32(1):31–42

    Article  CAS  PubMed  Google Scholar 

  23. Metzger LJ, Pitman RK, Miller GA et al (2008) Intensity dependence of auditory P2 in monozygotic twins discordant for Vietnam combat: associations with posttraumatic stress disorder. J Rehabil Res Dev 45(3):437–449

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lewine JD, Thoma RJ, Provencal SL et al (2002) Abnormal stimulus-response intensity functions in posttraumatic stress disorder: an electrophysiological investigation. Am J Psychiatr 159(10):1689–1695

    Article  PubMed  Google Scholar 

  25. Paige SR, Reid GM, Allen MG et al (1990) Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans. Biol Psychiatry 27(4):419–430

    Article  CAS  PubMed  Google Scholar 

  26. Gallinat J, Bottlender R, Juckel G et al (2000) The loudness dependency of the auditory evoked N1/P2-component as a predictor of the acute SSRI response in depression. Psychopharmacology 148(4):404–411

    Article  CAS  PubMed  Google Scholar 

  27. Juckel G, Pogarell O, Augustin H et al (2007) Differential prediction of first clinical response to serotonergic and noradrenergic antidepressants using the loudness dependence of auditory evoked potentials in patients with major depressive disorder. J Clin Psychiatry 68(8):1206–1212

    Article  PubMed  Google Scholar 

  28. Lee BH, Park YM, Lee SH et al (2015) Prediction of long-term treatment response to selective serotonin reuptake inhibitors (SSRIs) using scalp and source loudness dependence of auditory evoked potentials (LDAEP) analysis in patients with major depressive disorder. Int J Mol Sci 16(3):6251–6265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lee TW, Yu YW, Chen TJ et al (2005) Loudness dependence of the auditory evoked potential and response to antidepressants in Chinese patients with major depression. J Psychiatry Neurosci 30(3):202–205

    PubMed  PubMed Central  Google Scholar 

  30. Linka T, Müller BW, Bender S et al (2005) The intensity dependence of auditory evoked ERP components predicts responsiveness to reboxetine treatment in major depression. Pharmacopsychiatry 38(03):139–143

    Article  CAS  PubMed  Google Scholar 

  31. Mulert C, Juckel G, Brunnmeier M et al (2007) Prediction of treatment response in major depression: integration of concepts. J Affect Disord 98(3):215–225

    Article  CAS  PubMed  Google Scholar 

  32. Paige SR, Fitzpatrick DF, Kline JP et al (1994) Event-related potential amplitude/intensity slopes predict response to antidepressants. Neuropsychobiology 30(4):197–201

    Article  CAS  PubMed  Google Scholar 

  33. Wade EC, Iosifescu DV (2016) Using EEG for treatment guidance in major depressive disorder. Biol. Psychiatry Cogn Neurosci Neuroimagin 1:411–422

    Google Scholar 

  34. Yoon S, Kim Y, Lee SH (2021) Does the loudness dependence of auditory evoked potential predict response to selective serotonin reuptake inhibitors?: a meta-analysis. Clin Pschopharmacol Neurosci 19(2):254

    Article  CAS  Google Scholar 

  35. Linka T, Sartory G, Wiltfang J et al (2009) Treatment effects of serotonergic and noradrenergic antidepressants on the intensity dependence of auditory ERP components in major depression. Neurosci Lett 463(1):26–30

    Article  CAS  PubMed  Google Scholar 

  36. Park YM, Lee SH, Park EJ (2012) Usefulness of LDAEP to predict tolerability to SSRIs in major depressive disorder: a case report. Psychiatry Investig 9(1):80–82

    Article  PubMed  PubMed Central  Google Scholar 

  37. Luck SJ (2014) An introduction to the event-related potential technique. MIT Press, Cambridge, MA

    Google Scholar 

  38. Nathan PJ, Segrave R, Phan KL et al (2006) Direct evidence that acutely enhancing serotonin with the selective serotonin reuptake inhibitor citalopram modulates the loudness dependence of the auditory evoked potential (LDAEP) marker of central serotonin function. Hum Psychopharmacol Clin Exp 21(1):47–52

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Support for this work was provided by the Department of Veterans Affairs, Clinical Sciences R&D Service, Merit Award Program (CX001627-01A1; PI: Pineles).

Disclosures

Dr. Abi-Raad is affiliated with Compumedics USA Inc., the manufacturer and distributor of the hardware and software described in this report. Other authors report no conflicts of interest related to this study disclosure.

Author information

Authors and Affiliations

  1. National Center for PTSD Women’s Health Sciences Division, VA Boston Healthcare System, Boston, MA, USA

    Suzanne L. Pineles, Shivani Pandey & Rachel Shor

  2. Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

    Suzanne L. Pineles & Rachel Shor

  3. Compumedics USA Inc, Compumedics-Neuroscan, Charlotte, NC, USA

    Ronnie F. Abi-Raad

  4. Department of Psychology, Middlebury College, Middlebury, VT, USA

    Matthew O. Kimble

  5. Psychiatry Department, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

    Scott P. Orr

Authors
  1. Suzanne L. Pineles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shivani Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel Shor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronnie F. Abi-Raad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew O. Kimble
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott P. Orr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suzanne L. Pineles .

Editor information

Editors and Affiliations

  1. Psychiatric Institute, University of Chicago, Chicago, IL, USA

    Graziano Pinna

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Pineles, S.L., Pandey, S., Shor, R., Abi-Raad, R.F., Kimble, M.O., Orr, S.P. (2023). Loudness Dependence of Auditory Evoked Potentials: A Promising Pre-treatment Predictor of Selective Serotonin Reuptake Inhibitor Response. In: Pinna, G. (eds) Translational Methods for PTSD Research. Neuromethods, vol 198. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3218-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-3218-5_14

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3217-8

  • Online ISBN: 978-1-0716-3218-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation