The effects of roflumilast, a phosphodiesterase type-4 (PDE4) inhibitor, on EEG biomarkers in schizophrenia

James Gilleen, Judith Nottage, Farah Yakub, Sarah Kerins, Lorena Valdearenas, Tolga Uz, Gez Lahu, Max Tsai, Frank Ogrinc, Steve Williams, Dominic Ffytche, Mitul Mehta, Sukhi Shergill

Research output: Contribution to journalArticle

Abstract

Background
Patients with schizophrenia have significant cognitive deficits, which may profoundly impair quality of life. These deficits are also observable at the neurophysiological level with patients demonstrating impaired Event Related Potentials (ERPs) in, for example, Auditory Oddball (Mismatch negativity (MMN), P300 and Auditory Steady State Response (ASSR) paradigms compared to healthy controls. However, currently there are no approved pharmacological treatments for these or other cognitive deficits in schizophrenia.
Methods
Using a randomised, double-blind, placebo-controlled, crossover design study in 18 patients with schizophrenia, the effect of the PDE4 inhibitor, Roflumilast (100µg and 250µg) - which has a beneficial effect on cognition - on MMN, P300 and ASSR ERPs, and working memory-related theta oscillations (3.5-7 Hz) was investigated. Patients underwent EEG recordings during cognitive task administration. Fifteen patients completed all sessions.
Results
250µg of Roflumilast significantly enhanced the amplitude of both the MMN (p=0.04) and the amplitude of working memory-related theta oscillations (p=0.02) compared to placebo.
Conclusions
These results point to the potential of PDE4 inhibitors as a treatment for cognitive deficits in schizophrenia, and also underline the utility of EEG to assay cognitive biomarkers in experimental medicine studies.

© 2020, The Author(s). This is an author produced version of a paper published in JOURNAL OF PSYCHOPHARMACOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.
Original languageEnglish
JournalJOURNAL OF PSYCHOPHARMACOLOGY
Publication statusAccepted/In press - 3 Jul 2020

Cite this

Gilleen, J., Nottage, J., Yakub, F., Kerins, S., Valdearenas, L., Uz, T., Lahu, G., Tsai, M., Ogrinc, F., Williams, S., Ffytche, D., Mehta, M., & Shergill, S. (Accepted/In press). The effects of roflumilast, a phosphodiesterase type-4 (PDE4) inhibitor, on EEG biomarkers in schizophrenia. JOURNAL OF PSYCHOPHARMACOLOGY.