The effects of roflumilast, a phosphodiesterase type-4 inhibitor, on EEG biomarkers in schizophrenia: A randomised controlled trial

2020 ◽  
Vol 35 (1) ◽  
pp. 15-22
Author(s):  
James Gilleen ◽  
Judith Nottage ◽  
Farah Yakub ◽  
Sarah Kerins ◽  
Lorena Valdearenas ◽  
...  

Background: Patients with schizophrenia have significant cognitive deficits, which may profoundly impair quality of life. These deficits are also evident at the neurophysiological level with patients demonstrating altered event-related potential in several stages of cognitive processing compared to healthy controls; within the auditory domain, for example, there are replicated alterations in Mismatch Negativity, P300 and Auditory Steady State Response. However, there are no approved pharmacological treatments for cognitive deficits in schizophrenia. Aims: Here we examine whether the phosphodiesterase-4 inhibitor, roflumilast, can improve neurophysiological deficits in schizophrenia. Methods: Using a randomised, double-blind, placebo-controlled, crossover design study in 18 patients with schizophrenia, the effect of the phosphodiesterase-4 inhibitor, roflumilast (100 µg and 250 µg) on auditory steady state response (early stage), mismatch negativity and theta (intermediate stage) and P300 (late stage) was examined using electroencephalogram. A total of 18 subjects were randomised and included in the analysis. Results: Roflumilast 250 µg significantly enhanced the amplitude of both the mismatch negativity ( p=0.04) and working memory-related theta oscillations ( p=0.02) compared to placebo but not in the other (early- or late-stage) cognitive markers. Conclusions: The results suggest that phosphodiesterase-4 inhibition, with roflumilast, can improve electroencephalogram cognitive markers, which are impaired in schizophrenia, and that phosphodiesterase-4 inhibition acts at an intermediate rather than early or late cognitive processing stage. This study also underlines the use of neurophysiological measures as cognitive biomarkers in experimental medicine.

2002 ◽  
Vol 13 (05) ◽  
pp. 260-269 ◽  
Author(s):  
Barbara Cone-Wesson ◽  
John Parker ◽  
Nina Swiderski ◽  
Field Rickards

Two studies were aimed at developing the auditory steady-state response (ASSR) for universal newborn hearing screening. First, neonates who had passed auditory brainstem response, transient evoked otoacoustic emission, and distortion-product otoacoustic emission tests were also tested with ASSRs using modulated tones that varied in frequency and level. Pass rates were highest (> 90%) for amplitude-modulated tones presented at levels ≥ 69 dB SPL. The effect of modulation frequency on ASSR for 500- and 2000-Hz tones was evaluated in full-term and premature infants in the second study. Full-term infants had higher pass rates for 2000-Hz tones amplitude modulated at 74 to 106 Hz compared with pass rates for a 500-Hz tone modulated at 58 to 90 Hz. Premature infants had lower pass rates than full-term infants for both carrier frequencies. Systematic investigation of ASSR threshold and the effect of modulation frequency in neonates is needed to adapt the technique for screening.


2020 ◽  
pp. 155005942098270
Author(s):  
Sarah Ahmed ◽  
Jennifer R. Lepock ◽  
Romina Mizrahi ◽  
R. Michael Bagby ◽  
Cory J. Gerritsen ◽  
...  

Aim Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients’ real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. Methods A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. Results In CHR patients, lower 40-Hz PLF correlated with lower social functioning. Conclusions Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.


2018 ◽  
Vol 662 ◽  
pp. 152-157 ◽  
Author(s):  
Inga Griskova-Bulanova ◽  
Kastytis Dapsys ◽  
Sigita Melynyte ◽  
Aleksandras Voicikas ◽  
Valentinas Maciulis ◽  
...  

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