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Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies.

Publication ,  Journal Article
Hufford, MR; Davis, VG; Hilt, D; Dgetluck, N; Geffen, Y; Loebel, A; Haig, G; Santarelli, L; Keefe, RSE
Published in: Schizophr Res
October 2014

OBJECTIVE: Cognition is affected by circadian rhythms over the course of a day. Circadian rhythms in cognitive functioning are driven by a variety of both endogenous and exogenous factors. Patients with schizophrenia are known to have disturbed circadian rhythms that can affect their cognitive functioning. We examined the impact of time of day on cognitive test scores from subjects participating in clinical trials of potential pro-cognitive therapies for schizophrenia and then explored how this diurnal variation affected signal detection. METHOD: Baseline data from 8 separate schizophrenia clinical trials using the MATRICS Consensus Cognitive Battery (MCCB) were aggregated (Total N=2032). The MCCB assessments were divided into five 2-hour time intervals based on the start-time of the assessments (varying from 8:00 am to 5:59 pm) and then analyzed for differences by time interval. Next, data from two Phase 2 schizophrenia clinical trials of potential pro-cognitive therapies were analyzed to explore the impact of this diurnal variation on placebo separation. RESULTS: Time of day exerted a significant effect on baseline composite MCCB scores (p=.002). Follow-up comparisons revealed significant differences among multiple temporal epochs. In both Phase 2 clinical trials, subjects whose cognitive functioning was assessed at consistent times of day between their baseline and endpoint visits showed a more robust treatment response as compared to subjects assessed at inconsistent times of day. CONCLUSION: Cognitive functioning ebbs and flows over the course of the day. Maintaining consistency in the time of day of cognitive test administrations between visits can help to reduce the noise introduced by circadian rhythms, thereby enhancing signal detection in clinical trials of potential pro-cognitive therapies.

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Published In

Schizophr Res

DOI

EISSN

1573-2509

Publication Date

October 2014

Volume

159

Issue

1

Start / End Page

205 / 210

Location

Netherlands

Related Subject Headings

  • United States
  • Statistics, Nonparametric
  • Schizophrenic Psychology
  • Schizophrenia
  • Retrospective Studies
  • Psychiatry
  • Middle Aged
  • Male
  • Humans
  • Female
 

Citation

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Hufford, M. R., Davis, V. G., Hilt, D., Dgetluck, N., Geffen, Y., Loebel, A., … Keefe, R. S. E. (2014). Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies. Schizophr Res, 159(1), 205–210. https://doi.org/10.1016/j.schres.2014.07.018
Hufford, Michael R., Vicki G. Davis, Dana Hilt, Nancy Dgetluck, Yona Geffen, Antony Loebel, George Haig, Luca Santarelli, and Richard S. E. Keefe. “Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies.Schizophr Res 159, no. 1 (October 2014): 205–10. https://doi.org/10.1016/j.schres.2014.07.018.
Hufford MR, Davis VG, Hilt D, Dgetluck N, Geffen Y, Loebel A, et al. Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies. Schizophr Res. 2014 Oct;159(1):205–10.
Hufford, Michael R., et al. “Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies.Schizophr Res, vol. 159, no. 1, Oct. 2014, pp. 205–10. Pubmed, doi:10.1016/j.schres.2014.07.018.
Hufford MR, Davis VG, Hilt D, Dgetluck N, Geffen Y, Loebel A, Haig G, Santarelli L, Keefe RSE. Circadian rhythms in cognitive functioning among patients with schizophrenia: impact on signal detection in clinical trials of potential pro-cognitive therapies. Schizophr Res. 2014 Oct;159(1):205–210.
Journal cover image

Published In

Schizophr Res

DOI

EISSN

1573-2509

Publication Date

October 2014

Volume

159

Issue

1

Start / End Page

205 / 210

Location

Netherlands

Related Subject Headings

  • United States
  • Statistics, Nonparametric
  • Schizophrenic Psychology
  • Schizophrenia
  • Retrospective Studies
  • Psychiatry
  • Middle Aged
  • Male
  • Humans
  • Female