The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults

PLoS One. 2018 Sep 27;13(9):e0204621. doi: 10.1371/journal.pone.0204621. eCollection 2018.

Abstract

This study investigated the utility of the pupillary light reflex as a method of differentiating DSPD patients with delayed melatonin timing relative to desired/required sleep time (circadian type) and those with non-delayed melatonin timing (non-circadian type). All participants were young adults, with a total of 14 circadian DSPD patients (M = 28.14, SD = 5.26), 12 non-circadian DSPD patients (M = 29.42, SD = 11.51) and 51 healthy controls (M = 21.47 SD = 3.16) completing the protocol. All participants were free of central nervous system acting medications and abstained from caffeine and alcohol on the day of the assessment. Two pupillary light reflex measurements were completed by each participant, one with a 1s dim (~10 lux) light exposure, and one with a 1s bright (~1500 lux) light exposure. Circadian DSPD patients showed a significantly faster pupillary light reflex than both non-circadian DSPD patients and healthy controls. Non-circadian patients and healthy controls did not differ significantly. Receiver operating characteristic curves were generated to determine the utility of mean and maximum constriction velocity in differentiating the two DSPD phenotypes, and these demonstrated high levels of sensitivity (69.23--100%) and specificity (66.67-91.67%) at their optimal cut offs. The strongest predictor of DSPD phenotype was the mean constriction velocity to bright light (AUC = 0.87). These results support the potential for the pupillary light reflex to clinically differentiate between DSPD patients with normal vs. delayed circadian timing relative to desired bedtime, without the need for costly and time-consuming circadian assessments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Circadian Rhythm / physiology
  • Diagnosis, Differential
  • Diagnostic Errors
  • Female
  • Humans
  • Male
  • Phenotype
  • ROC Curve
  • Reflex, Pupillary / physiology*
  • Sleep Disorders, Circadian Rhythm / diagnosis*
  • Sleep Disorders, Circadian Rhythm / physiopathology*
  • Sleep Disorders, Circadian Rhythm / therapy
  • Sleep Wake Disorders / diagnosis*
  • Sleep Wake Disorders / physiopathology*
  • Sleep Wake Disorders / therapy
  • Young Adult

Grants and funding

This study was supported by the National Health and Medical Research Council, projects 1031513 awarded to SMW Rajaratnam, and 1087665 awarded to SWC, https://www.nhmrc.gov.au/.