Melatonin suppression by melanopsin-weighted light in patients with bipolar I disorder compared to healthy controls

Melatonin suppression by melanopsin-weighted light in patients with bipolar I disorder compared to healthy controls

J Psychiatry Neurosci 2020;45(2):79-87 | PDF | Appendix

Philipp Ritter, MD; Falk Wieland, PhD; Debra J. Skene, PhD; Andrea Pfennig, MD; Maria Weiss, MD; Michael Bauer, MD; Emanuel Severus, MD; Henry Güldner, PhD; Cathrin Sauer, DiplBiomath; Bettina Soltmann, MSc; Stefanie Neumann, MD

Background: Multiple lines of evidence suggest that the onset and course of bipolar disorder is influenced by environmental light conditions. Increased suppression of melatonin by light (supersensitivity) in patients with bipolar disorder has been postulated as an endophenotype by several studies. However, due to methodological shortcomings, the results of these studies remain inconclusive. This study investigated melatonin suppression in euthymic patients with bipolar I disorder using evening blue light specifically targeting the melanopsin system.

Methods: Melatonin suppression was assessed in euthymic patients with bipolar I disorder and healthy controls by exposure to monochromatic blue light (λmax = 475 nm; photon density = 1.6 × 1013 photons/cm2/s) for 30 minutes at 2300 h, administered via a ganzfeld dome for highly uniform light exposure. Serum melatonin concentrations were determined from serial blood sampling via radioimmunoassay. All participants received mydriatic eye drops and were genotyped for the PER3 VNTR polymorphism to avoid or adjust for potential confounding. As secondary outcomes, serum melatonin concentrations during dark conditions and after monochromatic red light exposure (λmax = 624 nm; photon density = 1.6 × 1013 photons/cm2/s) were also investigated. Changes in subjective alertness were investigated for all 3 lighting conditions.

Results: A total of 90 participants (57 controls, 33 bipolar I disorder) completed the study. Melatonin suppression by monochromatic blue light did not differ between groups (F1,80 = 0.56; p = 0.46). Moreover, there were no differences in melatonin suppression by monochromatic red light (F1,82 = 1.80; p = 0.18) or differences in melatonin concentrations during dark conditions (F1,74 = 1.16; p = 0.29). Healthy controls displayed a stronger increase in subjective alertness during exposure to blue light than patients with bipolar I disorder (t85 = 2.28; p = 0.027).

Limitations: Large interindividual differences in melatonin kinetics may have masked a true difference.

Conclusion: Despite using a large cohort and highly controlled laboratory conditions, we found no differences in melatonin suppression between euthymic patients with bipolar I disorder and healthy controls. These findings do not support the notion that supersensitivity is a valid endophenotype in bipolar I disorder.


Submitted Jan. 7, 2019; Revised Apr. 12, 2019; Accepted Apr. 12, 2019; Published online Sept. 11, 2019

Acknowledgements: The authors thank Dorothy Ritter for her linguistic contributions to this manuscript and Gerd Wunderlich, Rupert Overall and Klaus Fabel for providing the required laboratory facilities and assistance.

Affiliations: From the Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Ritter, Wieland, Pfennig, Weiss, Bauer, Severus, Sauer, Soltmann, Neumann); the Chair of Power Electronics, Institute of Electrical Power Engineering, TU Dresden (Wieland and Güldner); and the Department of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guilford, UK (Skene).

Funding: The project was funded by the German Ministry of Education and Science (Bundesministerium für Bildung und Forschung; BMBF), Grant 13N13399.

Competing interests: D. Skene is a co-director of Stockerland Ltd., UK. M. Bauer reports grants from Deutsche Forschungsgemeinscheaft (DFG), and Bundesministerium für Bildung und Forschung (BMBF); personal fees from Allergan, Aristo, Janssen, Lundbeck, Neuraxpharm, Sandoz, Servier and Sumitomo Dainippon; and nonfinancial support from Lilly, Neuraxpharm and Servier, all outside the submitted work. B. Soltmann is supported by a grant from the German Ministry of Research and Education (grant no. 13N13399). No other competing interests declared.

Contributors: P. Ritter, F. Wieland, D. Skene, A. Pfennig, H. Güldner, C. Sauer, B. Soltmann, and S. Neumann designed the study. P. Ritter, F. Wieland, M. Weiss, H. Güldner, C. Sauer, B. Soltmann, and S. Neumann acquired the data, which P. Ritter, F. Wieland, D. Skene, M. Bauer, E. Severus, H. Gülder, B. Soltmann and S. Neumann analyzed. P. Ritter, F. Wieland, C. Sauer, B. Soltmann, and S. Neumann wrote the article, which P. Ritter, D. Skene, A. Pfennig, M. Weiss, M. Bauer, E. Severus, H. Güldner, and B. Soltmann reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.190005

Correspondence to: P. Ritter, University Hospital Carl Gustav Carus Dresden, Fetscherstrasse 74, 01307 Dresden, Germany; philipp.ritter@ukdd.de