RESUMO
Background: Bipolar disorder is a severe chronic mental disorder. There is a bidirectional relationship between disease course and circadian phase. Significant circadian phase shifts occur during transitions between episodes, but episodes can also be elicited during euthymia by forced rapid changes in circadian phase. Although an instability of circadian phase has been described in multiple observational reports, no studies quantifying the propensity to phase shift following an experimental standardized stimulus have been published. This study therefore aimed to assess whether patients with bipolar I disorder (BDI) are more prone to phase delay following blue light exposure in the evening than healthy control subjects. Methods: Euthymic participants with BDI confirmed by Structured Clinical Interview for DSM-IV Axis I (n = 32) and healthy control subjects (n = 55) underwent a 3-day phase shift protocol involving exposure to a standardized dose of homogeneous, constant, narrow bandwidth blue light (478 nm, half bandwidth = 18 nm, photon flux = 1.29 × 1015 photons/cm2/s) for 2 hours at 9:00 pm via a ganzfeld dome on day 2. On days 1 and 3, serial serum melatonin assessments during total darkness were performed to determine the dim light melatonin onset. Results: Significant differences in the light-induced phase shift between BDI and healthy control subjects were detected (F 1,82 = 4.110; p = .046), with patients with bipolar disorder exhibiting an enhanced phase delay (η2 = 0.49). There were no significant associations between the magnitude of the phase shift and clinical parameters. Conclusions: Supersensitivity of patients with BDI to light-induced phase delay may contribute to the observed phase instability and vulnerability to forced phase shifts associated with the disorder.
RESUMO
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.
