Lysets betydning for døgnrytmeregulering: Nerveforbindelsen mellem øjet og hjernens biologiske ur Seminar: Lysets biologiske virkninger, 29 marts 2011 Jens Hannibal Klinisk Biokemisk afdeling, Bispebjerg Hospital Biologiske rytmer Vores øjne har to systemer som opfatter lys: Billeddannende Ikke-billede dannende (lysintensitetsmåler) 1
Eksempler på Circadiane rytmer Dage Blind Modified from Maywood, E. S. et al. Endocrinology 2007 Recorder : Måler antallet af hjulomdrejninger 12:12 LD Justeret rytme Computer Konstant mørke CT12 Subjektive nat Fritløbende SCN-lesion arrytmisk 0:00 6:00 12:00 18:00 2
Hjernes ur: Den suprachiasmatiske kerne (SCN) Hjernens ur er en samling af nerveceller, som styrer vores døgnrytmer. Hjernens ur Basal organisation af det circadiane system "Slave" oscillatore Øje (fotoreceptor) Lys Entrainment Pacemaker Circadian funktioner 3
Hjernens ur har ikke en periodelængde på 24 timer, men skal som et ur, der går for hurtigt eller for langsomt, stilles hver dag. Re-justering (entrainment) af et 8 timers faseskift (flyvning vest øst) 6 18 24 36 Vigtigste stimulus til at stille uret er lyset i omgivelserne. Time Fase-respons for lys Ikke-billede dannende system (Lysintensitetsmåler) 4
Billeddannende fotoperception anvender to typer af fotoreceptorer; stave og tappe Lysmåleren i øjet udgøres af en lille gruppe nerveceller som anvender melanopsin som fotopigment Human retina farvet for melanopsin 5
Melanopsin er fotopigment for lysmåleren i øjet og sender signal til hjernens ur Melanopsin opfatter blåt lys (480-500 nm) Hannibal et al. J. Neurosci 2002 Berson et al., Science Vol. 295. 2002 Ikke-billededannende fotoperception: Den retinohypothalamiske bane (RHT) VLPO Modified from Berson D, 2003 Guler et al., Nature 2008 6
Ikke-billede dannende fotoperception Justering af circadiane rytmer Regulere natlig frisætning af melatonin Masking Pupil refleks Søvn/vågen (hjerterytme) Humør (seasonal affective disorder) Guler et al., Nature 2008 Dark-adapted Light-adapted Days Light-adapted with synaptic block Blind Dacey et al. Nature 2005 7
Biologisk døgnrytme ude af fase med det astronomiske døgn (lys/mørke cyklus) Jet-lag (rejser over tidszoner (øst/vest)) Skifteholdsarbejde Søvn sygdomme (ASPS, DSPS) Neurodegenerative sygdomme (Alzheimer, Parkinson) Psykiatriske sygdomme (ADHD, Autisme) The Can-SAD Study: A Randomized Controlled Trial of the effectiveness of Light Therapy and Fluoxetine in Patients with Winter Seasonal Affective Disorder (SAD). Conclusions: Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment. Lam et al. Am J Psychiatry 2006; 163:805 812 Light therapy for non-seasonal depression Arja Tuunainen1, Daniel F Kripke2, Takuro Endo3 Authors conclusions For patients suffering from non-seasonal depression, light therapy offers modest though promising antidepressive efficacy, especially when administered during the first week of treatment, in the morning, and as an adjunctive treatment to sleep deprivation responders. Hypomania as a potential adverse effect needs to be considered. Due to limited data and heterogeneity of studies these results need to be interpreted with caution. 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Light therapy for managing cognitive, sleep, functional, behavioural, or psychiatric disturbances in dementia Dorothy Forbes1, Ivan Culum2, Andrea R Lischka2, Debra G Morgan3, Shelley Peacock4, Jennifer Forbes5, Sean Forbes6 Main results Eight trials met the inclusion criteria. However, three of the studies could not be included in the analyses because of inappropriate reported study analyses or inability to retrieve the required data from the investigators. This review revealed no adequate evidence of the effectiveness of light therapy in managing cognition, sleep, function, behaviour, or psychiatric disturbances associated with dementia. Authors conclusions There is insufficient evidence to assess the value of light therapy for people with dementia. Most of the available studies are not of high methodological quality and further research is required. 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. 8
Bright light therapy for sleep problems in adults aged 60+ Paul Montgomery1, Jane A Dennis2 Main results Reviewers found no trials on which to base conclusions for the effectiveness of this treatment. Authors conclusions When the possible side-effects of standard treatment (hypnotics) are considered, there is a reasonable argument to be made for clinical use of non-pharmacological treatments. In view of the promising results of bright light therapy in other populations with problems of sleep timing, further research into their effectiveness with older adults would seem justifiable. 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. 9