Three-week bright-light intervention has dose-related effects on threat-related corticolimbic reactivity and functional coupling.
BACKGROUND
Bright-light intervention is reported to successfully treat depression, in particular seasonal affective disorder, but the neural pathways and molecular mechanisms mediating its effects are unclear. An amygdala-prefrontal cortex corticolimbic circuit regulates responses to salient environmental stimuli (e.g., threat) and may underlie these effects. Serotonin signaling modulates this circuit and is implicated in the pathophysiology of seasonal and other affective disorders.


METHODS
We evaluated the effects of a bright-light intervention protocol on threat-related corticolimbic reactivity and functional coupling, assessed with an emotional faces functional magnetic resonance imaging paradigm at preintervention and postintervention. In a double-blind study conducted in the winter, 30 healthy male subjects received bright-light intervention (dose range between participants: .1-11.0 kilolux) for 30 minutes daily over a period of 3 weeks. Additionally, we considered serotonin transporter-linked polymorphic region (5-HTTLPR) genotype status as a model for differences in serotonin signaling and moderator of intervention effects.


RESULTS
Bright-light dose significantly negatively affected threat-related amygdala and prefrontal reactivity in a dose-dependent manner. Conversely, amygdala-prefrontal and intraprefrontal functional coupling increased significantly in a dose-dependent manner. Genotype status significantly moderated bright-light intervention effects on intraprefrontal functional coupling.


CONCLUSIONS
This is the first study to evaluate the effects of clinically relevant bright-light intervention on threat-related brain function. We show that amygdala-prefrontal reactivity and communication are significantly affected by bright-light intervention, an effect partly moderated by genotype. These novel findings support that this threat-related corticolimbic circuit is sensitive to light intervention and may mediate the therapeutic effects of bright-light intervention.
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O.
Patrick M
PM
Fisher
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O.
Martin K
MK
Madsen
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O.
Brenda
B
Mc Mahon
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Department of Biostatistics, University of Copenhagen, Copenhagen K.
Klaus K
KK
Holst
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O.
Sofie B
SB
Andersen
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre.
Helle R
HR
Laursen
Department of Cellular and Molecular Medicine, Copenhagen University, Copenhagen, Denmark.
Lis F
LF
Hasholt
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre.
Hartwig R
HR
Siebner
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O. Electronic address: gmk@nru.dk.
Gitte M
GM
Knudsen
D001921:Brain / Q000502:physiology* / Q000528:radiation effects; D001931:Brain Mapping; D004307:Dose-Response Relationship, Radiation; D004311:Double-Blind Method; D005149:Facial Expression; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology / Q000528:radiation effects; D009483:Neuropsychological Tests; D010556:Personality Tests; D010775:Photic Stimulation; D010789:Phototherapy; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012815:Signal Processing, Computer-Assisted; D014796:Visual Perception / Q000502:physiology* / Q000528:radiation effects; D055815:Young Adult
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
5-HTTLPR; Amygdala; bright-light therapy; fMRI; prefrontal cortex; serotonin