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Three-Week Bright-Light Intervention Has Dose-Related Effects on Threat-Related Corticolimbic Reactivity and Functional Coupling

  • Patrick M. Fisher
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O
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  • Martin K. Madsen
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O
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  • Brenda Mc Mahon
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O
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  • Klaus K. Holst
    Affiliations
    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
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  • Sofie B. Andersen
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O
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  • Helle R. Laursen
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre
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  • Lis F. Hasholt
    Affiliations
    Department of Cellular and Molecular Medicine, Copenhagen University, Copenhagen, Denmark
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  • Hartwig R. Siebner
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre
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  • Gitte M. Knudsen
    Correspondence
    Address correspondence to Gitte M. Knudsen, M.D., D.M.Sc., Copenhagen University Hospital Rigshospitalet, Neurobiology Research Unit, NRU 6931, Rigshospitalet, Blegdamsvej 9, Copenhagen O DK-2100, Denmark
    Affiliations
    Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen O

    Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen O
    Search for articles by this author
Published:December 23, 2013DOI:https://doi.org/10.1016/j.biopsych.2013.11.031

      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.

      Key Words

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      References

        • Pail G.
        • Huf W.
        • Pjrek E.
        • Winkler D.
        • Willeit M.
        • Praschak-Rieder N.
        • Kasper S.
        Bright-light therapy in the treatment of mood disorders.
        Neuropsychobiology. 2011; 64: 152-162
        • Terman M.
        Evolving applications of light therapy.
        Sleep Med Rev. 2007; 11: 497-507
        • Rosenthal N.E.
        • Sack D.A.
        • Gillin J.C.
        • Lewy A.J.
        • Goodwin F.K.
        • Davenport Y.
        • et al.
        Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy.
        Arch Gen Psychiatry. 1984; 41: 72-80
        • Vandewalle G.
        • Schwartz S.
        • Grandjean D.
        • Wuillaume C.
        • Balteau E.
        • Degueldre C.
        • et al.
        Spectral quality of light modulates emotional brain responses in humans.
        Proc Natl Acad Sci U S A. 2010; 107: 19549-19554
        • Praschak-Rieder N.
        • Willeit M.
        Treatment of seasonal affective disorders.
        Dialogues Clin Neurosci. 2003; 5: 389-398
        • Quirk G.J.
        • Mueller D.
        Neural mechanisms of extinction learning and retrieval.
        Neuropsychopharmacology. 2008; 33: 56-72
        • Phillips M.L.
        • Drevets W.C.
        • Rauch S.L.
        • Lane R.
        Neurobiology of emotion perception I: The neural basis of normal emotion perception.
        Biol Psychiatry. 2003; 54: 504-514
        • Stuhrmann A.
        • Suslow T.
        • Dannlowski U.
        Facial emotion processing in major depression: A systematic review of neuroimaging findings.
        Biol Mood Anxiety Disord. 2011; 1: 10
        • Holmes A.
        Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease.
        Neurosci Biobehav Rev. 2008; 32: 1293-1314
        • Fisher P.M.
        • Hariri A.R.
        Linking variability in brain chemistry and circuit function through multimodal human neuroimaging.
        Genes Brain Behav. 2012; 11: 633-642
        • Praschak-Rieder N.
        • Willeit M.
        Imaging of seasonal affective disorder and seasonality effects on serotonin and dopamine function in the human brain.
        Curr Top Behav Neurosci. 2012; 11: 149-167
        • Kalbitzer J.
        • Erritzoe D.
        • Holst K.K.
        • Nielsen F.A.
        • Marner L.
        • Lehel S.
        • et al.
        Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes.
        Biol Psychiatry. 2010; 30: 1033-1039
        • Hu X.Z.
        • Lipsky R.H.
        • Zhu G.
        • Akhtar L.A.
        • Taubman J.
        • Greenberg B.D.
        • et al.
        Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder.
        Am J Hum Genet. 2006; 78: 815-826
        • Lesch K.P.
        • Bengel D.
        • Heils A.
        • Sabol S.Z.
        • Greenberg B.D.
        • Petri S.
        • et al.
        Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
        Science. 1996; 274: 1527-1531
        • Grady C.L.
        • Siebner H.R.
        • Hornboll B.
        • Macoveanu J.
        • Paulson O.B.
        • Knudsen G.M.
        Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks.
        Eur Neuropsychopharmacol. 2013; 23: 368-378
        • Harmer C.J.
        • Mackay C.E.
        • Reid C.B.
        • Cowen P.J.
        • Goodwin G.M.
        Antidepressant drug treatment modifies the neural processing of nonconscious threat cues.
        Biol Psychiatry. 2006; 59: 816-820
        • Arce E.
        • Simmons A.N.
        • Lovero K.L.
        • Stein M.B.
        • Paulus M.P.
        Escitalopram effects on insula and amygdala BOLD activation during emotional processing.
        Psychopharmacology (Berl). 2008; 196: 661-672
        • Rosenthal N.E.
        • Genhart M.
        • Sack D.A.
        • Skwerer R.G.
        • Wehr T.A.
        Seasonal affective disorder: Relevance for treatment and research in bulimia.
        in: Hudson E.L. Pope H.G. Psychbioloy of Bulimia. American Psychiatric Press, Washington, DC1987: 205-228
        • Sexton T.
        • Buhr E.
        • Van Gelder R.N.
        Melanopsin and mechanisms of non-visual ocular photoreception.
        J Biol Chem. 2012; 287: 1649-1656
        • Terman J.S.
        • Terman M.
        • Lo E.S.
        • Cooper T.B.
        Circadian time of morning light administration and therapeutic response in winter depression.
        Arch Gen Psychiatry. 2001; 58: 69-75
        • Lewy A.J.
        • Bauer V.K.
        • Cutler N.L.
        • Sack R.L.
        • Ahmed S.
        • Thomas K.H.
        • et al.
        Morning vs evening light treatment of patients with winter depression.
        Arch Gen Psychiatry. 1998; 55: 890-896
        • Forsell Y.
        The Major Depression Inventory versus Schedules for Clinical Assessment in Neuropsychiatry in a population sample.
        Soc Psychiatry Psychiatr Epidemiol. 2005; 40: 209-213
        • McNair D.M.
        • Lorr M.
        • Droppleman L.
        Manual for the Profile of Mood States. EdITS/Educational and Industrial Testing Service, San Diego1992
        • Cohen S.
        • Kamarck T.
        • Mermelstein R.
        A global measure of perceived stress.
        J Health Soc Behav. 1983; 24: 385-396
        • Buysse D.J.
        • Reynolds III, C.F.
        • Monk T.H.
        • Berman S.R.
        • Kupfer D.J.
        The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research.
        Psychiatry Res. 1989; 28: 193-213
        • Deichmann R.
        • Gottfried J.A.
        • Hutton C.
        • Turner R.
        Optimized EPI for fMRI studies of the orbitofrontal cortex.
        Neuroimage. 2003; 19: 430-441
        • Lundqvist D.
        • Flykt A.
        • Ohman A.
        The Karolinska Directed Emotional Faces-KDEF [CD-ROM]. Department of Clinical Neuroscience, Psychology Section, Karolinska Institutet, Stockholm1998
        • Lancaster J.L.
        • Woldorff M.G.
        • Parsons L.M.
        • Liotti M.
        • Freitas C.S.
        • Rainey L.
        • et al.
        Automated Talairach atlas labels for functional brain mapping.
        Hum Brain Mapp. 2000; 10: 120-131
        • Lancaster J.L.
        • Summerln J.L.
        • Rainey L.
        • Freitas C.S.
        • Fox P.T.
        The Talairach Daemon, a database server for Talairach Atlas Labels.
        Neuroimage. 1997; 5: S633
        • Maldjian J.A.
        • Laurienti P.J.
        • Kraft R.A.
        • Burdette J.H.
        An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets.
        Neuroimage. 2003; 19: 1233-1239
        • Pandya D.N.
        • Van Hoesen G.W.
        • Mesulam M.M.
        Efferent connections of the cingulate gyrus in the rhesus monkey.
        Exp Brain Res. 1981; 42: 319-330
        • Barbas H.
        Anatomic basis of cognitive-emotional interactions in the primate prefrontal cortex.
        Neurosci Biobehav Rev. 1995; 19: 499-510
        • Ongur D.
        • Price J.L.
        The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.
        Cereb Cortex. 2000; 10: 206-219
        • Friston K.J.
        Functional and effective connectivity in neuorimaging: A synthesis.
        Hum Brain Mapp. 1994; 2: 56-78
        • Brett M.
        • Anton J.
        • Valabregue R.
        • Poline J.
        Region of interest analysis using an SPM toolbox.
        Neuroimage. 2002; 16: S497
        • Fisher P.M.
        • Meltzer C.C.
        • Price J.C.
        • Coleman R.L.
        • Ziolko S.K.
        • Becker C.
        • et al.
        Medial prefrontal cortex 5-HT2A density is correlated with amygdala reactivity, response habituation, and functional coupling.
        Cereb Cortex. 2009; 19: 2499-2507
        • Vickers A.J.
        • Altman D.G.
        Statistics notes: Analysing controlled trials with baseline and follow up measurements.
        BMJ. 2001; 323: 1123-1124
        • Mayberg H.S.
        Modulating dysfunctional limbic-cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment.
        Br Med Bull. 2003; 65: 193-207
        • Phillips M.L.
        • Drevets W.C.
        • Rauch S.L.
        • Lane R.
        Neurobiology of emotion perception II: Implications for major psychiatric disorders.
        Biol Psychiatry. 2003; 54: 515-528
        • Golden R.N.
        • Gaynes B.N.
        • Ekstrom R.D.
        • Hamer R.M.
        • Jacobsen F.M.
        • Suppes T.
        • et al.
        The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence.
        Am J Psychiatry. 2005; 162: 656-662
        • Kim M.J.
        • Gee D.G.
        • Loucks R.A.
        • Davis F.C.
        • Whalen P.J.
        Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest.
        Cereb Cortex. 2010; 21: 1667-1673
        • Kim M.J.
        • Whalen P.J.
        The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.
        J Neurosci. 2009; 29: 11614-11618
        • Ren C.
        • Luan L.
        • Wui-Man L.B.
        • Huang X.
        • Yang J.
        • Zhou Y.
        • et al.
        Direct retino-raphe projection alters serotonergic tone and affective behavior.
        Neuropsychopharmacology. 2013; 38: 1163-1175
        • Caspi A.
        • Hariri A.R.
        • Holmes A.
        • Uher R.
        • Moffitt T.E.
        Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits.
        Am J Psychiatry. 2010; 167: 509-527
        • Murthy N.V.
        • Selvaraj S.
        • Cowen P.J.
        • Bhagwagar Z.
        • Riedel W.J.
        • Peers P.
        • et al.
        Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain.
        Neuroimage. 2010; 52: 50-54
        • Button K.S.
        • Ioannidis J.P.
        • Mokrysz C.
        • Nosek B.A.
        • Flint J.
        • Robinson E.S.
        • Munafò M.R.
        Power failure: Why small sample size undermines the reliability of neuroscience.
        Nat Rev Neurosci. 2013; 14: 365-376
        • Rosenthal N.E.
        • Rotter A.
        • Jacobsen F.M.
        • Skwerer R.G.
        No mood-altering effects found after treatment of normal subjects with bright light in the morning.
        Psychiatry Res. 1987; 22: 1-9