P-1-15 Short-term availability of brain serotonin is crucial for antidepressant effect of light therapy

AbstractBackgroundLight therapy is frequently demonstrated by clinical trials to be effective to seasonal or non-seasonal major depression. However, the pathway underlying the light effect on mood remains unclear. Since a retino-raphe pathway was previously indicated to modulate 5-HT production, we hypothesize that the retinal projection into dorsal raphe nucleus (DRN) may play an important role in the light therapy for depression.MethodsA rat model of 14-day corticosterone administration (40 mg/kg/day subcutaneous injection) was mainly used to test the effect of light therapy on non-seasonal depressant-like behavior, and the involved neural circuitry and neurochemistry as well.ResultsBehavior results revealed that the bright light therapy especially with the blue light of 470 nm and 400 lux, effectively reversed the depression-like responses in those stressed rats. After elimination of retino-raphe projection using immunotoxin (Saporin) the effect of light therapy was significantly attenuated. Whereas activation of retino-raphe projection using HM3q chemogenetics was shown an effect similar to fluoxetine treatment. Furthermore, 5-HT3A positive GABA cells in the DRN were activated with high c-Fos expression that involved in an inhibition of 5-HT synthesis and a subsequent depressive behavior. While light therapy through retino-raphe projection deactivated the hyperaction of those GABA cells in the DRN; that eventually contributed to the antidepressant effect from light therapy.ConclusionsOur results indicate that the retino-raphe circuitry engaged antidepressant effect in DRN that contributed to the light therapy to the non-seasonal depression. 5-HT3A positive GABA cells in DRN was indicated to mediate this function of retino-raphe projection.

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The Antidepressant Effect of Light Therapy from Retinal Projections

Neuroscience Bulletin ◽

10.1007/s12264-018-0210-1 ◽

2018 ◽

Vol 34 (2) ◽

pp. 359-368 ◽

Cited By ~ 6

Author(s):

Xiaotao Li ◽

Xiang Li

Keyword(s):

Light Therapy ◽

Antidepressant Effect ◽

Retinal Projections ◽

Effect Of Light

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Treatment of Seasonal Affective Disorder with Light in the Evening

The British Journal of Psychiatry ◽

10.1192/bjp.147.4.424 ◽

1985 ◽

Vol 147 (4) ◽

pp. 424-428 ◽

Cited By ~ 82

Author(s):

Steven P. James ◽

Thomas A. Wehr ◽

David A. Sack ◽

Barbara L. Parry ◽

Norman E. Rosenthal

Keyword(s):

Sleep Deprivation ◽

Affective Disorder ◽

Seasonal Affective Disorder ◽

Bright Light ◽

Early Morning ◽

Antidepressant Effect ◽

Comparison Study ◽

Female Patients ◽

Dim Light ◽

Effect Of Light

A cross-over comparison study of exposure, in the evenings only, to bright versus dim light was carried out on nine female patients with seasonal affective disorder. A significant antidepressant effect of the bright lights was shown. No consistent observable effects were produced by the dim lights. These results support earlier studies demonstrating the efficacy of bright light given morning and evening. The antidepressant effect of light is not mediated by sleep deprivation, and the early morning hours are not crucial for a response.

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Light Therapy for Seasonal Affective Disorder the Effects of Timing

The British Journal of Psychiatry ◽

10.1192/bjp.166.5.607 ◽

1995 ◽

Vol 166 (5) ◽

pp. 607-612 ◽

Cited By ~ 34

Author(s):

Y. Meesters ◽

J. H. C. Jansen ◽

D. G. M. Beersma ◽

A. L. Bouhuys ◽

R. H. Van Den Hoofdakker

Keyword(s):

Affective Disorder ◽

Seasonal Affective Disorder ◽

Response Rates ◽

Light Therapy ◽

Light Treatment ◽

Therapeutic Outcome ◽

Short Term ◽

Rank Ordering ◽

Term Rank

BackgroundSixty-eight patients with seasonal affective disorder participated in a 10 000-lux light treatment study in which two questions were addressed: do response rates differ when the light is applied at different times of the day and does short-term rank ordering of morning and evening light influence response rates?MethodThree groups of patients received a 4-day light treatment: (I) in the morning (8.00–8.30 a.m., n = 14), (II) in the afternoon (1.00–1.30 p.m., n = 15) or (III) in the evening (8.00–8.30 p.m., n = 12). Two additional groups of patients received two days of morning light treatment followed by two days of evening light (IV, n = 13) or vice versa (V, n = 14).ResultsResponse rates for groups I, II and III were 69, 57 and 80% respectively, with no significant differences between them. Response rates for groups IV and V were 67 and 50% respectively; this difference was not significant and these percentages did not differ significantly from those of groups I and III.ConclusionsThe results indicate that the timing of light treatment is not critical and that short-term rank ordering of morning and evening light does not influence therapeutic outcome.

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Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlaa143 ◽

2020 ◽

Vol 79 (12) ◽

pp. 1344-1353

Author(s):

Qinghe Meng ◽

Jianjun Jiang ◽

Xiaohong Hou ◽

Lixia Jia ◽

Xiaoxiao Duan ◽

...

Keyword(s):

Blue Light ◽

Seasonal Affective Disorder ◽

Neural Mechanism ◽

Light Therapy ◽

Male Rats ◽

Antidepressant Effect ◽

Light Deprivation ◽

Sprague Dawley ◽

Neurotrophic Activity ◽

Immobility Time

Abstract Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.

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Development of winter depression and the effect of light therapy

Nordic Journal of Psychiatry ◽

10.3109/08039489409078130 ◽

1994 ◽

Vol 48 (2) ◽

pp. 75-79 ◽

Cited By ~ 2

Author(s):

Henrik Dam ◽

Jeanne Molin ◽

Tom G. Bolwig ◽

Gordon Wildschiodtz ◽

Erling T. Mellerup

Keyword(s):

Light Therapy ◽

Winter Depression ◽

Effect Of Light

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Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission

Psychological Medicine ◽

10.1017/s003329179900152x ◽

2000 ◽

Vol 30 (1) ◽

pp. 79-87 ◽

Cited By ~ 26

Author(s):

R. W. LAM ◽

T. A. BOWERING ◽

E. M. TAM ◽

A. GREWAL ◽

L. N. YATHAM ◽

...

Keyword(s):

Affective Disorder ◽

Repeated Measures ◽

Seasonal Affective Disorder ◽

Bright Light ◽

Light Therapy ◽

Brain Serotonin ◽

Tryptophan Depletion ◽

Control Session ◽

Double Blind ◽

Plasma Tryptophan

Background. Serotonergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed that SAD patients, in clinical remission with light therapy during the winter, experienced transient depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD patients who were in natural summer remission.Methods. Twelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were obtained before, and 5 h after, ingesting an amino acid (AA) mixture±tryptophan. Experimental RTD and control sessions were scheduled 1 week apart.Results. The RTD session resulted in significant reduction in total and free plasma tryptophan levels compared to the control session. The behavioural data were analysed using repeated measures analysis of variance. This analysis found significant main effects of time (higher scores after AA ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant interaction effects between the three factors. Thus, there were no significant behavioural effects of RTD compared to the sham depletion control session.Conclusions. The summer remission experienced by SAD patients is not dependent on plasma tryptophan levels (and presumably brain serotonin function) in the same manner as that of remission after light therapy. These results conflict with those of other laboratories, perhaps because of differences in study samples.

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