Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? – A pilot study☆
Introduction
The seasonal pattern of recurrent episodes of depression, either unipolar or bipolar, has become known as seasonal affective disorder (SAD) [1], [2], [3]. The precise pathogenesis of SAD is still elusive despite several explanatory theories [2], [4]. Both DSM-IV and ICD-10 are open with regard to the season during which a major depressive episode recurs [1], [2], [3], [5], although ICD-10 has only provisional diagnostic criteria for SAD [5]. Since winter SAD is far more prevalent than summer SAD, the term SAD usually refers to winter SAD [3]. It has been estimated that the prevalence of SAD is around 1.2% in general populations, but the prevalence figures differ a lot due to methodological differences in epidemiological studies [3].
Although evidence has not been fully confirmed [6], bright light therapy (BLT) is widely accepted as first-line treatment of SAD in guidelines of high repute [7], [8], [9]. In a systematic review and meta-analysis, the effect size for the reduction of depressive symptoms by BLT (eight randomized control trials (RCTs)) in the treatment of SAD was 0.84 (95% CI 0.60–1.08) [10]. However, there was significant heterogeneity among the studies. Correspondingly, the guideline of the National Institute for Health and Clinical Excellence (NICE) found that when compared with waiting list controls, bright light reduced depressive symptoms significantly [6]. However, the guideline concludes that it is unclear whether this effect is greater than placebo effect [6]. In addition, a statistically significant reduction of depressive symptoms has been found in the treatment of SAD by using dawn simulation [11], with an effect size (five RCTs) of 0.73 (0.37–1.08) in a meta-analysis [10]. However, the corresponding evidence has been questioned [6].
Section snippets
The hypothesis
The mechanism of action of BLT and dawn simulation in the treatment of SAD is still widely unknown [7], [11]. On the other hand, there is evidence that in mammals, (a) significant amount of light penetrates the skull bone and reaches the brain, and (b) extra ocular transcranial phototransduction has certain physiological influences such as changed reproductive cycles and increased brain serotonin levels (cf. Campbell et al. 2001) [12]. Therefore, we have challenged the existing conceptual
Description of the bright light device
We developed a non-invasive photon application device, a VALKEE bright light device (Valkee Ltd., Oulunsalo Finland), which was approved as a medical device in the European Union on 30 March 2010. It was specially designed to target bright light treatment transcranially towards the brain via ear canals. The light was produced by using light-emitting diodes (LEDs), which were attached to earplugs. The light intensity at the end of both light guides in the ear canals was 6.0–8.5 lumens (lm) during
Consequences of the hypothesis and discussion
We have challenged the existing conceptual framework concerning the mechanisms of action of bright light in the treatment of SAD, i.e., that light therapy would only be mediated through the eyes [13]. For example, OPN3 [19], [20], while existing in protein level in human brain [25], [26] might play a role in non-visual phototransduction. We have initiated our human brain opsin research branch by showing that OPN3 exists in several different brain areas outside the visual pathway [26].
Role of the funding source
This study was partly funded by Oulu Deaconess Institute and Valkee Ltd.
Conflict of interest statement
MT is a minor shareholder in Valkee Ltd., was reimbursed by Pfizer for attending one conference, was paid by Pfizer, BMS, Eli Lilly, Servier and Astra Zeneca for speaking on different educational occasions, and has received advisory panel payments from Pfizer and H. Lundbeck A/S for three meetings. JN is a shareholder and CSO of VALKEE Ltd. company (Oulu, Finland), which is a producer and developer of the bright light devices for SAD. MSc. AL and JJ report no financial relationships with
References (42)
- et al.
Seasonal affective disorder
Lancet
(1998) - et al.
Dawns simulation and bright light in the treatment of SAD: a controlled study
Biol Psychiatry
(2001) - et al.
Characterization of a novel human opsin gene with wide tissue expression and identification of embedded and flanking genes on chromosome 1q43
Genomics
(2001) - et al.
Melanopsin: an exciting photopigment
Trends Neurosci
(2008) - et al.
Different structural organization of the encephalopsin gene in man and mouse
Gene
(2002) - et al.
Protein kinases and light: unlikely partners in a receptor localization puzzle
Physiol Behav
(2002) - et al.
A randomized, placebo-controlled trial of bright light and high-density negative air ions for treatment of seasonal affective disorder
Psychiatry Res
(2010) Diagnostic and statistical manual of mental disorders
(1994)- et al.
The diagnosis, symptomatology, and epidemiology of seasonal affective disorder
CNS Spectr
(2005) - et al.
Is seasonal affective disorder a bipolar variant?
Curr Psychiatr
(2010)
Management of seasonal affective disorder
BMJ
Practice guideline for the treatment of patients with major depressive disorder (revision)
Am J Psychiatry
Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. V. Complementary and alternative medicine treatments
J Affect Disord
The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence
Am J Psychiatry
Extraocular phototransduction and circadian timing systems in vertebrates
Chronobiol Int
Eye versus skin phototherapy of seasonal affective disorder
Am J Psychiatry
The opsins
Genome Biol.
The evolution of irradiance detection: melanopsin and the non-visual opsins
Philos Trans R Soc Lond B Biol Sci
Evolution of opsins and phototransduction
Philos Trans R Soc Lond B Biol Sci
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2022, Psychiatry ResearchCitation Excerpt :Non-seasonal depression usually presents with symptoms associated with abnormal circadian rhythms (circadian mood swings, altered social rhythms, and irregular sleep-wake patterns) (Allen et al., 1993a, 1993b). Light therapy has been shown to be effective in treating seasonal affective disorder (Timonen et al., 2012). On the basis of previous research, many studies have sought to explore the safety and efficacy of light therapy interventions for non-seasonal depression.
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2020, Psychiatry ResearchCitation Excerpt :Patients with non-seasonal depression always present symptoms associated with circadian abnormalities (irregular sleep-wake patterns, altered social rhythms and circadian mood swings) (Allen et al., 1993; Lieverse et al., 2011; Oldham and Ciraulo, 2014). And Light therapy has been widely demonstrated as an effective treatment for seasonal affective disorder (Lam, 1994; Timonen et al., 2012). Based on these symptoms, many studies attempted to use light therapy to treat patients with non-seasonal depression and focused on the effects of light therapy on non-seasonal depression.
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2015, Medical HypothesesCitation Excerpt :Previous work on severe depression has shown that electroconvulsive treatment and transcranial magnetic stimulation were of approximately equal efficacy, but a small trial of single treatments with PBM [23] compared favourably with both these modalities and it was recommended further investigation be carried out. Interestingly, Timonen et al. [44] in an uncontrolled study of bright light treatment for seasonal affective depression (SAD) in Finland at latitude 65° N, treated 13 patients with bright light given via LEDs in the ear canals, challenging the received wisdom that SAD light treatment could only operate via visual opsins. Treatment was given 5 times weekly for 4 weeks and 10 of the 13 patients achieved full remission (Hamilton depression score < 7).
Brain photobiomodulation therapy on neurological and psychological diseases
2024, Journal of BiophotonicsLight Delivery Approaches for Brain Photobiomodulation
2023, Synthesis Lectures on Biomedical Engineering
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The work was conducted by the University of Oulu, Institute of Health Sciences (General Practice), P.O. Box 5000, FIN-90014 Oulu, Finland.
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These authors equally contributed to this work.