Major depressive episode (MDE) are severe and common psychiatric disorders that affect up to 20% of the general population. MDE cause a decrease in psychosocial functioning, quality of life, and is associated with a high rate of suicides. They will be the leading cause of disability by 2030 according to the World Health Organization. The international effort carried out to identify biomarkers of MDE has been hampered by the heterogenous nature of MDE (unipolar, bipolar, seasonal, non-seasonal) and their heterogeneous response to treatment. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light therapy (LT). It was demonstrated that LT, as a first line treatment of MDE with and without seasonal pattern (± SP), has comparable efficacy to antidepressants. LT has the advantage of being also effective in improving both sleep, alertness and circadian rhythms, which may be altered in depression, contrary to antidepressant drugs that target mainly mood. Further research is warranted to determine the most efficient lighting parameters to use depending on depression characteristics, as well as to identify signature biomarkers of response. Besides, no studies have directly evaluated both subjective and objective biomarkers of sleep, wake, biological rhythms, and light signalling pathways and activation in patients with MDE ± SP. The main objective of the research will be to identify the signature of response to LT examining the correlation between the measures of biological and clinical parameters before LT and their evolution at the end of the procedure, and the therapeutic response. The primary endpoint of the study will be the therapeutic response to LT measured by the difference of MADRS score between Visit 1 and Visit 4 (end of the therapeutic protocol). Therapeutic response to LT considered as a success will be defined as at least a 50% reduction of MADRS score between the two visits.
Major Depressive Episodes (MDE) are severe and common conditions that affect up to 20% of the general population. MDE cause a decrease in psychosocial functioning, quality of life, and is associated with a high rate of suicides. They will be the leading cause of disability by 2030 according to the World Health Organization. The international effort carried out to identify biomarkers of MDE has been hampered by the heterogenous nature of MDE (unipolar, bipolar, seasonal, non-seasonal) and their heterogeneous response to treatment. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light therapy (LT). A recent meta-analysis demonstrated that LT, as a first line treatment of MDE with and without seasonal pattern (± SP), has comparable efficacy to antidepressants. LT has the advantage of being also effective in improving both sleep, alertness and circadian rhythms, which may be altered in depression, contrary to antidepressant drugs that target mainly mood. Further research is warranted to determine the most efficient lighting parameters to use depending on depression characteristics, as well as to identify signature biomarkers of response. Light exerts powerful biological effects on mood regulation. A growing body of research supports the efficacy of light therapy (LT) for MDE ± SP. Light information is conveyed to the brain through intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the melanopsin photopigment. However, the respective contribution of the different photoreceptive systems (rods, cones, melanopsin) and the precise brain circuits that mediate the impact of light on depressive behaviours are not well understood. Recently, we summarised the two distinct retinabrain pathways of light effects on mood in humans and animals (mostly demonstrated in animal research): i) a suprachiasmatic nucleus (SCN)-dependent pathway (a.k.a the circadian pathway) with mood actions via synchronisation of circadian rhythms and other direct effects, and ii) a SCN-independent pathway with mood effects through modulation of the homeostatic process of sleep, alertness, and emotion regulation. It is now well-known that light plays a main role in mood regulation mainly via melanopsin-containing ipRGCs and their direct projections on brain structures. Interestingly, the amplitude of the prolonged pupil constriction after exposure to blue light, reflects the sensitivity of the melanopsin pathway, found to be reduced in MDE with SP and MDE without SP. The examination of retinal sensitivity using electroretinography (ERG) reported winter rod photoreceptors hyposensitivity to light in MDE with SP. Very few studies have shown an impact of LT on networks involved in MDE: emotion regulation networks (prefrontal-limbic anatomy and connectivity) and the glutamatergic system in the ACC. Most studies used LT in combination with sleep deprivation and/or SSRIs. The retina-brain pathways involved are little known, probably because of their small anatomical size, requiring very high spatial resolution, but preclinical models strongly suggest that habenula and thalami nuclei (SCN independent pathway) are crucial for the antidepressive effects of light therapy. Interestingly, thanks to 7T high resolution MRI, a recent study in unmedicated MDE patients found an increased habenula volume associated with disease severity, and preliminary results indicate that functional connectivity of the thalamic subnuclei is associated with mood variation in MDE. Moreover, immune disruption is evident in MDD, and light may influence mood through its effects on the immune system, which is regulated by the circadian clock. The number of immune cells circulating in the blood oscillates throughout the day, with a peak during the resting phase, and recruitment to specific tissues occurring preferentially during the active phase. This migration is so important that injecting pro-inflammatory agents into mice during the resting phase results in 70% mortality, compared with 30% during the active phase, when immune cells are unavailable and mainly found in tissues. This circadian migration pattern also influences the vaccine response, with a better response during the resting phase when lymphocytes are circulating. In fact, there is a bidirectional relationship where inflammatory mediators regulate sleep by acting directly in specific brain systems and conversely, sleep deprivation leads to alterations in circulating immune cells. It is now recognized that inflammation plays a role in the pathophysiology of depression and that several migration markers are affected. Given this potential alteration in immune cell migration and the fact that analyses are performed during the day, current studies therefore fail to capture the complexity of immune disturbances associated with MDD. Beyond immune-related mechanisms, other biological factors may also play a role in the complex relationship between mood and disturbances of sleep and circadian rhythms. One such factor is Toxoplasma gondii (Tg) infection, a common parasitic condition affecting around 40% of the general population in France. Growing epidemiological evidence suggest a potential link between Tg infection and various neuropsychiatric disorders, including schizophrenia, mood disorders, and other behavioral and neurological conditions . Notably, Tg infection has been identified as a potential risk factor for the development of Major Depressive Disorder (MDD) as well as for insomnia in men over the age of 50. However, the heterogeneity in study designs and reported outcomes limits the generalizability and consistency of current findings. More recently, Professor Wallon's team demonstrated that Tg-infected mice exhibit altered sleep-wake cycles. More specifically, Tg-infected mice had reduced total sleep time and increased diurnal activity as compared to uninfected mice. These findings suggest that Tg infection may influence sleep architecture and host behavior, potentially facilitating parasite dissemination by increasing the host's exposure to predators. Despite its high prevalence and suspected relevance to psychiatric and neurological health, the relationship between Tg infection, mood regulation, and sleep remains poorly understood. Therefore, it is important to assess the prevalence of both recent and past Tg infections in MDD patients to better characterize this population and explore possible associations with sleep, biological rhythms and mood disturbances. MDE with winter SP (defined by DSM-5 TR criteria or with the SPAQ we validated in French) may occur annually in the autumn and winter due to the reduction of natural daylight, and affect approximately 1 to 10% of the general population depending on the latitude (5% in France). MDE with winter SP, also named seasonal affective disorder and including both unipolar and bipolar disorders, are associated with specific abnormalities of mood-photic regulation, in both SCN-dependent and SCN-independent pathways. For instance, the serotonin reuptake transporter (5-HTT), considered as an important central biomarker in SP pathophysiology, has been found significantly reduced in the anterior cingulate (ACC) and the prefrontal cortex (PFC) after 2 weeks of LT, in association with decreased symptomatology. In addition, recent studies in SP reported several sleep objective abnormalities using polysomnography (PSG), but these studies did not compare MDE ± SP. In addition, frequent sleep comorbidities, such as sleep apnea, have been reported, with deleterious impact on response to MDE treatment. PSG gave access to macro- and micro-architecture of sleep and to sleep homeostasis via slow wave density analysis, but also to interhemispheric connection (reported to be altered in MDE), to ultradian sleep regulation and to the interplay between sleep and sympathovagal balance. Our recent meta-analysis reported that patients with SP showed increased REM sleep and decreased REM latency during acute phase and also during remitted phases, without alteration of the slow wave sleep. Our work rather confirmed the chronobiological hypotheses of SP with a phase advance of circadian rhythms as a trait marker. Finally, some studies observed specific biological clock alterations like a longer duration of melatonin secretion during winter than in summer for patients with SP. These changes of the secretion pattern of melatonin may desynchronize endogenous rhythms and alter sleep architecture in these patients. To date, no studies have directly evaluated both subjective and objective biomarkers of sleep, wake, biological rhythms, and light signalling pathways and activation in patients with unipolar and bipolar MDE ± SP. In this global context, this timely project aims to identify a signature of a good response to LT in order to implement personalised medicine in psychiatry and increase probability of antidepressant success, using an innovative multimodal approach that allows the identification of new composite signatures and new combinations of biomarkers. The main objective of the research will be to identify the signature of response to LT examining the correlation between the measures of biological and clinical parameters before LT and their evolution at the end of the procedure, and the therapeutic response. This is a prospective multi-centers clinical exploratory one-arm one-intervention. Eligible MDD patients presenting to the emergency room, or to a psychiatric consultation, or hospitalised for a depressive episode with or without SP (balanced exposure 1:1) will be recruited. SP will be defined according to DSM-5 TR criteria and further investigated with the seasonal pattern assessment questionnaire (SPAQ) that examine subdimensions such as mood, sleep, social contacts, food intakes and weight, and validated in French in patients with MDD. Patients will be evaluated clinically by a psychiatrist and all the inclusion and exclusion criteria will be checked. Patients will be included at V1 and will be treated for 4 weeks with LT. We chose 4 weeks of treatment as an acceptable and recommended delay to change the antidepressant strategy in case of no response. The primary endpoint of the study will be the therapeutic response to LT measured by the difference of MADRS score between Visit 1 and Visit 4 (end of the therapeutic protocol).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
173
It consists of daily exposure to 10 000-lux fluorescent white light box (French light box, Dayvia®, Slim style device) for 30 minutes. Patients with a diagnosis of major depressive episode (MDE) will be treated for 4 weeks by light therapy in the morning after awakening, preferably between 7 and 9 am. Patients with bipolar depression and medicated will need to be pre-treated with a mood stabiliser antimanic agent to limit the risk of manic switch. In case of treatment-emergent hypomanic symptoms assessed with the YMRS for all patients, the exposition to LT will be reduced to 15 min or stopped if the patient is already at 15 min. In case of LT cessation for hypomanic switch, the patient will be considered as responder.
Bichat - Claude-Bernard Hospital
Paris, France
Therapeutic response to luminotherapy measured by the difference of Montgomery-Asberg Depression Rating Scale (MADRS) score between Visit 1 (inclusion) and Visit 4 (5 weeks)
Measurement of the depression severity score obtained from the Montgomery-Asberg Depression Rating Scale (MADRS) questionnaire before and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse depression severity.
Time frame: At baseline (visit 1 - week 0) and visit 4 (week 5)
Change in depressive symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the depressive severity score obtained from the Montgomery-Asberg Depression Rating Scale (MADRS) questionnaire before, during and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse depression severity.
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in manic symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the manic severity score obtained from the Young Mania Rating Scale (YMRS) questionnaire before, during and after light therapy treatment. Score range (min - max): 0-60. Higher score relates to worse maniac symptoms severity.
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in suicidality symptoms from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the suicidality severity score obtained from the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire before, during and after light therapy treatment. Suicidal ideation score range (min-max): 0-5. Higher score indicates greater severity of suicidal ideation (0 = no risk ; 5 = high risk).
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in sleep quality from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep quality score obtained from the Pittsburgh Sleep Quality Index (PSQI) questionnaire before, during and after light therapy treatment. Score range (min-max): 0-21. Higher score indicates poorer sleep quality (0 = no sleep difficulties; 21 = major sleep difficulties).
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in insomnia severity from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of insomnia severity score obtained from the Insomnia Severity Index (ISI) questionnaire before, during and after light therapy treatment. Score range (min-max): 0-28. Higher score indicates greater severity of insomnia.
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Evolution of sleepiness severity during light therapy treatment in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleepiness score obtained from the Epworth Sleepiness Scale (ESS) questionnaire before, during and after light therapy treatment. Score range (min-max): 0-24. Higher score indicates greater daytime sleepiness.
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in chronotype from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of chronotype obtained from the Horne and Ostberg questionnaire before, during and after light therapy treatment. Score range (min-max): 0-86. Higher score indicates greater morningness (lower scores indicate greater eveningness).
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Change in social jetlag from baseline to post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of social jetlag obtained from the Munich ChronoType Questionnaire (MCTQ) before, during and after light therapy treatment. MCTQ assesses both chronotype and average sleep duration. * Chronotype (MSFsc, midpoint of sleep corrected) range: 0-24 hours. Higher MSFsc indicates later chronotype (MSFsc \< 4:00 = early chronotype; 4:00 ≤ MSFsc \< 5:00 = intermediate chronotype; MSFsc ≥ 5:00 = late chronotype). * Total sleep duration range: 0-24 hours. Higher score indicates longer average sleep duration.
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Measure of the seasonal pattern in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of seasonal pattern obtained from the Seasonal Pattern Assessment Questionnaire (SPAQ) at inclusion. Global seasonal score (GSS) range of the SPAQ (min-max): 0-24. Higher score indicates greater seasonality.
Time frame: At inclusion
Change in sleep latency from baseline to post-light therapy using sleep diary in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep latency based on the sleep diary completed by the patient
Time frame: From enrollment to week 5
Change in total sleep time from baseline to post-light therapy using sleep diary in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of total sleep time based on the sleep diary completed by the patient
Time frame: From enrollment to week 5
Change in time spent in bed from baseline to post-light therapy using sleep diary in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of time spent in bed based on the sleep diary completed by the patient
Time frame: From enrollment to week 5
Change in wake after sleep onset (WASO) from baseline to post-light therapy using sleep diary in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of wake after sleep onset (WASO) based on the sleep diary completed by the patient
Time frame: From enrollment to week 5
Change in sleep efficiency from baseline to post-light therapy using sleep diary in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep efficiency based on the sleep diary completed by the patient
Time frame: From enrollment to week 5
Change in presumed sleep time from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep time by actigraphy
Time frame: From enrollment to week 5
Change in wake after sleep onset (WASO) from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of wake after sleep onset (WASO) by actigraphy
Time frame: From enrollment to week 5
Change in fragmentation index from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of fragmentation index, reflecting the restlessness during the sleep period, by actigraphy. Fragmentation index is expressed in percentage. Sleep fragmentation index (SFI, actimetry): 0-100. Higher index indicates greater sleep fragmentation (0 = uninterrupted sleep; 100 = highly fragmented sleep).
Time frame: From enrollment to week 5
Change in sleep efficiency from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of sleep efficiency by actigraphy
Time frame: From enrollment to week 5
Change in rythm parameters from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the relative amplitude by actigraphy
Time frame: From enrollment to week 5
Change in rythm parameters from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the L5 and M10 onset phases (beginning of the 5 least active hours and 10 most active hours) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of standard Deviation (StDev) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Composite Phase Deviation (CPD) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of whole-signal metric (Interdaily Stability (IS)) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Sleep Regularity Index (SRI) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of social jet-lag (mid sleep during the week-end minor the week) by actigraphy
Time frame: From enrollment to week 5
Change in sleep-wake regularity from baseline to post-light therapy using actigraphy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of one metric of variability within days (IV) by actigraphy
Time frame: From enrollment to week 5
Measurement of the melanopsin sensitivity before and after LT in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the Post-illumination pupillary response (PIPR) recorded with pupillometry tool, which reflects the melanopsin sensitivity in response to different light spectra (blue, red and green) before and after light therapy treatment
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Subjective Light Sensitivity before and after LT in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Subjective Light Sensitivity measured thanks to visual analog scale before, during and after light therapy treatment. The Visual Analogue Scale ranges from 0 (no pain) to 10 (the worst imaginable pain).
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Subjective Light Pain before and after LT in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Subjective Light Pain measured thanks to visual analog scale before, during and after light therapy treatment. The Visual Analogue Scale ranges from 0 (no pain) to 10 (the worst imaginable pain).
Time frame: At inclusion, Visit 3 (week 2) and Last study visit (week 5)
Cone, rod and ganglion cells response to light therapy treatment in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Response latency of the retinal cells (cones, rods, and iPRGCs) measured thanks to electroretinograph tool in reaction to light stimuli.
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Cone, rod and ganglion cells response to light therapy treatment in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Amplitude of the retinal cells (cones, rods, and iPRGCs) measured thanks to electroretinograph tool in reaction to light stimuli.
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of N1, N2, N3, REM sleep latencies by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of N1, N2, N3, REM sleep duration by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of bedtime by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Light off by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of total sleep time (TST) by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of slow-wave sleep activity by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of wake after sleep onset (WASO) by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Final wake-up time by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Light on by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in sleep architecture before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Time to rise by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Change in ventilatory parameters before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of Apnea Hypopnea Index by polysomnography. The Apnea Hyponea Index can be lower than 5 (no apnea), between 5 and 15 (mild sleep apnea), between 15 and 30 (moderate sleep apnea) or higher than 30 (severe sleep apnea).
Time frame: At inclusion and Last study visit (week 5)
Change in ventilatory parameters before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of hypoxic burden by polysomnography
Time frame: At inclusion and Last study visit (week 5)
Objective sleep latency before and after LT in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Averaged sleep latency measured with Multiple Sleep Latency Test (pathological if under 8 minutes)
Time frame: At inclusion and Last study visit (week 5)
Change in biological circadian biomarkers before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the melatonin metabolites in urine before and after LT
Time frame: At inclusion and Last study visit (week 5)
Change in biological circadian biomarkers before and after post-light therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of the cortisol concentration in urine before and after LT
Time frame: At inclusion and Last study visit (week 5)
Change in blood immunological biomarkers before and after therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of cytokine in blood
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Change in blood immunological biomarkers before and after therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Measurement of peripheral blood mononuclear cells (PBMCs) in blood
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Change in blood immunological biomarkers before and after therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Characterization of the TCR repertoire composition of regulatory CD4 T lymphocytes (Tregs) in blood
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Change in blood immunological biomarkers before and after therapy in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Characterization of effector T lymphocytes (Teffs) in blood
Time frame: At Visit 2 (week 1) and Last study visit (week 5)
Evaluation of Toxoplasma gondii serology at baseline in each subgroupe (unipolar/bipolar with or not seasonality pattern)
Detection of IgG and IgM antibodies anti-toxoplasma in blood
Time frame: At Visit 2 (week 1)
Change in networks involved in MDE from baseline to post-light therapy in 40 patients (ratio 1:1 of seasonal and non seasonal pattern)
Measurement of glutamate concentration within the default mode network and the limbic system during rest and during an emotional related task, habenula and thalamic nuclei volumes using MRI 7T
Time frame: At inclusion and Last study visit (week 5)
Change in networks involved in MDE from baseline to post-light therapy in 40 patients (ratio 1:1 of seasonal and non seasonal pattern)
Measurement of functional connectivity within the default mode network and the limbic system during rest and during an emotional related task, habenula and thalamic nuclei volumes using MRI 7T
Time frame: At inclusion and Last study visit (week 5)
Change in networks involved in MDE at baseline in 20 controls
Measurement of glutamate concentration within the default mode network and the limbic system during rest and during an emotional related task, habenula and thalamic nuclei volumes using MRI 7T in controls in order to compare with patients at baseline.
Time frame: At inclusion
Change in networks involved in MDE at baseline in 20 controls
Measurement of functional connectivity within the default mode network and the limbic system during rest and during an emotional related task, habenula and thalamic nuclei volumes using MRI 7T in controls in order to compare with patients at baseline.
Time frame: At inclusion
Tolerance to light therapy
Collection of adverse events using adverse events scale adapted to light therapy (AES)
Time frame: At Visit 3 (week 2) and Last study visit (week 5)
Corneal light exposure
Average amount of light received daily by the patient. Measurement of temporal characteristics of light exposure (irradiances in all 5 alpha-opic ranges, including melanopic, every 15-seconds during 4 weeks as in MDE patients (a baseline week followed by 4 weeks, without LT in controls) .
Time frame: From enrollment to week 5
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