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Rubiño, M.A. Cristina Nicolau, Anna Riera, Aida Martín, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7293619/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Current research has shown that depressive symptoms are associated with sleep disturbances and misalignment of circadian rhythms. Thus, a chronobiological intervention associated with the usual antidepressant treatment on depressive symptoms may improve depressive symptoms as long with sleep quality, and circadian rhythms in patients with depression. Methods: The feasibility experimental study was carried out with a total of 38 participants: 21 outpatients suffering from a non-seasonal major depressive disorder (MDD) and 17 healthy volunteers (general population). Twenty-one patients were randomly assigned to two groups: 11 patients received a chronobiological intervention: daylight exposure treatment for 14 days in conjunction with pharmacological treatment (LIGHT group), while 10 patients received only pharmacological treatment (LIGHT group). Depressive severity at the inclusion was assessed with the Montgomery-Asberg Depression Scale (MADRS), and the International Neuropsychiatric Interview (MINI) was used to exclude comorbid psychiatric disorders. The evolution of depressive symptoms was assessed using the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16). Patients' sleep was evaluated using, Munich Chronotype Questionnaire and with Pittsburgh Sleep Quality Index (PSQI) and sleep agenda. In addition, circadian parameters were assessed using Kronowise ® device (KW6), and target sleep quality indices were calculated. Results: The intervention combining daylight exposure with pharmacological treatment demonstrated significant improvements in depressive symptoms. There was a noticeable trend towards subjective improvement in sleep quality. Data registered with the KW6 device indicated an improvement in motor activity and peripheral temperature rhythms. Conclusions: Depressive patients undergoing psychopharmacological treatment, who received a specific instruction to increase their exposure to daylight, improved their depressive symptoms, sleep quality, and circadian rhythms. antidepressant drugs bright light therapy circadian rhythms daylight depression mood sleep quality Figures Figure 1 Figure 2 Introduction Major depressive disorder (MDD) is a mental condition characterized by a persistent low or depressed mood, anhedonia or decreased interest in pleasurable activities, feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts, that causes social or occupational impairment [ 1 ]. MDD affects approximately 5% of the Spanish adult population annually [ 2 ]. In addition, in Mallorca primary care setting, between 25% and 35% of adult patients have mental disorders with 29% having a depressive disorder [ 3 ]. Depression is responsible for significant economic expenditure on health treatments. It has been estimated that the total annual social cost of depressive disorders in the Spanish adult population was €6,145 million in 2017 [ 2 ]. Antidepressant drugs (AD) are widely used for the treatment of MDD. However, approximately 50% of patients do not experience an adequate response to these therapies [ 4 ]. In addition, when they are effective, the number of depressive symptoms is reduced and decreases earlier. Daylight exerts different functions through different physiological mechanisms on the body's systems. A critical discovery revealed that there is a non-visual pathway via photoreceptors in the retinal ganglion cells that directly accesses the circadian clock through a retinal-hypothalamic tract. These cells contain a photopigment (melanopsin) with the highest sensitivity to short-wavelength, blue light. This is the major neural pathway by which light modulates the circadian system [ 5 ]. Additionally, it is the most powerful synchronizer acting in the circadian system for the adjustment of biological rhythms and has an antidepressant action, acting on multiple systems, stabilizing mood and emotion regulation [ 6 ]. Exposure to light, especially in the morning, allows an effective inhibition of melatonin in the first hours [ 7 ] and a greater amount of serotonin (enteric and cerebral) circulating throughout the day [ 8 ]. Exposure to daylight has a positive effect on the reduction of depressive symptoms [ 6 ] and an increase in exposure to daylight reduces the delay of the remission of depressive symptoms, leading to a reduction in the number of days spent in hospital [ 9 ]. The combination of antidepressant therapy and BLT accelerates and potentiates the pharmacological effects of antidepressants in non-seasonal depressive episodes [ 10 ]. For this reason, it is important to focus on the circadian system as it would be a crucial point in the therapeutic approach to depression [ 11 ]. The research we present posits that exposure to daylight in the morning will faster the remission of depressive symptoms and improve the adjustment of biological rhythms in depressive patients. Therefore, a scheduled chronobiological intervention with exposure to daylight in the morning in conjunction with antidepressant treatment in patients with non-seasonal major depression treated on an outpatient basis: a) will be more effective than the pharmacological treatment alone in the reduction of depressive symptoms, and b) improve the quality of sleep and the adjustment of circadian rhythms. The objectives of this study are: 1) To analyse the degree of acceptance and adherence to daylight therapy, as well as recruitment and adherence to the study, 2)To quantify light exposure with a device (KW6) to compare the intensity of daylight exposure in the morning and the day/night light contrast in patients receiving a chronotherapeutic intervention (LIGHT group) versus patients who do not receive it (non-LIGHT group), 3) To assess changes in depressive symptoms after 14, 21 and 28 days of follow-up, and 4) To evaluate the subjective and objective sleep quality of patients of both groups. Materials and Methods Participants Twenty-one patients attended a Mental Health Unit in Palma de Mallorca (Balearic Islands) presenting a non-seasonal major depressive episode, who started with a new antidepressive treatment or a change from the previous antidepressant treatment, due to lack of efficacy, and 17 healthy volunteers were recruited from the general population. The criteria for the selection of patients were: A) Inclusion criteria: 1) aged between 18 and 65 years of both genders, 2) diagnosis of non-seasonal major depressive disorder (MDD) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders [1], 3) had to obtain a score equal to or greater than 24 in the Spanish version [12] of the Montgomery-Asberg Depression Scale (MADRS) [13], and 4) had to understand the research objectives, that their participation was voluntary, and sign an informed consent. And B) Exclusion criteria: 1) substance abuse (> 24 g/day of alcohol in women, 40 g/day in men, use of cocaine, heroin, and other drugs of abuse), 2) had another psychiatric or neurological disorder, 3) had comprehension difficulties or low educational level, 4) had skin problems and eye sensitivity and/or photophobia, and 5) performing shift work. Study Design This was a feasibility study with a double-branch, randomized experimental design. Sampling was probability sampling with simple randomization. Patients were divided into two groups: LIGHT and non-LIGHT. All patients received the same written explanation about the aim of the study and procedure (included in the informed consent form). The only difference was that the LIGHT group received specific instructions to expose themselves to daylight in the morning along with the pharmacological antidepressant treatment prescribed by their psychiatrist. Health control participants (HCtrl) were recruited from the general population, matched by age and gender to the patients, to verify KW6 data between the depressive and non-depressive populations. Health controls reported no affective or emotional problem, did not take any psychotropic drug, and they continued with their usual routine of activities. All participants were located on the island of Mallorca (latitude: ~40°N) with a mean of 82% of sunny days, 5°C (night) and 22°C (day) and ~12 h of daylight. The recruitment was done in two periods: 1º) March to October 2021, and 2º) January-May 2023: we had to stop because of problems due to COVID-19 pandemic, and then, structural problems obliged to close the Mental Health Unit for several months. Interventions: Patients in the non-LIGHT group were given written general recommendations for healthy habits considered as placebo [14]: 1) exposure to sunlight at your convenience, 2) physical exercise appropriate to your needs, 3) sleep the amount of time you need, 4) recommendation to stay in or get out of bed at your convenience, and 5) eat a healthy and balanced diet. Patients in the LIGHT group were given specific written instructions to expose themselves to daylight for 14 days. The specific instruction was: ‘You must be outside, at least one hour daily, in the morning before 11:00 a.m. You can take a walk or just sit to expose yourself to daylight. You should not wear sunglasses. If direct sun exposure bothers you, you can wear a hat or stay in shady places. During this time, you cannot do a specific exercise (such as running or cycling) or other activities. They received, in addition, general recommendations for healthy habits in writing, as the non-LIGHT, excepted recommendation 1. Questionnaires and Scales The International Neuropsychiatric Interview (MINI) [15,16] to exclude other comorbid psychiatric disorders. - Montgomery-Asberg Depression Scale (MADRS) [13]. Clinician-performed scale validated for the Spanish population (Lobo et al., 2002) with 10 items to assess depression, uncontaminated by anxiety items. Minimum score of 0 and maximum score of 60. - Pittsburgh Sleep Quality Index (PSQI) [17,18]. Self-applied scale that collects information related to sleep in the last month in adults, with 24 questions. In correction, 7 partial components are generated: 1) subjective sleep quality, 2) latency, 3) duration, 4) efficiency, 5) disturbances, 6) medication use, and 7) daily dysfunction. The total score is obtained by adding the components, and ranges from 0 to 21 points. "Good sleepers" are people with a score of less than or equal to 5, and "bad sleepers" have a score greater than 5. - Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) [19]. It is a validated questionnaire for the Spanish population [20] of depressive symptomatology of the last week, self-applied, with 16 items and 9 categories: 1) sleep disturbances, 2) depressed mood, 3) changes in weight, 4) concentration, 5) self-criticism, 6) suicidal ideation, 7) interest, 8) energy level, 9) psychomotor alterations. Score from 0 to 27. - Sleep and activity agenda: this is a self-registration form on paper to record the time and frequency of sleep periods during the day and night. Light, Peripheral Temperature and Motor Activity Recording The ambulatory circadian monitoring device KW6 (Kronowise ® ; Kronohealth S.L., University of Murcia, Spain) [21], is a multi-sensor device worn on the non-dominant wrist. It records the motor activity (MA), peripheral temperature (PT), and light intensity (LI). Using from the MA data (the ‘time in movement’variable) during the assumed sleep period (23:00 to 07:50), the Actiwatch Activity and Sleep Analysis © 2001 Software (Actiwatch 2001, V1.16 Cambridge Neurotechnology) was employed to obtain the objective sleep quality parameters: 1) Efficiency, 2) Latency, 3) Percentage of immobility, 4) Percentage of mobility, and 5) Fragmentation. Therefore, sleep variables were analysed using both subjective instruments (agenda and PSQI) and objective instruments (KW6). Procedure After the initial assessment conducted by the psychiatrist, eligible patients were invited to participate in the study. Following an explanation of the protocol, participants were provided with a participant information sheet (PIS) and asked to read it. If they agree, they signed the Informed Consent (IC) form before being directed to the researchers (a biologist and a psychologist master students) for randomization and study protocol procedures. Each clinical evaluation session lasted approximately 50 minutes. The assessment and intervention protocol were as follows for the different groups: During visit 1 (week 1), the inclusion and exclusion criteria were reviewed, and the clinical interview was conducted using the MINI neuropsychiatric interview (for exclusion of patients with comorbid psychiatric disorders) and assessments including the PSQI and QIDS-SR16 were given to patients to fill them up. Additionally, participants were equipped with the KW6 device to record circadian parameters and light exposure intensity and were instructed to complete a sleep and activity agenda. They were randomized and received specific instructions based on their randomization. During visit 2 (day 14), the QIDS-SR16 was given to patients to fill it up, and data from the KW6 device were downloaded, followed by collection of the agenda. On visit 3 (day 23), another QIDS-SR16 assessment was performed, and the KW6 device reattached. Finally, during visit 4 (week4, day 28), the agenda was collected, the KW6 device was removed for data retrieval, and the PSQI and QIDS-SR16 were re-administered. HCtrl participants attended two visits. In the first, inclusion and exclusion criteria were revised, and demographic data were collected. They received the sleep and activity agenda and the KW6. The agenda and the KW6 were collected on a second visit after 5-7 days. Data analysis Statistical analyses were conducted using IBM SPSS Statistics 29.0 software. Parametric inferential statistics were employed with ANOVA with the register’s exposure light for 24 hours, and t-test to contrast the average day-night light scores between the LIGHT, non-LIGHT and HCtrl groups. In addition, effect sizes were with Eta squared ( η 2 ): η 2 = .01, small effect size; η 2 = .06, medium effect size; and η 2 = .14 or higher, large effect size. And d-Cohen ( d ): d = .20, small effect size; d = .05, medium effect size; and d = .80 or higher, large effect size [47]. Non-parametric inferential statistics were employed to average contrast using the Mann-Whitney U test ( U ) for independent samples (comparing averages between the LIGHT, non-LIGHT, LIGHT-HCtrl, and non-LIGHT-HCtrl groups). The Wilcoxon test was used for paired samples, such as pre-postintervention comparisons. Significance levels ( p value) were reported as follows: p < .001 (high), p < .01 (medium), p < .05 (low). Additionally, effect sizes for different variables in the LIGHT and non-LIGHT groups were calculated using rank biserial correlation ( r rb ): r rb .5, large effect [22]. Data collection and analysis were conducted using the Circadianware program specifically tailored to Kronowise ® (KW6) device. Data points deviating more than 3 times from the standard deviation of the average were also removed. The KW6 software performed parametric and non-parametric analyses of the variables Peripheric Temperature (PT), as a variable representative of autonomic balance at the skin vessel level), motor activity (MA), ‘time in movement’. The following indices were obtained to describe the circadian system [23]: 1) Midline Estimating Statistic of Rhythm (MESOR), 2) Inter-day stability index (IS), 3) Intra-day variability index (IV), 4) Relative amplitude (RA), and 5) Circadian Function Index (CFI). These variables are the parameters of the marker rhythms (MA and PT) of the sleep-wake rhythm for the study of the circadian system. The MA data recorded with the KW6 device were processed using the Actiwatch Activity and Sleep Analysis © 2001 Software, Ethical Aspects and Data Security This study was conducted in compliance with the principles of the Declaration of Helsinki [24], Organic Law 3/2018, on the 5 December, on the protection of personal data and guarantee of digital rights, and this study was approved by the Research Committee of the Son Espases University Hospital (HUSE, CI-481-20, 14th January 2021) and the Research Ethics Committee of the Balearic Islands (CEI-IB, IB 4429/21 PI, 24th February 2021). All participants signed the informed consent. Results Socio-Demographic Data Table 1 presents the sociodemographic data of the total sample. A higher participation of women was observed in all groups. There were no significant differences in relation to age. There were significant differences in years of education between the depression groups (LIGHT, non-LIGHT) and the HCtrl group. There were no differences between the two branches in MADRS at inclusion: the average scores and standard deviations of the MADRS for the LIGHT group were 26.36 (5.41) and MADRS for the non-LIGHT group were 26.90 (5.68). ----------------------- insert Table 1 here ------------------------- Exposure to Light Fig. 1 shows the Light intensity (lux) exposed during 24h for the LIGHT, non-LIGHT and HCtrl groups. ----------------------- insert Fig. 1 here ------------------------- The average scores and standard deviations of the light intensity were higher over 24 hours of 600.35 (1,070.85) lux for the LIGHT group than for the non-LIGHT group of 326.20 (394.18) lux, and the HCtrl group of 232.43 (186.42) lux. The contrast analysis with the ANOVA one-factor test (intergroups) showed a significant difference ( F (2, 431) = 7.69, p = .001, η 2 = .23), and the post hoc analysis with the Bonferroni test showed a significant difference between the LIGHT and non-LIGHT groups ( p = .006, d = 4.03) and between the LIGHT and HCtrl groups ( p = .001, d = 4.46). The average scores and standard deviations of the light intensity were higher in the awake period (08:00 to 23:00) of 969.66 (1,225.47) lux for the LIGHT group than for the non-LIGHT group of 479.93 (434.64) lux, and HCtrl group of 257.24 (196.16) lux. The t-test analysis showed a significant difference between the LIGHT and non-LIGHT groups ( t (177) = -4.28, p = .001, d = .53), between the LIGHT and HCtrl groups ( t (177) = -5.11, p = .001, d = .81), and between the non-LIGHT and HCtrl groups ( t (177) = -4.24, p = .001, d = .66). Also, the LIGHT group showed greater respect for darkness during the sleep period (23:00 to 07:50) than the other two groups. The average scores and standard deviations for the LIGHT group were 1.92 (4.53) lux, while the non-LIGHT group was 77.43 (40.48) lux, and the HCtrl group was 18.32(8.91) lux. The t-test analysis showed a significant difference between the LIGHT and non-LIGHT groups ( t (109) = 13.57, p = .001, d = 2.62), between the LIGHT and HCtrl groups ( t (109) = 12.11, p = .001, d = 2.32), and between the non-LIGHT and HCtrl groups ( t (109) = -10.91, p = .001, d = 2.02). The LIGHT group showed a higher day-night light contrast compared to the non-LIGHT and HCtrl groups. Effect of Daylight on Mood Table 2 and Fig. 2 summarize the evolution of the average QIDS-SR16 scores for the LIGHT and non-LIGHT groups during four visits (weeks). ----------------------- insert Table 2 here ------------------------- ----------------------- insert Fig. 2 here ------------------------- The individual direct and average scores and standard deviations for QIDS-SR 16 for all four visits can be seen in Table 2. Average scores contrast analyses with the Wilcoxon test showed significant differences for the LIGHT group between the scores of the initial and last visits ( Z = -2.55, p = .01, r rb = .46), and the non-LIGH group showed non-significant differences ( Z = -1.23, p = .22, r rb = .41). The LIGHT group showed a statistically significant reduction in depressive symptoms following exposure to daylight for 14 days over the 4-week study period. Contrast analysis of the average scores of the different components of the QIDS-SR16 for the LIGHT group for the initial and final visit evaluations. Then, significant differences were shown in the pre-post for the components "depressed mood" and "changes in weight" ( p .05). Munich Chronotype Questionnaire (MCTQ) The chronotype analysis showed a great variability in the chronotypes, and there were no significant differences between the LIGHT and non-LIGHT groups. The LIGHT group: 18.18% belonged to the "extreme evening" category, 18.18% to the "evening" category, 45.45% to "indefinite", 18.18% to "morning". The non-LIGHT group: 10% belonged to the "extreme evening" category, 10% to "evening", 70% to "indefinite", and 10% to "morning". Effect of Daylight on Sleep Quality Subjective Measures of Sleep PSQI provides information on the results for 7 components: 1) Subjective sleep quality, 2) Latency, 3) Duration, 4) Efficiency, 5) Disturbances, 6) Medication use, and 7) Daily dysfunction, and their categorisation, for the LIGHT and the non-LIGHT groups, respectively. The results were most remarkable, indicating that, for both groups, the overall score was above 5, a cut-off score that indicated poor sleep quality, both in the pre-treatment and postintervention scores. After the contrast of averages, no significant differences were shown in the seven components between pre- and postintervention scores, except for disturbances in the non-LIGHT group ( p = .046). The PSQI total scores for the LIGHT and non-LIGHT groups changed after the intervention. The decrease in the total score was greater in the LIGHT group ( Z = -1.94, p = .052, r rb = .16) than in the non-LIGHT group ( Z = -1.90, p = .06, r rb = .60). However, these changes showed a non-significant trend ( p > .05). Objective Measures of Sleep Table 3 shows the average scores (standard deviations) of the circadian parameters (MESOR, IS, IV, RA, and CFI) for peripheral temperature and motor activity circadian obtained with the KW6 for participants in the LIGHT, non-LIGHT, and HCtrl groups pre-postintervention. ----------------------- insert table 3 here ------------------------- In LIGHT group after exposure to daylight, circadian parameter scores MESOR, IS, and CFI showed a slight increase, whereas IV for PT showed a decrease. In addition, there was also an increase in IS, RA and CFI for MA, but there were no significant differences (all p ˃ .05). In the non-LIGHT group, the circadian parameter scores MESOR and RA for TP showed a slight increase, and an increase in MESOR and IS for MA after exposure to daylight (all p ˃ .05). Circadian parameters of PT and MA were not significant between the LIGHT, non-LIGHT and HCtrl groups. However, the results showed a non-significant trend of change for the LIGHT group after the intervention. Additionally, we obtained from the KW6 the variable ‘time in movement’. Table 6 shows the average scores (standard deviations), and percentages (%) of the variables: efficiency, latency, percentage of immobility, percentage of mobility and fragmentation of sleep (Table 4). ----------------------- insert Table 4 here ------------------------- Discussion The main objective of this study was to examine the feasibility and the impact of a chronobiological intervention on the progression of depressive symptoms in outpatients undergoing pharmacological treatment for a non-seasonal major depressive episode. The sample exhibited a higher percentage of female participants, consistent with the prevailing trends in depression prevalence and incidence rates [25], while age distribution was similar across both groups. Results confirmed the research hypothesis despite the relatively low number of participants: patients who increased the exposure to daylight (LIGHT group) in addition to the usual antidepressive treatment, showed significant differences in the pre-post analysis for pre- and postintervention in global QIDS-SR16 scores, and for the components ‘depressed mood’ and ‘changes in weight’ ( p < .05) in the QIDS-SR16 test. LIGHT group also improved the subjective quality of their sleep. Regarding objective sleep measures, we fail to find statistical differences among the two groups in the pre-postintervention average of different variables measured with KW6. Daylight Daylight is a primary regulator of circadian rhythms [26]. Insufficient exposure to daylight has been associated with various health risks, including depression, anxiety as well as sleep disturbances and obesity [27]. To examine the impact of daylight, participants in the experimental group (LIGHT) were instructed to increase their exposure over a 14-day period, spending at least one hour outdoors in the morning before 11:00 a.m. (see Fig. 1). Participants were advised not to do exercise during this time, they only were allowed to have a walk, to avoid the potential confounding effects of the exercise with the light. The morning period for daylight exposure was selected due to the effective suppression of melatonin production in the pineal gland during early morning hours [7], resulting in increased circulating serotonin levels throughout the day [28]. The analysis of light intensity data (from KW6) revealed higher levels in the LIGHT group during the designated chronobiological treatment period. This indicates good adherence to the regimen and underscores the feasibility of incorporating this approach as an adjunct to conventional antidepressant drug therapy. Mood Significant reductions in QIDS-SR16 scores were observed in the LIGHT group, whereas such reductions were not statistically significant in the non-LIGHT group (see Table 2 and Fig. 2). These findings suggest that daylight therapy was more effective to alleviate depressive symptoms in patients undergoing pharmacological treatment for depression. Improvements in the LIGHT group were particularly prominent in pre- and post-intervention global QIDS-SR16 scores, as well as in subcategories 2 (mood) and 3 (changes in weight and appetite), which were not observed in the non-LIGHT group.These results are consistent with findings from a previous study [11], which have indicated that exposure to daylight may contribute to the reduction of depression symptoms. Daylight, Sleep, and Depression The LIGHT group exhibited significantly higher light levels of daytime light exposures, while showing considerably lower nighttime light intensity compared to the other groups (see Fig. 1). The observed disparity in daylight exposure between the LIGHT and the HCtrl group may be attributed to most patients with depression being on sick leave, whereas healthy participants were working and may not experience direct light exposure at work (see Fig. 1) In addition of receiving higher light intensity during the day, the LIGHT group also demonstrated significantly lower nighttime light intensity compared to the other groups (see Fig. 2). These results align with prior investigations on light exposure and mental health [29], which identified a correlation between increased nocturnal light exposure and depressive symptoms in older individuals, highlighting the pivotal role of light in mental well-being. The lower levels of light intensity received by the LIGHT group and the higher day-night contrast may have contributed to the enhancement of mood. This finding underscores the importance of maintaining a robust light day-night contrast, which has been shown to be crucial for regulating biological rhythms [30]. We have no definite explanation why patients in LIGHT group have lower exposure to light at night. We hypothesize this is the consequence that they sleep better, and their circadian rhythms are improved through a strength of melatonin circadian rhythm. Subjective Sleep Quality We know that there is a clear relationship between sleep disorders and depression [31]. However, it is challenging to elucidate whether sleep problems worsen mood or whether depression causes a disturbance in sleep quality. This is likely a bidirectional relationship mediated by chronodisruption [32]. The results of this study showed that participants in the LIGHT and the non-LIGHT groups had high scores in the PSQI both pre-treatment (> 14) and post-intervention (> 11) as was also shown in previous studies [33]. After chronobiological intervention, scores obtained for the participants of the LIGHT group showed improvements in almost all components of sleep quality with significant differences for the daytime dysfunction component. Additionally, they increase their sleep duration (from 6-7 hours to > 7) and efficiency (from 65-74% to 75-84%) (see Table 4). These results are consistent with the Münch study, they found that light therapy can have a beneficial impact on sleep, improving sleep quality and duration. Non-LIGHT group showed a trend toward significant differences observed for sleep disturbances, although the magnitude of improvement was smaller compared to the LIGHT group. Recent reviews have supported the notion that sleep problems in older adults predispose them to depressive states. Furthermore, studies have highlighted specific sleep durations (less than 7 hours or greater than 8-9 hours) as risk factors for depression [34]. Objective Sleep Quality In the LIGHT group, all parameters (PT, IS, RA, and CFI) that indicated better stability and adjustment, increased; in contrast, the IV decreased, indicating a lower variability of the circadian rhythm. Similar changes were obtained in the MA, indicating greater stability (see Table 3). However, we can only describe trends since no significant differences were obtained. For the non-LIGHT group, the trend towards better rhythm adjustment was less evident and, in some cases, as in the fragmentation of the rhythm (IV) was in the opposite direction (see Table 3). Finally, these results were important knowing greater within- and inter-day instability is associated with worse anxiety and depression symptoms [35]. A rigorous methodology was employed, utilizing multisensory records obtained from Kronowise ® (followed by the extraction of objective sleep quality data using Actiwatch Activity and Sleep Analysis ® 2001 Software). This approach allowed for the examination of various components of sleep quality, including sleep efficiency, sleep latency, percentage of immobility, percentage of mobility, and sleep fragmentation (see Table 4). This objective evaluation was consistent with the subjective one using the PSQI [17,18], providing comprehensive and reliable information on sleep variables. Limitations and future directions This study presented some limitations: 1) The sample size represents a limitation for the interpretation of the results. 2) There is no basal record of light exposure of the patients pre-intervention, 3) Controlling for covariates such as gender, education, and the use of table and smart phones minutes before going to bed, 4) The HCtrl group was evaluated only with KW6 pre-treatment, and 5) We studied only the short-term effect of daylight exposure. Future research: 1) Enlarging the sample size to conduct an extensive study, and 2) Exploring the potential integration of chronobiological interventions, such as exposure to daylight, either as standalone therapy or as adjunctive treatment, into clinical practice guidelines for depression treatment and prevention in at-risk population, and 3) We believe that the involvement of nurses in this chronobiological intervention can make an important contribution to treatment and reduce the pressure of care. Conclusions In sum, this study provides: 1) Patients in the LIGHT group were significantly exposed to higher light intensity (amount) in the early hours of the morning than the non-LIGHT and the Control groups. The light day-night contrast was significantly higher in patients in the LIGHT group than in the non-LIGHT and the Control groups; 2) Depression symptoms measured with the QIDS-SR16 improved significantly in patients in the LIGHT group compared to the non-LIGHT group; 3) Subjective sleep quality measured with PSQI showed a non-statistically significant trend improvement in the LIGHT group after the intervention, and this was not the same for the non-LIGHT group; and 4) Objective sleep and circadian parameters showed a non-statistically significant trend improvement in the LIGHT group after the intervention. Declarations Acknowledgments The authors gratefully acknowledge the work of the reviewers that contribute to the improvement of this report. Authors thanks the staff of “Mental Health Unit Camí de Jesús” for their help in the recruitment and management of participants. And we are grateful to all depressive patients and healthy controls for their kind and disinterested collaboration Author’ Contributions J.A.R., participated in conceptualization, investigation, data curation, methodology, supervision, formal analysis, project administration, validation, resources, and visualization. M.C.N., participated in conceptualization, investigation, software, data curation, methodology, supervision, formal analysis, project administration, validation, resources, and visualization. A.R., participated in conceptualization, investigation, data curation, methodology, formal analysis, resources, and visualization. A.M., participated in conceptualization, investigation, software, data curation, methodology, project administration, resources, and visualization. F.C., participated in conceptualization, investigation, data curation, methodology, supervision, project administration, validation, resources, and visualization. All authors read and wrote the manuscript and approved it in its final manuscript. Funding The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Research Commission of the University Hospital Son Espases (HUSE) within the call for research grants of HUSE 2020. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request Ethics approval and consent to participate All participants were given instructions about the purpose and risks of the study and were required to give written informed consent. The experimental procedure was approved by the Research Ethics Committee of Hiroshima university (No. 30-02, 30-03). This study was performed in accordance with the Declaration of Helsinki. Competing Interests The authors declare that they have no conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author details 1 Functional and Clinical Neurophysiology: Biological Rhythms and Language (NRL) group, University of the Balearic Islands (UIB), 07122, Palma, Spain . 2 Health Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain. 3 Son Espases University Hospital (HUSE), 07010, Palma, Spain. 4 Neuropsychology and Cognition Research Group, Department of Psychology, University of the Balearic Islands (UIB). 5 University Institute for Research in Health Sciences (IUNICS), University of the Balearic Islands (UIB), 07122, Palma, Spain. 6 University College Alberta Giménez-Comillas Pontifical University (CESAG-UP Comillas) * Correspondence: [email protected] (F.C.); [email protected] (J.A.R) References American Psychiatric Association (APA). Guía de consulta de los criterios diagnósticos del DSM-5 ® : Spanish edition of the desk reference to the diagnostic criteria from DSM-5 ® . American Psychiatric Pub. 2014. Vieta E, Alonso J, Pérez-Sola V, et al. Epidemiology and costs of depressive disorder in Spain: the EPICO study. Eur Neuropsychopharmacol. 2021 Sep;50:93-103. https://doi.org/10.1016/j.euroneuro.2021.04.022 Roca M, Gili M, Garcia-Garcia M, et al. Prevalence and comorbidity of common mental disorders in primary care. J Affect Disord. 2009 Dec;119(1-3):52-8. https://doi.org/10.1016/j.jad.2009.03.014. Rush AJ, Bernstein IH, Trivedi MH, et al. An evaluation of the quick inventory of depressive symptomatology and the hamilton rating scale for depression: a sequenced treatment alternatives to relieve depression trial report. Biol Psychiatry. 2006 Mar 15;59(6):493-501. https://doi.org/10.1016/j.biopsych.2005.08.022. Hattar S, Liao HW, Takao M, et al. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002; 295 (5557): 1065-70. https://doi.org/10.1126/science.1069609. Wirz-Justice A, Skene DJ, Münch M. The relevance of daylight for humans. Biochem Pharmacol. 2021 Sep;191:114304. https://doi.org/10.1016/j.bcp.2020.114304. Tähkämö L, Partonen T, Pesonen AK. Systematic review of light exposure impact on human circadian rhythm. Chronobiol Int. 2019 Feb;36(2):151-170. https://doi.org/10.1080/07420528.2018.1527773. Lee R, McGee A, Fernandez FX. Systematic review of drugs that modify the circadian system's phase-shifting responses to light exposure. Neuropsychopharmacology. 2022 Mar;47(4):866-879. https://doi.org/10.1038/s41386-021-01251-8. Canellas F, Mestre L, Belber M, et al. Increased daylight availability reduces length of hospitalisation in depressive patients. Eur Arch Psychiatry Clin Neurosci. 2016 Apr;266(3):277-80. https://doi.org/10.1007/s00406-015-0601-5. Geoffroy PA, Schroder CM, Reynaud E, Bourgin P. Efficacy of light therapy versus antidepressant drugs, and of the combination versus monotherapy, in major depressive episodes: A systematic review and meta-analysis. Sleep Med Rev. 2019 Dec;48:101213. https://doi.org/10.1016/j.smrv.2019.101213. Tao L, Jiang R, Zhang K, et al. Light therapy in non-seasonal depression: An update meta-analysis. Psychiatry Res. 2020 Sep;291:113247. https://doi.org/10.1016/j.psychres.2020.113247. Lobo A, Chamorro L, Luque A, et al. Grupo de Validación en Español de Escalas Psicométricas (GVEEP). Validación de las versiones en español de la Montgomery-Asberg Depression Rating Scale y la Hamilton Anxiety Rating Scale para la evaluación de la depresión y de la ansiedad [Validation of the Spanish versions of the Montgomery-Asberg depression and Hamilton anxiety rating scales]. Med Clin (Barc). 2002 Apr 13;118(13):493-9. Spanish. https://doi.org/10.1016/s0025-7753(02)72429-9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. https://doi.org/10.1192/bjp.134.4.382. García-Toro M, Ibarra O, Gili M, et al. Adherencia a las recomendaciones sobre estilo de vida en pacientes con depresión. Rev Psiquiatr Salud. 2012; 5: 236-240. https://doi.org/10.1016/j.rpsm.2012.04.003 Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57. https://doi.org/10.1016/S0924-9338(97)83296-8. Ferrando L, Bobes J, Gibert J, et al. 1.1. MINI Entrevista Neuropsiquiátrica Internacional (MINI International Neuropsychiatric Interview, MINI). Instrumentos Detección Orientación Diagnóstica. 2000; 1-25. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. https://doi.org/10.1016/0165-1781(89)90047-4. Royuela RA, Macías FJ. Propiedades clinimétricas de la versión castellana del cuestionario de Pittsburgh. Vigilia-Sueño. 1997; 9: 81-94. Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003 Sep 1;54(5):573-83. doi: 10.1016/s0006-3223(02)01866-8. Erratum in: Biol Psychiatry. 2003 Sep 1;54(5):585. https://doi.org/10.1016/s0006-3223(02)01866-8 Gili M, Lopez-Navarro E, Homar C, et al. Psychometric properties of Spanish version of QIDS-SR16 in depressive patients. Actas Esp Psiquiatr. 2014 Nov-Dec;42(6):292-9. PMID: 25388771. Arguelles-Prieto R, Bonmati-Carrion MA, Rol MA, Madrid JA. Determining Light Intensity, Timing and Type of Visible and Circadian Light From an Ambulatory Circadian Monitoring Device. Front Physiol. 2019 Jun 26;10:822. https://doi.org/10.3389/fphys.2019.00822. Cohen J. A power primer. In. E. Kazdin (Ed.), Methodological issues and strategies in clinical research (4th ed., pp. 279-284). APA PsycNet. 2016. https://doi.org/10.1037/14805-018 Ortiz-Tudela E, Martinez-Nicolas A, Campos M, et al. A new integrated variable based on thermometry, actimetry and body position (TAP) to evaluate circadian system status in humans. PLoS Comput Biol. 2010 Nov 11;6(11):e1000996. https://doi.org/10.1371/journal.pcbi.1000996. Declaration of Helsinki. Ethical principles for medical research involving research involving human subjects. Available at: shorturl.at/sNUV4 (Accessed June 3, 2023). 2013. World Health Organization. Depression. General information. World Health Organization. 2023. Available at: https://www.who.int/es/news-room/fact-sheets/detail/depression (Accessed March 24, 2024) Wright KP Jr, Drake AL, Frey DJ, et al. Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun. 2015 Jul;47:24-34. https://doi.org/10.1016/j.bbi.2015.01.004. Dresp-Langley B. Children's Health in the Digital Age. Int J Environ Res Public Health. 2020 May 6;17(9):3240. https://doi.org/10.3390/ijerph17093240. Benedetti F, Barbini B, Colombo C, Smeraldi E. Chronotherapeutics in a psychiatric ward. Sleep Med Rev. 2007 Dec;11(6):509-22. https://doi.org/10.1016/j.smrv.2007.06.004. Obayashi K, Saeki K, Kurumatani N. Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort. Am J Epidemiol. 2018 Mar 1;187(3):427-434. https://doi.org/10.1093/aje/kwx290. Münch M, Brøndsted AE, Brown SA, et al. The effect of light on humans. Changing perspectives on daylight: Science, technology and culture. Sponsored supplement to science. A.A.S. 2017;16-23. Riemann D, Krone LB, Wulff K, Nissen C. Sleep, insomnia, and depression. Neuropsychopharmacology. 2020 Jan;45(1):74-89. https://doi.org/10.1038/s41386-019-0411-y. Neves AR, Albuquerque T, Quintela T, Costa D. Circadian rhythm and disease: Relationship, new insights, and future perspectives. J Cell Physiol. 2022 Aug;237(8):3239-3256. https://doi.org/10.1002/jcp.30815. Castellanos K, Lizcano A, Canche J, et al. Síndrome del retraso de la fase del sueño: una revisión bibliográfica. Revista de la Facultad de Medicina (México). 2022; 65: 47-58. https://doi.org/10.22201/fm.24484865e.2022.65.1.08. Lin J, Yang H, Zhang Y, et al. Association of time spent in outdoor light and genetic risk with the incidence of depression. Transl Psychiatry. 2023 Feb 3;13(1):40. https://doi.org/10.1038/s41398-023-02338-0. Nexha A, Pilz LK, Oliveira MAB, et al. Greater within- and between-day instability is associated with worse anxiety and depression symptoms. J Affect Disord. 2024 Jul 1;356:215-223. https://doi.org/10.1016/j.jad.2024.04.014. Tables Table 1 Sociodemographic data with averages and standard deviations, percentages, and p -value. LIGHT (Lt) non-LIGHT (non-Lt) Control (Ctrl) p-value Lt-non-Lt p-value Lt-Ctrl Sample size (n) 11 10 17 Gender F 8 (72.72%) 8 (80%) 11 (64.71%) M 3 (27.27%) 2 (20%) 6 (35.29%) Age (years) 49 (9.68) 52 (10.90) 50.11(8.98) .61 .62 Education (years) 10.36 (1.96) 11.5 (4.09) 16.47 (3.48) .52 .01 Lt, LIGHT group; non-Lt, non-LIGHT group; Ctrl, Control group; F, female; M, male p- value, p significance level: p < .001 (high), p < .01 (medium), p < .05 (low). LIGHT, group exposed to light; non-LIGHT, group with general recommendations for healthy habits; Control, group with a usual routine of activities P- value, p significance level: p < .001 (high), p < .01 (medium), p < .05 (low); d de Cohen (Effect size), d ≥ .20 small effect, d ≥ .50 medium effect, d ≥ .80 large effect, d ≥ 1.20 very large effect, d ≥ 2.0 effect largest (Cohen, 2016). Normative data with averages and standard deviations on time of exposure spent to different light intensities during the awake period: 1) morning from 08:00 to 15:50 hours, between 1000-10000 lux was of 45 (06) minutes, and 2) evening from 16:00 to 23:50 hours, between 1000-10000 lux was 34 (07) minutes, and the sleep period from 00:00 to 07:50 hours, < 10 lux was of 7 (.2) hours (Martínez-Nicolás et al., 2018). Table 2 Individual direct scores and averages (standard deviations) of QIDS-SR16 of the participants for the LIGHT and non-LIGHT groups. QIDS-SR16 LIGHT CODE PARTICIPANT Week 1 Week 2 Week 3 Week 4 16 14 - - 9 17 20 16 20 11 18 - 9 8 5 22 13 15 15 12 3 8 5 3 4 4 17 18 18 19 7 8 7 8 6 13 20 17 16 14 24 18 5 16 - 27 15 22 21 18 28 21 21 19 11 15.4 (4.48) 13.5 (6.14) 14.4 (5.71) 10.9 (4.87) non-LIGHT CODE PARTICIPANT Week 1 Week 2 Week 3 Week 4 19 17 18 17 20 20 9 9 11 11 21 13 8 10 7 5 17 14 9 14 8 14 21 11 22 9 18 18 20 20 10 21 - - 11 23 10 6 6 3 25 17 16 16 13 31 16 13 9 9 15.20 (3.71) 13.67 (5.12) 12.11 (4.54) 13 (6.15) LIGHT, LIGHT group; non-LIGHT, non-LIGHT group; QIDS-SR 16, Quick Inventory of Depressive Symptomatology-Self Report Table 3 Average scores and standard deviations of circadian parameters of peripheral temperature ((PT) and motor activity (MA) pre and post-intervention. Peripheral Temperature (ºC) MESOR IS IV RA CFI LIGHT Pre 32.54 (.58) .44 (.20) .003 (.001) .34 (.14) .59 (.11) Post 33.22 (1.20) .49 (.14) .002 (.001) .32 (.13) .60 (.08) non-LIGHT Pre 31.89 (.71) .45 (.11) .002 (.001) .21 (.10) .57 (.06) Post 32.31 (.64) .45 (.23) .004 (.003) .26 (.14) .57 (.10) Control Pre 32 (.45) .51 (.20) .002 (.001) .42 (.20) .64 (.13) Motor Activity (3-axis MEMS accelerometer) LIGHT Pre 52.37 (43.73) .35 (.1) .23 (.09) .86 (0.1) .70 (.07) Post 48.38 (38.62) .44 (.05) .23 (.07) .89 (.03) .73 (.02) non-LIGHT Pre 63.67 (42.16) .36 (.07) .25 (.04) .90 (.01) .71 (.02) Post 65.27 (48.17) .41 (.09) .25 (.05) .89 (.03) .7 (.04) Control Pre (baseline) 71.27 (44.73) .42 (.09) .26 (.04) .87 (.11) .72 (.06) LIGHT, LIGHT group; non-LIGHT, non-LIGHT group; Control, Control group; Pre, pre-treatment, Post, postintervention; PT, peripheral temperature; MA, motor activity; MESOR, Midline estimating statistic of rhythm; IS, inter-day stability; IV, intraday variability; RA, relative amplitude; CFI, circadian function index; Pre, pre-intervention, Post, post-intervention p- value showed no significant differences pre-post (all p > .05). Normative data for the different circadian parameters are as follows: PT, [MESOR = 33.57 (.09), IS = .57 (.02), IV = .20 (.01), RA = .03 (.00), CFI = .50 (.01)]; MA, [MESOR = 27.64 (.56), IS = .59 (.01), IV = .71 (.02), RA =.68 (.01), CFI = .64 (.01)] (Martínez-Nicolás et al., 2018). Table 4 Average scores, standard deviations and percentages of the objective measures obtained from the KW6 data, more specifically the variable ‘Time in Movement’ of the LIGHT, non-LIGHT and Control groups. Efficiency Latency % immobility % mobility Fragmentation LIGHT Pre 73.43 (8.34) 54 min. 76.15% (9.37) 23.85 (10.05) 62.86 (22.79) Post 73.23 (9.14) 32 min. 75.61% (9.67) 24.39 (9.67) 64.30 (19.19) non-LIGHT Pre 71.27 (11.25) 67 min. 79.35% (11.85) 20.65 (11.85) 53.59 (22.47) Post 71.44 (13.53) 47 min. 78.18% (8.59) 21.82 (8.59) 57.27 (16.59) Control Pre (baseline) 82.82 (4.65) 19 min. 82.13% (4.46) 17.87 (4.46) 50.89 (13.54) LIGHT, LIGHT group; non-LIGHT, non-LIGHT group; Control, Control group; Pre, pre-intervention, Post, post-intervention; min., minutes; %, percentages Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7293619","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":495563465,"identity":"84283743-3581-451a-ae08-b717d4f97636","order_by":0,"name":"José A. Rubiño","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYBACxgYogw+ImRkMGBj4GRjbiNPCBtMi2UBACxxAtACBwQEwGzdgbm9/+ODnjlo5NgbeZ9IFBXfkjG8ktz1gqKjD7bCeM8aGvWeOG7MxsJtJzzB4Zmx2I7HdgOHMYdxaZuSwSfC2HUtsY2Bjk+YxOJy47UZimwRj2wE8WtKf//zbdqwermXzDJCWf3gcNiPBjJm3rSaBDaZlgwRISwMzXr9Iy7YdMGxjZmO2nmFw2FjizMN2g4RjuP1iCAyxj2/b6uT52dsYbxf8OSzH357+7MGHGtwOM2wAU4ehkQIDCTg1MDDIQyjcZo6CUTAKRsEoYAAAlbtO8YOO/wUAAAAASUVORK5CYII=","orcid":"","institution":"University of the Balearic Islands","correspondingAuthor":true,"prefix":"","firstName":"José","middleName":"A.","lastName":"Rubiño","suffix":""},{"id":495563466,"identity":"80a51e22-eb6d-4f49-9f3f-5a25932260d9","order_by":1,"name":"M.A. Cristina Nicolau","email":"","orcid":"","institution":"University of the Balearic Islands","correspondingAuthor":false,"prefix":"","firstName":"M.A.","middleName":"Cristina","lastName":"Nicolau","suffix":""},{"id":495563467,"identity":"853302e1-44b4-4d7e-97a4-41eb2c1e4857","order_by":2,"name":"Anna Riera","email":"","orcid":"","institution":"University of the Balearic Islands","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Riera","suffix":""},{"id":495563468,"identity":"dc3df088-b600-444b-a2ca-1c74f6f08f84","order_by":3,"name":"Aida Martín","email":"","orcid":"","institution":"University of the Balearic Islands","correspondingAuthor":false,"prefix":"","firstName":"Aida","middleName":"","lastName":"Martín","suffix":""},{"id":495563469,"identity":"63d89985-faa7-4870-bddb-544aa6f5441b","order_by":4,"name":"Francesca Cañellas","email":"","orcid":"","institution":"University of the Balearic Islands","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Cañellas","suffix":""}],"badges":[],"createdAt":"2025-08-04 17:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7293619/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7293619/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88423819,"identity":"f3ba637e-2df2-48ff-9362-5fee4800eac4","added_by":"auto","created_at":"2025-08-06 09:40:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50609,"visible":true,"origin":"","legend":"\u003cp\u003eLight intensity (lux) over 24h for the LIGHT, non-LIGHT, and Control groups with Kronowise\u003csup\u003e®\u003c/sup\u003e device.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7293619/v1/fbb03150afc986aae4c4efcd.jpg"},{"id":88423818,"identity":"ad8d004c-c41e-46c0-85b4-ad654a58aa72","added_by":"auto","created_at":"2025-08-06 09:40:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31735,"visible":true,"origin":"","legend":"\u003cp\u003eAverage and standard deviation QIDS-SR16 direct scores for the LIGHT and non-LIGHT groups during the four weeks (visits) of the study.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7293619/v1/5a1955977a2d9b4fb59dbc25.jpg"},{"id":90215512,"identity":"9fb7414a-f17f-433b-b687-fe8a7a3ac111","added_by":"auto","created_at":"2025-08-30 06:01:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1160656,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7293619/v1/4d0bd5bb-4cde-4f99-9d5c-7ff3f7238d65.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Benefits of exposure to morning daylight on sleep, circadian rhythms, and symptoms of depression","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMajor depressive disorder (MDD) is a mental condition characterized by a persistent low or depressed mood, anhedonia or decreased interest in pleasurable activities, feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts, that causes social or occupational impairment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. MDD affects approximately 5% of the Spanish adult population annually [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In addition, in Mallorca primary care setting, between 25% and 35% of adult patients have mental disorders with 29% having a depressive disorder [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Depression is responsible for significant economic expenditure on health treatments. It has been estimated that the total annual social cost of depressive disorders in the Spanish adult population was \u0026euro;6,145\u0026nbsp;million in 2017 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Antidepressant drugs (AD) are widely used for the treatment of MDD. However, approximately 50% of patients do not experience an adequate response to these therapies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In addition, when they are effective, the number of depressive symptoms is reduced and decreases earlier.\u003c/p\u003e\u003cp\u003eDaylight exerts different functions through different physiological mechanisms on the body's systems. A critical discovery revealed that there is a non-visual pathway via photoreceptors in the retinal ganglion cells that directly accesses the circadian clock through a retinal-hypothalamic tract. These cells contain a photopigment (melanopsin) with the highest sensitivity to short-wavelength, blue light. This is the major neural pathway by which light modulates the circadian system [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Additionally, it is the most powerful synchronizer acting in the circadian system for the adjustment of biological rhythms and has an antidepressant action, acting on multiple systems, stabilizing mood and emotion regulation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Exposure to light, especially in the morning, allows an effective inhibition of melatonin in the first hours [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and a greater amount of serotonin (enteric and cerebral) circulating throughout the day [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eExposure to daylight has a positive effect on the reduction of depressive symptoms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and an increase in exposure to daylight reduces the delay of the remission of depressive symptoms, leading to a reduction in the number of days spent in hospital [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The combination of antidepressant therapy and BLT accelerates and potentiates the pharmacological effects of antidepressants in non-seasonal depressive episodes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. For this reason, it is important to focus on the circadian system as it would be a crucial point in the therapeutic approach to depression [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe research we present posits that exposure to daylight in the morning will faster the remission of depressive symptoms and improve the adjustment of biological rhythms in depressive patients. Therefore, a scheduled chronobiological intervention with exposure to daylight in the morning in conjunction with antidepressant treatment in patients with non-seasonal major depression treated on an outpatient basis: a) will be more effective than the pharmacological treatment alone in the reduction of depressive symptoms, and b) improve the quality of sleep and the adjustment of circadian rhythms.\u003c/p\u003e\u003cp\u003eThe objectives of this study are: 1) To analyse the degree of acceptance and adherence to daylight therapy, as well as recruitment and adherence to the study, 2)To quantify light exposure with a device (KW6) to compare the intensity of daylight exposure in the morning and the day/night light contrast in patients receiving a chronotherapeutic intervention (LIGHT group) versus patients who do not receive it (non-LIGHT group), 3) To assess changes in depressive symptoms after 14, 21 and 28 days of follow-up, and 4) To evaluate the subjective and objective sleep quality of patients of both groups.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwenty-one patients attended a Mental Health Unit in Palma de Mallorca (Balearic Islands) presenting a non-seasonal major depressive episode, who started with a new antidepressive treatment or a change from the previous antidepressant treatment, due to lack of efficacy, and 17 healthy volunteers were recruited from the general population.\u003c/p\u003e\n\u003cp\u003eThe criteria for the selection of patients were: A) Inclusion criteria: 1) aged between 18 and 65 years of both genders, 2) diagnosis of non-seasonal major depressive disorder (MDD) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders [1], 3) had to obtain a score equal to or greater than 24 in the Spanish version [12] of the Montgomery-Asberg Depression Scale (MADRS) [13], and 4) had to understand the research objectives, that their participation was voluntary, and sign an informed consent. And B) Exclusion criteria: 1) substance abuse (\u0026gt; 24 g/day of alcohol in women, 40 g/day in men, use of cocaine, heroin, and other drugs of abuse), 2) had another psychiatric or neurological disorder, 3) had comprehension difficulties or low educational level, 4) had skin problems and eye sensitivity and/or photophobia, and 5) performing shift work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a feasibility study with a double-branch, randomized experimental design. Sampling was probability sampling with simple randomization. Patients were divided into two groups: LIGHT and non-LIGHT. All patients received the same written explanation about the aim of the study and procedure (included in the informed consent form). The only difference was that the LIGHT group received specific instructions to expose themselves to daylight in the morning along with the pharmacological antidepressant treatment prescribed by their psychiatrist.\u003c/p\u003e\n\u003cp\u003eHealth control participants (HCtrl) were recruited from the general population, matched by age and gender to the patients, to verify KW6 data between the depressive and non-depressive populations. Health controls reported no affective or emotional problem, did not take any psychotropic drug, and they continued with their usual routine of activities. All participants were located on the island of Mallorca (latitude: ~40\u0026deg;N) with a mean of 82% of sunny days, 5\u0026deg;C (night) and 22\u0026deg;C (day) and ~12 h of daylight.\u003c/p\u003e\n\u003cp\u003eThe recruitment was done in two periods: 1\u0026ordm;) March to October 2021, and 2\u0026ordm;) January-May 2023: we had to stop because of problems due to COVID-19 pandemic, and then, structural problems obliged to close the Mental Health Unit for several months.\u003c/p\u003e\n\u003cp\u003eInterventions:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePatients in the non-LIGHT group were given written general recommendations for healthy habits considered as placebo [14]: 1) exposure to sunlight at your convenience, 2) physical exercise appropriate to your needs, 3) sleep the amount of time you need, 4) recommendation to stay in or get out of bed at your convenience, and 5) eat a healthy and balanced diet.\u003c/li\u003e\n \u003cli\u003ePatients in the LIGHT group were given specific written instructions to expose themselves to daylight for 14 days. The specific instruction was: \u0026lsquo;You must be outside, at least one hour daily, in the morning before 11:00 a.m. You can take a walk or just sit to expose yourself to daylight. You should not wear sunglasses. If direct sun exposure bothers you, you can wear a hat or stay in shady places. During this time, you cannot do a specific exercise (such as running or cycling) or other activities. They received, in addition, general recommendations for healthy habits in writing, as the non-LIGHT, excepted recommendation 1.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eQuestionnaires and Scales\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe International Neuropsychiatric Interview (MINI)\u0026nbsp;[15,16]\u0026nbsp;to exclude other comorbid psychiatric disorders.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e- Montgomery-Asberg Depression Scale (MADRS) [13]. Clinician-performed scale validated for the Spanish population (Lobo et al., 2002) with 10 items to assess depression, uncontaminated by anxiety items. Minimum score of 0 and maximum score of 60.\u003c/p\u003e\n\u003cp\u003e- Pittsburgh Sleep Quality Index (PSQI) [17,18]. Self-applied scale that collects information related to sleep in the last month in adults, with 24 questions. In correction, 7 partial components are generated: 1) subjective sleep quality, 2) latency, 3) duration, 4) efficiency, 5) disturbances, 6) medication use, and 7) daily dysfunction. The total score is obtained by adding the components, and ranges from 0 to 21 points. \u0026quot;Good sleepers\u0026quot; are people with a score of less than or equal to 5, and \u0026quot;bad sleepers\u0026quot; have a score greater than 5. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e- Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) [19]. It is a validated questionnaire for the Spanish population [20] of depressive symptomatology of the last week, self-applied, with 16 items and 9 categories: 1) sleep disturbances, 2) depressed mood, 3) changes in weight, 4) concentration, 5) self-criticism, 6) suicidal ideation, 7) interest, 8) energy level, 9) psychomotor alterations. Score from 0 to 27.\u003c/p\u003e\n\u003cp\u003e- Sleep and activity agenda: this is a self-registration form on paper to record the time and frequency of sleep periods during the day and night.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLight, Peripheral Temperature and Motor Activity Recording\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ambulatory circadian monitoring device KW6 (Kronowise\u003csup\u003e\u0026reg;\u003c/sup\u003e; Kronohealth S.L., University of Murcia, Spain) [21], is a multi-sensor device worn on the non-dominant wrist. It records the motor activity (MA), peripheral temperature (PT), and light intensity (LI). Using from the MA data (the \u0026lsquo;time in movement\u0026rsquo;variable) during the assumed sleep period (23:00 to 07:50), the Actiwatch Activity and Sleep Analysis\u003csup\u003e\u0026copy;\u003c/sup\u003e 2001 Software (Actiwatch 2001, V1.16 Cambridge Neurotechnology) was employed to obtain the objective sleep quality parameters: 1) Efficiency, 2) Latency, 3) Percentage of immobility, 4) Percentage of mobility, and 5) Fragmentation.\u003c/p\u003e\n\u003cp\u003eTherefore, sleep variables were analysed using both subjective instruments (agenda and PSQI) and objective instruments (KW6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter the initial assessment conducted by the psychiatrist, eligible patients were invited to participate in the study. Following an explanation of the protocol, participants were provided with a participant information sheet (PIS) and asked to read it. If they agree, they signed the Informed Consent (IC) form before being directed to the researchers (a biologist and a psychologist master students) for randomization and study protocol procedures. Each clinical evaluation session lasted approximately 50 minutes. The assessment and intervention protocol were as follows for the different groups:\u003c/p\u003e\n\u003cp\u003eDuring visit 1 (week 1), the inclusion and exclusion criteria were reviewed, and the clinical interview was conducted using the MINI neuropsychiatric interview (for exclusion of patients with comorbid psychiatric disorders) and assessments including the PSQI and QIDS-SR16 were given to patients to fill them up. Additionally, participants were equipped with the KW6 device to record circadian parameters and light exposure intensity and were instructed to complete a sleep and activity agenda. They were randomized and received specific instructions based on their randomization. During visit 2 (day 14), the QIDS-SR16 was given to patients to fill it up, and data from the KW6 device were downloaded, followed by collection of the agenda. On visit 3 (day 23), another QIDS-SR16 assessment was performed, and the KW6 device reattached. Finally, during visit 4 (week4, day 28), the agenda was collected, the KW6 device was removed for data retrieval, and the PSQI and QIDS-SR16 were re-administered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCtrl participants attended two visits. In the first, inclusion and exclusion criteria were revised, and demographic data were collected. They received the sleep and activity agenda and the KW6. The agenda and the KW6 were collected on a second visit after 5-7 days.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were conducted using IBM SPSS Statistics 29.0 software.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParametric inferential statistics were employed with ANOVA with the register\u0026rsquo;s exposure light for 24 hours, and t-test to contrast the average day-night light scores between the LIGHT, non-LIGHT and HCtrl groups. In addition, effect sizes were with Eta squared (\u003cem\u003e\u0026eta;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e): \u003cem\u003e\u0026eta;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = .01, small effect size; \u003cem\u003e\u0026eta;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = .06, medium effect size; and \u003cem\u003e\u0026eta;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = .14 or higher, large effect size. And d-Cohen (\u003cem\u003ed\u003c/em\u003e): \u003cem\u003ed\u003c/em\u003e = .20, small effect size; \u003cem\u003ed\u003c/em\u003e = .05, medium effect size; and \u003cem\u003ed\u003c/em\u003e = .80 or higher, large effect size [47].\u003c/p\u003e\n\u003cp\u003eNon-parametric inferential statistics were employed to average contrast using the Mann-Whitney U test (\u003cem\u003eU\u003c/em\u003e) for independent samples (comparing averages between the LIGHT, non-LIGHT, LIGHT-HCtrl, and non-LIGHT-HCtrl groups). The Wilcoxon test was used for paired samples, such as pre-postintervention comparisons. Significance levels (\u003cem\u003ep\u003c/em\u003e value) were reported as follows: \u003cem\u003ep\u003c/em\u003e \u0026lt; .001 (high), \u003cem\u003ep\u003c/em\u003e \u0026lt; .01 (medium), \u003cem\u003ep\u003c/em\u003e \u0026lt; .05 (low). Additionally, effect sizes for different variables in the LIGHT and non-LIGHT groups were calculated using rank biserial correlation (\u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e): \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e \u0026lt; .3, small effect; \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e = .3 to .50, medium effect; and \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e \u0026gt; .5, large effect [22].\u003c/p\u003e\n\u003cp\u003eData collection and analysis were conducted using the Circadianware program specifically tailored to Kronowise\u003csup\u003e\u0026reg;\u003c/sup\u003e (KW6) device. Data points deviating more than 3 times from the standard deviation of the average were also removed. The KW6 software performed parametric and non-parametric analyses of the variables Peripheric Temperature (PT), as a variable representative of autonomic balance at the skin vessel level), motor activity (MA), \u0026lsquo;time in movement\u0026rsquo;. The following indices were obtained to describe the circadian system [23]: 1) Midline Estimating Statistic of Rhythm (MESOR), 2) Inter-day stability index (IS), 3) Intra-day variability index (IV), 4) Relative amplitude (RA), and 5) Circadian Function Index (CFI). These variables are the parameters of the marker rhythms (MA and PT) of the sleep-wake rhythm for the study of the circadian system.\u003c/p\u003e\n\u003cp\u003eThe MA data recorded with the KW6 device were processed using the Actiwatch Activity and Sleep Analysis\u003csup\u003e\u0026copy;\u003c/sup\u003e 2001 Software,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Aspects and Data Security\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in compliance with the principles of the Declaration of Helsinki [24], Organic Law 3/2018, on the 5 December, on the protection of personal data and guarantee of digital rights, and this study was approved by the Research Committee of the Son Espases University Hospital (HUSE, CI-481-20, 14th January 2021) and the Research Ethics Committee of the Balearic Islands (CEI-IB, IB 4429/21 PI, 24th February 2021). All participants signed the informed consent.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eSocio-Demographic Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 presents the sociodemographic data of the total sample. A higher participation of women was observed in all groups. There were no significant differences in relation to age. There were significant differences in years of education between the depression groups (LIGHT, non-LIGHT) and the HCtrl group. There were no differences between the two branches in MADRS at inclusion: the average scores and standard deviations of the MADRS for the LIGHT group were 26.36 (5.41) and MADRS for the non-LIGHT group were 26.90 (5.68).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert Table 1 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposure to Light\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 1 shows the Light intensity (lux) exposed during 24h for the LIGHT, non-LIGHT and HCtrl groups.\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert Fig. 1 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e\n\u003cp\u003eThe average scores and standard deviations of the light intensity were higher over 24 hours of 600.35 (1,070.85) lux for the LIGHT group than for the non-LIGHT group of 326.20 (394.18) lux, and the HCtrl group of 232.43 (186.42) lux. The contrast analysis with the ANOVA one-factor test (intergroups) showed a significant difference (\u003cem\u003eF\u003c/em\u003e (2, 431) = 7.69, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003eη\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = .23), and the post hoc analysis with the Bonferroni test showed a significant difference between the LIGHT and non-LIGHT groups (\u003cem\u003ep\u003c/em\u003e = .006, \u003cem\u003ed\u003c/em\u003e = 4.03) and between the LIGHT and HCtrl groups (\u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = 4.46).\u003c/p\u003e\n\u003cp\u003eThe average scores and standard deviations of the light intensity were higher in the awake period (08:00 to 23:00) of 969.66 (1,225.47) lux for the LIGHT group than for the non-LIGHT group of 479.93 (434.64) lux, and HCtrl group of 257.24 (196.16) lux. The t-test analysis showed a significant difference between the LIGHT and non-LIGHT groups (\u003cem\u003et\u003c/em\u003e (177) = -4.28, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = .53), between the LIGHT and HCtrl groups (\u003cem\u003et\u003c/em\u003e (177) = -5.11, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = .81), and between the non-LIGHT and HCtrl groups (\u003cem\u003et\u003c/em\u003e (177) = -4.24, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = .66). Also, the LIGHT group showed greater respect for darkness during the sleep period (23:00 to 07:50) than the other two groups. The average scores and standard deviations for the LIGHT group were 1.92 (4.53) lux, while the non-LIGHT group was 77.43 (40.48) lux, and the HCtrl group was 18.32(8.91) lux. The t-test analysis showed a significant difference between the LIGHT and non-LIGHT groups (\u003cem\u003et\u003c/em\u003e (109) = 13.57, \u003cem\u003ep\u003c/em\u003e = .001, d = 2.62), between the LIGHT and HCtrl groups (\u003cem\u003et\u003c/em\u003e (109) = 12.11, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = 2.32), and between the non-LIGHT and HCtrl groups (\u003cem\u003et\u003c/em\u003e (109) = -10.91, \u003cem\u003ep\u003c/em\u003e = .001, \u003cem\u003ed\u003c/em\u003e = 2.02). The LIGHT group showed a higher day-night light contrast compared to the non-LIGHT and HCtrl groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of Daylight on Mood\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 and Fig. 2 summarize the evolution of the average QIDS-SR16 scores for the LIGHT and non-LIGHT groups during four visits (weeks).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert Table 2 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert Fig. 2 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e\n\u003cp\u003eThe individual direct and average scores and standard deviations for QIDS-SR 16 for all four visits can be seen in Table 2. Average scores contrast analyses with the Wilcoxon test showed significant differences for the LIGHT group between the scores of the initial and last visits (\u003cem\u003eZ\u003c/em\u003e = -2.55, \u003cem\u003ep\u003c/em\u003e = .01, \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e = .46), and the non-LIGH group showed non-significant differences (\u003cem\u003eZ\u003c/em\u003e = -1.23, \u003cem\u003ep\u003c/em\u003e = .22, \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e = .41). The LIGHT group showed a statistically significant reduction in depressive symptoms following exposure to daylight for 14 days over the 4-week study period.\u003c/p\u003e\n\u003cp\u003eContrast analysis of the average scores of the different components of the QIDS-SR16 for the LIGHT group for the initial and final visit evaluations. Then, significant differences were shown in the pre-post for the components \"depressed mood\" and \"changes in weight\" (\u003cem\u003ep\u003c/em\u003e \u0026lt; .05). The remaining components of the QIDS-SR16 showed a non-significant trend of change (\u003cem\u003ep\u003c/em\u003e \u0026gt; .05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMunich Chronotype Questionnaire (MCTQ)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe chronotype analysis showed a great variability in the chronotypes, and there were no significant differences between the LIGHT and non-LIGHT groups. The LIGHT group: 18.18% belonged to the \"extreme evening\" category, 18.18% to the \"evening\" category, 45.45% to \"indefinite\", 18.18% to \"morning\". The non-LIGHT group: 10% belonged to the \"extreme evening\" category, 10% to \"evening\", 70% to \"indefinite\", and 10% to \"morning\".\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of Daylight on Sleep Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubjective Measures of Sleep\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePSQI provides information on the results for 7 components: 1) Subjective sleep quality, 2) Latency, 3) Duration, 4) Efficiency, 5) Disturbances, 6) Medication use, and 7) Daily dysfunction, and their categorisation, for the LIGHT and the non-LIGHT groups, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results were most remarkable, indicating that, for both groups, the overall score was above 5, a cut-off score that indicated poor sleep quality, both in the pre-treatment and postintervention scores. After the contrast of averages, no significant differences were shown in the seven components between pre- and postintervention scores, except for disturbances in the non-LIGHT group (\u003cem\u003ep\u003c/em\u003e = .046). The PSQI total scores for the LIGHT and non-LIGHT groups changed after the intervention. The decrease in the total score was greater in the LIGHT group (\u003cem\u003eZ\u003c/em\u003e = -1.94, \u003cem\u003ep\u003c/em\u003e = .052, \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e = .16) than in the non-LIGHT group (\u003cem\u003eZ\u003c/em\u003e = -1.90, \u003cem\u003ep\u003c/em\u003e = .06, \u003cem\u003er\u003csup\u003erb\u003c/sup\u003e\u003c/em\u003e = .60). However, these changes showed a non-significant trend (\u003cem\u003ep\u003c/em\u003e \u0026gt; .05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective Measures of Sleep\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 shows the average scores (standard deviations) of the circadian parameters (MESOR, IS, IV, RA, and CFI) for peripheral temperature and motor activity circadian obtained with the KW6 for participants in the LIGHT, non-LIGHT, and HCtrl groups pre-postintervention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert table 3 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e\n\u003cp\u003eIn LIGHT group after exposure to daylight, circadian parameter scores MESOR, IS, and CFI showed a slight increase, whereas IV for PT showed a decrease. In addition, there was also an increase in IS, RA and CFI for MA, but there were no significant differences (all \u003cem\u003ep\u003c/em\u003e ˃ .05). In the non-LIGHT group, the circadian parameter scores MESOR and RA for TP showed a slight increase, and an increase in MESOR and IS for MA after exposure to daylight (all \u003cem\u003ep\u003c/em\u003e ˃ .05). Circadian parameters of PT and MA were not significant between the LIGHT, non-LIGHT and HCtrl groups. However, the results showed a non-significant trend of change for the LIGHT group after the intervention.\u003c/p\u003e\n\u003cp\u003eAdditionally, we obtained from the KW6 the variable ‘time in movement’. Table 6 shows the average scores (standard deviations), and percentages (%) of the variables: efficiency, latency, percentage of immobility, percentage of mobility and fragmentation of sleep (Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e-----------------------\u003c/p\u003e\n\u003cp\u003einsert Table 4 here\u003c/p\u003e\n\u003cp\u003e-------------------------\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main objective of this study was to examine the feasibility and the impact of a chronobiological intervention on the progression of depressive symptoms in outpatients undergoing pharmacological treatment for a non-seasonal major depressive episode. The sample exhibited a higher percentage of female participants, consistent with the prevailing trends in depression prevalence and incidence rates [25], while age distribution was similar across both groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults confirmed the research hypothesis despite the relatively low number of participants: patients who increased \u0026nbsp;the exposure to daylight (LIGHT group) in addition to the usual antidepressive treatment, showed significant differences in the pre-post analysis for pre- and postintervention in global QIDS-SR16 scores, and for the components \u0026lsquo;depressed mood\u0026rsquo; and \u0026lsquo;changes in weight\u0026rsquo; (\u003cem\u003ep\u003c/em\u003e \u0026lt; .05) in the QIDS-SR16 test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLIGHT group also improved the subjective quality of their sleep. Regarding objective sleep measures, we fail to find statistical differences among the two groups in the pre-postintervention average of different variables measured with KW6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDaylight\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDaylight is a primary regulator of circadian rhythms [26]. Insufficient exposure to daylight has been associated with various health risks, including depression, anxiety as well as sleep disturbances and obesity [27].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo examine the impact of daylight, participants in the experimental group (LIGHT) were instructed to increase their exposure over a 14-day period, spending at least one hour outdoors in the morning before 11:00 a.m. (see Fig. 1). Participants were advised not to do exercise during this time, they only were allowed to have a walk, to avoid the potential confounding effects of the exercise with the light. The morning period for daylight exposure was selected due to the effective suppression of melatonin production in the pineal gland during early morning hours [7], resulting in increased circulating serotonin levels throughout the day [28].\u003c/p\u003e\n\u003cp\u003eThe analysis of light intensity data (from KW6) revealed higher levels in the LIGHT group during the designated chronobiological treatment period. This indicates good adherence to the regimen and underscores the feasibility of incorporating this approach as an adjunct to conventional antidepressant drug therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMood\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSignificant reductions in QIDS-SR16 scores were observed in the LIGHT group, whereas such reductions were not statistically significant in the non-LIGHT group (see Table 2 and Fig. 2). These findings suggest that daylight therapy was more effective to alleviate depressive symptoms in patients undergoing pharmacological treatment for depression. Improvements in the LIGHT group were particularly prominent in pre- and post-intervention global QIDS-SR16 scores, as well as in subcategories 2 (mood) and 3 (changes in weight and appetite), which were not observed in the non-LIGHT group.These results are consistent with findings from a previous study [11], which have indicated that exposure to daylight may contribute to the reduction of depression symptoms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDaylight, Sleep, and Depression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe LIGHT group exhibited significantly higher light levels of daytime light exposures, while showing considerably lower nighttime light intensity compared to the other groups (see Fig. 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe observed disparity in daylight exposure between the LIGHT and the HCtrl group may be attributed to most patients with depression being on sick leave, whereas healthy participants were working and may not experience direct light exposure at work (see Fig. 1)\u003c/p\u003e\n\u003cp\u003eIn addition of receiving higher light intensity during the day, the LIGHT group also demonstrated significantly lower nighttime light intensity compared to the other groups (see Fig. 2). These results align with prior investigations on light exposure and mental health [29], which identified a correlation between increased nocturnal light exposure and depressive symptoms in older individuals, highlighting the pivotal role of light in mental well-being. The lower levels of light intensity received by the LIGHT group and the higher day-night contrast may have contributed to the enhancement of mood.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis finding underscores the importance of maintaining a robust light day-night contrast, which has been shown to be crucial for regulating biological rhythms [30]. We have no definite explanation why patients in LIGHT group have lower exposure to light at night. We hypothesize this is the consequence that they sleep better, and their circadian rhythms are improved through a strength of melatonin circadian rhythm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubjective Sleep Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe know that there is a clear relationship between sleep disorders and depression [31]. However, it is challenging to elucidate whether sleep problems worsen mood or whether depression causes a disturbance in sleep quality. This is likely a bidirectional relationship mediated by chronodisruption [32].\u003c/p\u003e\n\u003cp\u003eThe results of this study showed that participants in the LIGHT and the non-LIGHT groups had high scores in the PSQI both pre-treatment (\u0026gt; 14) and post-intervention (\u0026gt; 11) as was also shown in previous studies [33]. After chronobiological intervention, scores obtained for the participants of the LIGHT group showed improvements in almost all components of sleep quality with significant differences for the daytime dysfunction component. Additionally, they increase their sleep duration (from 6-7 hours to \u0026gt; 7) and efficiency (from 65-74% to 75-84%) (see Table 4). These results are consistent with the M\u0026uuml;nch study, they found that light therapy can have a beneficial impact on sleep, improving sleep quality and duration. Non-LIGHT group showed a trend toward significant differences observed for sleep disturbances, although the magnitude of improvement was smaller compared to the LIGHT group.\u003c/p\u003e\n\u003cp\u003eRecent reviews have supported the notion that sleep problems in older adults predispose them to depressive states. Furthermore, studies have highlighted specific sleep durations (less than 7 hours or greater than 8-9 hours) as risk factors for depression [34].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective Sleep Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the LIGHT group, all parameters (PT, IS, RA, and CFI) that indicated better stability and adjustment, increased; in contrast, the IV decreased, indicating a lower variability of the circadian rhythm. Similar changes were obtained in the MA, indicating greater stability (see Table 3). However, we can only describe trends since no significant differences were obtained. For the non-LIGHT group, the trend towards better rhythm adjustment was less evident and, in some cases, as in the fragmentation of the rhythm (IV) was in the opposite direction (see Table 3). Finally, these results were important knowing greater within- and inter-day instability is associated with worse anxiety and depression symptoms [35].\u003c/p\u003e\n\u003cp\u003eA rigorous methodology was employed, utilizing multisensory records obtained from Kronowise\u003csup\u003e\u0026reg;\u003c/sup\u003e (followed by the extraction of objective sleep quality data using Actiwatch Activity and Sleep Analysis\u003csup\u003e\u0026reg;\u003c/sup\u003e 2001 Software). This approach allowed for the examination of various components of sleep quality, including sleep efficiency, sleep latency, percentage of immobility, percentage of mobility, and sleep fragmentation (see Table 4). This objective evaluation was consistent with the subjective one using the PSQI [17,18], providing comprehensive and reliable information on sleep variables.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations and future directions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study presented some limitations: 1) The sample size represents a limitation for the interpretation of the results. 2) There is no basal record of light exposure of the patients pre-intervention, 3) Controlling for covariates such as gender, education, and the use of table and smart phones minutes before going to bed, \u0026nbsp;4) The HCtrl group was evaluated only with KW6 pre-treatment, and 5) We studied only the short-term effect of daylight exposure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFuture research: 1) Enlarging the sample size to conduct an extensive study, and 2) Exploring the potential integration of chronobiological interventions, such as exposure to daylight, either as standalone therapy or as adjunctive treatment, into clinical practice guidelines for depression treatment and prevention in at-risk population, and 3) We believe that the involvement of nurses in this chronobiological intervention can make an important contribution to treatment and reduce the pressure of care.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn sum, this study provides: 1) Patients in the LIGHT group were significantly exposed to higher light intensity (amount) in the early hours of the morning than the non-LIGHT and the Control groups. The light day-night contrast was significantly higher in patients in the LIGHT group than in the non-LIGHT and the Control groups; 2) Depression symptoms measured with the QIDS-SR16 improved significantly in patients in the LIGHT group compared to the non-LIGHT group; 3) Subjective sleep quality measured with PSQI showed a non-statistically significant trend improvement in the LIGHT group after the intervention, and this was not the same for the non-LIGHT group; and 4) Objective sleep and circadian parameters showed a non-statistically significant trend improvement in the LIGHT group after the intervention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the work of the reviewers that contribute to the improvement of this report. Authors thanks the staff of \u0026ldquo;Mental Health Unit Cam\u0026iacute; de Jes\u0026uacute;s\u0026rdquo; for their help in the recruitment and management of participants. And we are grateful to all depressive patients and healthy controls for their kind and disinterested collaboration\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.A.R., participated in conceptualization, investigation, data curation, methodology, supervision, formal analysis, project administration, validation, resources, and visualization. M.C.N., participated in conceptualization, investigation, software, data curation, methodology, supervision, formal analysis, project administration, validation, resources, and visualization. A.R., participated in conceptualization, investigation, data curation, methodology, formal analysis, resources, and visualization. A.M., participated in conceptualization, investigation, software, data curation, methodology, project administration, resources, and visualization. F.C., participated in conceptualization, investigation, data curation, methodology, supervision, project administration, validation, resources, and visualization. All authors read and wrote the manuscript and approved it in its final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Research Commission of the University Hospital Son Espases (HUSE) within the call for research grants of HUSE 2020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants were given instructions about the purpose and risks of the study and were required to give written informed consent. The experimental procedure was approved by the Research Ethics Committee of Hiroshima university (No. 30-02, 30-03). This study was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eFunctional and Clinical Neurophysiology: Biological Rhythms and Language (NRL) group, University of the Balearic Islands (UIB), 07122, Palma, Spain . \u003csup\u003e2\u003c/sup\u003eHealth Research Institute of the Balearic Islands (IdISBa), 07010, Palma, Spain. \u003csup\u003e3\u003c/sup\u003eSon Espases University Hospital (HUSE), 07010, Palma, Spain. \u003csup\u003e4\u003c/sup\u003eNeuropsychology and Cognition Research Group, Department of Psychology, University of the Balearic Islands (UIB). \u003csup\u003e5\u003c/sup\u003eUniversity Institute for Research in Health Sciences (IUNICS), University of the Balearic Islands (UIB), 07122, Palma, Spain. \u003csup\u003e6\u0026nbsp;\u003c/sup\u003eUniversity College Alberta Gim\u0026eacute;nez-Comillas Pontifical University (CESAG-UP Comillas)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003eCorrespondence:
[email protected] (F.C.);
[email protected] (J.A.R)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican Psychiatric Association (APA). Gu\u0026iacute;a de consulta de los criterios diagn\u0026oacute;sticos del DSM-5\u003csup\u003e\u0026reg;\u003c/sup\u003e: Spanish edition of the desk reference to the diagnostic criteria from DSM-5\u003csup\u003e\u0026reg;\u003c/sup\u003e. American Psychiatric Pub. 2014.\u003c/li\u003e\n\u003cli\u003eVieta E, Alonso J, P\u0026eacute;rez-Sola V, et al. Epidemiology and costs of depressive disorder in Spain: the EPICO study. Eur Neuropsychopharmacol. 2021 Sep;50:93-103. https://doi.org/10.1016/j.euroneuro.2021.04.022\u003c/li\u003e\n\u003cli\u003eRoca M, Gili M, Garcia-Garcia M, et al. Prevalence and comorbidity of common mental disorders in primary care. J Affect Disord. 2009 Dec;119(1-3):52-8. https://doi.org/10.1016/j.jad.2009.03.014.\u003c/li\u003e\n\u003cli\u003eRush AJ, Bernstein IH, Trivedi MH, et al. 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Greater within- and between-day instability is associated with worse anxiety and depression symptoms. J Affect Disord. 2024 Jul 1;356:215-223. https://doi.org/10.1016/j.jad.2024.04.014.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Sociodemographic data with averages and standard deviations, percentages, and\u003cem\u003e\u0026nbsp;p\u003c/em\u003e-value.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"501\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Lt)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-LIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(non-Lt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Ctrl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-value\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLt-non-Lt\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-value\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLt-Ctrl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample size\u0026nbsp;(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e8 (72.72%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e8 (80%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e11 (64.71%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e3 (27.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e2 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e6 (35.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e49 (9.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e52 (10.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e50.11(8.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e10.36 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e11.5 (4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e16.47 (3.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLt, LIGHT group; non-Lt, non-LIGHT group; Ctrl, Control group; F, female; M, male\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;p-\u003c/em\u003evalue,\u003cem\u003e\u0026nbsp;p\u003c/em\u003e significance level: \u003cem\u003ep\u003c/em\u003e \u0026lt; .001 (high), \u003cem\u003ep\u003c/em\u003e \u0026lt; .01 (medium), \u003cem\u003ep\u003c/em\u003e \u0026lt; .05 (low).\u003c/p\u003e\n\u003cp\u003eLIGHT, group exposed to light; non-LIGHT, group with general recommendations for healthy habits; Control, group with a usual routine of activities\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue, \u003cem\u003ep\u003c/em\u003e significance level: \u003cem\u003ep\u003c/em\u003e \u0026lt; .001 (high), \u003cem\u003ep\u003c/em\u003e \u0026lt; .01 (medium), \u003cem\u003ep\u003c/em\u003e \u0026lt; .05 (low); \u003cem\u003ed\u003c/em\u003e de Cohen (Effect size), \u003cem\u003ed\u003c/em\u003e \u0026ge; .20 small effect, \u003cem\u003ed\u003c/em\u003e \u0026ge; .50 medium effect, \u003cem\u003ed\u0026nbsp;\u003c/em\u003e\u0026ge; .80 large effect, \u003cem\u003ed\u003c/em\u003e \u0026ge; 1.20 very large effect, \u003cem\u003ed\u003c/em\u003e \u0026ge; 2.0 effect largest (Cohen, 2016). Normative data with averages and standard deviations on time of exposure spent to different light intensities during the awake period: 1) morning from 08:00 to 15:50 hours, between 1000-10000 lux was of 45 (06) minutes, and 2) evening from 16:00 to 23:50 hours, between 1000-10000 lux was 34 (07) minutes, and the sleep period from 00:00 to 07:50 hours, \u0026lt; 10 lux was of 7 (.2) hours (Mart\u0026iacute;nez-Nicol\u0026aacute;s et al., 2018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eIndividual direct scores and averages (standard deviations) of QIDS-SR16 of the participants for the LIGHT and non-LIGHT groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQIDS-SR16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCODE\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePARTICIPANT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4133%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.5818%;\"\u003e\n \u003cp\u003e15.4 (4.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.1739%;\"\u003e\n \u003cp\u003e13.5 (6.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.2962%;\"\u003e\n \u003cp\u003e14.4 (5.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.5408%;\"\u003e\n \u003cp\u003e10.9 (4.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-LIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCODE\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePARTICIPANT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Week 1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeek 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp; 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2533%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2619%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.9078%;\"\u003e\n \u003cp\u003e15.20 (3.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9.4185%;\"\u003e\n \u003cp\u003e13.67 (5.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 8.5623%;\"\u003e\n \u003cp\u003e12.11 (4.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.2168%;\"\u003e\n \u003cp\u003e13 (6.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLIGHT, LIGHT group; non-LIGHT, non-LIGHT group; QIDS-SR 16, Quick Inventory of Depressive Symptomatology-Self Report\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eAverage scores and standard deviations of circadian parameters of peripheral temperature ((PT) and motor activity (MA) pre and post-intervention.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 566px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeripheral Temperature (\u0026ordm;C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMESOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u003cstrong\u003eRA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCFI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e32.54 (.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.44 (.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.003 (.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.34 (.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.59 (.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e33.22 (1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.49 (.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.002 (.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.32 (.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.60 (.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-LIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e31.89 (.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.45 (.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.002 (.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.21 (.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.57 (.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e32.31 (.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.45 (.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.004 (.003)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.26 (.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.57 (.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e32 (.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.51 (.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.002 (.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.42 (.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.64 (.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 566px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMotor Activity (3-axis MEMS accelerometer)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e52.37 (43.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.35 (.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.23 (.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.86 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.70 (.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e48.38 (38.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.44 (.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.23 (.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.89 (.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.73 (.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-LIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e63.67 (42.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.36 (.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.25 (.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.90 (.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.71 (.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e65.27 (48.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.41 (.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.25 (.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.89 (.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.7 (.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003cp\u003e(baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e71.27 (44.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e.42 (.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e.26 (.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e.87 (.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e.72 (.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLIGHT, LIGHT group; non-LIGHT, non-LIGHT group; Control, Control group; Pre, pre-treatment, Post, postintervention; PT, peripheral temperature; MA, motor activity; MESOR, Midline estimating statistic of rhythm; IS, inter-day stability; IV, intraday variability; RA, relative amplitude; CFI, circadian function index; Pre, pre-intervention, Post, post-intervention\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ep-\u003c/em\u003evalue showed no significant differences pre-post (all \u003cem\u003ep\u003c/em\u003e \u0026gt; .05). Normative data for the different circadian parameters are as follows: PT, [MESOR = 33.57 (.09), IS = .57 (.02), IV = .20 (.01), RA = .03 (.00), CFI = .50 (.01)]; MA, [MESOR = 27.64 (.56), IS = .59 (.01), IV = .71 (.02), RA =.68 (.01), CFI = .64 (.01)] (Mart\u0026iacute;nez-Nicol\u0026aacute;s et al., 2018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eAverage scores, standard deviations and percentages of the objective measures obtained from the KW6 data, more specifically the variable \u0026lsquo;Time in Movement\u0026rsquo; of the LIGHT, non-LIGHT and Control groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"603\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEfficiency\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLatency\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e% immobility\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e% mobility\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFragmentation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e73.43 (8.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e54 min.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e76.15% (9.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e23.85 (10.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e62.86 (22.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e73.23 (9.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e32 min.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e75.61% (9.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e24.39 (9.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e64.30 (19.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-LIGHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e71.27 (11.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e67 min.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e79.35% (11.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e20.65 (11.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e53.59 (22.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e71.44 (13.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e47 min.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e78.18% (8.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e21.82 (8.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e57.27 (16.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003cp\u003e(baseline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e82.82 (4.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e19 min.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e82.13% (4.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e17.87 (4.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e50.89 (13.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLIGHT, LIGHT group; non-LIGHT, non-LIGHT group; Control, Control group; Pre, pre-intervention, Post, post-intervention; min., minutes; %, percentages\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"antidepressant drugs, bright light therapy, circadian rhythms, daylight, depression, mood, sleep quality","lastPublishedDoi":"10.21203/rs.3.rs-7293619/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7293619/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCurrent research has shown that depressive symptoms are associated with sleep disturbances and misalignment of circadian rhythms. Thus, a chronobiological intervention associated with the usual antidepressant treatment on depressive symptoms may improve depressive symptoms as long with sleep quality, and circadian rhythms in patients with depression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The feasibility experimental study was carried out with a total of 38 participants: 21 outpatients suffering from a non-seasonal major depressive disorder (MDD) and 17 healthy volunteers (general population). Twenty-one patients were randomly assigned to two groups: 11 patients received a chronobiological intervention: daylight exposure treatment for 14 days in conjunction with pharmacological treatment (LIGHT group), while 10 patients received only pharmacological treatment (LIGHT group). Depressive severity at the inclusion was assessed with the Montgomery-Asberg Depression Scale (MADRS), and the International Neuropsychiatric Interview (MINI) was used to exclude comorbid psychiatric disorders. The evolution of depressive symptoms was assessed using the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16). Patients' sleep was evaluated using, Munich Chronotype Questionnaire and with Pittsburgh Sleep Quality Index (PSQI) and sleep agenda. In addition, circadian parameters were assessed using Kronowise\u003csup\u003e®\u003c/sup\u003e device (KW6), and target sleep quality indices were calculated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The intervention combining daylight exposure with pharmacological treatment demonstrated significant improvements in depressive symptoms. There was a noticeable trend towards subjective improvement in sleep quality. Data registered with the KW6 device indicated an improvement in motor activity and peripheral temperature rhythms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Depressive patients undergoing psychopharmacological treatment, who received a specific instruction to increase their exposure to daylight, improved their depressive symptoms, sleep quality, and circadian rhythms.\u003c/p\u003e","manuscriptTitle":"Benefits of exposure to morning daylight on sleep, circadian rhythms, and symptoms of depression","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-06 09:40:39","doi":"10.21203/rs.3.rs-7293619/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a5461782-ef70-4fa6-920e-084a7c3fe12a","owner":[],"postedDate":"August 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-30T05:53:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-06 09:40:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7293619","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7293619","identity":"rs-7293619","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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