Relationship between sun exposure and seasonal affective disorder symptoms in rural older people with different personalities: a cross-sectional study.

OBJECTIVES: Evidence suggests that environmental support, personality traits, and psychological factors can influence seasonal changes in human mood and behavior, particularly in rural middle-aged women and older people. This study aimed to quantify the associations between personality traits, seasonal affective disorder symptoms, and sun exposure in rural older people. METHODS: This study is a cross-sectional analytical study, the participants were 300 rural older persons from 12 natural villages and 5 geriatric service centers in 4 different cities in Jiangxi Province, China. The Eysenck Personality Questionnaire (EPQ), the Personal Inventory of Depression and Seasonal Affective Disorder (PIDS-SA-SimpChi), and the Sunlight Exposure Scale were used to conduct follow-up interviews throughout the year. Spatial analysis was performed using ArcGIS and Geodetic Probes. The data were analyzed using SPSS 21 and Amos 23.0 mediated models. RESULTS: Rural older people with low sun exposure exhibited higher personality trait scores (p < 0.001). Personality traits were directly associated with seasonal affective disorder symptoms(p < 0.01); Sun exposure mediated this effect in rural older people (p < 0.05). CONCLUSION: High-scoring personalities are more typical of rural older people with low sun exposure, and there is a greater risk of emotional and behavioral instability. Latitudinal differences are not a determinant of SAD. Increased sun exposure is associated with symptom relief. The promotion of light therapy devices in rural areas with low sunlight is warranted.

Exploring perceived relationships between weather, climate and mental health: biometeorological perspectives of healthcare practitioners.

Over the last decade, there has been an increase in research examining the influence of weather and climate in mental health caseloads. Variations in temperature, sunshine hours, cloud cover, precipitation and extreme weather events have been statistically linked to diagnoses and increases in hospital admissions for several mental health conditions. This study aimed to explore whether mental health practitioners perceive there to be a link between mental health and daily, seasonal, or inter-annual shifts in various climate variables in South Africa, and the timing and causal mechanisms thereof. Semi-structured interviews were conducted with 50 practicing healthcare practitioners, and the data was analysed using thematic analysis. The findings of this research show that all 50 participants were aware of the link between weather, climate and mental health, primarily through their awareness of seasonal affective disorder. Of the 50 participants, 38 participants could explain the aetiology of seasonal affective disorder. Participants perceived sunlight and temperature to exert an influence on mental health. All 50 participants perceived exposure to sunlight to exert a positive influence on several mental health conditions. Of the 50 participants, 36 participants perceived increases in temperature to exert an adverse effect on mental health symptomology. A minority of 11 participants perceived precipitation to influence mental health conditions such as seasonal affective disorder, bipolar disorder, and substance abuse disorder. Participants' perceptions of the influence of precipitation on mental health provided a unique potential explanation of this relationship, which, at the time of writing, has not been discussed in formal research.

Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography.

BACKGROUND: Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. METHODS: Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females). RESULTS: No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT. CONCLUSIONS: In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. CLINICALTRIALS.GOV IDENTIFIER: NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).

Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

BACKGROUND: Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. METHODS: Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. RESULTS: In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). CONCLUSION: Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Light Therapy for Adolescent Depression: A Scoping Review.

PURPOSE: Depressive disorders in adolescents are a major health concern associated with developmental, social, and educational impairment. Bright Light Therapy (BLT) is a feasible and effective treatment for depressive disorders in adults, but few controlled trials have been conducted with children or adolescents. This scoping review focuses on the current state of knowledge for BLT in the treatment of adolescent depression. We reviewed the literature for novel data and methodologic approaches using BLT and pediatric and young adult populations. RECENT FINDINGS: BLT is a tolerable treatment with few side effects. However, there is a marked lack of well-powered studies to support BLT as a treatment for depressive disorders in adolescent populations. Given evidence of tolerability and positive treatment effect on depression in the adult literature, research is needed to establish the efficacy, feasibility, and acceptability of BLT in adolescents.

Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior.

Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.

Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions. METHODS: We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range). RESULTS: Of 582 articles retrieved, we included nine RCTs (n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], -1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = -0.11; 95% CI, -2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated. CONCLUSIONS: The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.

Sunshine on my shoulders makes me happy. . . especially if I'm less intelligent: how sunlight and intelligence affect happiness in modern society.

The savanna theory of happiness proposes that, due to evolutionary constraints on the human brain, situations and circumstances that would have increased our ancestors' happiness may still increase our happiness today, and those that would have decreased their happiness then may still decrease ours today. It further proposes that, because general intelligence evolved to solve evolutionarily novel problems, this tendency may be stronger among less intelligent individuals. Because humans are a diurnal species that cannot see in the dark, darkness always represented danger to our ancestors and may still decrease our happiness today. Consistent with this prediction, the analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data shows that exposure to sunlight was associated with happiness but the association was significantly weaker among more intelligent individuals.

Bipolar II disorder has the highest prevalence of seasonal affective disorder in early-onset mood disorders: Results from a prospective observational cohort study.

BACKGROUND: Many mood disorder patients experience seasonal changes in varying degrees. Studies on seasonality have shown that bipolar disorder has a higher prevalence rate in such patients; however, there is limited research on seasonality in early-onset mood disorder patients. This study estimated the prevalence of seasonality in early-onset mood disorder patients, and examined the association between seasonality and mood disorders. METHODS: Early-onset mood disorder patients (n = 378; 138 major depressive disorder; 101 bipolar I disorder; 139 bipolar II disorder) of the Mood Disorder Cohort Research Consortium and healthy control subjects (n = 235) were assessed for seasonality with Seasonality Pattern Assessment Questionnaire (SPAQ). RESULTS: A higher global seasonality score, an overall seasonal impairment score, and the prevalence of seasonal affective disorder (SAD) and subsyndromal SAD showed that mood disorder subjects had higher seasonality than the healthy subjects. The former subject group had a significantly higher mean overall seasonal impairment score than the healthy subjects (p < .001); in particular, bipolar II disorder subjects had the highest prevalence of SAD, and the diagnosis of bipolar II disorder had significantly higher odds ratios for SAD when compared to major depression and bipolar I disorder (p < .05). CONCLUSIONS: Early-onset mood disorders, especially bipolar II disorder, were associated with high seasonality. A thorough assessment of seasonality in early-onset mood disorders may be warranted for more personalized treatment and proactive prevention of mood episodes.

Seasonal sensitivity and psychiatric morbidity: study about seasonal affective disorder.

BACKGROUND: Seasonal Affective Disorder is a recurrent depressive disorder which usually begins in the fall/winter and enters into remission in the spring/summer, although in some cases may occur in the summer with remission in the autumn-winter. In this study the authors evaluated the association between seasonal changes in mood and behavior with psychiatric disturbance. METHOD: Descriptive, cross-sectional study. Participants, students attending higher education and vocational courses (N = 324), were evaluated with the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Screening Scale for Mental Health (ER80). RESULTS: Among the respondents, 12.7% showed seasonal affective disorder (SAD), 29.0% showed subsyndromal seasonal affective disorder (s-SAD) and 58.3% did not show significant seasonal affective symptomatology. As for psychiatric morbidity, 36.6% of subjects with SAD and 13.8% of those with s-SAD were considered "psychiatric cases" whereas for subjects without SAD this value was only 3.2%. CONCLUSIONS: There is a statistically significant association between psychiatric morbidity and seasonal affective disorder. This association corroborates the importance of the Seasonal Pattern Assessment Questionnaire in screening for seasonal fluctuations in mood and behavior related disorders, and the clinical need for recognition of these conditions, particularly associated suffering and disabilities.

Bimodal effects of sunlight on major depressive disorder.

BACKGROUND: Seasonal patterns in the effect of sunlight on depression, where depression decreases when sunlight increases, have been observed in previous studies. In this study, we demonstrate a bimodal effect of sunlight on depression - short-term increases in sunlight increase depression and long-term increases in sunlight decrease depression. The analysis showed that the significant effect of sunlight is temporary and appears only when seasonal changes are severe within a given year. METHODS: We analyzed approximately 530,000 cases where patients visited hospital for depression in Korea from January 1 to December 31, 2016. We measured the daily average amount of sunlight and daily sunlight for the 30 days previous to the day of measurement using data from 96 weather stations. To analyze the effect of sunlight, several climatic variables and local dummies were added to the negative binomial model, and the period in which the effect of sunlight was significant was derived as a term of the interaction between the month variable and sunlight. RESULTS: When the average effects of climatic factors such as temperature, precipitation, and humidity were removed, the number of cases of depression increased when the daily average amount of sunlight increased [IRR = 1.024 (95% CI: 1.009 to 1.039)]; this effect was significant only in January and May. The number of cases of depression decreased with higher daily average sunlight for the previous 30 days increasing [IRR = 0.917 (95% CI: 0.892 to 0.944)], and this effect was significant only in January, March, and May. CONCLUSIONS: The effect of sunlight on depression appears in both the short and long terms, but the effect is significant only for limited periods. The data examined in this study supports a pattern where short-term daily sunlight increases depression and daily sunlight for the previous 30 days decreases depression.

Light therapy for seasonal affective disorder in visual impairment and blindness - a pilot study.

OBJECTIVE: Seasonal and non-seasonal depression are prevalent conditions in visual impairment (VI). We assessed the effects and side effects of light therapy in persons with severe VI/blindness who experienced recurrent depressive symptoms in winter corresponding to seasonal affective disorder (SAD) or subsyndromal SAD (sSAD). RESULTS: We included 18 persons (11 with severe VI, 3 with light perception and 4 with no light perception) who met screening criteria for sSAD/SAD in a single-arm, assessor-blinded trial of 6 weeks light therapy. In the 12 persons who completed the 6 weeks of treatment, the post-treatment depression score was reduced (p < 0.001), and subjective wellbeing (p = 0.01) and sleep quality were improved (p = 0.03). In 6/12 participants (50%), the post-treatment depression score was below the cut-off set for remission. In four participants with VI, side effects (glare or transiently altered visual function) led to dropout or exclusion. CONCLUSION: Light therapy was associated with a reduction in depressive symptoms in persons with severe VI/blindness. Eye safety remains a concern in persons with residual sight.

Converging evidence that short-active photoperiod increases acetylcholine signaling in the hippocampus.

Seasonal variations in environmental light influence switches between moods in seasonal affective disorder (SAD) and bipolar disorder (BD), with depression arising during short active (SA) winter periods. Light-induced changes in behavior are also seen in healthy animals and are intensified in mice with reduced dopamine transporter expression. Specifically, decreasing the nocturnal active period (SA) of mice increases punishment perseveration and forced swim test (FST) immobility. Elevating acetylcholine with the acetylcholinesterase inhibitor physostigmine induces depression symptoms in people and increases FST immobility in mice. We used SA photoperiods and physostigmine to elevate acetylcholine prior to testing in a probabilistic learning task and the FST, including reversing subsequent deficits with nicotinic and scopolamine antagonists and targeted hippocampal adeno-associated viral administration. We confirmed that physostigmine also increases punishment sensitivity in a probabilistic learning paradigm. In addition, muscarinic and nicotinic receptor blockade attenuated both physostigmine-induced and SA-induced phenotypes. Finally, viral-mediated hippocampal expression of human AChE used to lower ACh levels blocked SA-induced elevation of FST immobility. These results indicate that increased hippocampal acetylcholine neurotransmission is necessary for the expression of SA exposure-induced behaviors. Furthermore, these studies support the potential for cholinergic treatments in depression. Taken together, these results provide evidence for hippocampal cholinergic mechanisms in contributing to seasonally depressed affective states induced by short day lengths.

The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Bright light therapy (BLT) has been used as a treatment for seasonal affective disorder (SAD) for over 30 years. This meta-analysis was aimed to assess the efficacy of BLT in the treatment of SAD in adults. METHOD: We performed a systematic literature search including randomized, single- or double-blind clinical trials investigating BLT (≥1,000 lx, light box or light visor) against dim light (≤400 lx) or sham/low-density negative ion generators as placebo. Only first-period data were used from crossover trials. The primary outcome was the post-treatment depression score measured by validated scales, and the secondary outcome was the rate of response to treatment. RESULTS: A total of 19 studies finally met our predefined inclusion criteria. BLT was superior over placebo with a standardized mean difference of -0.37 (95% CI: -0.63 to -0.12) for depression ratings (18 studies, 610 patients) and a risk ratio of 1.42 (95% CI: 1.08-1.85) for response to active treatment (16 studies, 559 patients). We found no evidence for a publication bias, but moderate heterogeneity of the studies and a moderate-to-high risk of bias. CONCLUSIONS: BLT can be regarded as an effective treatment for SAD, but the available evidence stems from methodologically heterogeneous studies with small-to-medium sample sizes, necessitating larger high-quality clinical trials.

Ethics analysis of light and vitamin D therapies for seasonal affective disorder.

OBJECTIVE: The aim of this ethics analysis was to highlight the overt and covert value issues with regard to two health technologies (light therapy and vitamin D therapy), the health technology assessment (HTA) and the disease of seasonal affective disorder (SAD). The present ethics analysis served as a chapter of a full HTA report that aimed to assist decision makers concerning the two technologies. METHOD: First, we used the revised Socratic approach of Hofmann et al. to build overarching topics of ethical issues, and then, we conducted a hand search and a comprehensive systematic literature search on between 12 and 14 February 2019 in seven databases. RESULTS: The concrete ethical issues found concerned vulnerability of the target population and the imperative to treat depressive symptoms for the sake of preventing future harm. Further disease-related ethical issues concerned the questionable nature of SAD as a disease, autonomy, authenticity, and capacity for decision making of SAD patients, and the potential stigma related to the underdiagnosis of SAD, which is contrasted with the concern over unnecessary medicalization. Regarding the interventions and comparators, the ethical issues found concerned their benefit-harm ratios and the question of social inequality. The ethical issues related to the assessment process relate to the choice of comparators and the input data for the selected health economic studies. CONCLUSIONS: The concrete ethical issues related to the interventions, the disease, and the assessment process itself were made overt in this ethics analysis. The ethics analysis provided an (additional) value context for making future decisions regarding light and vitamin D therapies.

Seasonal variation in antidepressant prescriptions, environmental light and web queries for seasonal affective disorder.

The state of an individual's mental health depends on many factors. Determination of the importance of any particular factor within a population needs access to unbiased data. We used publicly available data-sets to investigate, at a population level, how surrogates of mental health covary with light exposure. We found strong seasonal patterns of antidepressant prescriptions, which show stronger correlations with day length than levels of solar energy. Levels of depression in a population can therefore be determined by proxy indicators such as web query logs. Furthermore, these proxies for depression correlate with day length rather than solar energy.Declaration of interestNone.

Light as a modulator of emotion and cognition: Lessons learned from studying a diurnal rodent.

Light profoundly affects the behavior and physiology of almost all animals, including humans. One such effect in humans is that the level of illumination during the day positively contributes to affective well-being and cognitive function. However, the neural mechanisms underlying the effects of daytime light intensity on affect and cognition are poorly understood. One barrier for progress in this area is that almost all laboratory animal models studied are nocturnal. There are substantial differences in how light affects nocturnal and diurnal species, e.g., light induces sleep in nocturnal mammals but wakefulness in diurnal ones, like humans. Therefore, the mechanisms through which light modulates affect and cognition must differ between the chronotypes. To further understand the neural pathways mediating how ambient light modulates affect and cognition, our recent work has developed a diurnal rodent model, the Nile grass rat (Arvicanthis niloticus), in which daytime light intensity is chronically manipulated in grass rats housed under the same 12:12 hour light/dark cycle. This simulates lighting conditions during summer-like bright sunny days vs. winter-like dim cloudy days. Our work has revealed that chronic dim daylight intensity results in higher depression- and anxiety-like behaviors, as well as impaired spatial learning and memory. Furthermore, we have found that hypothalamic orexin is a mediator of these effects. A better understanding of how changes in daytime light intensity impinge upon the neural substrates involved in affect and cognition will lead to novel preventive and therapeutic strategies for seasonal affective disorder, as well as for non-seasonal emotional or cognitive impairments associated with light deficiency.

Seasonal fluctuations in psychological distress amongst women diagnosed with early breast cancer receiving radiotherapy.

OBJECTIVE: Seasonal effects on patients diagnosed with depression/anxiety-related psychological disorders have varying impacts on symptom severity. Seasonal changes in psychological distress may be due to decreased daylight exposure during the fall/winter seasons. Patients receiving radiation therapy (RT) for early-stage invasive breast cancer (EIBC) are at high risk for developing depressive symptoms. Of interest is whether seasonal factors influence the psychological symptoms of patients being treated for EIBC. METHODS: Patients treated with RT for EIBC between January 2011 and June 2017 were identified. Patients who completed at least one Edmonton Symptom Assessment Scale (ESAS-r) pre-RT and post-RT were included in our analysis. Patients receiving RT during the autumn and winter (November-March) were compared with patients receiving RT during the spring and summer (April-August). Psychological distress was evaluated based on patient-reported depression, anxiety, and overall wellbeing on the ESAS-r. Data on systemic treatment and radiation were extracted from existing databases. RESULTS: Eight-four patients treated with RT in spring/summer and 102 patients treated with RT in autumn/winter were included. Patients receiving RT during spring/summer had better wellness score prior to RT, compared with those receiving RT during winter/autumn (P = .03). However, patients receiving RT in the spring/summer had worse symptom trajectories across three domains of depression, anxiety, and wellbeing (P = .03, P = .008, and P < .0001, respectively). CONCLUSIONS: Seasonality influenced the symptoms reported by patients with EIBC receiving RT. Future studies are needed to understand when during treatment patients are at highest risk for psychological distress and how seasonality may influence high-risk periods.

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.

Decreased retinal sensitivity in depressive disorder: a controlled study.

OBJECTIVE: To compare pupil responses in depressed patients with a seasonal pattern, depressed patients without a seasonal pattern and healthy controls as a function of daylight hours on the testing day. METHOD: Patients suffering from a major depressive episode were included in wintertime. The pupil light reflex was measured at inclusion and in the following summer using a binocular pupillometer. A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was used to assess rod, cone and melanopsin-containing intrinsic photosensitive retinal ganglion cell input to the pupil reflex. RESULTS: The mean group pupil responses associated with a melanopsin-mediated sustained pupil response at 400 lux blue light were significantly reduced in the depressed subjects (N = 39) as compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a reduction in number of daylight hours was significantly associated with a reduction in sustained pupil response (P = 0.007). All groups showed an equal effect of daylight hours on the melanopsin-mediated sustained pupil response. CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light is reduced in depressed patients. These results further emphasize the interaction of light exposure with depression.