Developing a clinical decision tool based on electroretinogram to monitor the risk of severe mental illness.

BACKGROUND: We have shown that electroretinograms can discriminate between patients with severe mental illness (SMI) and healthy controls in previous studies. We now intend to enhance the development and clinical utility of ERG as a biological tool to monitor the risk of SMI. METHODOLOGY: A sample of 301 SMI patients (bipolar disorder or schizophrenia) and 200 controls was first split into a training (N = 401) and testing dataset (N = 100). A logistic regression using ERG was modeled in the training data, while external validation and discriminative ability were assessed in the testing data. A decision curve analysis was used to test clinical usefulness. Moreover, the identification of thresholds of uncertainty based on the two-graph ROC and the interval of uncertainty was used to enhance prediction. RESULTS: The discriminative assessment of the ERG showed very high sensitivity (91%) and specificity (89%) after considering uncertainty levels. Furthermore, for prediction probabilities ranging from 0.14 to 0.95 in the testing data, the net benefit of using our ERG model to decide whether to intervene or not exceeded that of never or always intervening. CONCLUSION: The ERG predicted SMI risk with a high level of accuracy when uncertainty was accounted for. This study further supports the potential of ERG to become a useful clinical decision tool to decide the course of action for subjects at risk of SMI. However, further investigation is still needed in longitudinal studies to assess the external validity of the instrument.

Loss of Bmi1 causes anomalies in retinal development and degeneration of cone photoreceptors.

Retinal development occurs through the sequential but overlapping generation of six types of neuronal cells and one glial cell type. Of these, rod and cone photoreceptors represent the functional unit of light detection and phototransduction and are frequently affected in retinal degenerative diseases. During mouse development, the Polycomb group protein Bmi1 is expressed in immature retinal progenitors and differentiated retinal neurons, including cones. We show here that Bmi1 is required to prevent post natal degeneration of cone photoreceptors and bipolar neurons and that inactivation of Chk2 or p53 could improve but not overcome cone degeneration in Bmi1(-/-) mice. The retinal phenotype of Bmi1(-/-) mice was also characterized by loss of heterochromatin, activation of tandem repeats, oxidative stress and Rip3-associated necroptosis. In the human retina, BMI1 was preferentially expressed in cones at heterochromatic foci. BMI1 inactivation in human embryonic stem cells was compatible with retinal induction but impaired cone terminal differentiation. Despite this developmental arrest, BMI1-deficient cones recapitulated several anomalies observed in Bmi1(-/-) photoreceptors, such as loss of heterochromatin, activation of tandem repeats and induction of p53, revealing partly conserved biological functions between mouse and man.

Evaluation of the effects of blue-enriched white light on cognitive performance, arousal, and overall appreciation of lighting.

Introduction: Light's non-visual effects on the biological clock, cognitive performance, alertness, and mental health are getting more recognized. These are primarily driven by blue light, which triggers specific retinal cells containing melanopsin. Traditionally, research on light has relied on correlated color temperature (CCT) as a metric of its biological influence, given that bluer light corresponds to higher Kelvin values. However, CCT proves to be an inadequate proxy of light's biological effects. A more precise metric is melanopic Equivalent Daylight Illuminance (mel-EDI), which aligns with melanopsin spectrum. Studies have reported positive cognitive impacts of blue-enriched white light. It's unclear if the mixed results are due to different mel-EDI levels since this factor wasn't assessed. Method: Given recent recommendations from experts to aim for at least 250 mel-EDI exposure daily for cognitive benefits, our aim was to assess if a 50-minute exposure to LED light with 250 mel-EDI could enhance concentration and alertness, without affecting visual performance or comfort compared to conventional lighting producing around 150 mel-EDI. To ensure mel-EDI's impact, photopic lux levels were kept constant across conditions. Conditions were counterbalanced, parameters included subjective sleepiness (KSS; Karolinska Sleepiness Scale), concentration (d2-R test), visual performance (FrACT; Freiburg Visual Acuity and Contrast Test), general appreciation (VAS; Visual Analogous Scale), preferences and comfort (modified OLS; Office Lighting Survey). Results: The experimental light significantly reduced sleepiness (p = 0.03, Cohen's d = 0.42) and also decreased contrast sensitivity (p = 0.01, Cohen's d = 0.50). The conventional light was found to be more comfortable (p = 0.002, Cohen's d = 0.62), cheerful (p = 0.02, Cohen's d = 0.46) and pleasant (p = 0.005, Cohen's d = 0.55) while the experimental light was perceived as brighter (p = 0.004, Cohen's d = 0.58) and tended to be more stimulating (p = 0.10). Notably, there was a preference for conventional lighting (p = 0.004, Cohen's d=0.56) and concentration was equally improved in both conditions. Discussion: Despite the lack of further improvement in concentration from exposure to blue-enriched light, given the observed benefits in terms of vigilance, further research over an extended period would be justified. These findings could subsequently motivate cognitive optimization through lighting for workers that would benefit from artificial lighting such as in northern regions.

Evaluation of electroretinography (ERG) parameters as a biomarker for ADHD.

BACKGROUND: The retina is recognized as an accessible part of the brain due to their common embryonic origin. The electroretinogram (ERG) has proven to be a valuable tool for detecting schizophrenia and bipolarity. We therefore investigated its ability to detect ADHD. METHODS: The cone and rod luminance response functions of the ERG were recorded in 26 ADHD subjects (17 women and 9 men) and 25 controls (16 women and 9 men). RESULTS: No significant differences were found between the mixed groups, but sexual dysmorphia was observed in the significant results. In males, a significant prolonged cone a-wave latency was observed in the ADHD group. In females, we observed a significant decrease in the cone a- and b-wave amplitudes and a trend for a prolonged cone b-wave latency as well as a higher scotopic mixed rod-cone a-wave in the ADHD group. CONCLUSION: The data obtained in this study show the potential of the ERG to detect ADHD, warranting further large-scale studies.

A Blue-Enriched Light Intervention Counteracts the Alertness Decrement Among Mine Workers on Extended 12-Hour Night Shift Periods.

OBJECTIVE: The aim of the study is to assess whether a blue-enriched light intervention improves nocturnal alertness and daytime sleep of night workers. METHODS: Thirteen miners performing 12-hour night shifts for 12 consecutive nights were exposed to a baseline and a blue-enriched light condition. All subjects wore an actigraph and completed a Psychomotor Vigilance Task at the beginning and at the end of each shift. Data were analyzed with linear mixed models. RESULTS: In the blue-enriched light condition, the daily increase in median reaction time (RT), mean RT, slowest 10% of RT, and fastest 10% of RT was lower than that observed in the baseline condition between day 1 and 12 ( P ≤ 0.05). CONCLUSIONS: The addition of blue-enriched light during a long period of extended night shifts counteracts most of the daily decline in nocturnal alertness observed in the standard lighting condition, irrespectively of sleep duration and sleep efficiency.

Imagery datasets for photobiological lighting analysis of architectural models with shading panels.

This paper describes eight imagery datasets including around 12000 images grouped in 1220 sets. The images were captured inside an architectural model aimed at exploring the impact of shading panels on photobiological lighting parameters. The architectural model represents a generic space at 1:10 scale with a single side fully glazing façade used to install shading panels. The datasets present interior lighting conditions under different shading configurations in terms of surface colors and glossiness, horizontal and vertical orientations and upwards, downwards, and left/right inclinations of panels, V-shape opening, low to high densities, and top and bottom positions at the window. The experiments of shading panel configurations were conducted under four to six different exterior overcast daylighting conditions simulated with very cool to very warm color temperatures and high to low intensities inside an artificial sky chamber. The datasets include bracketed low dynamic range (LDR) images which enable generating high dynamic range (HDR) images for photobiological lighting evaluations. Images were captured from the side and back viewpoints inside the model by using Raspberry Pi camera modules mounted with fisheye lenses. The datasets are reusable and useful for architects, lighting designers, and building engineers to study the impact of architectural variables and shading panels on photobiological lighting conditions in space. The datasets will also be interesting for computer vision specialists to run machine learning techniques and train artificial intelligence for architectural applications. The datasets are partially used in Parsaee, et al. [1]. The datasets are compiled as part of a doctoral dissertation in architecture at Laval University authored by Mojtaba Parsaee [2]. The datasets are shared through two Mendeley data repositories [3,4].

For a structured response to the psychosocial consequences of the restrictive measures imposed by the global COVID-19 health pandemic: the MAVIPAN longitudinal prospective cohort study protocol.

INTRODUCTION: The COVID-19 pandemic and associated restrictive measures have caused important disruptions in economies and labour markets, changed the way we work and socialise, forced schools to close and healthcare and social services to reorganise. This unprecedented crisis forces individuals to make considerable efforts to adapt and will have psychological and social consequences, mainly on vulnerable individuals, that will remain once the pandemic is contained and will most likely exacerbate existing social and gender health inequalities. This crisis also puts a toll on the capacity of our healthcare and social services structures to provide timely and adequate care. The MAVIPAN (Ma vie et la pandémie/ My Life and the Pandemic) study aims to document how individuals, families, healthcare workers and health organisations are affected by the pandemic and how they adapt. METHODS AND ANALYSIS: MAVIPAN is a 5-year longitudinal prospective cohort study launched in April 2020 across the province of Quebec (Canada). Quantitative data will be collected through online questionnaires (4-6 times/year) according to the evolution of the pandemic. Qualitative data will be collected with individual and group interviews and will seek to deepen our understanding of coping strategies. Analysis will be conducted under a mixed-method umbrella, with both sequential and simultaneous analyses of quantitative and qualitative data. ETHICS AND DISSEMINATION: MAVIPAN aims to support the healthcare and social services system response by providing high-quality, real-time information needed to identify those who are most affected by the pandemic and by guiding public health authorities' decision making regarding intervention and resource allocation to mitigate these impacts. MAVIPAN was approved by the Ethics Committees of the Primary Care and Population Health Research Sector of CIUSSS de la Capitale-Nationale (Committee of record) and of the additional participating institutions. TRIAL REGISTRATION NUMBER: NCT04575571.

Atypical pattern of rod electroretinogram modulation by recent light history: a possible biomarker of seasonal affective disorder.

Our goal was to challenge both normal controls and patients with seasonal affective disorders (SAD) to various light histories and then measure their retinal response modulation using the electroretinogram (ERG) in both winter and summer. In winter and summer, 11 normal controls and 12 SAD patients were exposed to three different light conditions for 1 h (10,000, 100 and 5 lux) followed by an ERG. Groups showed similar ERG amplitudes in the 100 lux condition. Compared with the 100-lux condition, in controls, the ERG response was significantly increased in the 5-lux condition; in SAD, it was significantly decreased in the 10,000-lux condition. This pattern was present in both seasons. This is the first time a retinal response modulation anomaly has been observed in SAD patients in both the depressed and euthymic states. Retinal response modulation may represent an interesting biomarker of the disease for future research.

Timely use of in-car dim blue light and blue blockers in the morning does not improve circadian adaptation of fast rotating shift workers.

Circadian adaptation to night work usually does not occur in naturalistic conditions, largely due to exposure to low levels of light during the night and light in the morning on the way home. This leads to circadian misalignment, which has documented deleterious effects on sleep and functioning during waking hours. Chronic circadian misalignment is also being increasingly associated with long-term health comorbidities. As the circadian system is mostly sensitive to short wavelengths (i.e., blue light) and less sensitive to long wavelengths (i.e., red light), shaping light exposure in a "wavelength-wise" manner has been proposed to promote partial adaptation to night shifts, and, therefore, alleviate circadian rhythms disruption. This report presents results from two cross-over designed studies that aimed to investigate the effects of three different light conditions on circadian phase, sleepiness, and alertness of police patrol officers on a rotating shift schedule. The first study took place during summer (n = 15) and the second study (n = 25) during winter/early spring. In both studies, all participants went through three conditions composed of four consecutive night shifts: 1) in-car dim blue light exposure during the night shift and wearing of blue-blocking glasses (BBG) in the morning after 05:00 h; 2) in-car red light exposure during the night shift and wearing of BBG in the morning after 05:00 h; 3) a control condition with no intervention. To assess circadian phase position, salivary melatonin was collected hourly the night before and the night after each condition. Sleep was monitored by wrist actigraphy. Also, a 10-min Psychomotor Vigilance-Task was administered at the beginning and end of each night shift and the Karolinska Sleepiness Scale was completed every 2 h during each night shift. In the summer study, no difference was found in alertness and sleepiness between conditions. Participants though exhibited greater (≈3 h) phase delay after four consecutive night shifts in the control condition (in which morning light exposure was expected to prevent phase delay) than after the blue and red conditions (≈2 h) (in which wearing BBG were expected to promote phase delay). In the second study performed during the winter/early spring, a comparable ≈2 h phase delay was found in each of the three conditions, with no difference in alertness and sleepiness between conditions. In conclusion, participants in both studies exhibited modest phase delay across the four night shifts, even during the control conditions. Still, re-entrainment was not fast enough to produce partial circadian adaptation after four night shifts. A greater number of consecutive night shifts may be necessary to produce enough circadian alignment to elicit benefits on sleepiness and alertness in workers driving a motorized vehicle during night shifts. In-car dim blue light exposure combined with the wearing of BBG in the morning did not show the expected benefits on circadian adaptation, sleepiness, and alertness in our studies. Higher levels of light may be warranted when implementing light intervention in a motorized vehicle setting.

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice.

Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG). In this study, cone and rod ERGs were performed in male and female C57BL/6 mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Our results suggest that CSDS reduces the amplitude of both oscillatory potentials and a-waves in the rods of resilient but not susceptible males. Similar effects were revealed following the analysis of the cone b-waves, which were faster after CSDS in resilient mice specifically. In females, rod ERGs revealed age-related changes with no change in cone ERGs. Finally, our analysis suggests that baseline ERG can predict with an efficacy up to 71% the expression of susceptibility and resilience before stress exposition in males and females. Overall, our findings suggest that retinal activity is a valid biomarker of stress response that could potentially serve as a tool to predict whether males and females will become susceptible or resilient when facing CSDS.

[When a season means depression]. / Quand la saison devient synonyme de dépression.

Although becoming more and more recognized among physicians and psychiatrists the etiology of seasonal affective disorder (SAD) remains unclear. Indeed, the only incontestable fact is the close link between the decrease in sunlight occurring during fall and winter and the onset of depressive symptoms. But why does this seasonal decrease in the amount of light trigger a depression in some individuals while not affecting others? Why and how has sun exposure such an impact on brain-mood regulation? This review intends to shed some light on the main neurochemical hypotheses that have been advanced for the past 25 years. While several hypotheses have been advanced to explain SAD, the present review will focus on three major suspects which are: (1) melatonin due to its crucial role in circadian rhythms (2) serotonin which has been linked with depressive disorders in general and atypical symptoms and (3) catecholamine because as for serotonin, many data reported an implication of these neurotransmitter family in depressive disorders. However, similarly to other reviews about SAD, we conclude that none of those could explain the pathophysiology of this northern disease on its own.

Good Sleep Quality and Progressive Increments in Vigilance During Extended Night Shifts: A 14-Day Actigraphic Study in Underground Miners.

OBJECTIVE: Assess the change in sleep and vigilance of underground miners during long periods of extended shifts. METHODS: Seventy miners worked 14 consecutive 12-hour day and/or night shifts. Also, they wore an actigraph and completed a visual analog scale for vigilance four times per shift. Linear regression models with mixed effects were used. RESULTS: Sleep efficiency was higher during day shifts than during night shifts (86,5 vs 85.5, P < 0.05) but sleep duration did not differ (6:34 vs 6:44, n.s.). Mean vigilance level at Time 3 (02h00) was significantly lower than that at Time 1 (19h00) during the first 10 night shifts whereas mean vigilance level at Time 4 (05h30) remained significantly lower for the 14 night shifts. CONCLUSIONS: Underground miners exhibit good sleep quality despite evidence of limited circadian adaptation in terms of nighttime vigilance.

Electroretinography may reveal cognitive impairment among a cohort of subjects at risk of a major psychiatric disorder.

INTRODUCTION: Almost a third of the offspring of parents diagnosed with schizophrenia or bipolar disorder could develop a mental disorder or related symptoms. The objectives of this study were to test the existence of two distinct subgroups of youth at-risk, according to their retinal response to luminance measured with electroretinography (ERG), and to relate the resulting cluster memberships with the cognitive clusters previously reported. METHODOLOGY: A clustering analysis was performed with ERG measurements in 107 at-risk offspring. Each subgroup was compared to a healthy control group of 203 individuals. The ERG subgroup memberships were then associated with the cognitive clusters. RESULTS: A two-cluster solution was obtained: HR-Cluster1 (n=53) showed a control-like ERG profile and HR-Cluster2 (n=54) showed reduced rod amplitudes and prolonged cone latencies of the b-wave. Subjects in the HR-Cluster2 were 2.7 times more likely to belong to the most detrimental cognitive subgroup than subjects in the HR-Cluster1 (49% Vs 18%). CONCLUSION: At-risk offspring showed two distinct ERG profiles: a control-like and an altered profile. A higher risk of impaired cognitive function was observed in subjects with the altered ERG profile, suggesting the ERG as a potential biomarker of susceptibility to mental illness among youth at risk.

The Electroretinogram May Differentiate Schizophrenia From Bipolar Disorder.

BACKGROUND: The retina is recognized as an approachable part of the brain owing to their common embryonic origin. The electroretinogram (ERG) has proved to be a valuable tool to investigate psychiatric disorders. We therefore investigated its accuracy as a tool to differentiate schizophrenia (SZ) from bipolar disorder (BP) even after balancing patients for their main antipsychotic medication. METHODS: ERG cone and rod luminance response functions were recorded in 150 patients with SZ and 151 patients with BP and compared with 200 control subjects. We created a subgroup of subjects-45 with SZ and 45 with BP-balanced for their main antipsychotic medication. RESULTS: A reduced cone a-wave amplitude and a prolonged b-wave latency were observed in both disorders, whereas a reduced cone b-wave amplitude was present in SZ only. Reduced mixed rod-cone a- and b-wave amplitudes were observed in both disorders. Patients with SZ were distinguishable from control subjects with 0.91 accuracy, 77% sensitivity, and 91% specificity with similar numbers for patients with BP (0.89, 76%, and 88%, respectively). Patients with SZ and patients with BP could be differentiated with an accuracy of 0.86 (whole sample) and 0.83 (subsamples of 45 patients with 80% sensitivity and 82% specificity). Antipsychotic dosages were not correlated with ERG parameters. CONCLUSIONS: The ERG waveform parameters used in this study provided a very accurate distinction between the two disorders when using a logistic regression model. This supports the ERG as a tool that could aid the clinician in the differential diagnosis of SZ and BP in stabilized medicated patients.

Requirement of myeloid cells for axon regeneration.

The role of CD11b+ myeloid cells in axonal regeneration was assessed using axonal injury models and CD11b-TK(mt-30) mice expressing a mutated HSV-1 thymidine kinase (TK) gene regulated by the myeloid-specific CD11b promoter. Continuous delivery of ganciclovir at a sciatic nerve lesion site greatly decreased the number of granulocytes/inflammatory monocytes and macrophages in the distal stump of CD11b-TK(mt-30) mice. Axonal regeneration and locomotor function recovery were severely compromised in ganciclovir-treated CD11b-TK(mt-30) mice. This was caused by an unsuitable growth environment rather than an altered regeneration capacity of neurons. In absence of CD11b+ cells, the clearance of inhibitory myelin debris was prevented, neurotrophin synthesis was abolished, and blood vessel formation/maintenance was severely compromised in the sciatic nerve distal stump. Spinal cord-injured axons also failed to regenerate through peripheral nerve grafts in the absence of CD11b+ cells. Therefore, myeloid cells support axonal regeneration and functional recovery by creating a growth-permissive milieu for injured axons.

Impact of oral melatonin on the electroretinogram cone response.

BACKGROUND: In the eye, melatonin plays a role in promoting light sensitivity at night and modulating many aspects of circadian retinal physiology. It is also an inhibitor of retinal dopamine, which is a promoter of day vision through the cone system. Consequently, it is possible that oral melatonin (an inhibitor of retinal dopamine) taken to alleviate circadian disorders may affect cone functioning. Our aim was to assess the impact of melatonin on the cone response of the human retina using electroretinography (ERG). METHODS: Twelve healthy participants aged between 18 to 52 years old were submitted to a placebo-controlled, double-blind, crossover, and counterbalanced-order design. The subjects were tested on 2 sessions beginning first with a baseline ERG, followed by the administration of the placebo or melatonin condition and then, 30 min later, a second ERG to test the effect. RESULTS: Following oral melatonin administration, a significant decrease of about 8% of the cone maximal response was observed (mean 6.9 muV +/- SEM 2.0; P = 0.0065) along with a prolonged b-wave implicit time of 0.4 ms +/- 0.1, 50 minutes after ingestion. CONCLUSION: Oral melatonin appears to reach the eye through the circulation. When it is administered at a time of day when it is not usually present, melatonin appears to reduce input to retinal cones. We believe that the impact of melatonin on retinal function should be taken into consideration when used without supervision in chronic self-medication for sleep or circadian disorder treatment.

Influence of timed nutrient diet on depression and light sensitivity in seasonal affective disorder.

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall-winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO-rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO- or protein-rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM-IV-diagnosed depressed women with SAD (n=22, 19-63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating approximately 1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH-SAD (with 21-item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21-HDRS score (mean+/-SD) decreased from 19.6+/-6.4 to 14.4+/-7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.

Impact of light therapy on rod and cone functions in healthy subjects.

Light therapy is an effective treatment for patients with seasonal affective disorders and is commonly used at an intensity of 10,000 lx. The aim of this study was to investigate the direct impact of light therapy on cones and rods photoreceptors using the electroretinogram (ERG) technique. Twelve healthy subjects were exposed for 60 min to three light conditions: 10,000 lx, 100 lx and 5 lx. ERG cone and rod luminance response functions were obtained immediately after exposures. Cone function was not affected by any light conditions. Maximal response achieved by the rods was significantly lower following the 100 lx and 10,000 lx conditions when compared with the 5 lx condition. Retinal rod sensitivity was significantly lower in the 10,000 lx condition when compared with the 12 lx condition. A decrease in rod function can readily be observed at 100 lx, that is, at regular indoor lighting. This decrease could be related to the triggering of retinal dopamine production, which would favour day vision over night vision. The further decrease in light sensitivity observed after 60 min at 10,000 lx may be perceived as a protective mechanism of the rod system against bright light.

Electroretinographic anomalies in medicated and drug free patients with major depression: Tagging the developmental roots of major psychiatric disorders.

The retina is tagged as an approachable part of the brain due to its common embryonic origin and appears as a promising site of investigation for psychiatric disorders. Retinal function is assessed best with the electroretinogram (ERG), which was obtained in a large sample of patients with major depressive disorder and matched controls. ERG cone and rod luminance response functions were recorded in non-dilated eyes in 100 major depressive disorder patients (MDD) and 100 controls, (mean age of 42.8 and 40.9y. o. respectively). Amongst MDD patients, 17 were drug free (mean age 41.2y. o). In medicated patients, at the cone level, a prolonged b-wave was observed (p≤0.01). In drug free patients a prolonged b-wave was discovered only when averaging the implicit time of the 3 highest b-wave amplitudes of the photopic hill. For the medicated patients, the mixed rods/cones a-wave was reduced (p=0.01) whereas a trend (p=0.06) was observed for the pure rod b-wave (reduced) and the mixed rods/cones (reduced and prolonged; p=0.05). In drug free patients, a similar pattern could be observed in terms of effect sizes. Overall, medicated and drug free MDD patients shared some deficits suggesting that some anomalies are present above and beyond the effect of medication. Of interest, the prolonged cone and reduced rod amplitude were reported by our group in schizophrenia patients, suggesting a common neurodevelopmental root of major psychiatric disorders.