Retinal markers of therapeutic responses in major depressive disorder: Effects of antidepressants on retinal function.

BACKGROUND: One goal of research into major depressive disorder (MDD) is to develop markers to predict and monitor the response to psychotropic treatments. The retina is endowed with a complex neurotransmission system, composed of the main neurotransmitters involved in the pathophysiology of MDD. The retina is therefore a relevant site of investigation for the identification of reliable and robust markers. However, the effects of antidepressants on the human retina are poorly studied. Here, we seek to study the potential specific effects of various antidepressants on retinal function in MDD patients. METHODS: We assessed retinal function using flash (fERG), pattern (PERG) and multifocal (mfERG) electroretinogram in 19 MDD patients treated using antidepressants at baseline and at weeks 4, 8 and 12. RESULTS: We observed reduced b-wave amplitude of photopic fERG 3.0 in patients treated with Selective Serotonin Reuptake Inhibitor (SSRI) in comparison with patients treated with Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) or Tricyclic Antidepressant (TCAD). We also showed that SNRIs were associated both with a decrease in PERG P50 implicit time and an increase in fERG 3.0 b-wave amplitude. TCADs were associated with an increase in fERG flicker 3.0 a- and b-wave amplitude. CONCLUSIONS: This is the first study in real-life conditions to show a specific effect of various antidepressants on retinal function evaluated by electroretinogram. Further investigations should be led to specify the effects of antidepressants on ERG in order to isolate reliable and reproducible markers for predicting and monitoring the response to antidepressants.

Retinal electroretinogram features can detect depression state and treatment response in adults: A machine learning approach.

BACKGROUND: Major depressive disorder (MDD) is a major public health problem. The retina is a relevant site to indirectly study brain functioning. Alterations in retinal processing were demonstrated in MDD with the pattern electroretinogram (PERG). Here, the relevance of signal processing and machine learning tools applied on PERG was studied. METHODS: PERG - whose stimulation is reversible checkerboards - was performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards in 24 MDD patients and 29 controls at the inclusion. PERG was recorded every 4 weeks for 3 months in patients. Amplitude and implicit time of P50 and N95 were evaluated. Then, time/frequency features were extracted from the PERG time series based on wavelet analysis. A statistical model has been learned in this feature space and a metric aiming at quantifying the state of the MDD patient has been derived, based on minimum covariance determinant (MCD) mahalanobis distance. RESULTS: MDD patients showed significant increase in P50 and N95 implicit time (p = 0,006 and p = 0,0004, respectively, Mann-Whitney U test) at the inclusion. The proposed metric extracted from the raw PERG provided discrimination between patients and controls at the inclusion (p = 0,0001). At the end of the follow-up at week 12, the difference between the metrics extracted on controls and patients was not significant (p = 0,07), reflecting the efficacy of the treatment. CONCLUSIONS: Signal processing and machine learning tools applied on PERG could help clinical decision in the diagnosis and the follow-up of MDD in measuring treatment response.

Tutor-Student Partnership in Practice OSCE to Enhance Medical Education.

BACKGROUND: Training of examiners is essential to ensure the quality of objective structured clinical examination (OSCE). We aimed to study a perceived effectiveness of tutor-student partnership in a practice OSCE module by novice OSCE tutors and medical students. METHOD: We implemented a practice OSCE at a medical faculty in France with novice tutors and third year medical students as partners. Each tutor (n = 44) served as a partner for the group of 5 students in the conception of the scenario and as an evaluator of the tutored station. Students (n = 303) were involved in the conception of a case and the roles of a physician, evaluator and a simulated patient. Data were obtained through self-assessment questionnaires. Descriptive statistics were used to analyze items of the questionnaires. Free-form answers were coded and analyzed thematically. RESULTS: A total of 36 tutors (82%) and 185 students (61%) responded to the questionnaires. The intervention was well perceived. Thirty-two percent of the tutors reported some difficulties in the assessment of student performance and were disposed to receive further training. Fifty-five percent of the students considered the participation in the OSCE case development appropriate to their level of knowledge, and 70% perceived it as beneficial allowing them to set their learning goals. CONCLUSION: This initiative provides a relevant method beneficial to OSCE tutors, medical students, and the faculty. Tutors learn how to assess student performance according to expected achievement levels. It allows students to be engaged as partners in co-creation of learning and teaching. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01421-9.

Complete evaluation of retinal function in Major Depressive Disorder: From central slowdown to hyperactive periphery.

BACKGROUND: Developing easy-to-access biomarkers is crucial in Major Depressive Disorder. The retina has already been suggested as relevant. However, there is a need for a global and local assessment of whole retinal function using a reproducible, standardized protocol allowing for comparison across studies. Our aim is to assess whole retinal function in patients with actual unipolar Major Depressive Episode (MDE) using pattern, flash and multifocal electroretinogram (ERG) according to the International Society for Clinical Electrophysiology of Vision standardized protocols. METHODS: We assessed retinal function in 14 males and females with MDE, diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, and in age- and sex-matched healthy controls. RESULTS: Comparing the patients with the controls, we observed the following using multifocal ERG: a significant increase in N1 peak time in ring 3 and a decrease in P1 amplitude in ring 2; using pattern ERG: a significant increase in P50 peak time; using flash ERG: a decrease in a- and b-wave peak time and an increase in the b-wave amplitude in dark-adapted 3.0, a decrease in a- and b-wave peak time and an increase in both wave amplitudes in light-adapted 3.0, and a decrease in the b-wave peak time in light-adapted flicker. LIMITATIONS: Sample size. Contribution of pharmacological treatments to the outcomes cannot be formally excluded. CONCLUSIONS: Patients with MDE exhibit delayed signaling in the central retina and hyperreactivity to light in the periphery. Central retinal function may be a marker of psychomotor retardation and cognitive impairment in MDE.

Portable light therapy in the treatment of unipolar non-seasonal major depressive disorder: study protocol for the LUMIDEP randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD) affects more than 264 million people worldwide and is associated with an impaired quality of life as well as a higher risk of mortality. Current routine treatments demonstrate limited effectiveness. Light therapy (LT) on its own or in combination with antidepressant treatments could be an effective treatment, but the use of conventional LT devices use is restrictive. Portable LT devices allow patients to continue with their day-to-day activities and therefore encourage better treatment compliance. They have not been evaluated in MDD. METHODS AND ANALYSIS: The study is a single-centre, double-blind, randomised controlled trial assessing the efficacy of LT delivered via a portable device in addition to usual care (medical care and drug treatment) for inpatients and outpatients with unipolar non-seasonal MDD. Over the course of 8 weeks, patients use the device daily for 30 min at medium intensity as soon as possible after waking up and preferably between 07:00 and 09:00. All patients continue their usual care with their referring physician. N=50 patients with MDD are included. The primary outcome measure is depressive symptom severity assessed using the Montgomery-Åsberg Depression Rating Scale between baseline and the eighth week. Secondary outcome measures are sleep quality assessed using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale and anxiety level assessed on the Hamilton Anxiety Rating Scale, between baseline and week 8. Further parameters relating to cognitive function are measured at baseline and after the intervention. An ancillary study aims to evaluate the impact of MDD on the retina and to follow its progression. Main limitations include risk of discontinuation or non-adherence and bias in patient selection. ETHICS AND DISSEMINATION: The study protocol was approved by Ile de France X's Ethics Committee (protocol number 34-2018). Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03685942.

New insights on the role of the retina in diagnostic and therapeutic strategies in major depressive disorder.

Major depressive disorder (MDD) affects people worldwide. MDD treatments include antidepressants, which involve a delayed onset of action, long-term treatment, side effects and, frequently, only partial efficacy. The lack of access to the living brain, and the complex and still poorly elucidated pathophysiology of MDD, hinders treatment development. There is not only a need for new treatment strategies, but also for new approaches to investigating the pathophysiology of MDD. Light therapy is a well-established treatment acting through the retina. Since the retina is part of the central nervous system, it has been suggested as a useful area for investigating mental illness. In this article, we will first set out the evidence that MDD affects the retina's structure and function. We will then review studies evaluating the efficacy of light therapy in unipolar non-seasonal MDD. Finally, we discuss the disruption of melatoninergic pathways in MDD, its assessment through the retina and the treatment of this disruption with light therapy.