Major depressive disorder: hypothesis, mechanism, prevention and treatment

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 9, 2024

Abstract Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, pathological mechanisms MDD underlying effects pharmacological treatments for are complex unclear, additional diagnostic therapeutic strategies still needed. The currently widely accepted theories pathogenesis include neurotransmitter receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis cytokine neuroplasticity hypothesis systemic influence but these cannot completely explain mechanism MDD. Even it hard to adopt only one reveal MDD, thus recent years, great progress has been made elucidating roles multiple organ interactions identifying novel approaches multitarget modulatory strategies, further revealing disease features Furthermore, some newly discovered potential targets studied antidepressants have attracted widespread attention, reagents even approved clinical treatment methods such as phototherapy acupuncture effective improvement symptoms. In this work, we comprehensively summarize latest research on diagnosis preventive medicines, well related trials.

Язык: Английский

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Regulation of pupil size in natural vision across the human lifespan

Royal Society Open Science, Год журнала: 2024, Номер 11(6)

Опубликована: Июнь 1, 2024

Vision is mediated by light passing through the pupil, which changes in diameter from approximately 2 to 8 mm between bright and dark illumination. With age, mean pupil size declines. In laboratory experiments, factors affecting can be experimentally controlled. How reflects change retinal input visual environment under natural viewing conditions unclear. We address this question a field experiment ( N = 83, 43 female, 18–87 years) using custom-made wearable video-based eye tracker with spectroradiometer measuring near-corneal spectral irradiance. Participants moved indoor outdoor environments varying spectrum engaged range of everyday tasks. Our data confirm that light-adapted determined level, better model fit melanopic over photopic units, it decreased increasing yielding steeper slopes at lower levels. found no indication sex, iris colour or reported caffeine consumption affects size. exploratory results point role photoreceptor integration controlling steady-state The provide evidence for considering age personalized lighting solutions against use illuminance alone assess impact real-world conditions.

Язык: Английский

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Efficacy of biologically-directed daylight therapy on sleep and circadian rhythm in Parkinson's disease: a randomised, double-blind, parallel-group, active-controlled, phase 2 clinical trial

EClinicalMedicine, Год журнала: 2024, Номер 69, С. 102474 - 102474

Опубликована: Фев. 10, 2024

BackgroundNew non-pharmacological treatments for improving non-motor symptoms in Parkinson's disease (PD) are urgently needed. Previous light therapies modifying sleep behaviour lacked standardised protocols and were not personalised an individual patient chronotype. We aimed to assess the efficacy of a biologically-directed therapy PD that targets retinal inputs circadian system on sleep, as well other motor functions.MethodsIn this randomised, double-blind, parallel-group, active-controlled trial at Queensland University Technology, Australia, participants with mild moderate computer randomised (1:1) receive one two had same photometric luminance visual appearance allow blinding investigators intervention. One these lights matched natural daylight (Day Mel), which is known stimulate melanopsin cells. The treatment arm study, specifically supplemented stimulation cells (Enhanced targeting deficits system. Both administered 30 min per day over 4-weeks patient's chronotype, while monitoring environmental exposure actigraphy. Co-primary endpoints change from baseline mean macrostructure (polysomnography, PSG) endocrine biomarker phase (dim melatonin secretion onset, DLMO) weeks 4 6. Participants data analysed using intention treat principle. All evaluated by applying mixed model analysis. registered Australian New Zealand Clinical Trials Registry, ACTRN12621000077864.FindingsBetween February 4, 2021 August 8, 2022, 144 consecutively screened, 60 enrolled randomly assigned There was no significant difference co-primary outcomes between groups overall or any timepoint during follow-up. (95% CI) PSG, N3% 24.15 (19.82–28.48) Day Mel (n = 23) 19.34 (15.20–23.47) Enhanced group 25) week (p 0.12); 21.13 (16.99–25.28) 26) 18.48 (14.34–22.62) 6, 0.37). DLMO (decimal time) 19.82 (19.20–20.44) 22) 19.44 (18.85–20.04) 24) 0.38); 19.90 (19.27–20.53) 19.04 (18.44–19.64) 6 0.05). However, both controlled Mel) enhanced interventions demonstrated improvement primary PSG macrostructure. restorative deep (PSG, N3) significantly improved [model-based CI): −3.87 (−6.91 −0.83), p 0.04]. phase-advance did reach statistical significance time-point. safety concerns severe adverse events related intervention.InterpretationBoth booster showed measures people PD. That there intervention may be due early stage. findings suggest indoor individuals' chronotype could effective PD, further studies evaluating now required utilising approach, including advanced PD.FundingThe Michael J Fox Foundation Research, Shake IT Up National Health Medical Research Council, Council.

Язык: Английский

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Are ipRGCs involved in human color vision? Hints from physiology, psychophysics, and natural image statistics

Vision Research, Год журнала: 2024, Номер 217, С. 108378 - 108378

Опубликована: Март 7, 2024

Human photoreceptors consist of cones, rods, and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). First studied in circadian regulation pupillary control, ipRGCs project to a variety brain centers suggesting broader involvement beyond non-visual functions. IpRGC responses are stable, long-lasting, with particular codification photoreceptor signals. In comparison the transient adaptive nature cone rod signals, ipRGCs' signaling might provide an ecological advantage different attributes color vision. Previous studies have indicated melanopsin's influence on visual yet its contribution perception humans remains debated. We summarized evidence hypotheses (from physiology, psychophysics, natural image statistics) about direct indirect human vision, by first briefly assessing current knowledge role melanopsin vision spectral then approached question activation eliciting percept, discussing using silent substitution method. Finally, we explore various avenues through which impact indirectly, such as peripheral matching, post-receptoral pathways, constancy, long-term chromatic adaptation, induction. While there is consensus brightness perception, confirming requires further investigation. proposed potential approaches for future research, emphasizing need empirical validation methodological thoroughness elucidate exact

Язык: Английский

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Jseun: Joint Semantic-Instance Segmentation of Point Cloud Via Neighbor Features for Indoor Scenes

Опубликована: Янв. 1, 2025

Язык: Английский

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A pupillary contrast response in mice and humans: Neural mechanisms and visual functions

Neuron, Год журнала: 2024, Номер 112(14), С. 2404 - 2422.e9

Опубликована: Май 1, 2024

Язык: Английский

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Mapping the Retina onto the Brain

Cold Spring Harbor Perspectives in Biology, Год журнала: 2023, Номер 16(2), С. a041512 - a041512

Опубликована: Дек. 5, 2023

Daniel Kerschensteiner1,2,3 and Marla B. Feller4,5 1Department of Ophthalmology Visual Sciences 2Department Neuroscience 3Department Biomedical Engineering, Washington University School Medicine, St. Louis, Missouri 63110, USA 4Department Molecular Cell Biology 5Helen Wills Institute, California, Berkeley, California 94720, Correspondence: mfeller{at}berkeley.edu; kerschensteinerd{at}wustl.edu

Язык: Английский

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The multistable melanopsins of mammals

Frontiers in Ophthalmology, Год журнала: 2023, Номер 3

Опубликована: Апрель 26, 2023

Melanopsin is a light-activated G protein coupled receptor that expressed widely across phylogeny. In mammals, melanopsin found in intrinsically photosensitive retinal ganglion cells (ipRGCs), which are especially important for “non-image” visual functions include the regulation of circadian rhythms, sleep, and mood. Photochemical electrophysiological experiments have provided evidence has at least two stable conformations thus multistable, unlike monostable photopigments classic rod cone photoreceptors. Estimates melanopsin’s properties vary, challenging efforts to understand how molecule influences vision. This article seeks reconcile disparate views offer practical guide complexities.

Язык: Английский

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Beyond Lux: Methods for Species and Photoreceptor-Specific Quantification of Ambient Light for Mammals

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 27, 2023

Abstract Background Light is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms associated with impaired health well-being across mammals. Appropriate lighting therefore crucial for indoor housed The most commonly used measurement lux. However, this employs spectral weighting function based on human perceived brightness not suitable ‘non-visual’ effects use species. In humans, photoreceptor-specific (α-opic) metrology system has been proposed as more appropriate way measuring light. Results Here we establish technology to allow α-opic approach be readily extended any mammalian species, accounting differences in photoreceptor types, photopigment sensitivities, eye anatomy. Since sensitivity can hard derive novel animals photoreceptors, developed high-throughput, easy-to-use, method sensitivities recombinantly expressed melanopsins it the melanopsin from 12 non-human We further address need simple strategies species-specific measures by developing an accessible online toolbox calculating these units validating open hardware, low-cost, multichannel sensor ‘point click’ measurement. finally demonstrate that measurements are superior photopic lux predictors physiological responses mice ecologically relevant comparisons photosensitivity between Conclusion Our study demonstrates accurately using existing unit holds promise improvements welfare animals, scientific research reproducibility, agricultural productivity, energy usage.

Язык: Английский

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Functional subtypes of rodent melanopsin ganglion cells switch roles between night and day illumination

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 27, 2023

Intrinsically photosensitive retinal ganglion cells (ipRGCs), contain the photopigment melanopsin, and influence both image non-image forming behaviors. Despite being categorized into multiple types (M1-M6), physiological variability within these suggests our current understanding of ipRGCs is incomplete. We used multi-electrode array (MEA) recordings unbiased cluster analysis under synaptic blockade to identify 8 functional clusters ipRGCs, each with distinct photosensitivity response timing. Cre mice drive expression channelrhodopsin in SON-ipRGCs, enabling localization dorsal retina. Additionally, we conducted a retrospective ipRGC photoresponses light stimuli across scotopic, mesopic, photopic intensities, aimed at activating rod cone inputs ipRGCs. Our results revealed shared identified clusters, demonstrating that encode visual information high fidelity low but poorly when melanopsin activation highest. Collectively, findings support framework least subtypes encoding luminance spike outputs, highlighting inherent diversity complexity suggesting reevaluation their contributions function perception varying conditions.

Язык: Английский

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