Depression is a multifactorial, chronic disorder and represents a leading cause of disability, with women exhibiting nearly twice the lifetime prevalence compared to men. Growing evidence indicates that this disparity cannot be explained by hormonal or psychosocial factors, but rather by dynamic interactions between environmental exposures, neuroendocrine signaling, and epigenetic regulation across development. This mini-narrative review aimed to examine how sex-specific exposome components interact with epigenetic mechanisms and synaptic remodeling processes to influence vulnerability to Major Depressive Disorder in women. The reviewed evidence demonstrates that fluctuations in ovarian hormones modulate HPA axis responsivity, neuroinflammatory signaling, and glutamatergic transmission through epigenetic regulation of stress-responsive genes such as NR3C1, SLC6A4, and BDNF, consequently influencing synaptic remodeling within corticolimbic circuits. Environmental and social exposures, particularly early-life adversity and psychosocial stressors, further interact with microglial activation and chromatin remodeling to produce long-lasting alterations in hippocampal and prefrontal plasticity. Collectively, these findings support a model in which sex-dependent neuroendocrine sensitivity amplifies exposome-driven epigenetic programming across the lifespan. Future research directions emerging from this synthesis include longitudinal life-course studies integrating multi-omic biomarkers, quantitative exposome assessment, and neuroimaging approaches to identify modifiable environmental targets and advance precision, sex-informed preventive and therapeutic strategies in depression.
Stage-specific ERP correlates of audiovisual facial emotion processing across depressive tendencies
Emotional dysregulation can emerge as early as the initial stages of depression. This study aimed to examine event-related potential characteristics during the perception of negative, positive, and neutral facial expressions in healthy individuals across depressive tendencies. Twenty-six healthy participants underwent ERP measurements during emotion recognition using a facial emotion recognition task in visual and audiovisual modalities. The Emotion Regulation Questionnaire (ERQ), the Difficulties in Emotion Regulation Scale (DERS-16), and the Beck Depression Inventory II (BDI-II) assessed cognitive strategy, emotion regulation difficulties, and depression severity, respectively. Facial affect elicited larger amplitudes compared to neutral faces, from the N170 and early posterior negativity (EPN) in the temporo-occipital region to the late positive potential (LPP) in the centroparietal region. Under audiovisual conditions, P1 peak latency to negative stimuli in the temporal region exhibited significant negative correlations with DERS-16 and BDI-II scores. N170 peak latency to positive stimuli also demonstrated a significant negative correlation with BDI-II scores. Under visual conditions, EPN amplitude to negative stimuli in the occipital region exhibited a significant positive correlation with BDI-II scores. P1 and N170 latencies, or neural response speeds, and EPN amplitude, which represents emotional reaction strength, correlate with depressive tendencies in healthy individuals. These early components function as initial neural signals that may serve as electrophysiological markers of abnormal emotional processing within neuropsychological functions prior to clinical depression.
Mechanistic research on the vestibular-hippocampal pathway in neurodegenerative diseases: an integrative perspective from molecular to behavioral levels
This paper systematically reviews the pivotal role and bidirectional regulatory mechanisms of the Vestibular-hippocampal pathway in the onset and progression of neurodegenerative diseases (such as Alzheimer’s disease), focusing on the common comorbidity of vestibular dysfunction and cognitive decline. Evidence spanning molecular to behavioral levels indicates that vestibular signal loss can induce hippocampal atrophy and spatial memory impairment through neuroinflammation, impaired synaptic plasticity, and disrupted theta rhythms. Conversely, hippocampal degeneration further impairs vestibular information integration, creating a vicious cycle. Intervention approaches such as vestibular rehabilitation, cognitive training, and neurostimulation show potential for slowing co-morbidity progression. Future research should focus on developing animal models simulating vestibular-neurodegenerative co-morbidity, conducting longitudinal clinical validation using multimodal imaging and electrophysiology techniques, and optimizing neuromodulation strategies and targeted molecular interventions to advance this mechanism toward early diagnosis and precision treatment.
Vitamin A status is associated with sleep, clock genes, and symptoms in children with autism spectrum disorder
BackgroundVitamin A signals through retinoic acid receptors and may influence neurodevelopment and the expression of clock genes. However, the biological pathway linking vitamin A status to sleep disturbance in ASD remains insufficiently defined. This study aimed to examine associations between vitamin A status and sleep problems, core symptoms, and clock genes in children with ASD, and to explore the mechanistic role of RARβ in regulating core clock genes.MethodsThis observational study included 361 children with ASD. Clinical symptoms were assessed using the Children’s Sleep Habits Questionnaire (CSHQ); the Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS). Peripheral blood mononuclear cell (PBMC) mRNA levels of RARβ and clock genes (BMAL1 and CLOCK) were quantified by qPCR. RARβ expression was knocked down in mice by stereotaxic injection of adeno-associated virus.ResultsChildren with lower vitamin A levels exhibited more severe sleep problems and autistic symptoms. Vitamin A levels showed a weak positive correlation with the expression of RARβ and BMAL1. RARβ knockdown reduced the expression of RARβ and clock genes in mouse brain tissue. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) confirmed RARβ occupancy at a predicted CLOCK regulatory region.ConclusionThis study provided evidence that vitamin A status was linked to sleep problems, symptom severity, and expression of clock genes in the morning in ASD. We also found that RARβ signaling may regulate the expression of clock genes. This finding provides new insights into the mechanisms underlying sleep disturbances in ASD, but further functional studies are needed to confirm these findings.
Methylome-Wide Association Study of Obsessive-Compulsive Disorder
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition influenced by both genetic and environmental risk factors. Epigenetic modifications, such as DNA methylation, may offer insights into biologically meaningful differences associated with the disorder.
Neural circuits encode prior knowledge of temporal statistics
Nature Neuroscience, Published online: 07 April 2026; doi:10.1038/s41593-026-02255-7
This study shows that cerebellar circuits learn and encode prior probabilities of event timing. Cell-type-specific neural activity reflects environmental statistics and guides predictive motor behavior, providing support for neural Bayesian inference.
STAT+: Merck’s experimental HIV prevention pill could be made for less than $5 a year, researchers say
An experimental HIV prevention pill being developed by Merck could be mass produced for less than $5 per patient a year according to a new analysis. Advocates argue the low cost means the company should find it easier to license the drug so that low- and middle-income countries can gain easy access.
The pill, dubbed MK 8527, is currently undergoing a pair of late-stage clinical trials that are expected to determine whether the medicine can lower HIV transmission when given to people at high risk of infection. The results are due in the latter half of 2027, according to separate postings on ClinicalTrials.gov.
Already, the pill is generating considerable interest after Merck released mid-stage results last summer showing its drug holds promise. In addition to being safe and effective, the study found it could protect against infection, a form of prevention known as pre-exposure prophylaxis or PrEP, within 24 hours after being taken. Merck noted the pill works in a novel way.
A star scientist showed that better genetics lessons could reduce racism. It was the death knell for his career
Every year, the Genetics Society of America bestows the Elizabeth W. Jones Award for Excellence in Education, recognizing someone who has helped the public better understand the science of DNA. It’s understood to be a lifetime achievement award; past recipients tend toward retirement age with decades of work behind them and stacks of textbooks to their names.
When this year’s winner, Brian Donovan, was announced at the end of February, many geneticists and science educators found it hard to celebrate the news. Not because he’s undeserving of the honor. Far from it. But because it seemed to confirm what many feared: that Donovan’s incandescent research career was over before it had barely begun.
STAT+: Research revealing how the brain flushes waste named STAT Madness Editors’ Pick
For her new research on the brain’s plumbing system, neuroscientist Maiken Nedergaard had to hone many techniques. Among them — coaxing her lab mice into restful sleep, even as they lay on microscope beds with tiny fiberoptic wires threaded into their brains.
“It was really hard to get the mice to sleep naturally,” said Nedergaard, who spent weeks cuddling the animals in her hands, so they’d learn to feel safe. “But then we said, ‘we really want to not have them disturbed.’”
The reason for this care? Nedergaard studies the glymphatic system, which removes waste from the brain during sleep, so ensuring her test subjects achieve a restorative snooze is central to her work.
AI-TOP Study Artificial Intelligence for Trigger Optimization.
Conditions: Infertility; Ovarian Stimulation; Artificial Intelligence
Interventions: Device: STIMAI®.; Other: Routine clinical management
Sponsors: Fundacion Dexeus
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Interventions: Device: STIMAI®.; Other: Routine clinical management
Sponsors: Fundacion Dexeus
Not yet recruiting