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.
Visual search characteristics in two-way skeet shooters of different performance levels during simulated target viewing
BackgroundVisual search plays a critical role in skeet shooting. Athletes must quickly and rapidly detect, track, and respond to fast-moving targets. Understanding how visual search characteristics differ between shooters of different performance levels during target viewing can provide insight into visuomotor control and visual information processing in dynamic tasks, particularly in skeet shooting.MethodsA 2 (level of performance: expert, novice) × 2 (target position: high house, low house) × 2 (target type: single target, double target) mixed experimental design was adopted. Differences in eye-movement behavior between expert and novice skeet shooters were analyzed using eye-tracking technology during simulated tasks of target viewing.ResultsThe expert group had the lowest reaction time, mean saccade amplitude, number of fixations, pupil diameter, and number of blink compared to the novice counterparts, and the experts had the longest fixation time. There was a variation in fixation and blink count among the target conditions, with significant main effects of target condition. Repeated-measures analysis indicated that there was a significant main effect of group across all the eye-movement and behavioral indicators and no significant group x target condition interaction. Analysis of visualization revealed that highly skilled shooters had more focused gaze patterns, smaller gaze patterns, and more consistent fixation patterns. Conversely, beginner shooters had a more diffuse gaze, more scattered fixation points, and more complicated gaze patterns.ConclusionVisual search strategies vary significantly between expert and novice skeet shooters during simulated target-viewing experiments. Compared to amateur shooters, expert shooters exhibit longer fixation times, fewer fixations, smaller saccade amplitudes, less blinking, smaller pupil sizes, and more focused and regular gaze paths. These properties suggest shorter and more efficient visual search behavior, more profound information, and more stable gaze organization during target tracking, reflecting more efficient task-relevant visual information processing.
Biomarkers for complex post-traumatic stress disorder: translational and evolutionary perspectives
Analysis of the prevalence of dyslipidemia in early-onset schizophrenia patients and its correlation with clinical characteristics
ObjectiveTo analyze the prevalence of dyslipidemia and related influencing factors in patients with early-onset schizophrenia (EOS).MethodsWe recruited 289 pediatric and adolescent EOS patients from October 2021 to June 2024 in the Third People’s Hospital of Fuyang. Researchers gathered comprehensive demographic and clinical records. Utilizing the 2023 Chinese Guidelines for Lipid Management, they calculated dyslipidemia prevalence and the incidence of irregularities in total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol. Subsequently, differences in dyslipidemia among different genders, body mass index, and antipsychotic medication groups were analyzed. Finally, independent influencing factors of dyslipidemia in EOS patients were explored.ResultsThe overall prevalence of dyslipidemia was 24.9% (72/289), with abnormal rates of TG, TC, HDL-C, LDL-C, and non-HDL-C being 15.9%, 6.6%, 6.6%, 4.2%, and 7.3%, respectively. Male patients, those who were overweight or obese, and those taking two antipsychotic drugs had significantly higher rates of dyslipidemia. Regression analysis showed that male gender (OR = 2.04, P = 0.016), overweight/obesity (OR = 4.55, P < 0.001), body roundness index (OR = 1.53, P = 0.005), and the use of two antipsychotic drugs (OR = 1.90, P = 0.030) were risk factors for dyslipidemia in EOS patients.ConclusionThe prevalence of dyslipidemia in EOS patients is relatively high. When monitoring lipid levels in clinical practice, particular attention should be paid to male patients, those who are overweight or obese, and those receiving combined drug therapy.
Esketamine ameliorates depression-like behavior in mice via modulation of the NRG1–ErbB4 pathway
BackgroundEsketamine has a significant and rapid antidepressant effect. Although studies have shown that Neuregulin 1 (NRG1) and it’s signaling pathway are associated with depression, the possible regulatory relationship of esketamine on the NRG1-ErbB4 pathway is not yet clear.MethodsTo induce depressive-like behavior in mice, a Chronic Social Defeat Stress (CSDS) model was established. Behavioral indicators were then employed to assess depression in these mice, categorized into control, susceptible, and resilient groups. Following intraperitoneal injection of a subanesthetic dose of esketamine, behavioral tests were conducted at 30 minutes and 24 hours post-injection to observe any improvements in depressive-like behavior. Additionally, changes in immunofluorescence and protein expression levels of NRG1-ErbB4 and GAD67 in the prefrontal cortex were evaluated.ResultsCompared with the control group, the CSDS susceptible group mice showed decreases in social interaction ratio in the contact area, sucrose preference ratio, NRG1 immunofluorescence protein expression in the prefrontal cortex and NRG1 expression in tissue homogenate; showed significant increases in immobility time; the expression of NRG1 decreased;no significant change in GAD67 and ErbB4 expression level. in After 30 minutes of intraperitoneal injection of esketamine, the expression of NRG1 in the prefrontal cortex of susceptible mice increased significantly. no significant change in GAD67 and ErbB4 expression level. After 30 minutes and 24 hours of intraperitoneal injection of esketamine, the social interaction ratio of susceptible group improved compared to the control group, and the duration of forced swimming immobility was significantly shortened.ConclusionThe subanesthetic dose of esketamine may regulate the NRG1-ErbB4 signaling pathway and improve depressive like behavior in mice.
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.
Cerebellar dysconnectivity in schizophrenia spectrum: task-based functional connectivity analysis and cognitive stratification
IntroductionSchizophrenia is conceptualized as a disorder of brain network dysconnectivity, yet relationships between neural alterations, cognitive deficits, and genetic risk remain unclear.MethodsWe examined 86 participants: schizophrenia patients (SCZ), unaffected siblings (SCZ-SIB), healthy controls (CON), and control siblings (CON-SIB). We used a multiscale graph-theoretic analysis of task-based fMRI during N-back working memory and unsupervised clinical-cognitive clustering.ResultsWe found that reduced cerebellum-sensorimotor (CER-SM) and cerebellum-cingulo-opercular (CER-CO) connectivity during the 1-back condition robustly discriminated SCZ from CON (AUC = 0.89). Critically, these dysconnectivity patterns were linked to clinical state, present in SCZ vs. SCZ-SIB but absent in SCZ-SIB vs. CON-SIB, suggesting illness expression rather than familial risk. Unsupervised clustering revealed three data-driven subtypes with distinct cognitive- symptomatic profiles: subtype 1 with relative preservation of verbal abilities (predominantly controls), subtype 2 with marked fluid cognitive impairment (enriched in SCZ), and subtype 3 with intermediate performance with working memory sparing (mixed composition). Cerebellar-cortical hypoconnectivity showed graded alignment across these profiles.DiscussionThese findings demonstrate that cerebellar dysconnectivity is most detectable under moderate cognitive load, tracks with clinical state, and covaries with transdiagnostic cognitive profiles, advancing circuit-based understanding of schizophrenia heterogeneity.
Minimal life by computer
Nature Biotechnology, Published online: 07 April 2026; doi:10.1038/s41587-026-03110-7
Progress toward a true virtual cell will depend on uniting AI’s pattern-finding power with the causal rigor of mechanistic models.