Journal of Neurogenetics

Sleep gets worse with age and is correlated with risk for disease and mortality. The possibility that poor sleep causes aging to accelerate has prompted interest in improving sleep to slow aging and prevent disease. However, the existing evidence on the link between poor sleep and accelerated aging is unclear. Here, we tested for correlation and causation between poor sleep and accelerated aging using five independent datasets of adults (total N > 64,000). We found strong evidence for a correlation between poor sleep and fast aging that is consistent across young, middle, and late adulthood and across aging biomarkers derived from different tissues and modalities. We found that this correlation is robust to the influence of chronic disease burden, but not to the influence of shared genetic and early environmental factors among twins. Finally, we found mixed evidence for a causal influence of poor sleep on accelerated aging using Mendelian randomization. Our findings indicate that the correlation between poor sleep and accelerated aging is highly robust; however, the claim that poor sleep causes aging to accelerate is not consistently supported.

Introduction: Bipolar disorder (BD) has been associated with increased medical burden and accelerated biological aging. Long non-coding RNAs (lncRNAs) regulate molecular pathways related to cellular senescence, inflammation, and telomere maintenance, which are implicated in both BD and aging. This study examined whether aging-related lncRNA expression reflects familial vulnerability or illness-specific effects, and whether childhood trauma and lifestyle factors modulate these signatures within a gene-environment framework. Methods: In this cross-sectional study, expression levels of aging-related lncRNAs, including Antisense Non-coding RNA in the INK4 Locus (ANRIL), HOX Transcript Antisense Intergenic RNA (HOTAIR), Nuclear Enriched Abundant Transcript 1 (NEAT1), Taurine Upregulated Gene 1 (TUG1), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), Growth Arrest-Specific 5 (GAS5), and Telomerase RNA Component (TERC), were measured in peripheral blood mononuclear cells (PBMCs) from individuals with bipolar disorder (BD) (n=68), siblings without BD diagnosis (SIB) (n=54), and healthy controls (HC) (n=70) using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Childhood trauma and lifestyle were assessed using the Childhood Trauma Questionnaire (CTQ) and the Healthy Lifestyle Profile II (HPLP-II). Principal component analysis generated a composite aging-related lncRNA factor. Results: At the individual transcript level, NEAT1 and TERC were elevated, whereas GAS5 was reduced, in both BD and SIB relative to HC. The aging-related lncRNA composite score was higher in BD and SIB than in HC (F = 7.315, p = 0.001). Familial liability to BD (presence vs. absence of familial liability) showed a significant main effect on the composite score (F(1,182)=8.18, p=0.005) and interacted with childhood trauma (F(1,182)=10.14, p=0.002). In multivariable models, total CTQ and physical neglect were independently associated with lower composite scores, while familial liability remained a positive predictor (all p<0.001). Conclusions: Aging-related lncRNA alterations mark familial vulnerability to BD and are shaped by childhood trauma within a gene-environment interaction framework.

Animals balance staying in a favorable environment with exploring new ones. In C. elegans chemotaxis, the process by which worms migrate toward an attractant has been extensively studied. However, what happens after they reach it remains largely unexplored, partly because conventional assays immobilize worms at the point of arrival. Here, we quantitatively analyzed chemotactic behavior upon reaching an attractive odor source using an immobilization-free chemotaxis assay. We observed that 62% animals left the isoamyl alcohol region after initially approaching it, a behavior we termed "leaving behavior." Quantitative analysis revealed that leaving behavior represents a distinct locomotor state compared with free-moving, high-concentration odor avoidance, and approach behavior. To test whether leaving behavior is related to olfactory adaptation, we analyzed mutants in adaptation-related genes. The proportion of leaving behavior was significantly increased in egl-4 loss-of-function mutants compared with wild-type animals, whereas arr-1 mutants showed no significant difference. These results suggest that egl-4 negatively regulates leaving behavior, suggesting a role for this kinase in stabilizing post-arrival behavioral states beyond its known function in olfactory adaptation. Our findings indicate that chemotaxis involves dynamic behavioral transitions even after reaching an attractant, consistent with an exploration-exploitation trade-off framework.

Relatively little is known regarding suicide among older adults in nursing homes. The aim of this study was to compare the incidence of suicide among older nursing home residents (NHR) with community-dwelling older people (CDP) using newly available, national, individual-level register data, and to assess differences with regard to socio-demographic characteristics. We obtained data on all older adults aged 65+ who were living in Austria at the end of October 2018 (n=1,665,450), including 155,020 NHR. Death by suicide was followed until the end of 2023. A total of 114 and 2,136 suicides were observed among NHR and CDP; corresponding to cumulative incidences of 14 and 27 per 100,000, respectively. Among NHR, suicide incidence was higher among males (28.0, 95% CI=22.1, 35.5), those aged 65-74 years (20.2, 95% CI=13.3, 30.6), with tertiary education (23.3, 95% CI=10.6, 50.6), divorced (25.0, 95% CI=16.2, 38.5), and residing in urban nursing homes (22.0, 95% CI=17.0, 28.4). Compared to CDP, more suicides in NHR occurred by poisoning and but few by firearms. In conclusion, we found that suicide incidence was lower among older NHR compared to CDP. More research on and preventive efforts against suicide among older NHR are needed.

Background Greater cognitive intra-individual variability (IIV) reflects increased heterogeneous performance across cognitive domains and has been linked to a higher risk of Alzheimer's disease (AD). However, it remains unclear whether cognitive IIV is linked to heterogeneous dispersion of regional AD pathology. Hence, we aimed to examine the association between cognitive IIV and AD neuroimaging biomarker IIV. Methods This study included participants with normal cognition (CN) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative. Cognitive IIV was computed as the within-person standard deviation of five domain-specific neuropsychological test z-scores. Four neuroimaging biomarker IIV metrics were similarly derived using regional amyloid-{beta} (n = 1,021), tau (n = 719), cortical thickness (n = 2,148), and combined amyloid-tau-neurodegeneration (ATN, n = 258). Associations between cognitive IIV and each biomarker IIV were evaluated using linear regression models, adjusted for relevant covariates. Results Higher cognitive IIV was associated with greater biomarker IIV across amyloid-{beta} ({beta} = 0.039, SE = 0.014, p = .006), tau ({beta} = 0.196, SE = 0.033, p < .001), cortical thinning ({beta} = 0.036, SE = 0.008, p < .001), and ATN ({beta} = 0.176, SE = 0.043, p < .001). Interaction analyses revealed that the associations of cognitive IIV with tau IIV, cortical thickness IIV, and ATN IIV were stronger in MCI than CN individuals. Significant interactions between cognitive IIV and biomarker positivity status showed that the effect with amyloid-{beta} IIV was attenuated in A- ({beta} = 0.004, SE = 0.014, p = .78) but that the effect with tau IIV remained robust even in T- individuals ({beta} = 0.088, SE = 0.022, p < .001). Conclusion Elevated cognitive IIV is associated with greater heterogeneity in cortical dispersion of AD-related pathology, particularly in prodromal AD and in the presence of abnormal pathology. As a novel measure that captures variation in topographical scattering of AD pathological burden across the cortex, AD biomarker IIV may offer research and clinical utility beyond evaluating absolute biomarker load or thresholds.

Background: Depressive and anxiety symptoms are prevalent among older adults and associated with increased dementia risk. In healthy older adults, higher step counts are associated with fewer depressive and anxiety symptoms; whether this holds in individuals with cognitive concerns (subjective cognitive decline [SCD] or mild cognitive impairment [MCI]) is unknown. In a randomised controlled trial, the 12-month APPLE-Tree group psychosocial lifestyle intervention produced small cognitive improvements but no change in step count. Objective: To test whether step count was associated with depressive and anxiety symptoms (cross-sectionally and over 24 months), and whether APPLE-Tree increased step count in participants with clinical anxiety or depression. Methods: We examined cross-sectional and longitudinal (12- and 24-month) associations between step count (two-week average from wrist-worn wearables) and depressive and anxiety symptoms (Hospital Anxiety and Depression Scale) using adjusted linear regressions, with a mediation analysis of self-perceived mobility. We also tested whether the intervention increased step count in those with baseline clinical anxiety or depression. Findings: We included 629 of 746 trial participants at baseline, of whom 376 contributed 12-month and 215 24-month data. At baseline, higher step counts were associated with fewer depressive symptoms ({beta} = -0.11, 95% CI -0.17 to -0.05, p < 0.001) but, counter to our hypothesis, more anxiety symptoms ({beta} = 0.12, 95% CI 0.06 to 0.19, p = 0.003). Over two years, change in step count was not associated with change in depressive or anxiety symptoms (all p [&ge;] 0.12). Self-perceived mobility problems mediated the association between step count and depressive but not anxiety symptoms. The intervention did not change step count in those with clinical anxiety or depression. Conclusions: This provides the first evidence in older adults with cognitive concerns that higher step counts are associated with fewer depressive but more anxiety symptoms. This may reflect heterogeneity of a population that includes those with prodromal dementia and cognitive health anxiety. Step count did not predict symptoms over time. Clinical implication: Step count may help distinguish anxiety and depressive symptoms in people presenting with cognitive concerns, or underlying reasons for cognitive concerns among those with functional cognitive disorders.

Motivation: Linkage disequilibrium score (LDSC) regression is a popular method to estimate heritability for complex traits using summary statistics and linkage disequilibrium (LD) reference panels, offering a practical alternative to methods requiring individual-level data. Despite its widespread use, LDSC regression can produce biased heritability estimates. The properties of LDSC regression were investigated using summary statistics from several large-scale Alzheimer's disease (AD) studies and a variety of LD reference panels. These heritability estimates were compared with those obtained from individual-level data. Results: When LDSC regression was applied to summary statistics obtained from meta-analysis, it led to an underestimation of heritability. This can occur if meta-analysis is used to combine studies of different ancestries leading to the caveat of the lack of an appropriate LD reference panel. Additionally meta-analyses often include studies with different phenotype definitions, that not only impacts heritability estimates but also makes them uninterpretable. Summary statistics generated from imputed variants, even those with high imputation accuracy, can lead to underestimation of heritability. For example, the heritability estimates for AD were reduced from 0.265 (se 0.148) to 0.160 (se 0.041) when imputed variants (INFO>0.9) were included compared to analyzing only genotype array variants. A decrease in heritability estimates was also observed when individual-level imputed variant data were analyzed using GCTA-GREML. Our findings highlight the caveats of estimating heritability using meta-analysis summary statistics or imputed data instead of genotyped or sequence data.

Background Physical activity levels are altered across neuropsychiatric disorders. While these traits are heritable, the genetic overlap between normal variation in activity levels and neuropsychiatric disorders that involve motor dysfunction such as schizophrenia and Parkinson's disease (PD) remains unexplored. Objectives To investigate the genetic overlap between physical activity, schizophrenia, and PD. Methods Multi-Trait Analysis of genome-wide association studies (GWAS) was used to boost the GWAS power for objectively measured physical activity (n=89,683) by leveraging three GWAS of self-reported activity (n=124,842-377,234). Genetic overlap between the activity, schizophrenia and PD was characterized using linkage disequilibrium score regression, causal mixture modeling, and local genetic correlations. Pleiotropic variants were identified using the conjunctional false discovery rate, annotated to genes, and investigated for enrichment of biological processes, tissue types and association with GWAS-catalog traits. Results Genetic correlations of physical activity with schizophrenia and PD were negligible (rg=-0.02-0.02, p>0.05), but polygenic overlap was substantial, reflecting mixed effect directions. We identified 32 independent variants shared with schizophrenia and 11 with PD, including CRHR1, MAPT and KANSL1 within the 17q21.31 region. Schizophrenia-shared variants mapped to genes differentially expressed in subcortical regions, especially amygdala and basal ganglia. Gene-set analyses revealed enrichment for mental health and cognitive-behavioural traits (schizophrenia-shared genes) versus structural brain phenotypes and neurodegenerative disorders (PD-shared genes). Conclusions Despite negligible genetic correlations, physical activity shares substantial genetic architecture with schizophrenia and PD. Shared genes implicated brain regions and traits spanning motor and cognitive-affective function, consistent with the psychomotor nature of physical activity.

Study Objectives Co morbid insomnia and sleep apnea (COMISA) is challenging clinically and difficult to treat. Our goal was to assess how much COMISA is the mere addition of two phenotypes or display features indicative of genuine statistical interactions. Methods A total of 152,487 patients from 240 sleep centers across 30 US states were included. Insomnia was defined as difficulty initiating/maintaining sleep with daytime fatigue/sleepiness occurring "often"/"always". OSA was defined as having an Apnea Hypopnea Index (AHI) more than 15 events/h. Modified Poisson regression was conducted to evaluate multiplicative interactions between insomnia and OSA on common comorbidities and sleep symptoms. Additive interactions were also examined. Linear regression models were used to evaluate additive interactions for PSG parameters. The false discovery rate was controlled using the Benjamini Hochberg procedure. Results After adjustment for confounders, insomnia and OSA demonstrated positive interactions for depression, chronic muscular pain, headache, subjective excessive daytime sleepiness (EDS), naps, and pre-sleep anxious and muscular tension (adjusted p < 0.05). Furthermore, insomnia and OSA demonstrated positive interactions for parameters related to respiratory disturbance, including AHI, oxygen desaturation index (ODI), respiratory disturbance index (RDI), total arousal index (AI) and respiratory AI, and negative interactions for minimum oxygen saturation and percentage of rapid eye movement stage (REM%) (adjusted p < 0.05). Furthermore, the adverse effects of insomnia and OSA on AHI, ODI, RDI and REM% were substantially amplified in males. Conclusions Our findings demonstrate that insomnia and OSA do not merely coexist but genuinely interact synergistically to amplify selected adverse clinical outcomes.

Tau pathology is central to Alzheimers disease and related tauopathies, yet mechanisms driving neuronal dysfunction and degeneration downstream of pathological changes in tau remain poorly understood. Drosophila melanogaster models provide a genetically tractable system with an intact nervous system and short lifespan that allows investigation of mechanisms of many diseases. However, in Drosophila, developmental expression of human tau frequently causes lethality and developmental phenotypes, limiting the study of neurodegenerative disease processes. Further, sex is rarely considered in Drosophila studies of tau pathology despite clear sex differences being observed in many aspects of human tauopathies. Here, we used an inducible, pan-neuronal GeneSwitch system to express human tau isoforms exclusively in adulthood, enabling the dissection of tau toxicity independent of development. We combined longitudinal behavioural monitoring with lifespan and neurodegeneration analyses, and performed a targeted genetic screen to identify modifiers of tau-induced dysfunction. Adult-onset tau expression produced striking, sexually dimorphic effects on survival and behaviour. Neuronal expression of the human tau isoform with 4 microtubule binding repeats and neither alternatively spliced N-terminal exon (0N4R tau) caused pronounced neurodegeneration and reduced lifespan, which was exacerbated in flies expressing the phospho-mimetic 0N4R-TauE14 variant. Tau expression produced sexually dimorphic effects on survival and behaviour, with females exhibiting a greater reduction in lifespan, while the induction-dependent increase in vacuolar neurodegeneration was broadly comparable between sexes. Behaviourally, tau expression induced elevated daytime inactivity in females, whereas males exhibited hyperactivity, revealing opposing functional outcomes between sexes. A targeted genetic screen further identified modifiers of tau-dependent behavioural impairment. APOE2 expression in glia, syndecan overexpression in neurons, and increased global expression of the chaperone heat shock protein 90 all reduced 0N4R-TauE14-induced behavioural changes. Seventeen candidate perturbations enhanced the TauE14-induced behavioural phenotype, including manipulations of APOE3, CLU, INPP5D/INPP5K, BIN1/Amph, synaptogyrin, LRP1, NPC1, and Hsp90 pathways. Together, these findings establish an adult-onset Drosophila model of tauopathy that uncouples neurotoxicity from development, reveals sex as a major determinant of tau-induced behavioural outcomes in flies, and uncovers genetic modulators of tau-induced dysfunction. This work highlights the importance of incorporating sex as a biological variable and provides a platform for mechanistic and translational studies of tauopathy.

In many insect species, mating is coordinated through multimodal signaling, yet less obvious channels are often overlooked. In the burying beetle Nicrophorus vespilloides, chemical communication is well-documented, but the role of substrate-borne vibrational signals (stridulations) during courtship remains unknown. We investigated whether stridulation is essential for mating success through two sets of experiments. First, we found a positive correlation between the frequency of stridulations and both the number and duration of copulation events. Second, we employed a silencing experiment to test the necessity of these signals by silencing males, females, or both partners. We found no significant differences between silenced and control groups regarding the frequency or duration of physical contact and mounting events, suggesting that stridulation is not required for mate recognition or the initiation of courtship. However, the proportion of successful copulations relative to mounting events was significantly lower when females were silenced. These results suggest that while N. vespilloides relies on a redundant multimodal system that likely utilizes chemical cues to initiate mating, vibrational signals, particularly from the female, may play a critical role in facilitating successful copulation. This study provides the first evidence for the role of stridulation in the mating behavior of N. vespilloides and highlights the potential for female-mediated vibrational signaling in burying beetle courtship.

Reporters are widely used in Drosophila genetics to visualize gene expression and cell lineages. However, uncharacterized limitations in specific reporter lines can lead to data misinterpretation. Here, we identify a consistent, driver-independent tdTomato signal in the adult proventriculus from the widely used lexAop-tdTomato.nls reporter line. This signal was observed across multiple lexA driver combinations and was directly detectable in lexAop-tdTomato.nls responder-alone adult proventriculi lacking any lexA driver and without antibody staining. In contrast, no comparable native red fluorescence was detected in larval proventriculi under the same no-antibody imaging condition. Mouse and rabbit anti-RFP immunostaining further supported the presence of proventriculus-associated tdTomato/RFP antigen in adult responder-alone animals. In larval responder-alone proventriculi, antibody-amplified staining was antibody-source-dependent: a detectable signal was observed only with rabbit anti-RFP, whereas mouse and rat anti-RFP produced no reliable detectable signal under the same staining condition. A driver-matched comparison using lexAop-RFP.nls did not reproduce the proventricular signal, arguing against detectable ectopic activity of the tested lexA driver in this tissue. However, because lexAop-tdTomato.nls and lexAop-RFP.nls differ in reporter/transgene architecture and possibly genomic insertion context, the underlying cause cannot be assigned specifically to the lexAop sequence. Our findings highlight the necessity of including driver-negative and no-antibody controls when using this reporter line in adult Drosophila proventriculus and gut studies.

Background: Behavioral crises are common and distressing in children with neurodevelopmental or behavioral conditions, and many escalate to emergency service use. Access to behavioral therapy is often constrained. Smartphone applications, in-home systems, and wearable sensors that could support caregivers during crises at home are in active development, but few studies have asked caregivers what they would accept or want from such tools. Methods: We conducted a single-center cross-sectional online survey (REDCap) of caregivers of children aged 5-17 years with neurodevelopmental or behavioral conditions, recruited as a convenience sample through flyers, email invitations, and in-person invitations during clinic visits from the neurobehavioral continuum of care at Cincinnati Children's Hospital Medical Center. The response rate is undetermined due to the open-ended recruitment process. Prior behavioral-crisis experience was not an eligibility requirement. The 24-item instrument covered crisis burden, service utilization, caregiver confidence and training, therapy access and barriers, and technology preferences. Analyses were estimation-first (proportions with Wilson 95% confidence intervals [CIs]; medians with interquartile ranges [IQRs]); three pre-specified bivariate analyses used ordinal methods (Kendall's tau-b and Jonckheere-Terpstra for ordinal pairs; Friedman for repeated ratings of five support functions). Recruitment is ongoing toward a target of 75; this interim analysis includes the first 55 respondents, and all findings are hypothesis-generating. Results: All 55 respondents reported that their child had experienced a behavioral crisis; 44% (95% CI 31-57%) reported crises at least weekly, and 35% (95% CI 23-48%) had ever used 911 or an emergency department for a crisis. Half of caregivers (51%) felt not at all or only a little confident managing crises, and only 46% (95% CI 33-59%) had received informal or formal crisis-management training. The most frequent barrier to behavioral therapy was long waitlists (51%; 95% CI 38-64%). Stated openness to hypothetical technology-based crisis support was high, with 64% (95% CI 50-75%) very interested in a smartphone app or in-home support system, 80% (95% CI 68-88%) willing to have their child use a wearable sensor (1 of 55 declined), and 49% (95% CI 36-62%) willing to share video or audio with a future support tool (a further 42% answered "maybe"; 9% declined). The most-valued features were a personalized crisis plan (58%) and safe de-escalation scripts (49%); the most-cited concern was privacy and data security (36%). Conclusions: In this small, self-selected, single-center sample, caregivers of children with neurodevelopmental or behavioral conditions reported substantial crisis burden, limited training, and constrained access to therapy, alongside high stated openness to technology-based crisis support; personalization and privacy were their leading priorities. These preliminary, hypothesis-generating findings can inform the design of caregiver-facing crisis-support technologies and larger representative studies.

Background Older adults evaluated by consultation-liaison psychiatry services (CLPS) often present with complex psychiatric and medical comorbidity, frequent psychotropic exposure and a high prevalence of frailty. However, the relative contribution of these factors to clinical outcomes remains unclear. Methods We conducted a multicentre prospective cohort study including 465 consecutive patients aged more than 65 years evaluated by CLPS in 10 general hospitals in Spain between January and July 2024. Psychiatric history, postconsultation psychiatric diagnoses, psychotropic use, age group (65-74 vs older than 75 years) and frailty assessed using the Clinical Frailty Scale were recorded. Outcomes included falls, institutionalisation, access to mental health follow-up and mortality at 1 and 3 months after discharge. Results The mean (SD) age was 77.4 (7.8) years and 55.9% were women. Psychiatric history was present in 68.8% of patients and 55.8% received a new psychiatric diagnosis, most commonly delirium. Psychotropic use was frequent (71.6%), particularly antidepressants (49.0%) and benzodiazepines (42.6%). Psychotropic polypharmacy was associated with falls. Frailty was prevalent (60.2%) and independently associated with early mortality, whereas age was the main predictor of mortality between 1 and 3 months. Older age was also associated with a lower likelihood of specialised mental health follow-up. Conclusions Among older adults evaluated by CLPS, frailty and medical comorbidity appear to outweigh psychiatric variables in predicting outcomes. Integrating comprehensive geriatric assessment and medication review into CLPS may improve care for this population.

Study Objectives To develop and initially validate the Circadian Disruption Index (CDI), a self-report measure of circadian disruption, and obtain preliminary evidence of its responsiveness to circadian health education. Methods In Study 1, 244 participants completed a 22-item CDI version and external measures. The sample was randomly divided for exploratory and confirmatory factor analyses. Internal consistency, external associations, and discrimination of poor sleep quality were examined. In Study 2, 72 postgraduate students completed the CDI before and 1 week after a 16-hour circadian health education program in an uncontrolled pre-post design. Results Analyses yielded a 15-item, three-factor structure comprising rhythm stability and light exposure, behavioral habits and diet, and sleep quality and subjective complaints. Total-score internal consistency was acceptable (Cronbach's = 0.871). Confirmatory factor analysis showed a comparative fit index of 0.902 and a root mean square error of approximation of 0.072, although the Tucker-Lewis index was 0.882. CDI scores correlated with sleep quality, chronotype, corrected midsleep on free days, depression, and anxiety, but not social jetlag. The area under the curve for poor sleep quality was 0.807 (95% confidence interval, 0.753-0.862), with an exploratory cutoff of [&le;] 23. In Study 2, CDI scores decreased from 22.26 to 19.88 (p = 0.002; Cohen's dz = 0.36). Conclusions The CDI demonstrated satisfactory internal consistency, a meaningful multidimensional structure, and responsiveness to short-term changes following circadian health education, supporting its potential utility for assessing circadian disruption and monitoring circadian-related behavioral changes.

Background: Sleep disruption is prevalent in people with neurodevelopmental disorders such as autism but is not clear whether it occurs as an endophenotype or secondary to other behaviours. The ABCD Study is a population-based longitudinal study that monitors the health, demography and lifestyle of over 11,000 children in the US. In this study we leverage these data to investigate whether traits consistent with autism (social responsiveness) are associated with sleep disruption independent of lifestyle and other behavioural measures. Methods: Autistic traits were assessed using the Social Responsiveness Scale at age 11, and sleep disruption and behavioural outcomes were assessed at ages 11 and 13 years using the Sleep Disturbance Scale, and the Child Behaviour Check List, respectively. Demographic, health and lifestyle-related variables were assessed by caregiver questionnaires. Regression models were applied to investigate associations between autistic traits and sleep outcomes. Results: There was a significant cross-sectional association between sleep disturbance and SRS at age 11 years old that was independent of sex, ethnicity, socioeconomic position, physical activity, sedentary behaviour and anxiety/depression ({beta} = 0.12, 95% CI (0.07, 0.17); p < 0.001), that persisted at age 13, and that was modulated by chronotype, with evening types showing a stronger association. Discussion: Social responsiveness assessed in early adolescence (age 11) were associated with sleep disruption independent of multiple confounding factors and were prospectively associated with sleep disruption at age 13 years. These findings contribute to the evidence that disruption of sleep and circadian timing may have a primary role in the neurobiological mechanisms that mediate autistic traits.

Background: Bidirectional next-day associations between sleep disturbances and affective symptoms have been shown in previous research, yet the consecutive day effects between these factors remains poorly understood. Methods: We analysed longitudinal ecological momentary assessment (EMA) data obtained from a subsample of young persons in the Brazilian High-Risk Cohort (BHRC) study collected in 2020-2021. Participants reported sleep quality each morning and rated affective symptoms relating to mood, anxiety, and energy four times daily for 28 days. We selected 88 individuals (17.83{+/-}1.74 years, 56 [63.6%] female gender) with at least one instance where individuals were observed three-days in a row. Within-person bidirectional next-day effects between sleep quality and affective symptoms were estimated using mixed-effects regression analysis adjusting. We then applied g-estimation approaches to estimate the effect that lagged sleep quality and consecutive improvements in sleep quality had on affective symptoms. Results: Sleep quality and affective symptoms had bidirectional next-day effects, with sleep quality tending to have greater influence on affective symptoms than the reverse. Improved lagged sleep quality had positive effects on affective symptoms incrementally above the prior night's sleep quality. Also, improvement of sleep quality across consecutive days had incremental and approximately equal effects on affective symptoms. Conclusions: Sleep quality and affective symptoms exhibit a feedback loop, whereby poor sleep quality influences affective symptoms over consecutive days. Breaking these feedback loops, by improving sleep quality across several consecutive nights should improve affective symptoms. This supports interventions that target sustained improvement in sleep and possibly circadian regulation to improve affective symptoms.

Non-suicidal self-injury (NSSI) among adolescents is a prevalent mental health problem and an important indicator of potential suicide risk. Early objective identification and neural mechanism analysis are therefore crucial for clinical screening and intervention. Traditional assessments mainly rely on self-report scales and clinical interviews, which are vulnerable to subjective bias, clinical experience, and missed diagnosis. Electroencephalography (EEG), with its non-invasive, low-cost, and high-temporal-resolution characteristics, provides a promising physiological basis for identifying NSSI-related neural abnormalities. However, EEG-based intelligent recognition of adolescent NSSI remains limited, and existing studies often emphasize classification performance while lacking systematic neurophysiological interpretation. To address these issues, this study proposes CGA-NSSI, a lightweight deep learning framework for adolescent NSSI recognition. The model integrates a one-dimensional convolutional neural network, bidirectional gated recurrent unit, and multi-head self-attention mechanism to extract local spatiotemporal EEG features, model long-range temporal dependencies, and focus on key pathology-related time segments and channels. A standardized preprocessing pipeline, together with Mixup augmentation and Focal Loss, is further used to alleviate sample imbalance and improve robustness in small clinical EEG datasets. Experiments on a real-world adolescent clinical EEG dataset show that CGA-NSSI can effectively identify NSSI-related EEG patterns under imbalanced sample conditions. Interpretability and functional connectivity analyses further reveal prefrontal-centered cross-regional network reorganization, excessive static functional coupling, reduced dynamic connectivity fluctuations, and increased abnormal state occupancy. These findings suggest that CGA-NSSI not only improves objective NSSI recognition but also provides neurophysiological evidence for understanding adolescent self-injury.

The electrophysiological process of auditory transduction in insects remains largely conjecture due to the unknown role of ion channels localised to the cilia, but experimental evidence supports either NompC or Nan-Iav as the auditory mechanotransduction ion channel. Here, we knocked down two key genes that code for the two candidate sound-activated ion channels using dsRNA-mediated RNA interference. We measured sound-evoked activity of the auditory nerve and intracellular electrical currents from the ciliated ending of individual auditory receptors. We found that the sound-evoked nerve activity was reduced in nompC, nan and ift88 knockdown. Using whole-cell patch clamp recordings we found that nompC and nan knockdown resulted in reduced sound-evoked transduction current. Stochastic depolarisations hypothesised to be mediated from one of the candidate mechanotransduction ion channels, either NompC or Nan-Iav, where not affected by knockdown of either channel. The discrete depolarisations are therefore mediated through another unidentified ion channel. We test the hypothesis that discrete depolarisations are graded action potentials that travel toward the soma through noise analysis of the transduction current and analysis of discrete depolarisations to voltage-steps. As a positive control we also knocked down ift88, a protein essential for transporting proteins, including ion channels, along the cilium and found both the transduction current and the discrete depolarisations decreased. Key pointsO_LIInjection of dsRNA decreased RNA of nompC and nan C_LIO_LISound-evoked nerve activity is reduced for RNAi-mediated knockdown of nompC and nan C_LIO_LINompC and Nan both contribute to the transduction current C_LIO_LIThe stochastic discrete depolarisations are not due to NompC or Nan-Iav ion channel but to a third unidentified ion channel. C_LIO_LINoise analysis of the transduction current and the discrete depolarisations suggests they are graded action potentials that travel in the direction of the soma. C_LIO_LIKnockdown of ift88 reduced both the transduction current and discrete depolarisations. C_LI Significance StatementInsects are important to understand, economically, agriculturally and medically. However, we still do not understand fundamental aspects of how insects detect their own body movements, vibrations and sound. These senses are detected by insect chordotonal organs, specialised miniaturised mechanoreceptors that convert movements into electrical signals through specialised ion channels. Previous experimental work has advocated either NompC or Nan-Iav as the mechanosensitive ion channel. Here, for the first time, we reduced the expression of both nompC and nan and measured the sound-evoked transduction current directly from neurons in a specialised auditory chordotonal organ. In contradiction to previous studies, we show that both ion channels contribute to the transduction current and find that electrical signals termed "discrete depolarisations" travel toward the soma.

Background The global prevalence of autism spectrum disorder (ASD) has significantly increased over the past two decades. Despite substantial research advances, critical aspects, including etiology, diagnostic biomarkers, and pharmacological interventions, remain incompletely elucidated. This persistent knowledge gap warrants systematic mapping of the field's evolution to inform future research priorities. Methods A bibliometric analysis of ASD-related publications indexed in Web of Science was conducted from January 2020 to May 2025. Following a systematic deduplication process, original articles, reviews, case reports, and clinical trials were included in the analysis. The analytical framework comprised co-authorship networks, institutional collaboration patterns, national research contributions, and keyword co-occurrence structures, all of which were examined using CiteSpace (version 5.8.R3) and VOSviewer. Results After deduplication, 8,162 publications (January 2020-May 2025) were analyzed. The annual output grew steadily, confirming ASD as a sustained priority in neuroscience. Research remains academia-driven, led by the United States, with China as the second-largest contributor. Chinese institutions place greater emphasis on mechanistic and developmental phenotyping, which aligns with national priorities. These studies maintain strong methodological rigor, and their growing volume underscores the central role of ASD in translational neuroscience. Conclusion Future research on ASD should focus on strengthening case identification, refining clinical phenotyping, and expanding large-scale cohort studies to advance our understanding of its etiology and identify reliable diagnostic biomarkers. It is equally important to develop and evaluate targeted interventions for core symptoms and integrate telemedicine into service delivery models. A critical yet understudied priority is improving the quality of life for autistic individuals and their families, an area in which research globally, including in China, requires greater depth and consistency. With China's growing investment in autism research, it is well-positioned to contribute to these pressing international challenges.