Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by a combination of genetic and environmental factors. With the increasing prevalence of ASD diagnosis, it is crucial to understand the mechanisms behind preventable causes, such as prenatal infections, and look for possible routes to improve outcomes. For example, maternal immune activation (MIA), the process by which immunogens that enter the maternal system lead to a maternal inflammatory response, has been well established as associated with increased ASD diagnosis. However, the mechanisms have not been fully elucidated and the options for targeting MIA as a preventative measure are uncertain. The maternal cytokine response is considered a crucial mechanism underlying MIA-induced neurodevelopmental changes, with key contributing cytokines, which include interleukin (IL)-6 and IL-17a. These cytokines can be produced in the maternal periphery and placenta, leading to the transmission of maternal cytokines into the fetal brain and causing upregulation of endogenous production. In the fetal brain, IL-6 and IL-17a act on microglia, the innate immune cells of the central nervous system, to further induce pro-inflammatory cytokine production. Furthermore, microglia alter fetal brain neurocircuitry, leading to lifelong, ASD-like dysregulation. The vagus nerve, the primary nerve of the parasympathetic nervous system, may serve as a target for intervention. The cholinergic anti-inflammatory pathway can be targeted by vagus nerve stimulation (VNS) and can lead to the downregulation of peripheral cytokines. This review is intended to summarize the cytokine-related mechanisms of MIA, the role of fetal microglia in dysregulation, and to assess the potential for VNS as a preventative treatment measure for MIA-induced alterations.
Toward an NGF-based therapy for Rett syndrome
Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Although recent therapeutic advances, such as the approval of Trofinetide, offer partial relief, no comprehensive curative treatment is currently available. Among the emerging strategies, nerve growth factor (NGF) has gained attention due to its neurotrophic and immunomodulatory properties. This review, in addition to discussing the key features of RTT and the role of growth factors, also highlights recent evidence supporting NGF-based strategies for RTT, focusing on two independent studies that tested intranasal administration of NGF-like molecules in Mecp2-mutant mice. Both recombinant human NGF (rhNGF) and a modified, “painless” variant (hNGFp) improved behavioral (cognitive and motor) symptoms. While rhNGF primarily restored mitochondrial function, hNGFp restored neuroinflammatory responses through microglial regulation. Despite differences in molecular mechanisms and dosages, both molecules demonstrated efficacy without adverse effects, especially when administered intranasally, preventively, and over longer periods. These findings suggest that NGF may act through dual mechanisms, by supporting energy homeostasis and regulating immune responses. The use of intranasal delivery further enhances translational potential by overcoming blood–brain barrier limitations. Together, these studies provide a strong rationale for pursuing NGF-based therapies in RTT and encourage further investigations to optimize dosing, timing, and safety in preclinical and clinical settings.
Impact of extremely low frequency electromagnetic fields exposure on sleep quality and mental health in a Tunisian power plant: a cross-sectional study
IntroductionExtremely low-frequency electromagnetic fields (ELF-EMFs) are ubiquitous in our daily life. They may have an impact not only on physical health but also on mental health.ObjectivesTo assess the impact of occupational exposure to the ELF-EMFs on sleep quality, depression, anxiety and stress among workers at the Tunisian Electricity and Gas Company (TEGC).MethodsThis was a cross-sectional study. The study population included two groups: an exposed group (EG), consisting of power plant employees, and a non-exposed group (NEG), consisting of administrative workers. Exposure to ELF-EMFs was assessed via spot measurements using a magnetometer. Sleep quality, depression, anxiety and stress were assessed by the French versions of the Pittsburgh Sleep Quality Index (PSQI) and the Depression, Anxiety and Stress Scale (DASS-21).ResultsSeventy-seven participants in the EG and 88 participants in the NEG were included in the study. The median value of the ELF-EMFs was 5.86 μT at the power plant [min 0.1, max 40.34 μT]. According to the PSQI global score, 64.9% of the EG had poor sleep quality versus 29.5% of the NEG. Depression was registered in 24.7% of EG and in 3.4% of NEG. Anxiety was noted in 23.4% of the EG and in none of the NEG. Stress was found in 46.8% of the EG and none of the NEG. After multivariate analysis, ELF-EMF exposure was significantly associated with poor sleep quality and depression.ConclusionThe present study revealed that ELF-EMFs can affect sleep and mental health. Further studies are needed to explain the mechanism involved.
Associations of psychological distress, gaming motives and internet gaming disorder in adolescents: a network analysis
Background and objectiveThe rapid popularization of the Internet among Chinese adolescents has resulted in the emergence of a public major concern known as Internet Gaming Disorder (IGD). As demonstrated by previous studies, an association has been demonstrated among emotional distress, gaming motives and IGD. Nevertheless, the specific pathways connecting these constructs remain to be elucidated. The present study aims to explore the network structure characterizing the interactions among these three constructs and to identify potential targets for psychological interventions.MethodsThis was a cross-sectional survey conducted in city of Hangzhou. A total of 3,795 middle school students were included in the analysis. The 21-item Depression Anxiety Stress Scale (DASS-21), the Motives for Online Gaming Questionnaire (MOGQ), and the Chinese version of the Ten-Item Internet Gaming Disorder Test (IGDT-10) were used to assess emotional distress, gaming motives and IGD symptoms, respectively. Network analyses were performed using R4.5.1 software to explore the interrelationships among emotional distress, gaming motives and IGD symptoms, and identify the core symptoms and bridge symptoms.ResultsIn the depression combined network model, the presence of bridge symptoms was indicated by no initiative (D2), gaming for escape or mood relief (IGD8) and fantasy motive (fan). In anxiety combined network model, the bridge symptoms included coping motive(cop), gaming for escape or mood relief (IGD8), withdrawal (IGD2), mouth dryness (A1), and fear of embarrassment (A4). The bridge symptoms in the stress combined network model were gaming for escape or mood relief (IGD8), difficulty winding down (S1), withdrawal (IGD2), nervous energy expenditure (S3), and coping motive (cop).ConclusionThe present study explored complex network structure among psychological distress, gaming motivation, and IGD. and suggested fantasy and coping motive as bridges connecting psychological distress and IGD. Besides, our research identified no initiative, mouth dryness, difficulty winding down, fear of embarrassment, and nervous energy expenditure as the best targets for intervention to reduce IGD.
Sex-specific impact of vitamin D and B9 concentrations on neuroticism: a polygenic score-based study
IntroductionNeuroticism is a personality domain with prognostic value for physical and mental health. To properly inform public health policy, it is crucial to uncover the mechanisms underlying high neuroticism. Many internal and external factors that affect brain development and functioning and therefore might contribute to the variability of neuroticism remain understudied. Among them, the impact of vitamin sufficiency is of great interest, as it is a modifiable factor. This study aimed to evaluate the associations of neuroticism with vitamin D (VD) and vitamin B9 (VB9) using polygenic scores (PGS) in a nonclinical cohort.MethodsWe analyzed data from 348 healthy unrelated individuals, including neuroticism scores on the Eysenck Personality Inventory, VD-PGS, VB9-PGS and PGS for neuroticism-related traits.ResultsThe analysis controlling for demographic and genetic confounders revealed a negative association between VB9-PGS and neuroticism scores in women and a positive association between VD-PGS and neuroticism scores in men. The highest values of the VD-PGS were observed in men, who scored high on both neuroticism and extraversion. In men, unlike women, neuroticism scores were not correlated with PGS for neuroticism but were associated with PGS for bipolar disorder type 1 and alcohol use disorders.ConclusionThe results suggest that the effects on neuroticism of genetic propensity for suboptimal vitamin D and B9 concentrations might differ across the two sexes. The findings are consistent with the idea of the importance of vitamin B9 for emotional stability in women and indicate the involvement of genetic factors predisposing to higher vitamin D levels in excitability-related components of neuroticism in men.
Mental health in the time of polycrisis: geopolitical determinants and modern psychiatry
Psychiatry is increasingly being practised in environments affected by geopolitical instabilities, including economic fragmentation, democratic backsliding, and widening inequities. The confluence of these phenomena contributes to what has been described as a contemporary polycrisis, encompassing synchronous disruptions that reinforce one another and threaten collective wellbeing. Nevertheless, psychiatric research and clinical work have generally remained oriented towards immediate determinants and risk factors, overlooking the macro-level political and institutional dynamics that can condition stressor exposure and mental health disparities. Amidst, interconnected crises, this paper advances geopsychiatry as a framework for understanding how distal geopolitical determinants translate into psychiatric vulnerabilities across communities and societies. Focussing on armed conflicts, climate change, and forced migration as emblematic domains of polycrisis, it highlights how these compounding phenomena are generating direct mental health burdens and may amplify harms via secondary pathways. Moreover, it contends that the psychiatric consequences of polycrisis are unlikely to be ameliorated through patient-centred interventions alone, but also require innovative approaches responsive to structural inequalities and material forces that transcend borders. In this context, work from geopsychiatry can offer important implications for modern psychiatry, highlighting a need for a more globally representative evidence base, potential clinical adaptations, and policy engagement that better attends to the geopolitical determinants of mental health.
Adult attachment and intimate relationship satisfaction among university students: the chain mediating roles of appreciation and sense of giving
BackgroundSatisfying intimate relationships are fundamental to young adults’ psychological well-being. Although adult attachment theory provides a robust framework for understanding relationship quality, the mechanisms linking higher attachment anxiety and avoidance to lower relationship satisfaction remain underexplored. This study tested a chain mediation model in which appreciation (both expressed and felt) and sense of giving sequentially mediate the link between insecure attachment and relationship satisfaction.MethodsA cross-sectional survey was conducted with 536 university students (mean age = 21.67 years; 55.8% female) currently in romantic relationships. Participants completed validated self-report questionnaires assessing higher attachment avoidance and anxiety, appreciation (appreciating one’s partner and feeling appreciated), sense of giving, and relationship satisfaction. Chain mediation analyses were performed using the SPSS PROCESS macro with 5,000 bootstrap resamples to evaluate the significance of indirect effects.ResultsAttachment significantly and negatively predicted relationship satisfaction. In the first chain mediation model, higher levels of both attachment avoidance and anxiety were negatively associated with appreciation of one’s partner. Appreciation, in turn, was positively associated with a greater sense of giving, which was subsequently linked to higher relationship satisfaction. After controlling for demographic and relational covariates, the key findings remained robust. The sequential indirect effect (Attachment → Appreciating → Giving → Satisfaction) was significant for both higher attachment avoidance (effect = -0.17, 95% CI [-0.22, -0.14]) and anxiety (effect = -0.07, 95% CI [-0.10, -0.03]). Similarly, the sequential indirect effect through feeling appreciated (Attachment → Feeling Appreciated → Giving → Satisfaction) was significant for both higher avoidance (effect = -0.10, 95% CI [-0.14, -0.07]) and anxiety (effect = -0.09, 95% CI [-0.12, -0.06]).ConclusionInsecure attachment was negatively associated with intimate relationship satisfaction through a sequential pathway involving appreciation and sense of giving. These cross-sectional findings suggest that appreciation processes may represent a promising intervention target. Clinical or preventive strategies enhancing the expression and perception of appreciation could potentially improve relationship satisfaction among young adults with insecure attachment orientations.
The value of patient-focused drug development
Nature Medicine, Published online: 24 April 2026; doi:10.1038/s41591-026-04364-z
The value of patient-focused drug development
Targeted therapies plus radiotherapy for diffuse intrinsic pontine glioma: the randomized phase 2 BIOMEDE trial
Nature Medicine, Published online: 24 April 2026; doi:10.1038/s41591-026-04354-1
In a biomarker-driven trial evaluating radiotherapy with erlotinib, everolimus or dasatinib in patients with newly diagnosed diffuse intrinsic pontine glioma, the primary endpoint of overall survival was not met, but features associated with long-term survival were defined, and everolimus emerged as a potential candidate for further testing.
Cross-reactive anti-prophage antibodies and bacterial heteroresistance implicated in phage therapeutic failure
Nature Medicine, Published online: 24 April 2026; doi:10.1038/s41591-026-04301-0
A 22-year-old patient with cystic fibrosis and chronic, drug-resistant Bordetella bronchialis infection received compassionate-use phage therapy. Serum samples revealed that pre-existing antiphage immunity existed before treatment, indicating that future studies must evaluate antiphage immunity across the entire treatment regimen.