Breast cancer (BC) is a leading cause of mortality among women. Comorbidity with mood disorders is a condition either disregarded or underdiagnosed in BC patients, but that might ultimately jeopardize health trajectories. This is supported by evidence indicating that the same biological pathways relevant for mood disorders may also underlie tumorigenesis. In this study, we aimed at deriving a reliable biosignature of mental health vulnerability in BC patients. We conducted a cross-sectional study in a population of 44 women diagnosed with BC who underwent surgery before receiving adjuvant chemotherapy. All subjects were scored for symptoms of depression, anxiety and stress; blood samples were used to measure relevant biomarkers of inflammation, energy homeostasis and brain plasticity, while circadian cortisol rhythm was assessed in the saliva. Based on a rigorous statistical approach, we identified a specific immune- metabolic biosignature of depression relying upon each subject’s BMI, IL-5 and leptin. Following the validation of the model, we defined a cut-off value to identify those subjects who are at elevated risk of poor prognosis based on our biosignature. This signature holds potential for the timely identification of those individuals for whom depressive symptoms are sustained by a deranged immune-metabolic milieu and might therefore be at higher risk of poorer health outcomes. Our results strengthen the importance of accounting for brain-body communication in cancer and suggest that routine screening for mental health in BC patients should be prioritized in order to put in place tailored intervention strategies to improve health outcomes.

The beneficial effects of omega-3 polyunsaturated fatty acids (PUFA) supplementation during pregnancy have been associated with reduced risk of preterm birth and low birthweight. However, inconsistent findings have been reported regarding their impact on children's neurodevelopmental trajectories. We performed a comprehensive systematic review with meta-analysis of preclinical studies to assess the effects of prenatal omega-3 supplementation on long-term outcomes in offspring and to identify key relevant neurodevelopmental domains to guide the design and prioritization of future clinical follow-up studies. The databases consulted included PubMed/Medline, Scopus and Web of Science. Thirty-five studies were included in the systematic review, and 19 studies were included in the meta-analysis. Relevant information such as characteristics of nutritional interventions, maternal conditions, offspring characteristics and article attributes were extracted. Sample sizes, means, and standard deviation or standard error for the outcome measures were also extracted. The search yielded 3198 articles; 35 met inclusion criteria, with 11 included in a random-effects meta-analysis of memory retention, and 8 in a meta-analysis of brain-derived neurotrophic factor (BDNF) levels. Our findings show that maternal omega-3 PUFA supplementation during pregnancy improves memory retention (SMD=0.671; CI 95 %: 0.163-1.179; p = 0.010) and increases levels of BDNF (SMD=0.838; CI 95 %: 0.369-1.307; p = 0.000) in the offspring. These effects are more pronounced in offspring exposed to prenatal adversities. Maternal omega-3 supplementation shows promise in mitigating oxidative stress and inflammation, although findings remain heterogeneous. Maternal omega-3 supplementation appears as a safe and effective means to improve offspring neurodevelopment, with stronger effects under adverse gestational conditions, highlighting its potential for at-risk populations.

IntroductionMajor depressive and bipolar disorders are prevalent mental health conditions sharing the presence of major depressive episodes (MDEs). While psychopharmacological and psychological therapies are first-line treatments for MDEs, the response is often incomplete. New approaches focused on the human-nature relationship might complement antidepressant treatments, improving response. MethodsThis observational pilot study aims to assess the feasibility of implementing regular exposure to green environments such as woods, forests, large parks, and gardens for at least forty-five minutes twice a week in a sample of patients experiencing a MDE who require adjustments to their antidepressant therapy. It also has the purpose of detecting changes in symptoms and inflammatory biomarkers at follow-up after six weeks.ResultsFifty-three patients were evaluated at the baseline; thirty-one completed the study. Nineteen (61%) of the completers reported regular exposure to greenery during the study. At follow-up, actively exposed patients showed trends of improvements in depressive symptoms, lower levels of C-reactive protein and interleukin-6, and higher adiponectin concentrations.DiscussionThis result suggests that incorporating green exposure into clinical practice is feasible and potentially useful. However, more rigorous evaluations on larger samples are needed to verify whether exposure to greenery may complement MDEs treatment and favorably impact MDE-associated inflammatory processes.

While a clear association between maternal obesity and an increased risk for neuropsychiatric disorders in the offspring has been described, the underlying mechanisms remain poorly understood. We hypothesised that a maternal high-fat diet (mHFD) would act as a stressor, increasing glucocorticoids, resulting in an altered redox balance and disrupted neuronal plasticity of the limbic system. Such enduring effects would impair the emotional and cognitive profile, neuroendocrine responses, and metabolic and redox homeostasis in the adult offspring. We utilised a mouse model and a translational cellular model employing human neurons derived from inducible Pluripotent Stem Cells (iPSCs) to evaluate the impact of mHFD on neurodevelopment and to test the protection afforded by the antioxidant N-acetyl-cysteine (NAC). Our approach combined behavioural and metabolic phenotyping, biochemical assays, morphological assessment, and targeted gene expression analysis. Results indicate that prenatal administration of NAC prevented anxiety-like and risk-taking behaviours, cognitive impairments and metabolic alterations in mHFD adult mouse offspring, particularly in females. These changes were accompanied by hippocampal downregulation of genes involved in neuronal plasticity, such as BDNF. Using human neurons in vitro, pre-treatment with NAC rescued the negative effects of glucocorticoids on neuronal plasticity via a BDNF-mediated mechanism. The protective effects of NAC over mHFD in females suggest that rebalancing the redox status could be exploited as an overall strategy to buffer the negative effects of early adversities on neurodevelopment.

Major depressive disorder and bipolar disorders are prevalent mental health conditions that significantly impact quality of life and life expectancy. These mood disorders involve major depressive episodes (MDE), which pose a substantial burden for patients and their families. While psychopharmacological therapies are a first-line treatment for MDE, the response is often incomplete. New approaches focused on the human-nature relationship may potentially complement antidepressant treatments, thus reducing psychopharmacological needs. This study aims to evaluate whether green exposure affects depressive symptoms and inflammatory biomarker levels in patients with MDE. This prospective study examined the association between exposure to green environments such as woods, forests, large parks, and gardens for at least 45 minutes twice a week, depressive symptoms, and inflammatory biomarkers in 31 patients with an ongoing MDE. The findings suggest that exposure to greenness, together with the modification of antidepressant therapy, is associated with improved depressive symptoms, lower levels of inflammatory biomarker interleukin-6, and higher concentrations of adiponectin after six weeks of treatment. These results suggest that exposure to green environments may have a favorable impact both on mental health and on inflammatory processes, and thus represent a complementary therapeutic strategy. Such information could be relevant to clinicians and urban planners.

Adverse maternal conditions during pregnancy result in an increased risk for neuropsychiatric disorders in the offspring, although the underlying mechanisms are poorly understood. We have recently shown that two distinct insults, prenatal stress (PNS) or maternal high-fat diet (mHFD), increase inflammation and oxidative stress in the brain of adolescent female mice. Here, we sought to investigate the early mechanisms underlying such effects, focusing on the placenta and fetal brain, as well as the protective effects of the antioxidant N-acetyl-cysteine (NAC), in C57Bl6/N mice. We used a multi-disciplinary approach combining proteomic, metabolomic, lipidomic and histological analysis to characterize the structural and functional changes of the placenta; moreover, a targeted gene expression analysis was carried out in the brains of male and female fetuses to evaluate oxidative stress and inflammatory-related changes. Our data highlight comparable, but sex-specific, responses to the two maternal stressors, which target placenta and fetal brain, and are buffered by NAC administration. Placental function was specifically disrupted in males, with signaling pathways of cardio-metabolic risk emerging in this sex. By contrast, fetal brain was affected in females, with an increased expression of genes related to inflammation and oxidative stress. In conclusion, we provide evidence for an early origin of sex-dependent embedding of prenatal adverse experiences in different organs which might explain differential susceptibility to later disease trajectories.

Current evidence points to a research-practice gap in mental health. There is a specific unmet need to identify novel strategies to improve diagnostic criteria, especially when clinical manifestations overlap as in the case of bipolar (BD) and major depressive disorder (MDD). Based on the rapidly evolving notion that affective disorders are characterized by disrupted brain-body communication, current efforts of neuropsychiatric research are converging towards the identification of specific clusters of peripheral interconnected biomarkers. We argue that these can capture the complexity of the disease as they are linked to the fundamental pathophysiological mechanisms underlying BD or MDD, and can thus deliver an unbiased biosignature. Here we provide a critical viewpoint on the promises and challenges of biomarkers to identify reliable biosignatures of affective disorders. Novel methodological insight and relevant biomarkers are discussed with a main focus on immunometabolic derangements and disrupted redox balance. Major advancements are reviewed taking into consideration that an unbiased diagnosis can only derive from a deep understanding of how biological, psychological, and social factors interact ultimately affecting the clinical manifestation of affective disorders.

Predicting disease trajectories in patients with major depressive disorder (MDD) can allow designing personalized therapeutic strategies. In this study, we aimed to show that measuring patients’ plasticity – that is the susceptibility to modify the mental state – identifies at baseline who will recover, anticipating the time to transition to wellbeing. We conducted a secondary analysis in two randomized clinical trials, STAR*D and CO-MED. Symptom severity was assessed using the Quick Inventory of Depressive Symptomatology while the context was measured at enrollment with the Quality-of-Life Enjoyment and Satisfaction Questionnaire. Patients were retrospectively grouped based on both their time to response or remission and their plasticity levels at baseline assessed through a network-based mathematical approach that operationalizes plasticity as the inverse of the symptom network connectivity strength. The results show that plasticity levels at baseline anticipate time to response and time to remission. Connectivity strength among symptoms is significantly lower – and thus plasticity higher – in patients experiencing a fast recovery. When the interplay between plasticity and context is considered, plasticity levels are predictive of disease trajectories only in subjects experiencing a favorable context, confirming that plasticity magnifies the influence of the context on mood. In conclusion, the assessment of plasticity levels at baseline holds promise for predicting MDD trajectories, potentially informing the design of personalized treatments and interventions. The combination of high plasticity and the experience of a favorable context emerges as critical to achieve recovery.

In pursuit of excellence in scholarly publishing, the Neuroscience editorial team shares valuable insights that are essential for authors, reviewers, and the broader scientific community. Firstly, we emphasize that impactful research is built on rigorous study design and execution. Beyond fundamental methodological safeguards such as randomization and blinded analysis, we highlight the importance of thoughtfully selecting study models, with deliberate attention to biological variables like sex and gender, as well as appropriate nomenclature. Secondly, as technological innovations reshape research landscapes, we advocate for combining methodological rigor with suitable analytical tools to ensure robust data collection and transparent reporting. Thirdly, for manuscripts reaching the revision stage, we frame the response to reviewers as a strategic process that requires objectivity, diplomacy, and evidence-based rebuttals where necessary. Finally, we call for intentional prioritization of inclusivity and diversity across all stages of scientific inquiry - from laboratory collaborations to editorial decisions - and urge stakeholders to actively counteract implicit biases in manuscript evaluation and citation practices. By embedding these principles into the scientific workflow, we argue that the research community can foster not only greater rigor but also a more equitable and innovative scholarly ecosystem.

BACKGROUND:The role of physical activity (PA) in addressing mental health issues across the lifespan is expanding. Although the focus is primarily on the adult population, this underestimates the potential implementation of these complementary interventions in children and adolescents. AIM:We synthesize the outcomes of umbrella reviews addressing the effectiveness of structured PA on young people's mental health. METHODS:We searched the literature following the PRISMA-ScR methodology for systematic searches consulting the electronic databases of Pubmed, Cochrane Reviews Library, PsycINFO, and PsycArticles, with pre-established eligibility criteria. RESULTS:We included 13 umbrella reviews, published from 2011 to 2023, comprising 91 systematic and meta-analytic reviews. Exercise is the most frequent form of PA (11/13), followed by sports (4/13), dance (3/13), and yoga (1/13). The most consistent positive effects of PA in this portion of the population concerned depressive symptoms, followed by anxiety symptoms. Promising effects were reported for attention, hyperactivity, and impulsivity. Other mental health-related outcomes that emerged as positively influenced by PA concern suicidal ideation, self-esteem, and social functioning, with positive effects of exercise and sport. CONCLUSIONS:We suggest that structured PA has promising effects on youth's mental health although more evidence needs to be gathered. Indeed, although most of the umbrella reviews were of high quality, some methodological weaknesses of primary studies were noted, such as the large data heterogeneity, which, if not adequately addressed, can lead to results that underestimate the complexity of applying PA in clinical practice. Future RCT studies are needed to verify the effectiveness of rigorous PA programs on selected psychopathologies, allowing to expand the current evidence-based recommendations and guidelines, tailoring interventions comprising sport and physical activity to the specific needs of youth.

L'agricoltura sociale è sempre più riconosciuta come elemento di innovazione sociosanitaria, grazie al suo potenziale nell'inserimento sociale e lavorativo di persone con disabilità mentale e/o in condizioni di svantaggio. Tuttavia, la ricerca e la valutazione quantitativa in questo ambito sono ancora agli inizi, e le evidenze sugli effetti su comportamento e abilità sociali e lavorative restano limitate. Questo contributo descrive lo "Strumento Operativo per l'Inserimento socio-lavorativo in Agricoltura – SOIA", adottato nel Progetto Territori Solidali Organizzati – TSO (Regione Lazio, PO FSE 2014-2020) per monitorare i percorsi personalizzati di inclusione socio-lavorativa di 25 partecipanti con fragilità o disagio psichico, selezionati e presi in carico dalle aziende agricole partner. L'analisi dei questionari SOIA ha evidenziato l'efficacia dei percorsi, confermando lo strumento come valido supporto per valutare e monitorare abilità e comportamenti lavorativi nei contesti di agricoltura sociale.

OBJECTIVE:Parental stress in pediatric epilepsy is often linked to seizure-related factors. However, less is known about the contribution of child cognitive functioning, behavioral symptoms, and treatment complexity to caregiver burden. This study aimed to investigate how these variables, along with sociodemographic factors, predict perceived parental stress. METHODS:We conducted a cross-sectional study including 117 children with epilepsy and 149 caregivers. Cognitive functioning was classified through standardized assessments; behavioral symptoms were evaluated using the Child Behavior Checklist (CBCL); and parental stress was measured with the Parenting Stress Index-Short Form (PSI-SF). Clinical variables included epilepsy etiology, seizure control, drug resistance, and medication regimen. Group comparisons and regression models were used to explore predictors of stress. RESULTS:Higher stress levels were observed among parents of children with moderate intellectual disability, compared to those with normal cognition. Clinical-range behavioral symptoms-especially internalizing problems-were significantly associated with elevated stress across PSI domains. Parents of children receiving polytherapy or with drug-resistant epilepsy reported higher levels of dysfunctional parent-child interaction. Lower educational attainment was also linked to greater stress. Although no stress differences emerged by caregiver gender, most participants were mothers. Notably, elevated Defensing Responding scores suggested a potential underreporting of caregiver burden. SIGNIFICANCE:These findings indicate that child cognitive and behavioral characteristics, along with treatment complexity, play a greater role in parental stress than core epilepsy variables alone. It is notable that, the tendency to underreport stress may obscure caregiver needs, especially in clinical settings relying solely on self-report measures. Routine caregiver screening and multimodal assessment strategies-including interviews and observations-should be integrated into epilepsy care pathways. Supporting caregiver well-being is essential to sustaining family functioning. It aligns with the priorities outlined in the World Health Organization (WHO) Intersectoral Global Action Plan (IGAP), which highlights caregiver support as a key pillar of person- and family-centered care for neurological conditions.

Good brain health plays a significant role in an individual's well-being and profoundly impacts the collective economy and society. Brain development does not stop at birth, and some aspects continue throughout childhood and adolescence, allowing the full development of cognitive functions. Different determinants related to physical health, healthy environments, safety and security, life-long learning and social connection as well as access to quality services influence the way our brains develop, adapt and respond to stress and adversity. Ongoing progress in neurobiology and cognitive neuroscience allows the design of better prevention and intervention strategies to help avoid brain deficits and/or limit their impact and maintain brain health. The European Brain Council (EBC) convened an expert meeting during the Federation of European Neuroscience Societies (FENS) Forum 2024 to address youth brain health challenges. In recent years, the importance of brain health has garnered significant attention across scientific, medical and policy-making communities. Although much focus has traditionally been on neurodegenerative conditions affecting the elderly, a paradigm shift towards prioritizing brain health in youth is both timely and necessary. This shift can profoundly impact individual lives and society, necessitating an interdisciplinary approach that brings neuroscience to the forefront of public health and informs evidence-based policy. The topic is of utmost importance as EBC launched this year a new campaign on No Health Without Brain Health rallying support with its member organizations and the wider brain community for the increased prioritization of brain health on EU health and research agendas.

Brain health is a pressing global concern. Poor diet quality is a recognized major environmental risk factor for brain disorders and one of the few that is modifiable. There is substantial evidence that nutrition impacts brain development and brain health across the life course. So why then is the full potential of nutrition not utilized to improve brain function? This commentary, which is based on discussions of the European Brain Research Area BRAINFOOD cluster, aims to highlight the most urgent research priorities concerning the evidence base in the area of nutrition and brain health and identifies 3 major issues that need to be addressed: (1) increase causal and mechanistic evidence on the link between nutrition and brain health, (2) produce effective messages/education concerning the role of food for brain health, and (3) provide funding to support collaborative working across diverse stakeholders.

It is becoming increasingly recognized that, in addition to psychological stress, unbalanced maternal nutritional habits can threaten fetal brain development. Maternal obesity is one of the most pressing public health problems facing the world today, as about 40% of pregnant women are obese or gain excessive weight worldwide. This condition can negatively impact offspring's brain development, increasing the risk for autism spectrum disorders, cognitive deficits, attention deficit hyperactivity disorder, as well as anxiety and depression. In the context of fetal development, nutritional interventions may represent a feasible and safe approach for preventing the negative effects of maternal obesity. We argue that maternal Omega-3 supplementation, among the many dietary strategies available, is especially promising as it buffers oxidative stress and inflammation, both recognized as candidate mechanisms underlying the negative long-term effects of maternal obesity on the offspring. Notwithstanding the current knowledge, both preclinical studies and clinical trials are needed to refine current strategies addressing dietary content and length of administration according to individual characteristics and needs.

Introduction Bipolar disorder (BD) is characterised by heterogeneous phenotypic manifestations that may affect the achievement of a timely diagnosis delaying its therapeutic management. Increased circulating levels of pro-inflammatory cytokines and cortisol (CORT) have been observed in BD patients in addition to decreased levels of Brain-Derived-Neurotrophic Factor (BDNF) suggesting that the interaction among these mediators may play a role in the occurrence of affective episodes overall disrupting brain plasticity. However, knowledge on BD etiopathogenesis is still limited, including the causal relationship with inflammatory and neuroendocrine markers. Objectives To assess whether variations in peripheral neuroendocrine and inflammatory markers during acute phases of the disease and euthymia might predict the occurrence of affective episodes; to evaluate whether the interplay among these biomarkers might be exploited as a signature of BD. Methods We are currently recruiting BD patients during depressive or manic/hypomanic phases together with age- and sex-matched healthy controls (CTRLs). Complete blood count, pro-inflammatory, anti-inflammatory cytokines and BDNF will be assessed in serum; salivary cortisol awakening response test will be used to evaluate hypothalamic-pituitary-adrenal axis activity. MADRS, YMRS and HAM-A will be used to assess psychiatric symptoms, PSP and C-SSRS for global functioning and suicidal risk, IPSS and SRRS for stress levels and CIRS to evaluate physical comorbidities. All assessments will be carried out at the time of recruitment (T0) and after 3 (T1) and 6 (T2) months. Results Data have been so far collected on 28 BD patients (18 males, 10 females, age: 48.31±11.3) and 26 CTRLs (16 males, 10 females, age: 46.82±10.86). At T0, BD were characterised by a greater total number of white cells (7.83±1.86 BD vs. 6.78±1.87 CTRL, p<0.05), mean number of neutrophils (4.89±1.49 BD vs. 3.92±1.45 CTRL, p<0.05) and neutrophil/lymphocyte ratio (NLR) (2.52±1.1 BD vs. 1.9±0.69 CTRL, p<0.05). Moreover, BD patients showed overall a greater BMI (30.5±6.6 BD vs. 24.45±3.86 CTRL, p<.001). No difference was observed among groups with respect to sex and age. Conclusions Although preliminary, these results suggest that the active phases of BD are associated with a low-grade inflammatory state, potentially related to a different metabolic set-point in BD patients. Ultimately, this study will allow us to evaluate whether the presence of affective symptoms is correlated with fluctuations in the levels of inflammatory mediators, salivary cortisol and BDNF and to establish a reliable and highly predictive BD signature. “Funded by: Bando Ricerca Indipendente ISS 2021-2023 to A. Berry project code ISS20-9286e4091f8e” Disclosure of Interest None Declared