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Background: Enabling, supporting and promoting positive health-related behaviours is critical in addressing the major public health challenges of our time, and the multifaceted nature of behaviours requires an evidence-based approach. This statement seeks to suggest how a much-needed enhanced use of behavioural and cultural science and insights for health could be advanced. Study design and methods: and methods: Public health authorities of Europe and Central Asia and international partner organizations in September 2023 met in Copenhagen, Denmark, to discuss the way forward. Drawing on 1) country reporting to WHO, 2) interview study with public health authorities and 3) the meeting deliberations, this meeting statement was developed. Results: The meeting statement presents a joint call for step-change accelerated use of evidence-based approaches for health behaviours. Actionable next steps for public health authorities and international and regional development partners in health are presented. Conclusions: The way forward involves increased resource allocation, integration of behavioural insights into health strategies, advocacy through case and cost-effectiveness examples and capacity building.

Abstract Maternal obesity has been recognized as a stressor affecting the developing fetal brain, leading to long-term negative outcomes comparable to those resulting from maternal psychological stress, although the mechanisms have not been completely elucidated. In this study, we tested the hypothesis that adverse prenatal conditions as diverse as maternal stress and maternal obesity might affect emotional regulation and stress response in the offspring through common pathways, with a main focus on oxidative stress and neuroplasticity. We contrasted and compared adolescent male and female offspring in two mouse models of maternal psychophysical stress (restraint during pregnancy - PNS) and maternal obesity (high-fat diet before and during gestation - mHFD) by combining behavioral assays, evaluation of the hypothalamic–pituitary–adrenal (HPA) axis reactivity, immunohistochemistry and gene expression analysis of selected markers of neuronal function and neuroinflammation in the hippocampus, a key region involved in stress appraisal. Prenatal administration of the antioxidant N-acetyl-cysteine (NAC) was used as a strategy to protect fetal neurodevelopment from the negative effects of PNS and mHFD. Our findings show that these two stressors produce overlapping effects, reducing brain anti-oxidant defenses (Nrf-2) and leading to sex-dependent impairments of hippocampal Bdnf expression and alterations of the emotional behavior and HPA axis functionality. Prenatal NAC administration, by restoring the redox balance, was able to exert long-term protective effects on brain development, suggesting that the modulation of redox pathways might be an effective strategy to target common shared mechanisms between different adverse prenatal conditions.

Abstract Background The coronavirus disease of 2019 (COVID‐19) pandemic is an unprecedented traumatic event that has severely impacted social, economic, and health well‐being worldwide. The COvid Mental hEalth Trial was specifically designed to evaluate the impact of the COVID‐19 pandemic and its containment measures on the mental health of the Italian general population in terms of COVID‐19‐related acute stress disorder (ASD) symptoms. Methods The present cross‐sectional study is based on an online survey carried out in the period March–May 2020. Italian general adult population was invited to compile an anonymous survey, which included the severity of acute stress symptoms scale/National Stressful Events Survey Short Scale to investigate the occurrence and severity of ASD symptoms. Results The final sample consisted of 20,720 participants. During the lockdown, subjects with pre‐existing mental health problems reported a statistically significant higher risk of acute post‐traumatic symptoms compared to the general population (B: 2.57; 95% CI:2.04–3.09; p

Abstract Background Use of social media (SM) has exponentially grown particularly among youths in the past two years, due to COVID-19-related changing lifestyles. Based on the Italian COvid Mental hEalth Trial (COMET), we investigated the association between SM use and depressive symptoms among Italian young adults (aged 18–24). Methods The COMET is a nationwide multi-center cross-sectional study that investigated socio-demographic data, social networking addiction (BSNAS), depression, anxiety, and stress (DASS-21), as well as impulsiveness (BIS-15) and aggressiveness (AQ) in a large sample of youngsters, in order to assess the association between BSNAS and DASS-21 indices. Mediation analyses were performed to evaluate the role of impulsiveness and aggressive personality traits in the association between SM use (SMU) and depression. Results 75.8% of the sample (n = 491) had a problematic SMU. SMU was reduced by high AQ and high DASS-21 scores (F = 42.338, p

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 ± 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 ± 0.1 h vs. 4.9 ± 0.02; p

Abstract The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.

Background: The COVID-19 pandemic has heavily impacted social, economic and health systems worldwide. Necessary confinement measures have, in turn, contributed to the occurrence of several stress-related conditions and deterioration of pre-existing mental conditions, including insomnia. Objective: The present study sought to investigate the occurrence and severity of insomnia during the COVID-19 lockdown among psychiatric patients and in the general population in the largest Italian sample examined to date. Potential factors associated with a risk of developing insomnia in the global sample were examined as well. Methods: A sample of 20,720 people (5.5% of them being psychiatric patients) was assessed through an online survey conducted during lockdown between March and May 2020. To investigate the occurrence and severity of sleep related issues, the Insomnia Severity Index (ISI) was used. In order to evaluate factors associated with the severity of insomnia in the global sample, multivariate linear regression models were performed. Results: During the lockdown, patients with pre-existing mental disorders reported a mean higher score on the ISI scale (p

A growing body of evidence suggests that regular consumption of natural products might promote healthy aging; however, their mechanisms of action are still unclear. Rosmarinic acid (RA) is a polyphenol holding anti-inflammatory, antioxidant and neuroprotective properties. The aim of this study was to characterise the efficacy of an oral administration of RA in promoting healthspan in a mouse model of physiological aging. Aged C57Bl/6 male and female (24-month-old) mice were either administered with RA (500 mg/Kg) or a vehicle in drinking bottles for 52 days while 3-month-old mice receiving the same treatment were used as controls. All subjects were assessed for cognitive abilities in the Morris water maze (MWM) and for emotionality in the elevated-plus maze test (EPM). Brain-derived Neurotrophic Factor (BDNF) protein levels were evaluated in the hippocampus. Since the interaction between metabolic signals and cerebral functions plays a pivotal role in the etiopathogenesis of cognitive decline, the glycaemic and lipid profiles of the mice were also assessed. RA enhanced learning and memory in 24-month-old mice, an effect that was associated to improved glucose homeostasis. By contrast, the lipid profile was disrupted in young adults. This effect was associated with worse glycaemic control in males and with reduced BDNF levels in females, suggesting powerful sex-dependent effects and raising a note of caution for RA administration in young healthy adult subjects.

Equine-assisted activities (EAAs) are considered a suitable innovative rehabilitative practice for children with neurodevelopmental disorders, including autism spectrum disorder (ASD). While standardized scales have been previously used as a tool to evaluate the effects of EAAs on different domains of functioning in ASD children, few studies have considered an ethological approach as a means to describe human–horse interactions in the context of ASD. In this study, we aimed to evaluate the behavior of 19 children with ASD, in comparison with 19 typically developing children (TD), during EAA sessions. We developed an ethogram from the video recordings to assess spatial relationships, social interactions, and communicative behaviors displayed by the child toward the horse, as well as the occurrence of problem behaviors. Results indicate that children’s behaviors during EAA sessions are modulated by sex and age, while previous children’s experience with EAAs appeared to improve interpersonal distance and horse handling. Results from this study highlight the importance of exploring children’s behavioral responses during animal-assisted activities through direct measurements. This may allow linking the quality/strength of the child–horse relationship to the benefits obtained by the child, particularly in the social/communicative domain, a core symptom of ASD.

IntroductionAnimal Assisted Interventions (AAIs) are increasingly common in pediatric care settings as a means to promote the physical, mental, and emotional well-being of hospitalized children and adolescents.ObjectivesThe aim of this work was to review published studies implementing AAIs in hospital settings and to assess the effects of AAIs on the biobehavioral response to stress and pain, social behavior, quality of life and level of satisfaction with hospitalization in children and adolescents. Stress and burden, quality of life, mood and level of satisfaction with hospitalization in parents/caregivers as well as stress and burden, perception of the work environment and job satisfaction in hospital staff were also reviewed.MethodsAll published studies reporting quantitative assessments were systematically searched using PubMed, Scopus, ProQuest and Web of Science databases in accordance with PRISMA guidelines. The aim was to identify studies examining the effects of AAIs on behavioral, psychological and physiological responses to stress in children and adolescents (0–18 years) formally admitted to a hospital for a stay, as well as in those undergoing a visit for treatments or medical examinations.ResultsOf the 350 studies screened, 21 were eligible for inclusion. Most of them focused on stress, pain, and anxiety reduction in pediatric patients, and used both physiological parameters and behavioral and psychological observations/scales. All studies employed dogs. Results show the potential of AAIs to reduce anxiety and behavioral distress in pediatric patients while acting on physiological measures associated with arousal.ConclusionAlthough further, more rigorous studies are still needed, the findings of this review may have implications for clinical practices suggesting appropriate planning of AAIs by pediatric healthcare professionals.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=178993], identifier [CRD42020178993].

The COVID-19 pandemic has affected the mental and physical health of the general population at any age, but it is expected to have a protracted and severe consequences for younger populations. The pandemic has had several consequences on mental health including anger and irritability, depressive symptoms and somatic complaints, insomnia, lack of motivation, and loneliness. In particular, loneliness and its related negative feelings are thought to be particularly pronounced during young adulthood because of the many social changes that young people deal with during this period of life. Therefore, it is essential to evaluate the type of impact of the pandemic on the mental health of young people and their levels of loneliness experienced during the first phase of the lockdown. Based on the largest Italian study on the effects of the COVID-19 pandemic on the mental health of general population, in this paper we aim to: (1) describe the levels of loneliness in a national sample of Italian young adults aged 18–34 years, during the first wave of lockdown in 2020; (2) evaluate the clinical and socio-demographic differences in young adults reporting low vs. high levels of loneliness; (3) assess the role of clinical symptomatology, coping strategies, levels of resilience, and duration of lockdown as possible predictors of loneliness. The final sample consists of 8,584 people, mainly female (72.6%), single, with a mean age of 26.4 (±4.4) years. The mean score at the UCLA was 47.5 (±13.6), with 27% (N = 2,311) of respondents exceeding the cut-off for high levels of loneliness. High levels of loneliness were predicted by the presence of avoidant coping strategies, such as self-distraction (Beta coefficient, B = 0.369, 95% Confidence Interval, CI = 0.328–0.411), venting (B = 0.245, 95% CI = 0.197–0.293), denial (B = 0.110, 95% CI = 0.061–0.159), and emotional disengagement (B = 0.133, 95% CI = 0.080–0.185). Weeks of exposure to the pandemic were significantly associated with worsening of loneliness (p < 0.000). There is currently considerable interest in trying to reduce loneliness, both within the context of COVID-19 and more generally. Our results highlight that young people are at a higher risk of developing loneliness and suggest that more interventions and practical guidelines are needed.

Social isolation is a powerful stressor capable of affecting brain plasticity and function. In the case of breast cancer, previous data indicate that stressful experiences may contribute to a worse prognosis, activating neuroendocrine and metabolism pathways, although the mechanisms underlying these effects are still poorly understood. In this study, we tested the hypothesis that chronic isolation stress (IS) may boost hypothalamic–pituitary–adrenal (HPA) axis activity, leading to changes in the hypothalamic expression of genes modulating both mood and metabolism in an animal model of breast cancer. This centrally activated signaling cascade would, in turn, affect the mammary gland microenvironment specifically targeting fat metabolism, leading to accelerated tumor onset. MMTVNeuTg female mice (a model of breast cancer developing mammary hyperplasia at 5 months of age) were either group-housed (GH) or subjected to IS from weaning until 5 months of age. At this time, half of these subjects underwent acute restraint stress to assess corticosterone (CORT) levels, while the remaining subjects were characterized for their emotional profile in the forced swimming and saccharin preference tests. At the end of the procedures, all the mice were sacrificed to assess hypothalamic expression levels of Brain-derived neurotrophic factor (Bdnf), Neuropeptide Y (NpY), Agouti-Related Peptide (AgRP), and Serum/Glucocorticoid-Regulated Protein Kinase 1 (SgK1). Leptin and adiponectin expression levels, as well as the presence of brown adipose tissue (BAT), were assessed in mammary fat pads. The IS mice showed higher CORT levels following acute stress and decreased expression of NpY, AgRP, and SgK1, associated with greater behavioral despair in the forced swimming test. Furthermore, they were characterized by increased consumption of saccharin in a preference test, suggesting an enhanced hedonic profile. The IS mice also showed an earlier onset of breast lumps (assessed by palpation) accompanied by elevated levels of adipokines (leptin and adiponectin) and BAT in the mammary fat pads. Overall, these data point to IS as a pervasive stressor that is able to specifically target neuronal circuits, mastered by the hypothalamus, modulating mood, stress reactivity and energy homeostasis. The activation of such IS-driven machinery may hold main implications for the onset and maintenance of pro-tumorigenic environments.

COVID-19 is continuing to spread around the world, having a direct impact on people’s daily lives and health. Although the knowledge of the impact of the COVID-19 pandemic on mental health in the general population is now well established, there is less information on its effect on specific and vulnerable populations, such as children with chronic illness (CI). We conducted a multi-centered cross-sectional study among pediatric patients in six public children’s hospitals in Italy during the first lockdown, with the aim of assessing the proportion of children with CI presenting anxiety and depressive symptoms, and the clinical and demographic characteristics affecting such symptomatology. We included children with at least one chronic condition, with no cognitive delay, aged between 11 and 18 years. Brief standardized questionnaires were administered during medical scheduled visits to screen anxiety and depressive symptoms. We found a very high proportion of children showing mild to severe depressive and anxiety symptomatology (approximately 68% and 63%, respectively). Our results highlight the need of ensuring tailored psychological interventions to protect children with CI from the effect of the pandemic (and related restrictive measures such as quarantine and social distancing), with the final aim of promoting mental health and psychological well-being in this vulnerable population.

Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as “inflamed womb” may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota.

Abstract Background When facing a traumatic event, some people may experience positive changes, defined as posttraumatic growth (PTG). Methods Understanding the possible positive consequences of the pandemic on the individual level is crucial for the development of supportive psychosocial interventions. The present paper aims to: 1) evaluate the levels of PTG in the general population; 2) to identify predictors of each dimension of post-traumatic growth. Results The majority of the sample (67%, N = 13,889) did not report any significant improvement in any domain of PTG. Participants reported the highest levels of growth in the dimension of “appreciation of life” (2.3 ± 1.4), while the lowest level was found in the “spiritual change” (1.2 ± 1.2). Female participants reported a slightly higher level of PTG in areas of personal strength (p

Curcumin is a pleiotropic compound found in the rhizome of Curcuma longa (turmeric) [...]

Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes.Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the effect of prenatal stress (PNS), an experimental paradigm associated with behavioral and molecular alterations relevant for psychiatric disorders. We identified 138 genes as being differentially methylated in the prefrontal cortex (PFC) and in the hippocampus (HIP) of male and female adult rats exposed to PNS. Among these genes, miR-30a and Neurod1 emerged as potential players for the negative outcomes associated with PNS exposure. Indeed, in addition to showing consistent methylation differences in both brain regions and in both sexes, and interacting with each other, they are both involved in Axon guidance and Neurotrophin signaling, which are important to neurodevelopmental disorders. We also found a significant reduction in the expression of a panel of genes (CAMK2A, c-JUN, LIMK1, MAP2K1, MAP2K2, PIK3CA and PLCG1) that belong to these two biological pathways and are also validated targets of miR-30a, pointing to a down-regulation of these pathways as a consequence of PNS exposure. Interestingly, we also found that miR-30a levels were significantly upregulated in depressed patients exposed to childhood trauma, as compared to control individuals. Importantly, we also found that a sub-chronic treatment with the atypical antipsychotic drug, lurasidone, during adolescence was able to prevent the up-regulation of miR-30a and normalized the expression of its target genes in response to PNS exposure.Our results demonstrate that miR-30a undergoes epigenetic changes following early life stress exposure and suggest that this miRNA could play a key role in producing broad and long-lasting alterations in neuroplasticity-related pathways, contributing to the etiology of psychiatric disorders.

The COVID-19 pandemic and its related containment measures—mainly physical distancing and isolation—are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The “COVID-IT-mental health trial” is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1—COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2—COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3—COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4—COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups.

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented traumatic event influencing the healthcare, economic, and social welfare systems worldwide. In order to slow the infection rates, lockdown has been implemented almost everywhere. Italy, one of the countries most severely affected, entered the “lockdown” on March 8, 2020. Methods The COvid Mental hEalth Trial (COMET) network includes 10 Italian university sites and the National Institute of Health. The whole study has three different phases. The first phase includes an online survey conducted between March and May 2020 in the Italian population. Recruitment took place through email invitation letters, social media, mailing lists of universities, national medical associations, and associations of stakeholders (e.g., associations of users/carers). In order to evaluate the impact of lockdown on depressive, anxiety and stress symptoms, multivariate linear regression models were performed, weighted for the propensity score. Results The final sample consisted of 20,720 participants. Among them, 12.4% of respondents (N = 2,555) reported severe or extremely severe levels of depressive symptoms, 17.6% (N = 3,627) of anxiety symptoms and 41.6% (N = 8,619) reported to feel at least moderately stressed by the situation at the DASS-21. According to the multivariate regression models, the depressive, anxiety and stress symptoms significantly worsened from the week April 9–15 to the week April 30 to May 4 (p

Background: Autism spectrum disorder (ASD) is a complex developmental condition that affects the whole family. The gap between childrens’ needs and their satisfaction, especially regarding what concerns the presence of social and healthcare services, is still a source of burden, particularly after the transition to adulthood. Our study aimed to gather a comprehensive view on how parents of adults with ASD perceive (and interact with) health and social services, and how the provision of care impacts family quality of life with the aim to advise ASD intervention programs. The goal is to identify specific areas of change useful to influence autism intervention strategies so that they more effectively meet the needs of young people with autism and their families. Methods: We conducted two focus groups with parents of young adults with ASD. A semi-structured focus group methodology was adopted. The QoL conceptual framework guided data collection and analysis as part of a directed theory-driven content analysis approach. Results: The lack of structured care pathways and the low level of integration of different services were the main limits reported by parents during the focus group, while a shared positive perception of the experience conducted together as caring families emerged. Conclusions: The experience here reported claims for a greater role of the institutions in order to facilitate the building of networks that are really inclusive for persons with autism in society and to support the implementation of innovative solutions for the welfare system. Furthermore, parents stressed the need for the provision of support to the family.

The COVID-19 pandemic represents an unprecedented public health emergency, with consequences at the political, social, and economic levels. Mental health services have been called to play a key role in facing the impact of the pandemic on the mental health of the general population. In the period March–May 2020, an online survey was implemented as part of the Covid Mental Health Trial (COMET), a multicentric collaborative study carried out in Italy, one of the Western countries most severely hit by the pandemic. The present study aims to investigate the use of mental health resources during the first wave of the pandemic. The final sample consisted of 20,712 participants, mainly females (N = 14,712, 71%) with a mean age of 40.4 ± 14.3 years. Access to mental health services was reported in 7.7% of cases. Among those referred to mental health services, in 93.9% of cases (N = 1503 subjects) a psychological assessment was requested and in 15.7% of cases (N = 252) a psychiatric consultation. People reporting higher levels of perceived loneliness (OR 1.079, 95% CI 1.056–1.101, p < 0.001), practicing smart-working (OR 1.122, 95% CI 0.980–1.285, p = 0.095), using avoidant (OR 1.586, 95% CI 1.458–1.725, p < 0.001) and approach (OR 1.215, 95% CI 1.138–1.299, p < 0.001) coping strategies more frequently accessed mental health services. On the other hand, having higher levels of perceived social support (OR 0.833, 95% CI 0.795–0.873, p < 0.001) was associated with a reduced probability to access mental health services. The COVID-19 pandemic represents a new threat to the mental health and well-being of the general population, therefore specific strategies should be implemented to promote access to mental healthcare during the pandemic and afterwards.

The effects of the COVID-19 pandemic on mental health are now well documented, however, few studies have been focused on the role of coping strategies and resilience in counterbalancing these detrimental effects. Data are derived from the COvid Mental hEalth Trial (COMET), a national multicentric trial carried out in the Italian general population. The final sample consisted of 20,720 participants, 53.1% (n = 11,000) of the sample reported low levels of resilience. Adaptive coping strategies and resilience levels did not have any significant protective impact on the levels of depressive, anxiety, and stress symptoms. Only self-distraction was a risk factor for poor mental health (Beta Coefficient, B = 0.1, 95% Confidence Interval, CI: 0.003 to 0.267 for stress symptoms; B = 0.2; 95% CI: 0.077 to 0.324 for anxiety symptoms and B = 0.2, 95% CI: 0.105 to 0.382 for depressive symptoms). High levels of resilience were predicted by adaptive coping strategies, such as acceptance (B = 1.8, CI 95% = 1.4–2.7). Exposure to the different weeks of lockdown, being infected by COVID-19, and being a healthcare professional did not influence the levels of resilience. Our findings should be carefully considered, since the low levels of resilience may represent the missing link between the pandemic and the current increase in mental health problems.

Little is known about the impact of equine-assisted interventions (EAI) on equids’ perception of humans. In this study 172 equids, living in 12 riding centres, were submitted to a standardised human–horse relationship test: the motionless person test. Age, sex, type (horse/pony), housing, and feeding conditions of subjects were recorded. Overall, 17 equids worked in EAI, 95 in riding school lessons (RS), and 60 in both (EAI-RS). There were high inter-individual variations in the number of interactive behaviours directed towards the experimenter: negative binomial general linear models showed that activity was the most important factor: RS equids performed more interactive behaviours than EAI (p = 0.039) and EAI-RS (p < 0.001) equids. Daily quantity of hay appeared as the second most important factor (equids with more than 3 kg interacted more than equids with less than 3 kg, p = 0.013). Individual characteristics were also important as horses interacted more than ponies (p = 0.009), geldings more than mares (p = 0.032), and 3–15-year-old equids more than equids over 15 years (p = 0.032). However, there was no interaction between factors. The lower number of interactive behaviours of EAI equids leads to different hypotheses—namely, selection on temperament, specific training, or compromised welfare (apathy). In any case, our results raised new lines of questions on EAI.

Equine-assisted interventions (EAIs) are well-known complementary practices combining physical activity with emotional/cognitive stimulation. They are especially suited for children with autism spectrum disorders (ASD) who need a high degree of physical and psychological enrichment. Even though EAIs have become a common practice, stress responses in horses interacting with individuals that can manifest inappropriate behaviours, such as ASD children, have not been thoroughly investigated. Our multicentre study aimed to investigate behavioural and physiological indices of stress in horses involved in EAI standardised sessions with children with ASD compared to typically developing (TD) children. A controlled within-subject design with repeated measurements involving 19 horses and 38 children was adopted. Stress-related behaviours, heart rate, heart rate variability, and eye temperature were recorded during the riding sessions. Moreover, blood samples were collected from horses before and after each session to monitor changes in blood adrenocorticotropic hormone (ACTH), cortisol, and catecholamines. Results indicate that, in general, stress responses in horses involved in EAIs did not differ as a function of the horse being ridden by children with ASD or TD. A lower sympathetic tone in horses involved in ASD sessions was found, while in the mounting and dismounting phases, horses displayed behavioural signs of stress, independently from children’s behaviour. We conclude that professionals working in EAI should increase their awareness of animal welfare and refine riding practices, taking into account horse’s needs.

Due to the global increase in lifespan, the proportion of people showing cognitive impairment is expected to grow exponentially. As target-specific drugs capable of tackling dementia are lagging behind, the focus of preclinical and clinical research has recently shifted towards natural products. Curcumin, one of the best investigated botanical constituents in the biomedical literature, has been receiving increased interest due to its unique molecular structure, which targets inflammatory and antioxidant pathways. These pathways have been shown to be critical for neurodegenerative disorders such as Alzheimer’s disease and more in general for cognitive decline. Despite the substantial preclinical literature on the potential biomedical effects of curcumin, its relatively low bioavailability, poor water solubility and rapid metabolism/excretion have hampered clinical trials, resulting in mixed and inconclusive findings. In this review, we highlight current knowledge on the potential effects of this natural compound on cognition. Furthermore, we focus on new strategies to overcome current limitations in its use and improve its efficacy, with attention also on gender-driven differences.

A growing body of evidence suggests the consumption of high-fat diet (HFD) during pregnancy to model maternal obesity and the associated increase in oxidative stress (OS), might act as powerful prenatal stressors, leading to adult stress-related metabolic or behavioral disorders. We hypothesized that administration of antioxidants throughout gestation might counteract the negative effects of prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy) on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13 weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl-cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body weight of the offspring was assessed following birth, up to weaning and at adulthood. The metabolic, neuroendocrine and emotional profile of the adult offspring was tested at 3-months of age. Prenatal HFD increased mother’s body weight and offspring’s weight at the time of weaning, when administered in conjunction with NAC. In females, NAC administration reduced high levels of leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in greater glucose tolerance and insulin sensitivity while increasing adiponectin levels, as well as increasing exploratory behavior, an effect accompanied by reduced plasma corticosterone levels in response to restraint stress. Analysis of glutathione levels in the hypothalamus and in brown adipose tissue indicates that, while HFD administration to pregnant dams led to reduced levels of glutathione in the offspring, as in the male hypothalamus, NAC was able to revert this effect and to increase glutathione levels both in the periphery (Brown Adipose Tissue, both males and females) and in the central nervous system (males). Overall, results from this study indicate that the body redox milieu should be tightly regulated during fetal life and that buffering OS during pregnancy can have important long-term consequences on metabolic and behavioral endpoints.

Neuroferritinopathy is a rare genetic disease with a dominant autosomal transmission caused by mutations of the ferritin light chain gene (FTL). It belongs to Neurodegeneration with Brain Iron Accumulation, a group of disorders where iron dysregulation is tightly associated with neurodegeneration. We studied the 498–499InsTC mutation which causes the substitution of the last 9 amino acids and an elongation of extra 16 amino acids at the C-terminus of L-ferritin peptide. An analysis with cyclic voltammetry on the purified protein showed that this structural modification severely reduces the ability of the protein to store iron. In order to analyze the impact of the mutation in vivo, we generated mouse models for the some pathogenic human FTL gene in FVB and C57BL/6J strains.Transgenic mice in the FVB background showed high accumulation of the mutated ferritin in brain where it correlated with increased iron deposition with age, as scored by magnetic resonance imaging. Notably, the accumulation of iron–ferritin bodies was accompanied by signs of oxidative damage. In the C57BL/6 background, both the expression of the mutant ferritin and the iron levels were lower than in the FVB strain. Nevertheless, also these mice showed oxidative alterations in the brain. Furthermore, post-natal hippocampal neurons obtained from these mice experienced a marked increased cell death in response to chronic iron overload and/or acute oxidative stress, in comparison to wild-type neurons. Ultrastructural analyses revealed an accumulation of lipofuscin granules associated with iron deposits, particularly enriched in the cerebellum and striatum of our transgenic mice. Finally, experimental subjects were tested throughout development and aging at 2-, 8- and 18-months for behavioral phenotype. Rotarod test revealed a progressive impaired motor coordination building up with age, FTL mutant old mice showing a shorter latency to fall from the apparatus, according to higher accumulation of iron aggregates in the striatum. Our data show that our 498–499InsTC mouse models recapitulate early pathological and clinical traits of the human neuroferritinopathy, thus providing a valuable model for the study of the disease. Finally, we propose a mechanistic model of lipofuscine formation that can account for the etiopathogenesis of human neuroferritinopathy.

Prenatal stress (PNS) might affect the developmental programming of adult chronic diseases such as metabolic and mood disorders. The molecular mechanisms underlying such regulations may rely upon long-term changes in stress-responsive effectors such as Brain-Derived Neurotrophic Factor (BDNF) that can affect neuronal plasticity underlying mood disorders and may also play a role in metabolic regulation. Based upon previous data, we hypothesized that PNS might lead to greater vulnerability to an obesogenic challenge experienced at adulthood. In order to investigate our hypothesis, pregnant Sprague-Dawley female rats underwent a chronic procedure of restraint stress during the last week of gestation. The adult offspring were then challenged with a high fat diet (HFD) over 8 weeks and tested for metabolic and emotional endpoints. Moreover, brain specific changes in Bdnf expression levels were also assessed. Overall, HFD resulted in increased caloric intake, insulin resistance, impaired glucose tolerance and higher circulating levels of leptin, while PNS increased the leptin/adiponectin ratio, an index of metabolic risk in adult male subjects. Interestingly, HFD consumption increased anxiety-like behaviors in the Elevated Plus Maze, particularly in males, and this effect was buffered by PNS. Levels of Bdnf were finely modulated by PNS and HFD in a region- and sex-dependent fashion: female offspring overall showed greater plasticity, possibly mediated through increased total Bdnf mRNA expression both in the hippocampus and in the hypothalamus. In conclusion, while the experience of maternal stress during intrauterine life promotes metabolic dysfunction induced by a HFD at adulthood, the interaction between PNS and HFD is positive in male subjects, and in agreement with the match-mismatch hypothesis, resulting in a reduction of anxious behaviors.

Animal models with an eco-ethological relevance can help in identifying novel and reliable stress-related markers. To this end, 3-month-old C57BL/6J male mice were exposed to social defeat (SD) stress for 10 days as this stressor shows good face and predictive validity for several models of human affective disorders including depression, social phobia and post-traumatic stress disorder. Social avoidance and pain threshold were assessed 24 h and 4 weeks after the end of SD stress, while corticosterone was assayed at the beginning and at the end of the stressful procedure (days 1 and 10). SD subjects were characterized by increased corticosterone levels (30 min following stress exposure), increased latency to approach the social target in the short-term as well as increased emotionality in the long-term. Moreover, an increase in nociceptive threshold (stress-induced analgesia) was found both in the short-term and 4 weeks after the end of stress. These data indicate that the SD paradigm is able to induce emotional changes associated with a stressful/traumatic event. In addition, they indicate that variations in the nociceptive threshold might represent a physiological marker of both short- and long-term effects of stress.

Europe has the highest proportion of elderly people in the world. Cardiovascular disease, type 2 diabetes, sarcopenia and cognitive decline frequently coexist in the same aged individual, sharing common early risk factors and being mutually reinforcing. Among conditions which may contribute to establish early risk factors, this review focuses on maternal obesity, since the epidemic of obesity involves an ever growing number of women of reproductive age and children, calling for appropriate studies to understand the consequences of maternal obesity on the offspring's health and for developing effective measures and policies to improve people's health before their conception and birth. Though the current knowledge suggests that the long-term impact of maternal obesity on the offspring's health may be substantial, the outcomes of maternal obesity over the lifespan have not been quantified, and the molecular changes induced by maternal obesity remain poorly characterized. We hypothesize that maternal insulin resistance and reduced placental glucocorticoid catabolism, leading to oxidative stress, may damage the DNA, either in its structure (telomere shortening) or in its function (via epigenetic changes), resulting in altered gene expression/repair, disease during life, and pathological ageing. This review illustrates the background to the EU-FP7-HEALTH-DORIAN project.

Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.

There is a growing interest for the potential health benefits of human-animal interactions. Although scientific evidence on the effects is far from being consistent, companion animals are used with a large number of human subjects, ranging from children to elderly people, who benefit most from emotional support. Based on a comprehensive review of the literature, this paper examines the potential for domesticated animals, such as dogs, for providing emotional and physical opportunities to enrich the lives of many frail subjects. In particular, we focus on innovative interventions, including the potential use of dogs to improve the life of emotionally-impaired children, such as those affected by autism spectrum disorders. Overall an ever increasing research effort is needed to search for the mechanism that lie behind the human-animal bond as well as to provide standardized methodologies for a cautious and effective use of animal-assisted interventions.

The FISE (Federazione Italiana Sport Equestri) Pindar is a multicentre research project aimed at testing the potential effects of therapeutic riding on schizophrenic patients. Twenty-four subjects with a diagnosis of schizophrenia were enrolled for a 1 year-treatment involving therapeutic riding sessions. All subjects were tested at the beginning and at the end of treatment with a series of validated test batteries (BPRS and 8 items-PANSS). The results discussed in this paper point out an improvement in negative symptoms, a constant disease remission in both early onset and chronic disease subjects, as well as a reduced rate of hospitalization.

Ferritin is the main intracellular protein of iron storage with a central role in the regulation of iron metabolism and detoxification. Nucleotide insertions in the last exon of the ferritin light chain cause a neurodegenerative disease known as Neuroferritinopathy, characterized by iron deposition in the brain, particularly in the cerebellum, basal ganglia and motor cortex. The disease progresses relentlessly, leading to dystonia, chorea, motor disability and neuropsychiatry features. The characterization of a good animal model is required to compare and contrast specific features with the human disease, in order to gain new insights on the consequences of chronic iron overload on brain function and behavior. To this aim we studied an animal model expressing the pathogenic human FTL mutant 498InsTC under the phosphoglycerate kinase (PGK) promoter. Transgenic (Tg) mice showed strong accumulation of the mutated protein in the brain, which increased with age, and this was accompanied by brain accumulation of ferritin/iron bodies, the main pathologic hallmark of human neuroferritinopathy. Tg-mice were tested throughout development and aging at 2-, 8- and 18-months for motor coordination and balance (Beam Walking and Footprint tests). The Tg-mice showed a significant decrease in motor coordination at 8 and 18 months of age, with a shorter latency to fall and abnormal gait. Furthermore, one group of aged naïve subjects was challenged with two herbicides (Paraquat and Maneb) known to cause oxidative damage. The treatment led to a paradoxical increase in behavioral activation in the transgenic mice, suggestive of altered functioning of the dopaminergic system. Overall, data indicate that mice carrying the pathogenic FTL498InsTC mutation show motor deficits with a developmental profile suggestive of a progressive pathology, as in the human disease. These mice could be a powerful tool to study the neurodegenerative mechanisms leading to the disease and help developing specific therapeutic targets.

Here we describe a pilot Dog-Assisted Activity program that was designed to improve wellbeing and social integration in a multi-cultural elementary classroom in which some episodes of bullying had been reported. We developed a 5-encounters protocol with the aim of introducing pet dogs into the class to stimulate understanding of different types of communication and behavior, ultimately facilitating positive relationships among peers. A preliminary evaluation was carried out in order to assess the effect of the program on teachers’ perception of children’s difficulties (e.g., peer relationship problems) and strengths (prosocial behaviors) by means of a brief behavioral screening tool, the Strengths and Difficulties Questionnaire (SDQ—Teacher version). Overall results indicate that, by means of the recognition of the dogs’ behavior and non-verbal communication, children were able to express their emotions and to show behaviors that had not been recognized by the teachers prior to the intervention. In particular, the SDQ Total Difficulties scores suggest that the teacher had increased awareness of the students’ difficulties as a result of the dog-assisted program. Overall, the presence of animals in the educational environment may provide enjoyment and hands-on educational experiences, enhanced psychological wellbeing, and increased empathy and socio-emotional development.

Equine assisted interventions (EAIs) are recently facing an increasing popularity, and are characterized by a wide diversity of practices. However, information on the welfare of animals involved in this kind of activity is often lacking. Horses are highly susceptible to work stressors related to physical constraints and/or to the need to control emotions while interacting with humans. Considerations of the emotional state of horses involved in EAIs have multiple valences: for the safety of humans and animals involved, for the quality and efficacy of interventions, as well as for ethical reasons. The aim of this unsystematic narrative review is to summarize the different approaches used for the evaluation of horses’ stress responses, investigate their application in the context of EAIs, and discuss some methodological considerations for researchers and practitioners involved in EAI. The sources of information are mostly based on electronic databases (i.e., Medline, Scopus and Google scholar), as well as on hand searches of the references of retrieved literature, and discussions with experts in the field. At present, a few studies have investigated horses’ stress responses during EAIs, and further studies are recommended, with the final aim to derive a reliable multidimensional method for assessing a horse’s reaction during therapeutic programs, ultimately helping professionals to better develop interventions by taking into consideration the animal’s perspective.