Attitude and concerns of healthy individuals regarding post-mortem brain donation. A qualitative study on a nation-wide sample in Italy.

BACKGROUND: Collecting post-mortem brain tissue is essential, especially from healthy "control" individuals, to advance knowledge on increasingly common neurological and mental disorders. Yet, healthy individuals, on which this study is focused, are still understudied. The aim of the study was to explore, among healthy potential brain donors and/or donors' relatives, attitude, concerns and opinion about post-mortem brain donation (PMBD). METHODS: A convenience sampling of the general population (twins and their non-twin contacts) was adopted. From June 2018 to February 2019, 12 focus groups were conducted in four Italian cities: Milan, Turin, Rome and Naples, stratified according to twin and non-twin status. A qualitative content analysis was performed with both deductive and inductive approaches. Emotional interactions analysis corroborated results. RESULTS: One hundred and three individuals (49-91 yrs of age) participated. Female were 60%. Participants had scarse knowledge regarding PMBD. Factors affecting attitude towards donation were: concerns, emotions, and misconceptions about donation and research. Religion, spirituality and secular attitude were implied, as well as trust towards research and medical institutions and a high degree of uncertainty about brain death ascertainment. Family had a very multifaceted central role in decision making. A previous experience with neurodegenerative diseases seems among factors able to favour brain donation. CONCLUSIONS: The study sheds light on healthy individuals' attitudes about PMBD. Brain had a special significance for participants, and the ascertainment of brain death was a source of debate and doubt. Our findings emphasise the importance of targeted communication and thorough information to promote this kind of donation, within an ethical framework of conduct. Trust in research and health professionals emerged as an essential factor for a collaborative attitude towards donation and informed decision making in PMBD.

An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity.

Background and Objectives: Non-cancer chronic pain (CP) results from the interaction between genetic and environmental factors. Twin studies help to estimate genetic and environmental contributions to complex traits such as CP. To date, twin studies on the heritability of pain phenotypes have relied almost exclusively on specific diagnoses, neglecting pain intensity. This study aims to estimate the genetic and environmental contributions to CP occurrence as a wide phenotype and its intensity among a non-clinical population. Materials and Methods: A nationwide online survey was conducted in February 2020 on 6000 adult twins enrolled in the Italian Twin Registry. A five-item questionnaire, designed and validated by our study group, was administered to detect the CP condition along with its intensity, underlying causes or triggers, treatments, and self-perceived efficacy. The twin study design was used to infer the relative weight of genes and environment on CP occurrence and intensity, and biometrical modelling was applied to these phenotypes. Results: A total of 3258 twins, aged ≥18, replied to the online survey (response rate 54%). These included 762 intact pairs (mean age: 39 years; age range: 18-82 years; 34% male; CP prevalence: 24%), of whom 750 pairs were subjected to biometrical modelling after the exclusion of pairs with either unknown zygosity or cancer-associated CP. Broad-sense heritability estimates were driven by non-additive genetic effects and were 0.36 (0.19-0.51) for CP occurrence and 0.31 (0.16-0.44) for CP intensity. No evidence emerged for either sex differences in genetic and environmental variance components or interactions of these components with age. Conclusions: Moderate non-additive genetic components were suggested for non-cancer CP occurrence and its intensity. These results encourage further research on the gene-gene interactions underlying CP liability and associated phenotypes, and also strengthen the need for prevention strategies to avoid CP occurrence or to decrease pain intensity.

Educational attainment of same-sex and opposite-sex dizygotic twins: An individual-level pooled study of 19 twin cohorts.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (ß = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (ß = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.

The Italian Twin Registry: An Update at 18 Years From Its Inception.

The Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years' research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics.

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells.

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.

Adult Empathy: Possible Gender Differences in Gene-Environment Architecture for Cognitive and Emotional Components in a Large Italian Twin Sample.

Empathy plays a central role in prosocial behavior and human cooperation. Very few twin researchers have investigated innate and environmental effects in adult empathy, and twin research on gender differences in these effects is sparse. The goal of this study was to examine innate and environmental influences on three components of an empathy scale frequently used with adults - the expression of cognitive (CE), emotional (EE), and social skills (SS) empathy - and to explore gender differences in the influences. Study participants were ~1,700 twins (18-65 years) enrolled in the Italian Twin Registry. Empathy was assessed with the Italian version of the Empathy Quotient (EQ), for which the three-factor structure (i.e., CE, EE, and SS) was confirmed. Twin correlations in monozygotic and dizygotic pairs, and males and females were estimated for the total EQ and subscale scores, and univariate genetic model fitting was carried out. Women's empathy (i.e., total EQ as well as CE and EE subdimensions) was predominantly driven by genetic factors and individual experiences, whereas for males, no genetic contribution or important shared and individual environmental effects emerged. Although of large magnitude, the gender differences did not reach statistical significance. Age did not moderate empathy heritability in adulthood. Only for the SS subscale were genetic and environmental proportions of variance similar for men and women. This study suggests possible gender-specific innate and environmental influences on empathy and its cognitive and emotional components that need to be confirmed in future studies.

[Italian Cystic Fibrosis Register - Report 2010]. / Registro italiano fibrosi cistica - Rapporto 2010.

UNLABELLED: The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in adulthood. No differences were observed between male and female. Incidence at birth was estimated 1/4,854 living births. 4. GENETICS: in 95.9% of patients, 2 (or more) CFTR mutations were identified. [delta]508F mutation was the most frequent (45.1%). 5. Respiratory function: analyses were performed on 2,966 out of 3,341 patients aged 7 years or older. FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Fourteen per cent of the patients within 2-18 years resulted malnourished. From 18 years onwards, optimal BodyMass Index (BMI) values were detected in 36.5%of males and in 28%of females. BMI also improved during age. 7. Transplantation: in 2010, 20 patients (10 males and 10 females) were bi-pulmunary transplanted; age was comprised between 11 and 46 years, median age at transplantation was 27.5 years. Eleven out of the 20 patients resulted still alive on the 31th December 2010. 8. Microbiology: analyses were performed on 3.272 patients (887 did not report these data) and were exclusively referred to tests performed in 2010. A percentage of 34 patients, younger than 18 years of age, was characterized by the presence of Pseudomonas aeruginosa compared to 61.8% of the older patients. Prevalence of Burkholderia Cepacia was 0.8% in patients aged up to 17 years; in patients aged more than 17 years, prevalence was 6.8%. Staphylococcus aureus meticillino sensitive prevalence was not correlated with patients' age. 9. MORTALITY: 34 patients aged from 0 to 45 years died in 2010 (16 males and 18 females). Respiratory insufficiency was the main cause of death (73.5%). CONCLUSIONS The report aims at being an instrument for CF community, with particular attention to the needs of patients and their families. Information collected within INCFR are an important starting point for further studies from health care perspectives. Finally, INCFR represents an important tool to foster research and innovative treatment for CF, as the rareness of the disease is a constraint to clinical trials and other studies set-up. A significant subset of data are regularly sent to the European Registry of Cystic Fibrosis.

Genetic and environmental influences underlying the relationship between autistic traits and temperament and character dimensions in adulthood.

BACKGROUND: In recent years, several twin studies adopted a dimensional approach to Autism Spectrum Disorders (ASD) and estimated the contribution of genetic and environmental influences to variation in autistic traits. However, no study was performed on adults over 18 years of age and all but two studies were based on parent or teacher ratings. Also, the genetic and environmental contributions to the interplay between autistic traits and adult personality dimensions have not been investigated. METHODS: A sample of 266 complete twin pairs (30% males, mean age 40 ± 12 years) drawn from the population-based Italian Twin Register was administered the Autism-Spectrum Quotient, Temperament and Character Inventory (TCI-125), and General Health Questionnaire (GHQ-12). Genetic structural equation modelling was performed with the Mx program. Estimates were adjusted for gender, age, and GHQ-12 score. RESULTS: Genetic factors accounted for 44% and 20%-49% of individual differences in autistic traits and TCI dimensions, respectively. Unshared environmental factors explained the remaining proportion of variance. Consistently with the notion of a personality profile in ASD characterised by obsessive temperament, autistic traits showed significant phenotypic correlations with several TCI dimensions (positive: HA; negative: NS, RD, SD, C). Genetic and unshared environmental correlations between AQ and these TCI dimensions were significant. The degree of genetic overlap was generally greater than the degree of environmental overlap. CONCLUSIONS: Despite some limitations, this study suggests that genetic factors contribute substantially to individual differences in autistic traits in adults, with unshared environmental influences also playing an important role. It also suggests that autistic traits and the majority of temperament and character dimensions share common genetic and environmental aetiological factors.

[Determinants of eating behaviour: the contribution of twin studies]. / Determinanti del comportamento alimentare: il contributo degli studi sui gemelli.

This review includes relevant twin studies conducted on eating habits and preferences, and on endophenotypes of disordered eating behaviour in general population, non-clinical settings. The twin study design is presented, along with its assumptions and possible applications in aetiological and public health epidemiology. Subsequently, the strategy for the search of the scientific literature and the exclusion criteria are reported. Then, the analysis of the studies included in this review is performed, with a brief description of targeted outcomes, twin model used, sample characteristics and findings. Finally, key messages emerging from the review are highlighted, emphasizing their value for bridging the current gaps in the understanding of determinants of eating behaviour and their mode of action.

Piccolipiù, a multicenter birth cohort in Italy: protocol of the study.

BACKGROUND: The fetal and infant life are periods of rapid development, characterized by high susceptibility to exposures. Birth cohorts provide unique opportunities to study early-life exposures in association with child development and health, as well as, with longer follow-up, the early life origin of adult diseases. Piccolipiù is an Italian birth cohort recently set up to investigate the effects of environmental exposures, parental conditions and social factors acting during pre-natal and early post-natal life on infant and child health and development. We describe here its main characteristics. METHODS/DESIGN: Piccolipiù is a prospective cohort of expected 3000 newborns, who will be recruiting in six maternity units of five Italian cities (Florence, Rome, Trieste, Turin and Viareggio) since October 2011. Mothers are contacted during pregnancy or at delivery and are offered to participate in the study. Upon acceptance, their newborns are recruited at birth and followed up until at least 18 years of age. At recruitment, the mothers donate a blood sample and complete a baseline questionnaire. Umbilical cord blood, pieces of umbilical cord and heel blood spots are also collected. Postnatal follow-up currently occurs at 6, 12, and 24 months of age using on-line or postal self administered questionnaire; further questionnaires and medical examinations are envisaged. Questionnaires collect information on several factors, including mother's and/or child's environmental exposures, anthropometric measures, reproductive factors, diet, supplements, medical history, cognitive development, mental health and socioeconomic factors. Health promotion materials are also offered to parents. DISCUSSION: Piccolipiù will broaden our understanding of the contribution of early-life factors to infant and child health and development. Several hypotheses on the developmental origins of health can be tested or piloted using the data collected from the Piccolipiù cohort. By pooling these data with those collected by other existing birth cohorts it will be possible to validate previous findings and to study rare exposures and outcomes.

Informed consent, and an ethico-legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study.

Birth cohort studies are important tools for life-course epidemiology, given the spectrum of the environmental, behavioural, and genetic factors that should be considered when making judgements on human health. Biobanks are valuable components of studies designed to investigate the genetic variability of diseases and improve phenotypic characterisation. In studies involving vulnerable populations and biobanks, it is essential to provide ethical reasoning and analyse the legal requirements. We describe the processes and the tools used in the iterative design of an appropriate informed consent model and the ethico-legal framework of the Piccolipiù study. The Piccolipiù study is a prospective population-based study funded by the Italian Ministry of Health that intends to enrol 3,000 newborns and their mothers in five Italian cities, and to store biological samples for future use. To realise these objectives, we performed a thorough evaluation of the literature, of national and international guidelines, and of the impact of the Italian legal requirements for research biobanking. Discussions among stakeholders facilitated the design of the informed consent and the ethico-legal framework. Several topics are addressed, including the suitability of a broad informed consent for paediatric biobanks, infant vulnerability, access to and sharing of data, and the disclosure of individual's genetic results. Discussion of the ethical and legal procedures adopted in epidemiological biobanking might be a fruitful ground for comparison both at the national level, where standardization and homogeneity are lacking, and at the international level, where different regulatory issues are often in the background and might hamper research biobanks networking.

An Italian Survey and Focus Groups on Fibromyalgia Impairment: Impact on Work and Possible Reasonable Accommodations.

Fibromyalgia symptoms affect the sufferers' working life; however, through reasonable accommodations in workplaces, they can continue to work satisfactorily. There are no Italian studies on factors that facilitate or hinder fibromyalgia-affected people's working life. Our objective was to explore, in a pre-pandemic setting, the quality of working life of fibromyalgia sufferers and reasonable accommodations to improve it. Quantitative and qualitative methods were applied; a survey-questionnaire, participatory-developed, was online-administered to a sample of self-reported FM sufferers (N = 1176). Then, two Focus Groups (FGs), involving 15 fibromyalgia-affected women, were held. Data were analyzed by a thematic analysis approach. Among survey-respondents, 20% were unemployed and only 14% went to work gladly. Variability of pain (84%) and fatigue (90%) were the most perceived reasons for difficulties at work. Negative relationships at work were reported by most participants. The FGs' discussions addressed different strategies for overcoming the main obstacle of "not being believed by colleagues and employers" and reasonable accommodations. However, a negative hopeless attitude towards the solution of problems at work was also apparent. Different critical issues in the workplace emerged from the survey and the FGs. Coordinated actions, according to a transdisciplinary approach, are needed to manage fibromyalgia-induced difficulties in the workplace.

An update on the Italian Twin Register: advances in cohort recruitment, project building and network development.

The Italian Twin Register has been in place for more than 10 years. Since its establishment, it has been focusing, on the one hand, on a continuous update of the existing information, and on the other hand, on new phenotypes and sample collection. Demographic data on about 140,000 twins have been updated using the municipality registries. The Italian Twin Register has been carrying out several new studies during the last few years. A birth cohort of twins, Multiple Births Cohort Study, has been started and the enrollment is ongoing. For this cohort, data on pregnancy and birth are collected, and periodical follow-ups are made. DNA is being collected for the twins and their parents. In the area of behavioral genetics, most efforts have been directed to psychological well being assessed with self-reported tools. Research on age-related traits continues with studies on arteriosclerosis development, early biomarkers in mild cognitive impairment, and the relation between lifestyle habits and mutagen sensitivity. The Italian Twin Register biobanking has grown in its size and in its know-how in terms of both technical issues and ethical procedures implementation. Furthermore, attitudes toward biobank-based research, together with willingness and motivation for donation, are being investigated. A valuable key resource for the Italian Twin Register is the possibility of linking twin data with disease registries. This approach has been yielding several important results, such as the recent study on the heritability of type 1 diabetes.

Stability and change in genetic and environmental influences on depressive symptoms in response to COVID-19 pandemic.

Background: The rapid spread of the new Coronavirus and the consequent restrictions to contain transmission generated an unprecedented psychological impact on the general population. The Italian Twin Registry performed a longitudinal study to investigate to what extent genetic and environmental influences contributed to changes in depressive symptoms. Methods: Data from adult twins were collected. All participants completed an online questionnaire including the 2-item Patient Health Questionnaire (PHQ-2) just before (February 2020) and immediately after the Italian lockdown (June 2020). Genetic modeling based on Cholesky decomposition was used to estimate the role of genetic (A) and both shared (C) and unshared (E) environmental factors in the observed longitudinal course of depressive symptoms. Results: Longitudinal genetic analysis was based on 348 twin pairs (215 monozygotic and 133 dizygotic pairs) with a mean age of 42.6 years (range 18-93 years). An AE Cholesky model provided heritability estimates for depressive symptoms of 0.24 and 0.35 before and after the lockdown period, respectively. Under the same model, the observed longitudinal trait correlation (0.44) was approximately equally contributed by genetic (46%) and unshared environmental (54%) influences, while longitudinal environmental correlation was lower than genetic correlation (0.34 and 0.71, respectively). Conclusions: Although the heritability of depressive symptoms was rather stable across the targeted time window, different environmental as well as genetic factors seemed to act before and after the lockdown, which suggests possible gene-environment interaction.

Investigating Genetic and Environmental Substrates of the Relationship between Positive Mental Health and Biological Aging-A Study Protocol.

BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità) funded a 30-month project (July 2021-January 2024) to conduct a twin study of the relationships between Positive Mental Health (PMH) and cellular longevity. Only a few previous studies have focused on the biomarkers of aging in relation to psychological well-being, and none of them exploited the potential of the twin design. METHOD: In this project, following the standard procedures of the Italian Twin Registry (ITR), we aim to recruit 200 adult twin pairs enrolled in the ITR. They are requested to complete a self-report questionnaire battery on PMH and to undergo a blood withdrawal for the assessment of aging biomarkers, i.e., telomere length and mitochondrial DNA functionality. The association between psychological and aging biomarker measures will be assessed, controlling for genetic and familial confounding effects using the twin study design. RESULTS AND CONCLUSIONS: Biomarker assays are underway. Once data are available for the total study sample, statistical analyses will be performed. The project's results may shed light on new mechanisms underlying the mind-body connection and may prove helpful to promote psychological well-being in conjunction with biological functioning.

[The use of sensitive data in epidemiology: remarks on the difficulties when interpreting the Italian legislation]. / Il trattamento dei dati sensibili in epidemiologia: riflessioni sulle difficoltà interpretative della normativa.

In recent years, the impact of the Italian legislation on the use of personal data (Legislative Decree 196/2003 and successive regulations) on epidemiological research has highlighted the need for reaching a balance between protecting sensitive data and making these data available for public health purposes. Complying with this legislation constitutes a number of challenges in the field of epidemiology, especially with respect to the use for research of health data that have been collected for purposes other than research. Based on the difficulties experienced by the National Center of Epidemiology, Surveillance and Health Promotion of the Italian National Institute of Health, in the present work we aim to promote what we feel is a more rational approach to the concept of "use of sensitive data". In particular, we address the importance of these data for research, the concept of identifiability as defined in current legislation, informed consent, and the lawful use of the data. Given that data networks have been replacing static archives, it is more realistic to strive for the protection of data confidentiality, as opposed to performing irreversible anonymization of data. We also stress the role that research and health institutions should play in clearly communicating to law and policy makers the importance of the data routinely collected by healthcare facilities in performing epidemiological research and surveillance, stressing the invaluable impact of these activities on the health of the population. We also emphasize the importance of strengthening the concept that public health prevention also begins with epidemiological research and surveillance.

The COVID-19 pandemic in Italy: Depressive symptoms immediately before and after the first lockdown.

BACKGROUND: Italy was one of the first countries to be heavily hit by the spread of the new Coronavirus. Longitudinal studies are needed to investigate the real effect of COVID-19 on adult mental health. The Italian Twin Registry carried out a study to investigate, over time, the course of depressive symptoms in the general population. METHODS: The study relies on data collected just before the beginning (February 2020) and the end (June 2020) of the first lockdown. Symptoms of depression were assessed using the Patient Health Questionnaire, and total scores or categorized depression scores were considered in the analyzes. RESULTS: A total of 1690 adult twins were recruited. The study showed a mean depression score of 1.11 immediately before lockdown and 1.20 immediately after, with an overall prevalence of depressive symptoms increasing from 33.6 to 38.9%. Depressive symptoms immediately after the restriction period were associated with Covid-19 symptoms affecting households, financial problems due to the pandemic and poor social support. Independently of the baseline risk of depressive symptoms, we observed an increased risk among younger and less educated people. Compared to the pre-lockdown period, women and middle-aged people also were found to be at greater risk of developing depressive symptoms. LIMITATIONS: Possible participation bias and residual selection bias. CONCLUSIONS: The study shows that the COVID-19 pandemic was associated with an increased depressive symptomatology and that, in such health emergency times, the most vulnerable persons are young adults, women, and those living in a socially, culturally, or economically disadvantaged environment.

Development and Validation of the Italian "Brief Five-Item Chronic Pain Questionnaire" for Epidemiological Studies.

Background: Chronic pain (CP) prevalence estimates addressing a wide phenotype are still quite fragmented and may vary widely due to the lack of standardized tools of investigation. There is an urgent need to update general population CP estimates. Methods: For this purpose, the Brief Five-item Chronic Pain Questionnaire was developed through experts' consultations for design and content validity assessment; literature analysis of measures used to investigate CP for general population surveys; understandability evaluation through a survey on a convenience sample of affected and non-affected individuals; reliability assessment by means of two double-wave online surveys carried out by the Italian Twin Registry; criterion and construct validity assessment through the third wave of the 2019 European Health Interview Survey (Ehis). Results: Key dimensions were defined to describe CP main aspects from a public health perspective. Literature analysis showed that validated questionnaires were rarely used to address important public health CP aspects. Understandability of the measure was good. Test-retest analyses showed adequate reliability of the measure: k values were at least "moderate" with highest values regarding CP "occurrence" and "intensity". Correlations of CP with well-known comorbidities (cancer, depression), and specific traits (age, education) as well as of CP and its intensity with "physical pain occurrence and intensity" detected in the Ehis 2019, confirmed, respectively, a good construct and criterion validity. Construct validity was also evaluated through the correlation between "perceived treatment effectiveness" and "interference of pain in daily life activities" as recorded in the Ehis 2019. Conclusion: The designed questionnaire is a brief self-administered measure, particularly suitable to detect persistent states of pain and related intensity in large-scale general population surveys by means of a first filtering item followed by four further items. It is, in fact, designed to detect CP possible underlying causes/triggers, drugs/treatments taking and frequency, and self-perceived effectiveness among CP sufferers. Further validation of the measure in different social and cultural contexts is desirable.