Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

Sociodemographic and clinical characteristics of paediatric patients admitted to a neuropsychiatric care hospital in the COVID-19 era

Background: Since the first months of 2020, Italy and the world have been facing the COVID-19 pandemic. In addition to the dangerous and potentially deadly effects on physical health, it has caused a radical change in the lifestyle of the population and a potential danger for mental health too. These events were inserted into the context of a growing epidemiological trend regarding children’s psychiatric disorders in the past decade. Aim: To study the population of patients admitted to a Neuropsychiatric Hospital Unit of North Italy in the first COVID-19 year, comparing them with the population of patients hospitalised during the year immediately before, according to sociodemographic and clinical variables. Methodology: The study is an observational retrospective cohort. In total, 198 patients hospitalised due to neuropsychiatric problems from February 2019 to March 2021 were recruited. Data were analysed through mean and standard deviation, t-test, percentages, chi square test, and the Fischer exact test. Results: Risk factors associated with mental health disorders were similar between the two years. The hospitalisation modality showed a decrease in scheduled hospitalisations compared to urgent ones, and among the reasons that led patients to hospitalisation there was a conspicuous increase in eating disorders. More suicidal and self-harming behaviours occurred in the COVID-19 group too, compared to the previous year. The methods used to attempt suicide were changed considerably, with a prevalence of that attempted within the home. Changes in pharmacological therapies also occurred, necessary for more than 80% of inpatients during the COVID year, with a greater use of neuroleptics. There were alarming data about hospitalisation relapses, which increased from 12.2% in the pre-COVID year to 35.0% in the COVID year. Conclusion: Data shed light on clinical and policy issues in mental health care during the developmental age. Since the COVID-19 health emergency is not yet over, and its effects, especially on mental health, will be long-term, it is necessary to implement services and activities dedicated to both primary and secondary prevention of neuropsychiatric diseases especially during adolescent ages

Alexithymia and Psychopathological Manifestations Centered on the Body: Somatization and Self-Harm

The present study aimed to investigate alexithymia and psychopathological manifestations centered on the body in a sample of adolescents with somatizing and/or self-harming issues to analyze the phenomenon of NSSI linked to Somatic Symptom Disorders (SSD). A sample of 184 adolescents between 12 and 19 years of age, was divided into three groups, one with NSSI (n = 49) and the second group with SSD (n = 57), comparing them with a third group of adolescents with SSD and NSSI (n = 78) to investigate their differences and similarities in psychopathological correlates and to analyze the mediation role of alexithymia and emotional dysregulation in NSSI and SSD related to internalizing problems. The battery of tests included the Toronto Alexithymia Scale (TAS20) and the Youth Self-Report 11–18 (YSR). The NSSI + SSD group scored higher than the other two groups on all the YSR scales. The affective syndromes were the only clinical condition that discriminated between the three groups. On all the other syndrome scales, the NSSI + SSD group differed from the other two groups, while there were no differences between the NSSI group and the SSD group. The NSSI + SSD group revealed a more severely deficient emotional self-regulation. Difficulty identifying feelings was a trait shared by adolescents with SSD and those engaging in NSSI, a more complex overall alexithymia profile was associated with the combination of self-harming behavior and somatization. Alexithymia and emotional dysregulation played a mediating role in the relationship between internalizing problems and somatization. We did not find a mediating role in alexithymia and emotional dysregulation in the relationship between internalizing problems and self-injurious behavior. The combination of NSSI and SSD gave rise to more severe psychopathological correlates, clinical levels of alexithymia, and more severe deficient emotional self-regulation. Results of mediation role indicated a link between alexithymia, emotional dysregulation, and somatization

Pesticides and fertility: An epidemiological study in Northeast Italy and review of the literature

An increasing number of observations suggestive for a causal link between pesticide exposure and reproductive dysfunctions have appeared in literature during recent years. The present epidemiological analysis was undertaken to evaluate whether living in rural areas, where large amounts of pesticides are applied, represents a risk factor for infertility. Fertility rate (FR) was taken as statistical indicator for potential changes in fertility mediated by pesticides. The study analyzed a large population from an agricultural area of the North Eastern Italy, the Veneto Region. According to the estimated quantities of sprayed pesticides, the area was divided in three sub-areas with expected low, intermediate and high pesticide exposure. Comparisons of FR failed to detect significant differences among populations from the three selected areas, while regression analysis showed a significant decrease of FR relative to the total amount of pesticides used. Although several investigative shortcomings prevent the results from being conclusive, this study seemingly challenges the hypothesis that living in rural areas where large amounts of pesticides are applied represents a risk factor for fertility

First trimester diclofenac exposure and pregnancy outcome

To assess the safety of diclofenac during pregnancy.OBJECTIVE: To assess the safety of diclofenac during pregnancy. METHODS: A prospective observational cohort study, evaluating follow-up data of women who contacted Teratology Information Services to get counseling. The exposed group included 145 pregnant women who were exposed to diclofenac between the 5th and the 14th gestational week. A contemporary control group (501 women) was randomly selected from among patients who contacted Teratology Information Services with regard to exposures to agents known not to be teratogenic during a similar period of pregnancy. RESULTS: Major birth malformations were not more common in the study group than in the control group (p=0.07). CONCLUSION: Our study suggests that the use of diclofenac is relatively safe during the first trimester of pregnancy and the studied sample size makes it possible to exclude a risk of congenital malformation higher than 3.3, with a power of 80%

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues