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

Parental bonding and children’s psychopathology: A transgenerational view point

Literature confirmed parental bonding as one of key factors influencing offspring’s psy-chopathology; the present study aimed to investigate, with a case-control study, the relationship between parental bonding and psychopathology in an Italian adolescent sample. The clinical sample was composed of 64 adolescents from 12 to 18 years old (Mage 15.00; S.D. 1.70) attending a Neuropsy-chiatric Unit of Veneto; the non-clinical sample was composed of 61 adolescents, from 13 to 18 years old (Mage 14.80; S.D. 1.32) attending middle and high school in the province of Padua and Pesaro (Italy); their parents (mothers and fathers) were also involved. In the study, self-reported tests were administered (Parental Bonding Instrument, Child Behavior Checklist, Youth Self Report). Our study confirmed a correlation between parental bonding and adolescent psychopathology: dysfunctional parenting styles (characterized by low care and high control) were more frequent among cases in contrast to controls. An effect of gender also appeared. In the Italian adolescent clinical sample, parental bonding, especially low parental care, was correlated to the emergence of psychopathology

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

CHILDREN WITH PSYCHOPATHOLOGY AND THEIR PARENTS FACING THE COVID-19 PANDEMIC: A CASE-CONTROL STUDY

Objective: This case-control study aimed to explore the effects of the COVID-19 outbreak on the mental well-being of pediatric psychiatric outpatients and their families, comparing them with children/adolescents and their parents from the general population. Method: The case group consisted of 168 subjects: 56 patients (6-18 years old) with psychiatric disorders, and their 112 parents. The healthy control group included 189 subjects: 63 children and adolescents with no psychopathologies, and their 126 parents. Both groups were assessed during the first COVID-19 lockdown in Italy (T0) and 4 months later (T1), by administering the CBCL6-18 and DASS-21. Results: Patients showed a good adaptation to the pandemic situation, while the children/adolescents in the healthy sample showed a greater variation in their general habits and a higher prevalence of stress symptoms during the lockdown. The patients’ parents likewise had fewer stress-related symptoms than caregivers in the healthy control group, both during the lockdown and 4 months later. At T0, patients’ mothers reported higher anxiety levels than mothers in the healthy group, while at T1 fathers of healthy children scored higher on the DASS-21 anxiety and stress scales than patients’ fathers. As concerns changes over time (T0-T1) in the parents’ psychological well-being, a general improvement was detected in both groups. Conclusions: The pandemic and quarantine measures were confirmed as significant stressors for all children and adolescents, and negatively affected their parents’ adaptation. The findings of this study point to the need for preventive interventions to support the mental health of all parents and their children in uncertain and stressful times

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

EXTERNALISING BEHAVIOURS, IMPULSIVITY, ALEXITHYMIA, AND EMOTIONAL DYSREGULATION IN ADOLESCENTS’ SUICIDALITY

Objective: suicide represents the second leading cause of death among adolescents (WHO, 2021). A deeper understanding of the characteristics that lead to it is crucial to increase the ability of clinicians in evaluating, treating, and preventing it. The objective of this study is to analyze the differences in impulsivity, externalizing behaviors, emotion dysregulation, and alexithymia between two groups of adolescents, the first presenting suicidal ideation (SI), the second presenting at least one suicide attempt (SA), in an ideation-to-action framework. Method: we conducted a retrospective study with 190 adolescents (Mage = 14.5, SD = 1.63; SI: n = 97, SA: n = 93). All were hospitalized in the Complex Operative Child Neuropsychiatry Hospital Unit (UOC-NPI) of the Hospital-University of Padua. Data were collected using the Youth Self-Report (YSR 11-18), Barratt’s Impulsiveness Scale (BIS-11) and the Toronto Alexithymia Scale (TAS-20) questionnaires. Results: the SA group obtained higher clinical scores in the YSR “rule-breaking behavior” and “conduct problems” scales, and in total TAS-20. Conclusions: the role of externalizing problems and alexithymia could open new frontiers in the understanding of suicide. These new data could be useful for the implementation of early screening protocols and for directing clinical interventions, promoting greater emotion regulation and anger management skills among patients

A Pre-Adolescent and Adolescent Clinical Sample Study about Suicidal Ideation, Suicide Attempt, and Self-Harming

Suicide is the second cause of death among adolescents, and nonsuicidal self-injury (NSSI) is one of the main risk factors for suicidal behavior. However, the possible variables specifically associated with suicidal ideation and suicide attempt, as well as the psychopathological characteristics linked to the concomitant presence of suicidal ideation/attempt and NSSI are still under-investigated in youth. The current study aimed to address these issues in a sample of 174 young Italian inpatients (Mage = 14.3 years ± 1.93, 78.2% girls). Sociodemographic and clinical variables were assessed through psycho-diagnostic interviews and ad hoc questionnaires. A binomial logistic regression was performed to identify the predictors of suicidal ideation and suicide attempt. Then, Kruskal–Wallis tests were run to analyze the psychopathological differences between patients with suicidal ideation and suicide attempt considering the coexistence of NSSI. The results highlighted that previous access to child mental health services and general psychopathological problems significantly predicted suicidal ideation, while previous hospitalizations, borderline personality functioning, and affective disorders significantly predicted suicide attempt. In general, inpatients with also NSSI reported higher levels of internalizing, somatic and total problems, impulsiveness, alexithymia, and emotional dysregulation. The clinical implications of our findings in terms of primary and secondary preventive programs are discussed

Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review

BackgroundEvidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE. MethodsWe described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science. ResultsSeven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life. DiscussionNeonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting. ConclusionsKetamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed