The developmental trajectories of the behavioral phenotype and neuropsychiatric functioning in Cornelia de Lange and Rubinstein Taybi syndromes: A longitudinal study.

Several changes in the behavioral phenotype arise with the growth of children affected by Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome (RSTS). However, previous research relied on a cross-sectional study design turning into age-related comparisons of different syndromic cohorts to explore age-dependent changes. We aim to outline the variating pathways of the neuropsychiatric functioning across the lifespan in CdLS and RSTS, through the setting up of a longitudinal study design. The sample included 14 patients with CdLS and 15 with RSTS. The assessments were carried out in two different timepoints. Our findings highlight that the cognitive profile of CdLS is subjected to a worsening trend with decreasing Intellectual Quotient (IQ) scores from T0 to T1, whereas RSTS shows a stable IQ over time. Patients affected by RSTS show greater improvements compared to CdLS in communication, daily living skills, social abilities, and motor skills across the lifespan. Both syndromes report an upward trend in behavioral and emotional difficulties even if CdLS exhibit a significant and major deterioration compared to individuals with RSTS. Being aware of the early dysfunctional patterns which might pave the way for later neuropsychiatric impairments is the first step for planning preventive interventions.

Age-Related Variations of Genetic and Environmental Contributions to the Covariation of Fear, Distress and Externalizing Symptoms: A Twin Study in Childhood and Adolescence.

The frequency with which Internalizing and Externalizing symptoms co-occur suggests that, behind both domains, there may be a common susceptibility represented by a general psychopathology factor. However, it's still unclear whether this common susceptibility is affected by age-related variations. Internalizing (i.e., Fear and Distress) and Externalizing symptoms were evaluated in 803 twin pairs from the population-based Italian Twin Registry. Model-fitting analysis was performed separately in the 6-14 and 15-18 age groups to estimate genetic and environmental contributions to the covariance among symptoms. For the 6-14 group, a multivariate Cholesky model best fitted the data, while, for the 15-18 group, the best fit was provided by a Common Pathway model in which nearly 50% of total variance of each trait was mediated by common genetic factors. Our findings support a common susceptibility behind Internalizing and Externalizing symptoms, mainly genetic in origin, that becomes more evident at the beginning of puberty.

The role of genetic and environmental factors in covariation between anxiety and anger in childhood.

Higher levels of anger expression, as well as lower levels of anger control, have been reported for adults with anxiety disorders compared to individuals without anxiety disorders. Different to the research on adults, very few studies examined the relationship between anxiety and anger in childhood. In our study, we investigated 398 Italian twin pairs (74 MZ male, 70 MZ female, 134 same-sex dizygotic-53 male, 81 female-, and 120 unlike-sex dizygotic twin pairs), aged 8-17 (mean 13.06 ± 2.59): (i) the heritability of a childhood anger phenotype; (ii) the association between five anxiety domains and anger; (iii) the role of possible common etiological factors in explaining the observed comorbidity and overlap in the risk between anxiety phenotypes and anger. The study demonstrated that anger, assessed by CBCL items, is heritable in children at a similar rate to prior studies (40%). Our research found low to moderate rate of correlation between anger and anxiety (from 0.10 to 0.19). Finally, the present study found that the majority of etiological influences on anxiety and anger are independent of each other. Data showed that shared environmental influences have some small effects on the phenotypic covariation between the anxiety phenotypes and anger (12%); whereas unique environmental influences have an almost negligible effect (1%). Our analyses did not reveal the effect of genetic effects in explaining the covariation between these phenotypes.

Videos look faster as children grow up: Sense of speed and impulsivity throughout primary school.

Previous research has documented systematic biases when adult observers judge the original speed of real-life video clips. What does the unfolding of events in videos-an increasingly pervasive "substitute reality"-look like as children grow up? The current study investigated the sense of speed during childhood and the relation with a number of performance and personality indexes. A group of 142 children aged 6-10 years adjusted the speed of video clips representing various scenes until reaching the apparent right speed. We found a tendency to underestimate speed; on average, videos played at their original speed were considered to be too slow. This tendency was larger in younger children and decreased with age (-3.16%/year). Uncertainty in judging video speed also decreased over the same age period (-10.79%/year). Children then performed a simple visuomotor task requiring response control, which revealed high accuracy and, in older children, faster responses. Children were also assessed for impulsivity/inattention and visuomotor habits through parents' questionnaires. When all variables were considered together, age and video game playing stood out as the only significant predictors of speed biases, both associated with an increase in apparent video speed. Thus, this study provides evidence of a change in the sense of speed during the primary school period, possibly involving the progressive overriding of a slow motion prior and/or the protracted calibration of perceptual mechanisms for speed constancy. The sense of speed, however, did not seem to be influenced by impulsivity traits in the population considered.

Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals.

Theory of Mind: A Brief Review of Candidate Genes.

Deficits in theory of mind (ToM), known as the ability to understand the other's mind, have been associated with several psychopathological outcomes. The present systematic review aims to summarize the results of genetic studies that investigated gene polymorphisms associated with mentalization performance tasks in children and adults. The systematic review was carried out following PRISMA guidelines, and the literature search was conducted in PubMed and EBSCOhost using the following keywords: 'theory of mind, mentalizing, mindreading' and 'gene, genetic basis'. Nineteen studies met the eligibility criteria for inclusion. Most of the literature focused on the role of DRD4, DAT1, OXTR, OXT, COMT, ZNF804A, AVP, AVPR, SCL6A4, EFHC2, MAO-A, and the family of GTF2I genes in influencing ToM. However, controversial results emerged in sustaining the link between specific genetic polymorphisms and mentalization abilities in children and adults. Available data show heterogeneous outcomes, with studies reporting an association between the same family genes in subjects of the same age and other studies reporting no correlation. This does not allow us to draw any solid conclusions but paves the way for exploring genes involved in ToM tasks.

Novel Approaches for the Treatment of Post-Traumatic Stress Disorder: A Systematic Review of Non-Invasive Brain Stimulation Interventions and Insights from Clinical Trials.

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms' severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects' clinical conditions.

Parent and Child Predictors of Internalizing and Externalizing Symptomatology during COVID-19.

The COVID-19 emergency has fostered an increasing risk of experiencing distress and negative emotions in parents that turned into heightened stress for children. In this study, we aim to evaluate the effects of parental stress, children's resilience, and previous adversities on the development of internalizing and externalizing symptoms in children. A series of questionnaires were completed by 158 Italian parents (148 mothers, 10 fathers, mean age = 41 years) concerning them and their school-aged children (N = 158, 76 boys, mean age = 7.4 years) at two critical time points (June 2020 and December 2020). Regression analyses showed that internalizing problems were predicted only by concurrent children's resilience, whereas externalizing problems were predicted by concurrent parental flooding, children's resilience, and early parental satisfaction. Therefore, internalizing and externalizing symptoms trajectories follow different routes and are predicted by both common and distinct factors. Supporting positive parenting attitudes and behavior should be recommended to prevent the worsening of children's externalizing behaviors. At the same time, nurturing resilience in pediatric systems might be useful in preventing or reducing children's internalizing symptoms.

Shared genetic influences between depression and conduct disorder in children and adolescents: A systematic review.

INTRODUCTION: The co-occurrence between major depression disorder (MDD) and conduct disorder (CD) is common across development and represents a significant risk factor for future psychiatric problems and long-term impairment. Large-scale quantitative genetic studies suggest that the MDD-CD co-occurrence may be partly explained by shared genetic vulnerability factors, in line with transdiagnostic models of psychopathology, but no systematic synthesis of the literature is currently available. METHODS: We therefore conducted a systematic review of the available genetic literature on the co-occurrence between MDD and CD in children and adolescents. We identified 10 eligible studies, including 5 cross-sectional bivariate/multivariate twin studies, 3 longitudinal bivariate/multivariate twin studies, and 2 latent profile/trajectory twin studies. RESULTS: Most of the reviewed studies found a strong contribution of shared genetic factors on the covariation between depression and conduct problems, in line with the prominent effect of a common genetic liability across development. LIMITATIONS: The scientific literature on this psychiatric comorbidity is still limited, as it solely consists of twin studies from high income countries. CONCLUSION: Considering the joint burden of MDD and CD on youth, families and society worldwide, future studies are needed to better investigate the shared risk processes of these frequently co-occurring conditions, in order to inform new treatments through personalized medicine.

The Mediation of Care and Overprotection between Parent-Adolescent Conflicts and Adolescents' Psychological Difficulties during the COVID-19 Pandemic: Which Role for Fathers?

BACKGROUND: There is evidence of a significant raise in youths' emotional and behavioral difficulties during the pandemic. Only a few studies have addressed parent-adolescent conflict, and none investigated the possible mediating effect of parenting in the association between conflicts with parents and adolescents' symptoms. This study aimed at investigating youths' psychological symptoms during the pandemic, focusing on the predicting effect of parent-adolescent conflict. The mediating role of care and overprotection was also explored, considering whether adolescent gender moderated this mediation. METHODS: 195 adolescents aged 14-18 years participated in an online longitudinal study. Perceived conflict with parents and parenting dimensions (Parental Bonding Instrument; PBI) were assessed at baseline (2021). Self-reported psychological difficulties (Strengths and Difficulties Questionnaire; SDQ) were collected at baseline and after one year (2022). RESULTS: A significantly severer symptomatology was found in adolescents having a conflictual relationship with one or both parents. Major conflicts with parents correlated with lower care and greater overprotection in mothers and fathers. However, parental overprotection and maternal care were not mediators of the relationship between conflict and youths' difficulties. The only exception was represented by paternal care that fully mediated this relationship in both adolescent males and females. CONCLUSIONS: Although further investigations are needed to overcome limitations due to the small sample, findings extend our insight into the impact of parent-adolescent conflict, highlighting the role of fathers' care and the need to maximize their involvement in clinical interventions.

Neural Correlates of Delay Discounting in the Light of Brain Imaging and Non-Invasive Brain Stimulation: What We Know and What Is Missed.

In decision making, the subjective value of a reward declines with the delay to its receipt, describing a hyperbolic function. Although this phenomenon, referred to as delay discounting (DD), has been extensively characterized and reported in many animal species, still, little is known about the neuronal processes that support it. Here, after drawing a comprehensive portrait, we consider the latest neuroimaging and lesion studies, the outcomes of which often appear contradictory among comparable experimental settings. In the second part of the manuscript, we focus on a more recent and effective route of investigation: non-invasive brain stimulation (NIBS). We provide a comprehensive review of the available studies that applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to affect subjects' performance in DD tasks. The aim of our survey is not only to highlight the superiority of NIBS in investigating DD, but also to suggest targets for future experimental studies, since the regions considered in these studies represent only a fraction of the possible ones. In particular, we argue that, based on the available neurophysiological evidence from lesion and brain imaging studies, a very promising and underrepresented region for future neuromodulation studies investigating DD is the orbitofrontal cortex.

Transcranial direct current stimulation (tDCS) over the orbitofrontal cortex reduces delay discounting.

Delay discounting (DD) is a quantifiable psychological phenomenon that regulates decision-making. Nevertheless, the neural substrates of DD and its relationship with other cognitive domains are not well understood. The orbitofrontal cortex (OFC) is a potential candidate for supporting the expression of DD, but due to its wide involvement in several psychological functions and neural networks, its central role remains elusive. In this study, healthy subjects underwent transcranial direct current stimulation (tDCS) while performing an intertemporal choice task for the quantification of DD and a working memory task. To selectively engage the OFC, two electrode configurations have been tested, namely, anodal Fp1-cathodal Fp2 and cathodal Fp1-anodal Fp2. Our results show that stimulation of the OFC reduces DD, independently from electrode configuration. In addition, no relationship was found between DD measures and either working memory performance or baseline impulsivity assessed through established tests. Our work will direct future investigations aimed at unveiling the specific neural mechanisms underlying the involvement of the OFC in DD, and at testing the efficacy of OFC tDCS in reducing DD in psychological conditions where this phenomenon has been strongly implicated, such as addiction and eating disorders.

We need to talk: The urgent conversation on chronic pain, mental health, prescribing patterns and the opioid crisis.

The opioid crisis' pathways from first exposure onwards to eventual illnesses and fatalities are multiple, intertwined and difficult to dissect. Here, we offer a multidisciplinary appraisal of the relationships among mental health, chronic pain, prescribing patterns worldwide and the opioid crisis. Because the opioid crisis' toll is especially harsh on young people, emphasis is given on data regarding the younger strata of the population. Because analgesic opioid prescription constitute a recognised entry point towards misuse, opioid use disorder, and ultimately overdose, prescribing patterns across different countries are examined as a modifiable hazard factor along these pathways of risk. Psychiatrists are called to play a more compelling role in this urgent conversation, as they are uniquely placed to provide synthesis and lead action among the different fields of knowledge and care that lie at the crossroads of the opioid crisis. Psychiatrists are also ideally positioned to gauge and disseminate the foundations for diagnosis and clinical management of mental conditions associated with chronic pain, including the identification of hazardous and protective factors. It is our hope to spark more interdisciplinary exchanges and encourage psychiatrists worldwide to become leaders in an urgent conversation with interlocutors from the clinical and basic sciences, policy makers and stakeholders including clients and their families.

A Twin Study of the Relationships between Cognitive Disengagement Syndrome and Anxiety Phenotypes in Childhood and Adolescence.

Data on the etiological factors underlying the co-occurrence of Cognitive Disengagement Syndrome (CDS) with anxiety symptoms are very limited. The present study investigated the nature of latent shared etiological elements in 400 Italian twin pairs aged 8-18, explaining the covariation between CDS and anxiety symptoms. Preliminary analysis demonstrated significant correlations between Child Behaviour Checklist/6-18 Sluggish Cognitive Tempo Scale and two (Somatic Anxiety, Generalized Anxiety) out of five Screen for Child Anxiety Related Disorders anxiety subscales. Results from causal analysis seem to exclude the hypothesis that co-occurrence between CDS and Anxiety Symptoms could be due to a direct phenotypic effect of one trait upon the other. Model fitting-analysis indicated that the aforementioned associations were partially explained by shared genetic and environmental factors influencing a common liability factor. A latent variable capturing the covariation between CDS and anxiety problems can be considered as a unifying (patho)physiological mechanism/system common to these constructs. Our results support the adoption of a broader view of the relationships between CDS and anxiety phenotypes in childhood and adolescence for both clinicians and educators.

Genetic and environmental contributions to separation anxiety: a meta-analytic approach to twin data.

BACKGROUND: Separation anxiety disorder (SAD) and separation anxiety symptoms (SA) have been studied both epidemiologically and genetically; however, large between-studies discrepancies emerge relative to the role of genetic, shared-, and nonshared environmental influences on these conditions. METHODS: Based upon available literature, 18 cohorts and 31,859 subjects belonging to twin samples in Europe, the United States, and Australia were included in three meta-analytic estimations of: the standardized variance components of etiological influences on SAD/SA, and on the effect of sex and rater. RESULTS: Meta-analytic estimations carried out on all cohorts showed that within-family (genetic 43% and shared environmental 17%) factors explain most of individual differences for SAD/SA. Meta-heritability estimates were higher among females (.52) than males (.26), whereas nonshared environmental effects were stronger for the latter (.74) than for the former (.41). When SAD/SA was rated by parents, the shared environmental influences were higher than those obtained with self-assessment instruments (.23 versus .05), but this may reflect an age difference between subsamples. CONCLUSIONS: A shared environmental effect is present and important in SAD/SA. Our results support at an etiological level the involvement of parents in treating SAD/SA in children, and the provision of specific strategies to parents to manage their own anxiety.

Cerebral responses to emotional expressions and the development of social anxiety disorder: a preliminary longitudinal study.

BACKGROUND: Cross-sectional studies report biased reactivity to facial expressions among shy children, anxious adolescents, and adults with social anxiety disorder (SAD). It remains unknown whether cerebral reactivity to facial expressions can predict longitudinally the development of SAD in adolescence and characterize the degree of social anxiety among the general population of adolescents. METHODS: In a longitudinal study of 21 general population volunteers characterized for behavioral and genetic variables, N400 event-related potentials, and 3-Tesla fMRI activations in response to happy/neutral/angry expressions were acquired at age 8-9 and 14-15, respectively. RESULTS: By stepwise regression, N400 amplitudes acquired at age 8-9 predicted the number of DSM-IV SAD symptoms at age 14-15, with the sole, significant (P = .018) contribution of the "anger" condition. Factorial ANOVA revealed increased (Voxel-Level P((FWE)) range: .02-.0001) bilateral fMRI activations of several brain areas, including the amygdala, in response to facial expressions compared to a fixation cross. The number of symptoms of DSM-IV SAD was positively correlated with left amygdala response to angry (P((FWE)) = .036) and neutral (P((FWE)) = .025) facial expressions. Factorial ANOVA revealed that the 5-HTTLPR -S allele was associated with heightened left amygdala response to anger (P((FWE)) = .05). CONCLUSION: Cerebral reactivity to facial expressions, anger especially, measured at different developmental stages by different techniques is associated with adolescence SAD. The 5-HTTLPR genotype affects the neural processing of interpersonal affective stimuli during development.

Cooperation with Teachers as a Mediator of the Relationship between Family Conflict and Children's Psychological Difficulties.

Parent-child conflict can have a series of negative consequences concerning youth emotional and behavioral development. The link between family conflict and children's externalizing symptoms is well established, whereas the association with internalizing symptoms is less explored. Within the school context, children are engaged in other meaningful relationships (i.e., with teachers and peers) which contribute to their growth. This cross-sectional study aimed at understanding whether a cooperative behavior with the teachers is able to mediate the association between parent-child conflict and children's psychopathological symptoms. We recruited 319 (150 boys) school-aged children (M = 11.3 years; SD = 1.8 years) and their parents and teachers. Children self-reported on their internalizing symptoms, whereas parents completed a questionnaire concerning their relationship with the child, and teachers rated children's behavior and internalizing/externalizing symptoms. Analyses conducted through Hayes' PROCESS tool showed that cooperation with the teacher partially mediated the association between parent-child conflict and child-reported depressive symptoms. Notably, cooperative behavior fully mediated the link between parent-child conflict and children's internalizing and externalizing symptoms reported by teachers. Difficulties exhibited at school partly derive from a conflictual home environment. Our findings showed that such problems can be reduced thanks to a cooperative relationship with the teacher.

Parenting Programs to Reduce Recurrence of Child Maltreatment in the Family Environment: A Systematic Review.

Physical maltreatment is a public health issue affecting millions of children in their lifetime, with a high risk of recurrency. Although there are several parenting programs (PPs) available, existing reviews on their effectiveness in preventing physical abuse recurrences have many limitations. The current systematic review aims at (1) providing a summary of evidence on the effectiveness of behavioral/cognitive-behavioral PPs in preventing physical re-abuse; (2) extending previous reviews by including reduction of child maltreatment recurrence as the main outcome but also focusing on the effect of PPs on maltreatment risk, parent and child psychopathology, and parent-child relationship; and (3) including only RCT with at least one follow-up. A PRISMA-compliant systematic review was performed in the EBSCOhost and PUBMED databases. In total, 93 articles were identified, of which 8 were included in the review. Among them, three reported a significant reduction in recidivism rates and maltreatment risk, and five improvements in parent-child relationships. Although limitations arise from methodological heterogeneity across studies, there is some evidence that some brief and manualized cognitive behavioral PPs can reduce the recurrence of child physical maltreatment and improve parent-child relationships. More studies are needed to give further support to PP effectiveness in protecting children from recurrent maltreatment.

Age-related hallmarks of psychopathology in Cornelia de Lange and Rubinstein-Taybi syndromes.

BACKGROUND AND AIM: There is mounting evidence highlighting that Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome's (RSTS) behavioral phenotypes are not stable over individual developmental trajectories and that several psychiatric disorders might arise with age. Our study aims to examine the specific hallmarks of psychopathology and behavioral phenotypes in four different age ranges: infancy and toddlerhood, early childhood, middle childhood, and adolescence, in both genetic syndromes. METHOD: The sample included 44 patients with CdLS (48% boys, age = 6.67 ± 4.36) and 31 with RSTS (48% boys, age = 6.89 ± 4.58) recruited through follow-ups. Cognitive, behavioral, and autism assessments were carried out with Griffith's scales or the Leiter-R, the Child Behavior Checklist, and the Child Autism Rating Scales 2. Multiple ANOVA 2 × 4 were run to outline behavioral phenotypic age-related syndromic markers and ANCOVA to value the weight of IQ and ASD-related traits on the psychopathological outcome. RESULTS: Findings showed that anxiety is a crucial phenotypic hallmark, independent of IQ but associated with autistic traits, that increases from infancy to adolescence in both CdLS and RSTS. CONCLUSION AND IMPLICATIONS: Being aware of the developmental challenges that growing children are called to face is essential for drawing up proper standards of assessment turning into target age-related interventions, ensuring these patients personalized healthcare and improvement in life quality.

The Cool Kids as a School-Based Universal Prevention and Early Intervention Program for Anxiety: Results of a Pilot Study.

The efficacy of the Cool Kids program has been consistently demonstrated both within Australia and internationally, but limited data are available on the use of Cool Kids as a universal program. The purpose of the study is to evaluate Cool Kids as a universal program for preventing childhood anxiety in the school context. There were 73 Italian children (35 boys and 36 girls, ages 10-13 years) attending the last year of primary school and the first year of middle school who participated in an active intervention based on a school adaptation of the Cool Kids protocol. Results of t-test analyses highlighted a downward trend of anxiety symptoms, especially in total anxiety, somatic anxiety, generalized anxiety, separation anxiety, social anxiety and school phobia at post-treatment assessed by children. Even the score of depression symptoms, measured as a second outcome measure, decreased after the treatment. This study contributes to the evidence base for the Cool Kids program as a universal program for preventing childhood anxiety in the school context. Although these preliminary results show some promise, their replication in future research is necessary given current study limitations.