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.

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.

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.

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.

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.

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.

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 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.

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.

Adolescent pain, anxiety, and depressive problems: a twin study of their co-occurrence and the relationship to substance use.

ABSTRACT: Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (ß = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions.

Behavioral markers of social anxiety in Cornelia de Lange Syndrome: A brief systematic review.

BACKGROUND: There is evidence that social impairments in Cornelia de Lange Syndrome (CdLS) differ from those observed in idiopathic autism as they are characterized mainly by social anxiety. However, the knowledge of the fundamental features of social anxiety symptoms in this target population is limited. This brief systematic review aims to investigate the relationship between social anxiety and CdLS through multiple cross-sectional comparisons. METHODS: PRISMA-P guidelines were followed, and the literature research was conducted in Pubmed, EBSCOhost, Google Scholar, and ScienceDirect using "Cornelia de Lange Syndrome" or "CdLS" and "social anxiety" as search terms. RESULTS: Six articles met the eligibility criteria. Results show that heightened levels of social anxiety in CdLS individuals occur before and after the social engagement and are mediated by both the nature of the social demand and the familiarity of the examiner they interact with. LIMITATIONS: The interpretation of results is limited by the wide heterogeneity of patients' age and sample size across the reviewed studies, and by the absence of a unique observational procedure to detect behaviors indicative of social anxiety in syndromic individuals. CONCLUSIONS: These findings have considerable clinical implications for intervention planning which might be generalized to all people with intellectual disability linked to a genetic syndrome.

Italian Children's Well-Being after Lockdown: Predictors of Psychopathological Symptoms in Times of COVID-19.

The first Italian lockdown imposed to fight the spread of COVID-19 caused important disruptions in families' everyday lives. The main aim of this research was to investigate the predictors of psychopathology in children aged 5-10 years, immediately after the national 2-month lockdown. A total of 158 Italian parents (148 mothers, 10 fathers, mean age = 41 years) were recruited and asked to complete an online research concerning their 158 children (76 boys, mean age = 7.4 years). Parents completed questionnaires on parent-child conflict, resilience, temperament, behavior, and previous adverse childhood experiences. Hierarchical regressions showed that children's psychopathology was predicted by low child resilience, high novelty seeking and harm avoidance, adverse experiences, and high flooding levels. Moreover, girls exposed to adverse experiences appeared more vulnerable to psychopathology. The recruitment of a convenience sample, the small sample size, and the cross-sectional design of our study limit the generalizability and interpretation of the present findings. Nonetheless, this research extends our knowledge of children's functioning in such an exceptional period. Shedding light on predictors of children's psychopathology following prolonged quarantine can indeed guide effective psychological interventions now and in future similar situations.

Parental Internalizing Psychopathology and PTSD in Offspring after the 2012 Earthquake in Italy.

Post-traumatic stress disorder (PTSD) is common in youths after earthquakes, with parental psychopathology among the most significant predictors. This study investigated the contribution and the interactional effects of parental internalizing psychopathology, the severity of exposure to the earthquake, and past traumatic events to predict PTSD in offspring, also testing the reverse pattern. Two years after the 2012 earthquake in Italy, 843 children and adolescents (9-15 years) living in two differently affected areas were administered a questionnaire on traumatic exposure and the UCLA PTSD Reaction Index. Anxiety, depression, and somatization were assessed in 1162 parents through the SCL-90-R. General linear model showed that, for offspring in the high-impact area, predictors of PTSD were earthquake exposure, past trauma, and parental internalizing symptoms, taken individually. An interaction between earthquake exposure and parental depression or anxiety (not somatization) was also found. In the low-impact area, youth PTSD was only predicted by earthquake exposure. The reverse pattern was significant, with parental psychopathology explained by offspring PTSD. Overall, findings support the association between parental and offspring psychopathology after natural disasters, emphasizing the importance of environmental factors in this relationship. Although further research is needed, these results should be carefully considered when developing mental health interventions.