Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes

Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice’s respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders

Unstable Maternal Environment, Separation Anxiety, and Heightened CO2 Sensitivity Induced by Gene-by-Environment Interplay

Background: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were crossfostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2- enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the trait’s stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett x = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some no

Psychometric Properties Of The Social Phobia And Anxiety Inventory For Children (Spai-C): A Sample Of Italian School-Aged Children From The General Population

Unarticulated assumptions rarely help our students. The assumption that students can learn to do high-quality literature reviews without guidance from program faculty is surely unhelpful. And our failure to articulate our performance expectations further deprives students of guidance. With most doctoral programs unwilling or unable to teach students to write high-quality literature reviews, students have turned to other sources. Unfortunately, those other sources often misdirect students and inculcate unproductive habits. Academic librarians have specialized knowledge and skills that are invaluable for our students. However, my experience is that they tend to focus on searching library databases, which is rarely a productive way to start. Similarly, most of the published research methodology textbooks and literature review reference books tend to focus on database searching (Onwuegbuzie and Leech, 2005). Taken together, it would be easy for students to conclude that “the review of literature is a preliminary, cursory exercise that must be endured prior to the start of the ‘real’ study” (Dellinger, 2005: 52)

Long-Lasting Effects of Changes in Daily Routine during the Pandemic-Related Lockdown on Preschoolers’ Language and Emotional–Behavioral Development: A Moderation Analysis

The quantity and quality of environmental stimuli and contexts are crucial for children’s development. Following the outbreak of SARS-CoV-2 (COVID-19), restrictive measures have been implemented, constraining children’s social lives and changing their daily routines. To date, there is a lack of research assessing the long-lasting impacts that these changes have had on children’s language and emotional–behavioral development. In a large sample of preschoolers (N = 677), we investigated (a) the long-lasting effects of changes in family and social life and in daily activities over the first Italian nationwide COVID-19-pandemic-related lockdown upon children’s linguistic and emotional–behavioral profiles and (b) how children’s demographic variables and lifelong family characteristics moderated these associations within a multiple-moderator framework. Our findings showed a relationship between the time spent watching TV/playing video games and affective problems that was moderated by the number of siblings. Our findings showed that children who could be at high risk in more normal circumstances, such as only children, have been particularly harmed. Therefore, assessing the long-term effects of lockdown-related measures and how these could have been moderated by potential risk/protective factors added significant information to the existing literature

Investigating cancer patient acceptance of Whole Body MRI

Background: Whole Body magnetic resonance imaging (WB-MRI) enables early cancer detection, without exposing the patient to ionizing radiation. Our aim was to investigate patients’ acceptance of WB-MRI as a procedure for cancer staging and follow up. Materials and methods: 135 oncologic subjects participated to the study. An ad hoc questionnaire was administered before and after WB-MRI, to assess patient's confidence and concerns about WB-MRI, psychological reactions, experience and perceived utility of the procedure. Results: Before undergoing WB-MRI, about 58% of the patients were concerned for cancer progression outcome. 80.4% felt that they were given good information about the exam and the most informed group also perceived and higher level of utility of WB-MRI and no risk. Among people reporting discomfort with the exam (51.9%) the main reasons were noise and exam duration. Despite this, 80% of patients expressed high levels of satisfaction, and the majority (69%) judged WB-MRI more acceptable than other diagnostic exams. Patients who believed to have received more information before the exam rated their global satisfaction higher. Conclusion: Our results show that WB-MRI examinations were well-accepted and perceived with high levels of satisfaction by most patients. WB-MRI appears to be equally or more tolerable than other total body imaging modalities (e.g. PET, CT), especially if they receive enough information from the radiologist

Adolescent anxiety and pain problems: A joint, genome-wide investigation and pathway-based analysis.

Both common pain and anxiety problems are widespread, debilitating and often begin in childhood-adolescence. Twin studies indicate that this co-occurrence is likely due to shared elements of risk, rather than reciprocal causation. A joint genome-wide investigation and pathway/network-based analysis of adolescent anxiety and pain problems can identify genetic pathways that subserve shared etiopathogenetic mechanisms. Pathway-based analyses were performed in the independent samples of: The Quebec Newborn Twin Study (QNTS; 246 twin pairs and 321 parents), the Longitudinal Study of Child Development in Quebec (QLSCD; n = 754), and in the combined QNTS and QLSCD sample. Multiple suggestive associations (p<1×10-5), and several enriched pathways were found after FDR correction for both phenotypes in the QNTS; many nominally-significant enriched pathways overlapped between pain problems and anxiety symptoms (uncorrected p<0.05) and yielded results consistent with previous studies of pain or anxiety. The QLSCD and the combined QNTS and QLSCD sample yielded similar findings. We replicated an association between the pathway involved in the regulation of myotube differentiation (GO:0010830) and both pain and anxiety problems in the QLSDC and the combined QNTS and QLSCD sample. Although limited by sample size and thus power, these data provide an initial support to conjoint molecular investigations of adolescent pain and anxiety problems. Understanding the etiology underlying pain and anxiety co-occurrence in this age range is relevant to address the nature of comorbidity and its developmental pathways, and shape intervention. The replication across samples implies that these effects are reliable and possess external validity