Patterns of sub-optimal change following CBT for childhood anxiety.

BACKGROUND: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment. METHODS: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors. RESULTS: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group. CONCLUSIONS: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier.

Intervention for School Anxiety and Absenteeism in Children (ISAAC): Mixed-Method Feasibility Study of a Coach-Assisted, Parent-Focused Online Program.

The aftermath of the Covid-19 pandemic has seen an increase in persistent school absenteeism and Emotionally-Based School Avoidance (EBSA). However, suitable evidence-based psychological interventions are often unavailable. We aimed to assess the feasibility and acceptability of a new parent-focused online program, Intervention for School Anxiety and Absenteeism in Children (ISAAC), which has been co-designed with parents and practitioners. This exploratory mixed-method study recruited participants from three schools in southern England, enrolling N = 9 parents for whom a child, aged 5-11 years, was experiencing signs of EBSA. The intervention consisted of three web-based psychoeducational modules respectively addressing parental stress, accommodating parenting behaviors, and communication with school staff. Module completion was assisted by weekly calls with a non-specialist "coach." Feasibility was measured using indicators of retention, module participation, overall program completion and coaching fidelity. Acceptability was assessed using semi-structured interviews, module ratings and written qualitative feedback. We also explored baseline-post change in parent-reported measures of children's school avoidance, absences, anxiety, parental stress, accommodating parenting behaviors, and quality of parent-school communication. Overall, the intervention was feasible to deliver to parents with six (67%) participants completing the full intervention. Participants found the intervention acceptable across thematic domains of affective attitude, burden, coherence, self-efficacy and perceived effectiveness. Participants particularly appreciated the coach's support. We observed small to moderate reductions in school avoidance behaviours (d with Hedges correction = 0.36), child anxiety (d with Hedges correction = 0.33) and accommodating behaviours (d with Hedges correction = 0.44) at the post timepoint compared to baseline. In conclusion, ISAAC shows early promise with the potential to deliver scalable online support for families affected by emerging EBSA. Future research should move toward establishing effectiveness in a randomized controlled trial.

Large-scale remote fear conditioning: Demonstration of associations with anxiety using the FLARe smartphone app.

OBJECTIVES: We aimed to examine differences in fear conditioning between anxious and nonanxious participants in a single large sample. MATERIALS AND METHODS: We employed a remote fear conditioning task (FLARe) to collect data from participants from the Twins Early Development Study (n = 1,146; 41% anxious vs. 59% nonanxious). Differences between groups were estimated for their expectancy of an aversive outcome towards a reinforced conditional stimulus (CS+) and an unreinforced conditional stimulus (CS-) during acquisition and extinction phases. RESULTS: During acquisition, the anxious group (vs. nonanxious group) showed greater expectancy towards the CS-. During extinction, the anxious group (vs. nonanxious group) showed greater expectancy to both CSs. These comparisons yielded effect size estimates (d = 0.26-0.34) similar to those identified in previous meta-analyses. CONCLUSION: The current study demonstrates that remote fear conditioning can be used to detect differences between groups of anxious and nonanxious individuals, which appear to be consistent with previous meta-analyses including in-person studies.

Maternal and paternal influences on childhood anxiety symptoms: A genetically sensitive comparison.

This study tested the theory that anxious fathers pose a quantitatively different environmental influence on childhood anxiety than anxious mothers. The analysed sample contained 502 linked adoption units from the Early Growth and Development Study (EGDS), a longitudinal multisite study that follows 561 adopted children (57.2% boys) and their adoptive and birth parents, who were recruited through US adoption agencies. A Bayesian latent growth model predicted child anxiety symptoms between 18 months and 4.5 years from inherited (birth parent anxiety) and rearing parent anxiety. This model revealed little evidence for a difference in the influence of maternal and paternal rearing parent anxiety on child anxiety symptoms. Contrary to theoretical predictions, anxiety in the rearing father is likely to have an equivalent influence to that of the mother on both child anxiety symptoms at 18 months old and their developmental trajectory over the preschool years.

Children of the Twins Early Development Study (CoTEDS): A Children-of-Twins Study.

The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent-child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.

DNA methylation of FKBP5 and response to exposure-based psychological therapy.

Differential DNA methylation of the hypothalamic-pituitary-adrenal axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences and may play a role in how well people respond to psychological treatments. Participants (n = 111) received exposure-based cognitive behavioural therapy (CBT) for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (ß = -4.26, p = 3.90 × 10-4 ), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p = .045) but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences.

The role of KIBRA in reconstructive episodic memory.

BACKGROUND: In order to retrieve episodic past events, the missing information needs to be reconstructed using information stored in semantic memory. Failures in these reconstructive processes are expressed as false memories. KIBRA single nucleotide polymorphism (rs17070145) has been linked to episodic memory performance as well as an increased risk of Alzheimer's disease and post-traumatic stress disorder (PTSD). METHODS: Here, the role of KIBRA rs17070145 polymorphism (male and female CC vs. CT/TT carriers) in reconstructive episodic memory in the Deese-Roediger-McDermott (DRM) paradigm was investigated in N = 219 healthy individuals. RESULTS: Female participants outperformed males in the free recall condition. Furthermore, a trend towards a gender x genotype interaction was found for false recognition rates. Female CT/TT carriers exhibited a lower proportion of false recognition rates for associated critical lures as compared to male CT/TT. Additionally, an association between KIBRA rs17070145 genotype, familiarity and recollection based recognition performance was found. In trials with correct recognition of listed items CT/TT carriers showed more "remember", but fewer "know" responses as compared to CC carriers. DISCUSSION AND CONCLUSION: Our findings suggest that the T-allele of KIBRA rs17070145 supports recollection based episodic memory retrieval and contributes to memory accuracy in a gender dependent manner. Findings are discussed in the context of the specific contribution of KIBRA related SNPs to reconstructive episodic memory and its implications for cognitive and emotional symptoms in dementia and PTSD.

The impact of treatment delivery format on response to cognitive behaviour therapy for preadolescent children with anxiety disorders.

BACKGROUND: Several delivery formats of cognitive behaviour therapy (CBT) for child anxiety have been proposed, however, there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child's primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT and guided parent-led CBT. The secondary goal was to investigate the impact of the child's primary anxiety diagnosis on rates of remission for the three treatment formats. METHODS: A sample of 1,253 children (5-12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of generalised anxiety disorder (GAD), social anxiety disorder (SoAD), specific phobia (SP) or separation anxiety disorder (SAD). Children and parents completed a semistructured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at preintervention, postintervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question. RESULTS: In children with primary GAD, SAD or SoAD, there were no significant differences between delivery formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. The difference between individual and group was not significant when follow-up data were examined separately. CONCLUSIONS: Data show there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required.

The dopamine D2 receptor mediates approach-avoidance tendencies in smokers.

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. Using the approach-avoidance task (AAT), we recently demonstrated that smokers show an increased approach-bias toward smoking-related cues but not toward naturally rewarding stimuli. Here, we examined the contribution of the DRD2 Taq1B polymorphism to smokers' and non-smokers' responsivity toward smoking versus naturally rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. In addition, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e., AAT modification paradigms, in smokers.

Genome-wide association study of facial emotion recognition in children and association with polygenic risk for mental health disorders.

Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight-year-old participants (n = 4,097) from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) faces test. Genome-wide genotype data was available from the Illumina HumanHap550 Quad microarray. Genome-wide association studies were performed to assess associations with recognition of individual emotions and emotion in general. Exploratory polygenic risk scoring was performed using published genomic data for schizophrenia, bipolar disorder, depression, autism spectrum disorder, anorexia, and anxiety disorders. No individual genetic variants were identified at conventional levels of significance in any analysis although several loci were associated at a level suggestive of significance. SNP-chip heritability analyses did not identify a heritable component of variance for any phenotype. Polygenic scores were not associated with any phenotype. The effect sizes of variants influencing emotion recognition are likely to be small. Previous studies of emotion identification have yielded non-zero estimates of SNP-heritability. This discrepancy is likely due to differences in the measurement and analysis of the phenotype.

Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders.

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow-up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear-based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders.

BACKGROUND: Anxiety disorders are common, and cognitive-behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. AIMS: To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). METHOD: Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. RESULTS: No variants passed a genome-wide significance threshold (P = 5 × 10(-8)) in either analysis. Four variants met criteria for suggestive significance (P<5 × 10(-6)) in association with response post-treatment, and three variants in the 6-month follow-up analysis. CONCLUSIONS: This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders.

BACKGROUND: We previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome. AIMS: To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). METHOD: Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. RESULTS: There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes. CONCLUSIONS: The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.

A Genome-Wide Test of the Differential Susceptibility Hypothesis Reveals a Genetic Predictor of Differential Response to Psychological Treatments for Child Anxiety Disorders.

BACKGROUND: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. METHODS: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. RESULTS: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). CONCLUSIONS: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.

Cognitive Vulnerabilities for Depression and Anxiety in Childhood: Specificity of Anxiety Sensitivity and Rumination.

BACKGROUND: Childhood anxiety and depression frequently co-occur. Exploring specificity in cognitive processes for anxiety and depression in childhood can provide insight into cognitive vulnerabilities contributing to the development of anxiety and depressive disorders and inform targeted psychological interventions. Anxiety sensitivity and rumination are robust cognitive vulnerabilities for anxiety and depression, respectively. However, despite conceptual similarities, they are rarely considered together within a single study. AIMS: The current study explored specific and shared associations between anxiety sensitivity subscales and rumination and anxiety and depressive symptoms in unselected children. METHOD: Multiple regression analyses explored to what extent specific self-reported anxiety sensitivity subscales (physical, social and mental concerns) and rumination predicted anxiety and depressive symptoms in 147 unselected children, aged 7-11 years. RESULTS: Physical and social concern subscales of anxiety sensitivity were specifically associated with anxiety, whilst rumination was specifically associated with depressive symptoms. The mental concerns subscale of anxiety sensitivity was independently associated with both anxiety and depressive symptoms. These associations were only partially mediated by rumination. CONCLUSIONS: Anxiety and depression in young people are characterized by specific and shared cognitions. Evidence for shared and specific associations between the cognitive vulnerabilities of anxiety sensitivity and rumination, and anxiety and depression highlight the utility of transdiagnostic research and confirm that cognitive therapies may benefit from targeting cognitive concerns relating specifically to the patient's presenting symptoms.

HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). METHODS: Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). RESULTS: Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. CONCLUSIONS: Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.

Epigenome-Wide DNA Methylation Analysis of Monozygotic Twins Discordant for Diurnal Preference.

Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins' buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding.

Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNß3 with sleep measures.

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNß3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours.

Perfect storm: emotionally based school avoidance in the post-COVID-19 pandemic context.

School absences have risen following the COVID-19 pandemic and persistent absenteeism remains high in primary and secondary schools in England compared with pre-pandemic levels. This coincides with an upward trend in emotionally based school avoidance (EBSA). EBSA adversely affects children's educational attainment, health, social functioning and life prospects and warrants early intervention before a pattern of absenteeism becomes entrenched. In this article, we consider how the COVID-19 pandemic and its sequelae have created a 'perfect storm' of conditions, amplifying known school, family and child-based risk factors for EBSA while simultaneously reducing access to support services. We then outline priorities for developing new EBSA interventions and argue for a multi-component approach, which works across education, health and social care, and voluntary sectors to address the complex interplay between risk factors. Given the difficulties that families often face in obtaining timely support for EBSA, it is also essential that new interventions are accessible, resource-efficient and scalable. To this end, we specifically discuss the potential for contextually-sensitive, parent-focused interventions that can be delivered online with minimal synchronous support from a trained coach or facilitator.

Intervention for school anxiety and absenteeism in children (ISAAC): Co-designing a brief parent-focused intervention for emotionally-based school avoidance.

Emotionally-based school avoidance (EBSA) is an important driver of persistent school absenteeism and may have worsened in the context of COVID-19. This paper describes the development of a brief parent-focused psychosocial intervention with the goal to address the lack of accessible early interventions for EBSA. The developmental process used a person-based approach with two phases. In Phase 1, qualitative data were collected about intervention preferences and priorities from N = 10 parents and N = 7 practitioners in a series of co-design workshops. Phase 2 refined an intervention blueprint based on iterative consultations with N = 4 parents and N = 3 practitioners. Framework analysis was used to organise findings around key intervention parameters, including relevant mechanisms, content, and delivery methods needed to provide effective, acceptable and feasible support for families affected by EBSA. The resulting blueprint incorporates three online modules to be delivered over three weeks with each module consisting of psychoeducational videos, self-completed learning tasks and a corresponding coaching session. Respective module content includes: (i) self-care strategies to increase parent wellbeing and self-efficacy; (ii) parenting strategies to change behavioural patterns that maintain child distress and avoidance of school; and (iii) strategic communication strategies to increase the quality of home-school relationships. The blueprint has been developed into a full prototype for a forthcoming feasibility study.

Since the onset of the Covid-19 pandemic, there has been a noticeable increase in children missing school. One significant contributor to this rise in absences is Emotionally-Based School Avoidance (EBSA). EBSA refers to a situation where a child stays home from school due to feelings of anxiety and distress about attending. Accessing timely support for children with EBSA can be difficult due to lengthy waiting lists for child and adolescent mental health services. This paper outlines the creation of a new, brief psychosocial intervention aimed at helping parents support their child experiencing EBSA. The development process involved two phases. In the first phase, we collaborated with 10 parents and 7 practitioners to gather ideas about the kind of support families require, what should be included in the intervention, and how to make it practical for families to use. Based on these discussions, we formulated a plan for the new intervention. The second phase refined this plan of the intervention to ensure its suitability for families. The intervention is called ISAAC: Intervention for School Anxiety and Absenteeism in Children. ISAAC consists of three online modules to be completed by parents over a three-week period. Each module includes videos, reflection activities and homework tasks which help the parent learn a new skill or try a different way of responding to their child's anxiety about attending school. Parents are also supported by a coach. The first module encourages parents to take care of their own wellbeing and manage stress. The second module helps parents to learn new ways to respond to their child's distress related to school attendance, while the third module provides guidance on effective communication with the child's school. The next step for this intervention is to see whether it is agreeable to parents and practical to deliver in the real-world.