The role of environmental sensitivity in the mental health of Syrian refugee children: a multi-level analysis.

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data. Child-caregiver dyads were recruited from informal tented settlements in Lebanon, and completed a battery of psychological instruments at baseline and follow-up (12 months apart). Univariate and multivariate Bayesian linear mixed models were used to examine a) the interrelationships between markers of sensitivity and b) the ability of sensitivity markers to predict anxiety, depression, post-traumatic stress disorder, and externalising behaviour. Self-reported sensitivity (using the Highly Sensitive Child Scale) significantly predicted a higher burden of all forms of mental illness across both waves, however, there were no significant cross-lagged pathways. Physiological and genetic markers were not stably predictive of self-reported sensitivity, and failed to similarly predict mental health outcomes. The measurement of environmental sensitivity may have significant implications for identifying and treating mental illness, especially amongst vulnerable populations, but clinical utility is currently limited to self-report assessment.

War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children.

Altered secretion of cortisol, the primary effector of the hypothalamus-pituitary-adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6-18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.

The important role of mothers during displacement: Direct and indirect effects of the refugee context on Syrian refugee children's mental health.

Refugee children are at increased risk for mental health problems, including post-traumatic stress, depression, and externalizing problems. The refugee environment, maternal mental health, and parenting may reduce or exacerbate that risk. This study investigated their direct and indirect associations with child mental health cross-sectionally in a sample of Syrian refugee child-mother dyads in Lebanon in 2017-19. Mediating pathways were tested using structural equation modeling with 1446 dyads (child: Mage = 11.39, 52.1% females) and again 1 year later with 872 (child: Mage = 12.17, 53.1% females) of the original sample. Mediating pathways from the refugee environment through maternal mental health and parenting to child outcomes were detected, emphasizing the importance of a holistic approach to refugee mental health.

Epilepsy severity mediates association between mutation type and ADHD symptoms in tuberous sclerosis complex.

The association between attention-deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0-16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early-onset and severe epilepsy in the first 2 years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early-onset epilepsy across syndromic and non-syndromic populations.

Predictors of psychological risk and resilience among Syrian refugee children.

OBJECTIVES: War-exposed refugee children are at elevated risk for mental health problems, but a notable proportion appear resilient. We aimed to investigate the proportion of Syrian refugee children who can be considered resilient, and applied a novel approach to identify factors predicting individual differences in mental health outcomes following war exposure. METHODS: The sample included 1,528 war-exposed Syrian refugee children and their primary caregiver living in refugee settlements in Lebanon. Children were classed as having low symptoms (LS) if they scored below clinically validated cut-offs for post-traumatic stress disorder (PTSD), depression and externalising behaviour problems. Children scoring above any cut-off were classified as having high symptoms (HS). Each LS child was matched with one HS who reported similar war exposure, to test what differentiates children with similar exposures but different outcomes. RESULTS: 19.3% of the children met our resilience criteria and were considered LS. At the individual level, protective traits (e.g. self-esteem; OR = 1.51, 95% CI [1.25, 1.81]) predicted LS classification, while environmental sensitivity (OR = 0.69, 95% CI [0.59, 0.82]), poorer general health (OR = 0.71, 95% CI [0.58, 0.87]) and specific coping strategies (e.g. avoidance; OR = 0.90, 95% CI [0.85, 0.96]) predicted HS classification. Social/environmental predictors included perceived social support (OR = 1.23, 95% CI [1.02, 1.49]), loneliness and social isolation (OR = 0.85, 95% CI [0.80, 0.90]), child maltreatment (OR = 0.96, 95% CI [0.94, 0.97]), and caregiver mental and general health (e.g. caregiver depression; OR = 0.94, 95% CI [0.92, 0.97]). CONCLUSIONS: Future research should take multiple dimensions of functioning into account when defining risk for mental health problems and consider the identified predictors as potential targets for interventions.

Perinatal adversities in tuberous sclerosis complex: Determinants and neurodevelopmental outcomes.

AIM: To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). METHOD: The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4-254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93-323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann-Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. RESULTS: Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. INTERPRETATION: Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. WHAT THIS PAPER ADDS: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.

Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH).

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017-January 2018), N = 3188 individuals participated [n = 1594 child-caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6-19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children's well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent-child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: m.pluess@qmul.ac.uk).

Long-term cognitive outcomes in tuberous sclerosis complex.

AIM: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC). METHOD: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2. RESULTS: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence. INTERPRETATION: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy. WHAT THIS PAPER ADDS: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC.

Impact of ASD Traits on Treatment Outcomes of Eating Disorders in Girls.

Evidence links high levels of Autism Spectrum Disorder Traits in women with chronicity of anorexia nervosa. This study reports through clinical audit the impact of ASD traits on treatment outcomes of girls who were referred for treatment in a specialist eating disorder service. Presence of current, but not early childhood, ASD traits was elevated in comparison with previously reported community samples. Current ASD traits were correlated with emotional disorders and with need for treatment augmentation (psychiatric inpatient or day patient admission), but this relationship was not significant after the contribution of depression had been controlled for. There was no difference in Morgan Russell Outcomes at discharge for those with high and low current ASD traits. Parent-reported ASD-related developmental difficulties were associated with attenuated change in self-reported cognitive symptoms of AN. This study highlights the need for further understanding of the aetiology, diagnostic significance and predictive utility for future relapse of elevated ASD traits in childhood eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Diagnosing autism spectrum disorder in community settings using the Development and Well-Being Assessment: validation in a UK population-based twin sample.

BACKGROUND: Increasing numbers of people are being referred for the assessment of autism spectrum disorder (ASD). The NICE (UK) and the American Academy of Pediatrics recommend gathering a developmental history using a tool that operationalises ICD/DSM criteria. However, the best-established diagnostic interview instruments are time consuming, costly and rarely used outside national specialist centres. What is needed is a brief, cost-effective measure validated in community settings. We tested the Development and Well-Being Assessment (DAWBA) for diagnosing ASD in a sample of children/adolescents representative of those presenting in community mental health settings. METHODS: A general population sample of twins (TEDS) was screened and 276 adolescents were selected as at low (CAST score < 12; n = 164) or high risk for ASD (CAST score ≥ 15 and/or parent reported that ASD suspected/previously diagnosed; n = 112). Parents completed the ASD module of the DAWBA interview by telephone or online. Families were visited at home: the ADI-R and autism diagnostic observation schedule (ADOS) were completed to allow a best-estimate research diagnosis of ASD to be made. RESULTS: Development and Well-Being Assessment ASD symptom scores correlated highly with ADI-R algorithm scores (ρ = .82, p < .001). Good sensitivity (0.88) and specificity (0.85) were achieved using DAWBA computerised algorithms. Clinician review of responses to DAWBA questions minimally changed sensitivity (0.86) and specificity (0.87). Positive (0.82-0.95) and negative (0.90) predictive values were high. Eighty-six per cent of children were correctly classified. Performance was improved by using it in conjunction with the ADOS. CONCLUSIONS: The DAWBA is a brief structured interview that showed good sensitivity and specificity in this general population sample. It requires little training, is easy to administer (online or by interview) and diagnosis is aided by an algorithm. It holds promise as a tool for assisting with assessment in community settings and may help services implement the recommendations made by NICE and the American Academy of Pediatrics regarding diagnosis of young people on the autism spectrum.

Feasibility and acceptability of phone-delivered psychological therapy for refugee children and adolescents in a humanitarian setting.

BACKGROUND: Refugee children are at high risk of mental health problems but face barriers to accessing mental health services, a problem exacerbated by a shortage of mental health professionals. Having trained lay counsellors deliver therapy via telephone could overcome these barriers. This is the first study to explore feasibility and acceptability of telephone-delivered therapy with refugee children in a humanitarian setting. METHODS: An evidence-based intervention, Common Elements Treatment Approach, was adapted for telephone-delivery (t-CETA) and delivered by lay counsellors to Syrian refugee children in informal tented settlements in the Beqaa region of Lebanon. Following delivery of t-CETA, semi-structured interviews were conducted with counsellors (N = 3) and with children who received t-CETA (N = 11, 45% female, age 8-17 years) and their caregivers (N = 11, 100% female, age 29-56 years) (N = 25 interviews). Thematic content analysis was conducted separately for interviews with counsellors and interviews with families and results were synthesized. RESULTS: Three themes emerged from interviews with counsellors and four themes from interviews with families, with substantial overlap between them. Synthesized themes were: counselling over the phone both solves and creates practical and logistical challenges; t-CETA is adapted to potential cultural blocks; the relationship between the counsellor and the child and caregiver is extremely important; the family's attitude to mental health influences their understanding of and engagement with counselling; and t-CETA works and is needed. Counselling over the phone overcame logistical barriers, such as poor transportation, and cultural barriers, such as stigma associated with attending mental health services. It provided a more flexible and accessible service and resulted in reductions in symptoms for many children. Challenges included access to phones and poor network coverage, finding an appropriate space, and communication challenges over the phone. CONCLUSIONS: Despite some challenges, telephone-delivered therapy for children shows promising evidence of feasibility and acceptability in a humanitarian context and has the potential to increase access to mental health services by hard-to-reach populations. Approaches to addressing challenges of telephone-delivered therapy are discussed. Trial Registration ClinicalTrials.gov ID: NCT03887312; registered 22nd March 2019.

Delivering therapy over telephone in a humanitarian setting: a pilot randomized controlled trial of common elements treatment approach (CETA) with Syrian refugee children in Lebanon.

BACKGROUND: In recent years, the number of forcibly displaced persons has risen worldwide, with approximately 40% being children and adolescents. Most of them are hosted in low- and middle-income countries (LMICs). Many individuals meet the criteria for mental health issues, which can also be exacerbated by a number of risk factors, including low socioeconomic status, displacement, and stressors linked to conflicts in their country or region of origin. However, the vast majority never receive treatment for their psychological problems due to multiple reasons, including a shortage of mental health professionals in LIMCs, transportation challenges in accessing clinics, and clinic hours conflicting with family commitments. In the current study we investigated whether individual psychotherapy delivered by trained lay counsellors over telephone to Syrian refugee children living in Lebanon is effective and overcomes barriers to treatment access. METHODS: After adaptation of Common Elements Treatment Approach (CETA) to remote delivery over telephone (t-CETA), preliminary effectiveness of the treatment modality was assessed with a pilot single blind randomised controlled trial including a total sample of 20 refugee children with diagnosed mental health problems. Data was analysed applying a Bayesian approach. RESULTS: There was a significant session-by-session decrease in self-reported mental health symptoms over the course of treatment. Independent assessments showed that t-CETA resulted in a greater reduction of symptoms than standard in-person treatment as usual. There was no difference between groups for impairment. Importantly, the majority of children allocated to t-CETA completed treatment whilst no children in the treatment as usual condition were able to do so. CONCLUSION: The study provides preliminary evidence that telephone-delivered psychotherapy in a humanitarian setting, delivered by lay counsellors under supervision, works and significantly increases access to treatment compared to traditional in-person treatment. However, findings remain to be replicated in larger trials. TRIAL REGISTRATION: Clinical Trials. gov ID: NCT03887312; registered 22nd March 2019.

Hair hormone data from Syrian refugee children: Perspectives from a two-year longitudinal study.

For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees' mental health. As a relatively new research method, however, there remain several complexities and uncertainties surrounding the use of hair hormones, from initial hair sampling to final statistical analysis, many of which are underappreciated in the extant literature, and restrict the potential utility of hair hormones. To promote awareness, we provide a narrative overview of our experiences collecting and analyzing hair hormone data in a large cohort of Syrian refugee children (n = 1594), across two sampling waves spaced 12 months apart. We highlight both the challenges faced, and the promising results obtained thus far, and draw comparisons to other prominent studies in this field. Recommendations are provided to future researchers, with emphasis on longitudinal study designs, thorough collection and reporting of hair-related variables, and careful adherence to current laboratory guidelines and practices.

Effects of war exposure on pubertal development in refugee children.

Increasing research shows pubertal development accelerates following threats while it decelerates following deprivation. Yet, these environmental stressors are unlikely to occur in isolation. We investigated how war exposure and energetic stress impact pubertal development using data from the longitudinal Biological Pathways of Risk and Resilience in Syrian Refugee Children study. Our sample included 1,600 male and female Syrian refugee children and their caregivers who lived in temporary settlements in Lebanon. We hypothesized that (a) energetic stress suppresses pubertal development; (b) war exposure accelerates pubertal timing in boys and increases risk of menarche in girls, but only when energetic stress is low; and (c) when energetic stress is elevated, effects of war exposure on pubertal development will be attenuated. Among boys, we did not find support for Hypothesis 1, but Hypotheses 2 and 3 were supported. Exposure to morbidity/mortality threats accelerated pubertal timing; this effect was attenuated under conditions of elevated energetic stress. Among girls, we found support for Hypothesis 1, but not for Hypotheses 2 and 3. Elevated energetic stress decreased the risk of menarche in girls. Neither war exposure, nor any interactions with energetic stress, predicted risk of menarche. Sensitivity analyses revealed a significant interaction between bombing exposure and the amount of time since leaving Syria. Bombing decreased the risk of menarche, but only for girls who had left Syria four or more years prior to data collection. We discuss implications for translational efforts advocating for puberty screening in medical and mental health settings to identify trauma-exposed youth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The culturally and contextually sensitive assessment of mental health using a structured diagnostic interview (MINI Kid) for Syrian refugee children and adolescents in Lebanon: Challenges and solutions.

Elevated rates of mental health difficulties are frequently reported in conflict-affected and displaced populations. Even with advances in improving the validity and reliability of measures, our knowledge of the performance of assessment tools is often limited by a lack of contextualization to specific populations and socio-political settings. This reflective article aimed to review challenges and share lessons learned from the process of administering and supervising a structured clinical interview. We administered the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) and used the Clinical Global Impression (CGI) severity scale with N = 119 Syrian refugee children (aged 8-17) resident in ITSs in Lebanon. Qualitative data were derived from supervision process notes on challenges that arose during assessments, analyzed for thematic content. Five themes were identified: (1) practical and logistical challenges (changeable nature of daily life, competing demands, access to phones, temporary locations, limited referral options); (2) validity (lack of privacy, trust, perceptions of mental health, stigma, false positive answers); (3) cultural norms and meaning (impact of different meanings on answers); (4) contextual norms (reactive and adaptive emotional and behavioral responses to contextual stress); and (5) co-morbidity and formulation (interconnected and complex presentations). The findings suggest that while structured assessments have major advantages, cultural and contextual sensitivity during assessments, addressing practical barriers to improving accessibility, and consideration for inter-connected formulations are essential to help inform prevalence rates, treatment plans, and public health strategies.

What drives change in children receiving telephone-delivered Common Elements Treatment Approach (t-CETA)? A multiple n = 1 study with Syrian refugee children and adolescents in Lebanon.

BACKGROUND: Although the evidence-base for mental health and psychosocial support (MHPSS) interventions in humanitarian settings is growing rapidly, their mechanisms of change remain poorly understood despite the potential to improve the effectiveness and reach of interventions. OBJECTIVE: This study aimed to explore the mechanisms or factors that drive change in a modular transdiagnostic telephone-delivered mental health intervention, Common Elements Treatment Approach (t-CETA). PARTICIPANTS AND SETTING: Participants were Syrian refugee children and adolescents living in tented settlements in Lebanon. METHODS: We used a multiple n = 1 design, drawing on secondary data from 9 children who completed t-CETA during a pilot randomized controlled trial. RESULTS: Children with historical war-related trauma were more likely to show significant improvement across symptom clusters by the end of treatment compared to children presenting with depression related to daily living conditions. Children also showed fluctuating symptoms during the early stages of treatment (engagement and cognitive restructuring) but significant decline in symptoms after the trauma module (prolonged imaginal exposure) and depression module (behavioral activation). Salient external life events identified were starting or dropping out of school, working, change in living conditions, family conflict and the October Revolution; and interpersonal factors of parental engagement (with or without full attendance) and counsellor skills in building rapport were also identified as having an impact on treatment success. CONCLUSIONS: Implications of our findings are discussed in terms of integrating active ingredients into MHPSS programming, and building on parental and multi-sector involvement in child and adolescent mental health care in humanitarian settings.

Oscillatory neural network alterations in young people with tuberous sclerosis complex and associations with co-occurring symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder.

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations on the TSC1/TSC2 genes, which result in alterations in molecular signalling pathways involved in neurogenesis and hamartomas in the brain and other organs. TSC carries a high risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), although the reasons for this are unclear. One proposal is that TSC-related alterations in molecular signalling during neurogenesis lead to atypical development of neural networks, which are involved in the occurrence of ASD and ADHD in TSC. We investigated this proposal in young people with TSC who have been studied longitudinally since their diagnosis in childhood. Electroencephalography (EEG) was used to examine oscillatory connectivity in functional neural networks and local and global network organisation during three tasks (resting-state, attentional and inhibitory control Go/Nogo task, upright and inverted face processing task) in participants with TSC (n = 48) compared to an age- and sex-matched group of typically developing Controls (n = 20). Compared to Controls, the TSC group showed hypoconnected neural networks in the alpha frequency during the resting-state and in the theta and alpha frequencies during the Go/Nogo task (P ≤ .008), as well as reduced local network organisation in the theta and alpha frequencies during the Go/Nogo task (F = 3.95, P = .010). There were no significant group differences in network metrics during the face processing task. Increased connectivity in the hypoconnected alpha-range resting-state network was associated with greater ASD and inattentive ADHD symptoms (rho≥.40, P ≤ .036). Reduced local network organisation in the theta-range during the Go/Nogo task was significantly associated with higher hyperactive/impulsive ADHD symptoms (rho = -.43, P = .041). These findings suggest that TSC is associated with widespread hypoconnectivity in neural networks and support the proposal that altered network function may be involved in the co-occurrence of ASD and ADHD in TSC.

Actigraph-Measured Movement Correlates of Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms in Young People with Tuberous Sclerosis Complex (TSC) with and without Intellectual Disability and Autism Spectrum Disorder (ASD).

Actigraphy, an objective measure of motor activity, reliably indexes increased movement levels in attention-deficit/hyperactivity disorder (ADHD) and may be useful for diagnosis and treatment-monitoring. However, actigraphy has not been examined in complex neurodevelopmental conditions. This study used actigraphy to objectively measure movement levels in individuals with a complex neurodevelopmental genetic disorder, tuberous sclerosis (TSC). Thirty participants with TSC (11-21 years, 20 females, IQ = 35-108) underwent brief (approximately 1 h) daytime actigraph assessment during two settings: movie viewing and cognitive testing. Multiple linear regressions were used to test associations between movement measurements and parent-rated ADHD symptoms. Correlations were used to examine associations between actigraph measures and parent-rated ADHD symptoms and other characteristics of TSC (symptoms of autism spectrum disorder (ASD), intellectual ability (IQ), epilepsy severity, cortical tuber count). Higher movement levels during movies were associated with higher parent-rated ADHD symptoms. Higher ADHD symptoms and actigraph-measured movement levels during movies were positively associated with ASD symptoms and negatively associated with IQ. Inter-individual variability of movement during movies was not associated with parent-rated hyperactivity or IQ but was negatively associated with ASD symptoms. There were no associations with tuber count or epilepsy. Our findings suggest that actigraph-measured movement provides a useful correlate of ADHD in TSC.

Regression in autism spectrum disorder: Reconciling findings from retrospective and prospective research.

The way in which the behavioral manifestations of autism spectrum disorder (ASD) emerge in infancy is variable. Regression-loss of previously acquired skills-occurs in a subset of children. However, the etiology and significance of regression remains unclear. Until recently, investigation of regression relied on retrospective report by parents or examination of home videos from early in life. However, home videos and retrospective report of the nature and timing of regression, and association with factors such as illness or immunization, is potentially subject to bias. The advent of prospective studies of infant siblings at familial high-risk of ASD has the potential to document regression as it occurs. Recent research has suggested that subtle loss of skills occurs in a larger proportion of children with ASD than previously assumed; however, there are few reports of clear-cut regressions, such as that involving dramatic loss of language and other established skills, in the prospective literature. This could be because of the following: clear-cut regression occurs less commonly than parent report suggests, study design limits the potential to detect regression, or there are differences between multiplex and simplex families in the rate of de novo genetic mutations and therefore regression risk. This review will bring together literature from retrospective and prospective research and attempt to reconcile diverging findings, with a specific focus on methodological issues. Changing conceptualizations of regression will be discussed, as well as etiological factors that may be associated with regression. The main challenges that need to be addressed to measure regression in prospective studies will be set out. Autism Research 2018, 11: 1602-1620. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Regression-a loss of previously established skills-occurs in a subset of children with ASD. Parental recall is not always accurate but studying younger siblings of children with ASD, 10-20% of whom will develop ASD, should make it possible to measure regression as it occurs. Clear-cut regression, like loss of language, has not often been reported in infant sibling studies, but recent research suggests that gradual loss of social engagement might be more common. This review looks at the evidence for regression from infant sibling studies and asks how study design affects the likelihood of capturing regression.

Autism Spectrum Disorders and Other Mental Health Problems: Exploring Etiological Overlaps and Phenotypic Causal Associations.

OBJECTIVE: Recent studies have highlighted the impact of coexisting mental health problems in autism spectrum disorders (ASD). No twin studies to date have reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the etiological overlap between the diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire. METHOD: Genetic and environmental influences on the covariance between ASD and coexisting problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: namely, that coexisting problems are the result of or result in ASD symptoms; that they increase recognition of ASD; or that they arise due to an over-observation bias/confusion when differentiating between phenotypes. RESULTS: More than 50% of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and approximately 25% met these criteria for the 3 reported problems. In comparison, between 13% and 16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was explained entirely by genetic influences and accompanied by a moderate genetic correlation (0.42). The opposite was true for the overlap with conduct problems, as nonshared-environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD. CONCLUSION: Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems-ASD overlap further supports the genetic independence of these 2 phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects.