Emotional and behavioral outcomes among youths with mental disorders during the first Covid lockdown and school closures in England: a large clinical population study using health care record integrated surveys.

PURPOSE: Emotional and behavioral problems in children and young people (CYP) have increased over the pandemic. Those with pre-existing mental disorders are more vulnerable but have been understudied. We investigated emotional and behavioral outcomes in this population; differences across diagnostic groups; and social, educational, and clinical determinants. METHODS: We invited 5386 caregivers and CYP (aged 5-17) under child mental health services pre-pandemic to complete an online survey on CYP's emotional/behavioral symptoms and pandemic-related circumstances, and integrated responses with clinicodemographic information extracted from electronic health records. We compared four parent-rated outcomes (total emotional/behavioral scores and emotional/behavioral changes as compared to before the pandemic) across the three most common diagnostic groups in our population (Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and emotional disorders (EmD)). We then estimated the association of clinicodemographic and pandemic-related characteristics with emotional/behavioral outcomes. RESULTS: A total of 1741 parents (32.3%) completed the survey. Parents of CYP with ADHD or ASD reported more behavioral difficulties (t(591) = 5.618 (0.001); t(663) = 6.527 (0.001)); greater emotional deterioration (t(591) = 2.592 (0.009); t(664) = 4.670 (< 0.001); and greater behavioral deterioration (t(594) = 4.529 (< 0.001); t(664) = 5.082 (< 0.001)) as compared to the EmD group. Those with ASD and EmD showed more emotional difficulties than ADHD (t(891) = - 4.431 (< 0.001); t(590) = - 3.254 (0.001)). Across diagnoses, poor parental mental health and challenges with education were most strongly associated with worse outcomes. CONCLUSIONS: Within our clinical population, CYP with ADHD/ASD were the most adversely affected during lockdown. Enhancing clinical service provision that tackles parental stress and supports education may help mitigate the impact of future restrictions.

The cumulative impact of attention deficit hyperactivity disorder, autism and intellectual disability for young people.

BACKGROUND: Neurodevelopmental conditions frequently co-occur. The aim of this paper was to determine whether there is a cumulative association between (1) the number of neurodevelopmental conditions, specifically hyperkinetic disorder (hereafter referred to as attention deficit hyperactivity disorder), autism spectrum disorder (hereafter referred to as autism) and intellectual disability, and (2) behavioural and socio-emotional problems and the level of clinician-rated functioning for young males and females. METHODS: In this cross-sectional study, diagnostic information, caregiver-rated behavioural and socio-emotional data (as conceptualised by the Strengths and Difficulties Questionnaire) and clinician-rated functioning scores (as conceptualised by the Children's Global Assessment Scale) were extracted from electronic patient records for 2768 young people aged 3-17 years (mean = 11.55, SD = 3.46). All data were extracted at baseline, that is, at the time the young person was diagnosed with attention deficit hyperactivity disorder, autism and/or an intellectual disability. Ordinal regression analyses tested associations between the number of neurodevelopmental conditions met (i.e. 1, 2 or 3) and behavioural and socio-emotional outcomes and functioning. RESULTS: After controlling for age and biological sex, the number of neurodevelopmental conditions was associated with higher levels of inattention/hyperactivity and peer problems, lower levels of prosocial behaviour and poorer clinician-rated functioning. Although these findings were consistent for males, a cumulative association was not identified for females, except for clinician-rated functioning. CONCLUSIONS: For young people, the presence of multiple neurodevelopmental conditions may have a cumulative impact across domains, but this may differ between males and females.

Remote assessment of ADHD in children and adolescents: recommendations from the European ADHD Guidelines Group following the clinical experience during the COVID-19 pandemic.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

Is there an increased risk of perinatal mental disorder in women with gestational diabetes? A systematic review and meta-analysis.

AIM: Gestational diabetes (GDM) and mental disorder are common perinatal morbidities and are associated with adverse maternal and child outcomes. While there is a relationship between type 2 diabetes and mental disorder, the relationship between GDM and mental disorder has been less studied. We conducted a systematic review and meta-analysis of the prevalence of mental disorders in women with GDM and their risk for mental disorders compared with women without GDM. METHODS: Published, peer-reviewed literature measuring prevalence and/or odds of GDM and perinatal mental disorders was reviewed systematically. Risk of bias was assessed using a checklist. Two independent reviewers were involved. Analyses were grouped by stage of peripartum, i.e. antepartum at the time of GDM diagnosis and after diagnosis, and in the postpartum. RESULTS: Sixty-two studies were included. There was an increased risk of depressive symptoms in the antenatal period around the time of diagnosis of GDM [odds ratio (OR) 2.08; 95% confidence interval (CI) 1.42, 3.05] and in the postnatal period (OR 1.59; 95% CI 1.26, 2.00). CONCLUSIONS: Given the potential relationship between GDM and perinatal mental disorders, integration of physical and mental healthcare in women experiencing GDM and mental disorders could improve short- and long-term outcomes for women and their children.

Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire.

BACKGROUND: Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. METHOD: We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. RESULTS: Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72-0.82] and positive predictive value of 0.76 (95% CI 0.70-0.80), the specificity of 0.29 (95% CI 0.20-0.38) and negative predictive value of 0.36 (95% CI 0.22-0.40) were low. Thus, 64% of those who scored below the AQ cut-off were 'false negatives' who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may 'mimic' ASD and inflate AQ scores, leading to false positives. CONCLUSIONS: The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.

Comparison of parental estimate of developmental age with measured IQ in children with neurodevelopmental disorders.

BACKGROUND: Formal IQ tests are an important part of the diagnostic and needs-based assessment process for children with neurodevelopmental disorders. However, resources for such assessments are not always available. It has been suggested that parental estimates of their child's developmental age could serve as a proxy IQ when formal measures are unavailable. METHOD: Parental estimates of their child's developmental age were converted to a developmental quotient (DQ) in 197 children with Autism Spectrum Disorder (ASD) aged 4-9 years, and 108 children with ADHD and intellectual disability (ADHD + ID) aged 7-15 years. Formal IQ assessments were then conducted. Parents completed the Social Communication Questionnaire ((SCQ), a measure of autism symptomatology) and a demographic questionnaire. RESULTS: In the ASD sample, 58% of parent estimates were within 15 points (i.e. one standard deviation) of the child's measured IQ score. Lower measured IQ and lower SCQ total score predicted higher parental accuracy. In the ADHD + ID sample, 74% of parental estimates were within 15 points of measured IQ. In this group, higher child IQ predicted greater parental accuracy. Parents in the ADHD + ID group were more likely to overestimate children's ability level than parents in the ASD group. CONCLUSIONS: In this study, the majority of parents of children with ADHD and ID were able to estimate their child's intellectual ability level with some accuracy. Parents of children with ASD were less accurate, but this may be because these parents were focussing more on children's level of adaptive functioning, which is known to be typically lower than cognitive ability in ASD.

Adolescent eating disorder behaviours and cognitions: gender-specific effects of child, maternal and family risk factors.

BACKGROUND: Eating disorder behaviours begin in adolescence. Few longitudinal studies have investigated childhood risk and protective FACTORS. AIMS: To investigate the prevalence of eating disorder behaviours and cognitions and associated childhood psychological, physical and parental risk factors among a cohort of 14-year-old children. METHOD: Data were collected from 6140 boys and girls aged 14 years. Gender-stratified models were used to estimate prospective associations between childhood body dissatisfaction, body mass index (BMI), self-esteem, maternal eating disorder and family economic disadvantage on adolescent eating disorder behaviours and cognitions. RESULTS: Childhood body dissatisfaction strongly predicted eating disorder cognitions in girls, but only in interaction with BMI in boys. Higher self-esteem had a protective effect, particularly in boys. Maternal eating disorder predicted body dissatisfaction and weight/shape concern in adolescent girls and dieting in boys. CONCLUSIONS: Risk factors for eating disorder behaviours and cognitions vary according to gender. Prevention strategies should be gender-specific and target modifiable predictors in childhood and early adolescence.

IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP).

BACKGROUND: Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of 'peaks' and 'troughs' at the subtest level. However, there are few data from epidemiological studies. METHOD: Comprehensive clinical assessments were conducted with 156 children aged 10-14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population. RESULTS: Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no 'peak' in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ. CONCLUSIONS: In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.

European guidelines on managing adverse effects of medication for ADHD.

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.

A white paper on a neurodevelopmental framework for drug discovery in autism and other neurodevelopmental disorders.

In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.

Sentence repetition in adolescents with specific language impairments and autism: an investigation of complex syntax.

BACKGROUND: Recent studies have indicated that many children with autism spectrum disorders present with language difficulties that are similar to those of children with specific language impairments, leading some to argue for similar structural deficits in these two disorders. AIMS: Repetition of sentences involving long-distance dependencies was used to investigate complex syntax in these groups. METHODS & PROCEDURES: Adolescents with specific language impairments (mean age = 15;3, n = 14) and autism spectrum disorders plus language impairment (autism plus language impairment; mean age = 14;8, n = 16) were recruited alongside typically developing adolescents (mean age = 14;4, n = 17). They were required to repeat sentences containing relative clauses that varied in syntactic complexity. OUTCOMES & RESULTS: The adolescents with specific language impairments presented with greater syntactic difficulties than the adolescents with autism plus language impairment, as manifested by higher error rates on the more complex object relative clauses, and a greater tendency to make syntactic changes during repetition. CONCLUSIONS & IMPLICATIONS: Adolescents with specific language impairments may have more severe syntactic difficulties than adolescents with autism plus language impairment, possibly due to their short-term memory limitations.

In utero characterisation of fetal growth by ultrasound scanning in the rabbit.

Fetal development is an important factor influencing the susceptibility of adults to metabolic diseases. In order to study the influence of fetal growth on further development in animal models like the rabbit, methods of measurement of fetal and placental size and viability must be established and validated. In this study, 42 New Zealand does bred naturally (N=12) or transferred with in vivo produced embryos (2, 4 or 6 embryos/doe) have been scanned every 2-3 days with a 7.5 MHz transabdominal probe from Day 7 post-coitum until term to measure fetal and placental growth. Vesicle, placental, fetal length and head size have thus been determined according to number of fetuses and time. In late gestation, the fetuses that were transferred in limited numbers to the uterus of does were significantly larger than their natural breeding counterparts probably due to reduced litter size.

Genetic influence on language delay in two-year-old children.

Previous work suggests that most clinically significant language difficulties in children do not result from acquired brain lesions or adverse environmental experiences but from genetic factors that presumably influence early brain development. We conducted the first twin study of language delay to evaluate whether genetic and environmental factors at the lower extreme of delayed language are different from those operating in the normal range. Vocabulary at age two was assessed for more than 3000 pairs of twins. Group differences heritability for the lowest 5% of subjects was estimated as 73% in model-fitting analyses, significantly greater than the individual differences heritability for the entire sample (25%). This supports the view of early language delay as a distinct disorder. Shared environment was only a quarter as important for the language-delayed sample (18%) as for the entire sample (69%).

Elephants in Pyjamas: Testing the Weak Central Coherence Account of Autism Spectrum Disorders Using a Syntactic Disambiguation Task.

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status.

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study.

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.

The Virginia Twin Study of Adolescent Behavioral Development. Influences of age, sex, and impairment on rates of disorder.

BACKGROUND: The Virginia Twin Study of Adolescent Behavioral Development is a cohort-longitudinal epidemiological study that uses the genetic twin design to study the development and maintenance of child psychiatric disorders. We determined the rates of DSM-III-R disorders, disorders with impairment, and age, sex, and comorbidity effects. METHODS: Families of 2762 white twins aged 8 to 16 years participated. Twins and their parents were asked systematically about risk factors and current psychiatric symptoms by means of investigator-based psychiatric interviews and questionnaires. The DSM-III-R diagnoses were made for major depressive disorder, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, oppositional defiant disorder, conduct disorder, and attention deficit hyperactivity disorder. RESULTS: The 3-month point prevalence for any DSM-III-R disorders was 413 per 1000, and that for disorders with associated impairment was 142 per 1000. Emotional disorders with impairment occurred in 89 per 1000, with girls being more commonly affected; behavioral disorders had a prevalence of 71 per 1000, with boys being more frequently affected. The proportion with disorder who also had functional impairment varied across disorders; anxiety and phobic disorders were particularly likely not to be accompanied by impairment. Rates of emotional and behavioral disorders increased over the age range. There was extensive comorbidity among disorders. CONCLUSIONS: The prevalence rates and patterns of findings from this study of twins are consistent with those of other epidemiological studies, supporting previous findings of few differences in rates of psychiatric disorder between twins and singletons. The importance of including measures of functional impairment is evident by its effect on rates of disorder and patterns of comorbidity.

The influence of genetic factors and life stress on depression among adolescent girls.

BACKGROUND: The possible causes of greater depression among adolescent girls were investigated by examining variation in the influence of genetic and environmental risk factors among 182 prepubertal female, 237 prepubertal male, 314 pubertal female, and 171 pubertal male twin pairs from the Virginia Twin Study of Adolescent Behavioral Development. OBJECTIVES: To compare the trajectory of depressive symptoms among boys and girls from childhood to adolescence; to analyze the role of genetic, shared, and unique environmental factors in depression among prepubertal and pubertal male and female twins; and to investigate a possible link between liability to depression and one salient index of the child's environment: past-year life events. METHODS: Child-reported depression was assessed using the Child and Adolescent Psychiatric Interview and ratings of past-year life events and pubertal status obtained by maternal questionnaire and interview, respectively. RESULTS: The impact of life events on depression was particularly evident in the adolescent girls. The results from model fitting indicate increased heritability for depression in this group, and its long-term consistency was mediated primarily by latent genetic factors. Model fitting also showed that at least part of the liability to depression and to life events can be linked to a common set of genes in the adolescent girls, and there is a notable developmental increase in the genetic variance for life events. CONCLUSIONS: The greater heritability for depression in pubertal girls, its genetic mediation over time, and the increase in genetic variance for life events may be one possible explanation for the emergence of increased depression among pubertal girls and its persistence through adolescence.

Dominant retinitis pigmentosa with reduced penetrance. Further studies of the electroretinogram.

Full-field electroretinograms (ERGs) were recorded after a ten-year interval from four affected patients in a family with dominant retinitis pigmentosa with reduced penetrance; all patients showed decreases in amplitude. Cone ERGs from affected patients (aged 11 to 15 years) in this family as well as from affected patients of comparable ages from two other families with this genetic type, were normal or slightly reduced in amplitude and substantially delayed in b-wave implicit time. In one family, an asymptomatic older patient, representing an apparent skipped generation, showed abnormal full-field cone and rod ERGs that differed in implicit times from those of young affected patients. Evidence is presented to support the idea that the abnormal full-field cone ERGs recorded from young affected patients are due to an abnormal extrafoveal cone contribution to their full-field responses.

Psychiatric disorder and cognitive function in a family with an inherited novel mutation of the developmental control gene PAX6.

The PAX family of developmental control genes are known to play important roles in the early patterning of the central nervous system. One member of this family, PAX6, is involved in eye development in invertebrates as well as in mouse and man, but is also widely expressed in the developing forebrain. Humans with a mutation in this gene have abnormalities of eye development, and the results presented here suggest, for the first time, that this mutation may also be associated with subtle abnormalities of frontal lobe function in the family studied. We carried out genotyping of individuals within a single family, with and without the characteristic eye abnormalities of PAX6 mutation, and only those individuals with the mutation showed significant abnormalities on tests of frontal lobe function. These individuals also had higher rates of psychiatric disorder. PAX6 is highly conserved between mouse and man, and although the neuroanatomical phenotype associated with PAX6 heterozygosity has only been studied in mice, the resultant cellular disorganization seen in mice is likely to be present in the human forebrain. Although these mice have no obvious behavioural phenotype, the results presented here suggest that humans with the equivalent mutation display a neurobehavioural phenotype.

Risk factors for genetic typing and detection in retinitis pigmentosa.

An outpatient population with retinitis pigmentosa was evaluated with respect to best corrected visual acuity, cycloplegic refractive error, appearance of the lenses, presence or absence of bone spicule pigmentation, age of onset of night blindness by history, and presence or absence of a history of parental consanguinity. The population included 489 affected patients subdivided into the four following groups: 69 (14.1%) dominant, 67 (13.7%) autosomal recessive, 34 (7.0%) X-chromosome-linked, and 319 (65.2%) isolate. Contingency table and life table analyses showed that significant differences existed for these criteria among the various groups. An analysis based on data from 35 families showed significant differences with respect to best corrected visual acuity and cylindrical refractive error when comparing affected patients with their age-matched normal relatives. These findings support the idea that observations in a routine ocular examination can aid in genetic classification of affected patients and in selection of relatives of affected patients who are at higher risk for having early stages of retinitis pigmentosa.