Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study.

Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39-2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33-3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84-9.07) for men and 6.45 years (95% CI: 1.37-11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78-10.27) for men and 14.59 years (95% CI: 9.45-19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. Interpretation: The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women. Funding: Dunhill Medical Trust, Medical Research Council, National Institute for Health and Care Research, and the Royal College of Psychiatrists.

Transgender identity in young people and adults recorded in UK primary care electronic patient records: retrospective, dynamic, cohort study.

Objectives: To quantify the change in proportion of young people and adults identified as transgender in UK primary care records and to explore whether rates differ by age and socioeconomic deprivation. Design: Retrospective, dynamic, cohort study. Setting: IQVIA Medical Research Data, a database of electronic primary care records capturing data from 649 primary care practices in the UK between 1 January 2000 and 31 December 2018. Participants: 7 064 829 individuals aged 10-99 years, in all four UK countries. Main outcome measures: Diagnostic codes indicative of transgender identity were used. Sex assigned at birth was estimated by use of masculinising or feminising medication and procedural/diagnostic codes. Results: 2462 (0.03%) individuals had a record code indicating a transgender identity. Direction of transition could be estimated for 1340 (54%) people, of which 923 were assigned male at birth, and 417 were assigned female at birth. Rates of recording in age groups diverged substantially after 2010. Rates of the first recording of codes were highest in ages 16-17 years (between 2010 and 2018: 24.51/100 000 person years (95% confidence interval 20.95 to 28.50)). Transgender codes were associated with deprivation: the rate of the first recording was 1.59 (95% confidence interval 1.31 to 1.92) in the most deprived group in comparison with the least deprived group. Additionally, the rate ratio of the proportion of people who identified as transgender was 2.45 (95% confidence interval 2.28 to 2.65) in the most deprived group compared with the least deprived group. Substantial increases were noted in newly recorded transgender codes over time in all age groups (1.45/100 000 person years in 2000 (95% confidence interval 0.96 to 2.10) to 7.81/100 000 person years in 2018 (6.57 to 9.22)). In 2018, the proportion of people with transgender identity codes was highest in the age groups 16-17 years (16.23 per 10 000 (95% confidence interval 12.60 to 20.57)) and 18-29 years (12.42 per 10 000 (11.06 to 13.90)). Conclusion: The rate of transgender identity recorded in primary care records has increased fivefold from 2000 to 2018 and is highest in the 16-17 and 18-29 age groups. Transgender diagnostic coding is associated with socioeconomic deprivation and further work should investigate this association. Primary and specialist care should be commissioned accordingly to provide for the gender specific and general health needs of transgender people.

Effectiveness of primary care psychological therapy services for treating depression and anxiety in autistic adults in England: a retrospective, matched, observational cohort study of national health-care records.

BACKGROUND: Autistic adults report a higher prevalence of anxiety and depression than adults without identified autism but have poorer access to appropriate mental health care. Evidence-based psychological therapies are recommended in treatment guidelines for autistic adults, but no study has investigated their effectiveness in large samples representative of the autistic population accessing routine care. This study aimed to examine therapy outcomes for autistic adults in a primary care service. METHODS: In this retrospective, matched, observational cohort study of national health-care records, we used the MODIFY dataset that used linked electronic health-care records, including national data, for individuals who accessed psychological therapy in primary care in Improving Access to Psychological Therapies (IAPT) services in 211 clinical commissioning group areas in England, UK. All adults aged 18 years or older who had completed a course of IAPT in 2012-19 were eligible, and were propensity score matched (1:1) with a comparison group without identified autism. Exact matching was used, when possible, for a range of sociodemographic factors. Primary outcomes were routine metrics that have been nationally defined and used to evaluate IAPT treatments: reliable improvement, reliable recovery, and reliable deterioration. Secondary outcomes were calculated pre-post treatment changes in scores for Patient Health Questionnaire-9, Generalised Anxiety Disorder Assessment-7, and Work and Social Adjustment Scale measures. Subgroup analyses investigated differential effects across a range of sociodemographic factors. FINDINGS: Of 2 515 402 adults who completed at least two sessions of IAPT in 2012-19, 8761 had an autism diagnosis (5054 [57·7%] male and 3707 [42·3%] female) and 1 918 504 did not (631 606 [32·9%] male and 1 286 898 [67·0%] female). After propensity score matching, 8593 autistic individuals were matched with an individual in the comparison group. During IAPT treatment, symptoms of depression and generalised anxiety disorder decreased for most autistic adults, but symptoms were less likely to improve in the autism group than in the comparison group (4820 [56·1%] of 8593 autistic adults had reliable improvement vs 5304 [61·7%] of 8593 adults in the matched group; adjusted odds ratio [ORadj] 0·75, 95% CI 0·70-0·80; p<0·0001) and symptoms were more likely to deteriorate (792 [9·2%] vs 619 [7·2%]; ORadj 1·34, 1·18-1·48; p<0·0001). In the comparison group, improved outcomes were associated with employment and belonging to a higher socioeconomic deprivation category, but this was not the case for autistic adults. INTERPRETATION: Evidence-based psychological therapy for depression or anxiety might be effective for autistic adults but less so than for adults without identified autism. Treatment moderators appear different for autistic individuals, so more research is needed to allow for better targeted and personalised care. FUNDING: Alzheimer's Society.

Attention-deficit hyperactivity disorder diagnoses and prescriptions in UK primary care, 2000-2018: population-based cohort study.

BACKGROUND: Rates of diagnosed attention-deficit hyperactivity disorder (ADHD) may be increasing in the UK. AIMS: Estimate incidence and prevalence of ADHD diagnoses and ADHD prescriptions in UK adults and children in primary care. METHOD: We conducted a cohort study using IQVIA Medical Research Data, a UK primary care database. Rates of ADHD diagnoses and ADHD prescriptions were calculated between 2000 and 2018 for individuals aged 3-99 years, analysed by age, gender, social deprivation status and calendar year. RESULTS: Of 7 655 931 individuals, 35 877 (0.5%) had ADHD diagnoses; 18 518 (0.2%) received ADHD medication prescriptions. Diagnoses and prescription rates were greater in men versus women, children versus adults, and deprivation status (nearly double in most deprived versus least deprived quintile). By 2018, the proportion of ADHD diagnoses was 255 per 10 000 (95% CI 247-263) in boys and 67.7 per 10 000 (95% CI 63.5-71.9) in girls; for adults, it was 74.3 per 10 000 (95% CI 72.3-76.2) in men and 20 per 10 000 (95%CI 19.0-21.0) in women. Corresponding figures for prescriptions were 156 per 10 000 (95% CI 150-163) in boys, 36.8 per 10 000 (95% CI 33.8-40.0) in girls, 13.3 per 10 000 (95% CI 12.5-14.1) in men and 4.5 per 10 000 (95% CI 4.1-5.0) in women. Except among 3- to 5-year-olds, the incidence and prevalence of ADHD diagnoses and prescriptions have increased from 2000 to 2018 in all age groups. The absolute increase was highest in children, but the relative increase was largest among adults (e.g. among men aged 18-29 years, approximately 20-fold and nearly 50-fold increases in diagnoses and prescriptions, respectively). CONCLUSIONS: The incidence and prevalence of both ADHD diagnoses and medication are highest among children. Proportionally, rates increased most among adults during 2000-2018. ADHD diagnoses and prescriptions are associated with socioeconomic deprivation.

Autism in England: assessing underdiagnosis in a population-based cohort study of prospectively collected primary care data.

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59-72% of autistic people, 0.77%-2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services. Funding: Dunhill Medical Trust, Economic and Social Research Council, Medical Research Council, National Institute for Health Research, the Wellcome Trust, and the Royal College of Psychiatrists.

The Tavistock First-Time Parent Study: a pilot randomised controlled feasibility trial of a brief couple-focused perinatal intervention to reduce inter-parental discord.

Numerous studies report that some first-time parents experience a decline in relationship quality and an increase in conflict after the birth of a first baby. Inter-parental discord that is frequent, intense, and poorly resolved increases the likelihood of relationship breakdown and adversely impacts child development. We investigated the feasibility of a brief preventative couple-focused psychotherapeutic intervention in the perinatal period in a general population sample. Sixty couples expecting their first baby were recruited from the Royal Free Hospital, London. Thirty were randomly assigned to treatment (TMT, a newly developed five-session couple-focused intervention), and 30 to usual care (TAU). Outcomes were collected at 28 weeks into pregnancy, 6-8 weeks after birth, and when the baby was 6 months old. The intervention was feasible and acceptable, evidenced by 100% attendance. However, no change in relationship quality or inter-parental discord was detected in either TMT or TAU groups across the transition to parenthood. The intervention did not improve outcomes vs. TAU. Depression assessed by the Hospital Anxiety and Depression Scale increased across the cohort and mood symptoms assessed by the Edinburgh Postnatal Depression Scale decreased in mothers but not fathers. The absence of a decline in relationship quality could reflect sample attributes: couples were older than average UK first-time parents, had high levels of educational qualifications, and low discord. Even in this low-risk sample, only 20 out of 30 TAU couples completed all three assessments, vs. 29 out of 30 TMT couples. Larger-scale RCTs of perinatal couple-focused psychosocial interventions may be hampered by selection effects and attrition. They may benefit from co-design with stakeholders and active control conditions.Trial registration: ISRCTN12258825; 1st May 2020 (retrospectively registered).

Fears, Reassurance, and Milestones: A Twitter Analysis around World Prematurity Day during the COVID-19 Pandemic.

Preterm birth (birth <37 completed weeks' gestation) is common, affecting 10.6% of live births globally (nearly 15 million babies per year). Having a new baby admitted to a neonatal unit often triggers stress and anxiety for parents. This paper seeks to explore experiences of preterm birth via Twitter. The intermingling of COVID-19 restrictions and World Prematurity Day allows for an understanding of both the additional stresses incurred as a consequence of the pandemic and the more "everyday" experiences in the NICU and beyond. The content analysis of the data included 3161 tweets. Three themes were identified: 1. COVID-19 was not the only trauma; 2. Raising awareness, especially World Prematurity Day; and, 3. Baby milestones. These themes highlight the multi-level challenges faced by parents of premature babies and the healthcare professionals involved in their care. The COVID-19 pandemic and the consequent restrictions imposed on parents' contact with their babies have resulted in immense emotional strain for families. The reported COVID-19 pandemic "baby blind spot" appears to particularly impact this group of babies. Improved understanding of the lived experiences of preterm babies and their families should inform greater awareness and improved support.

Neuropsychological deficits in Posterior Cortical Atrophy and typical Alzheimer's disease: A meta-analytic review.

AIMS: To identify cognitive tests that best differentiate between Posterior Cortical Atrophy (PCA) and typical Alzheimer's Disease (tAD), as well as PCA and healthy control (HC) participants. METHOD: Medline, PsycInfo and Web of Science were systematically searched using terms related to PCA, tAD, and cognitive testing. Seventeen studies were identified, including 441 PCA, 391 tAD, and 284 HC participants. Standardised effect sizes of mean scores were calculated to measure performance differences on cognitive tests for PCA versus tAD and PCA versus HC groups. Meta-analyses used a random effects model. RESULTS: The most discriminating cognitive tests for PCA and tAD presentations were measures of visuospatial function and verbal memory. Large, significant effect sizes were produced for all measures of visuospatial function, most notably for Rey-Osterrieth Copy (Hedges' g = -2.79), VOSP Fragmented letters (Hedges' g = -1.73), VOSP Dot Counting (Hedges' g = -1.74), and VOSP Cube Analysis (Hedges' g = -1.98). For measures of verbal memory, the RAVLT delay and Digit Span Backwards produced significant medium effects (Hedges' g = .62 and -.56, respectively). CONCLUSION: Establishing a common framework for testing individuals with PCA has important implications for diagnosis and treatment, and forms a practical objective for future research. Findings from this meta-analysis suggest that measures of visuospatial function and verbal memory would form an important part of this framework.

Editorial: Is Preterm Birth Overlooked in Child and Adolescent Psychiatry?

Obstetric factors have long been recognized as risk factors for the later development of poor mental health. One of the most consistently reported of these associations is for preterm birth (birth before 37 weeks' gestation), a form of early adversity that impacts health and development across the life course. Preterm birth is not uncommon: in 2014, 10.6% of live births globally (nearly 15 million babies) were preterm.1 Advances in neonatal care since the early 1990s have dramatically increased the numbers of babies who survive extreme preterm birth (birth at <28 weeks' gestation) in high-income countries. This has led to growing interest in how extreme preterm birth impacts longer term outcomes including psychosocial development across the life span.

Parenting Strategies Used by Parents of Children with ASD: Differential Links with Child Problem Behaviour.

Here, we explored the structure of the 'Parenting Strategies Questionnaire', a new scale designed to measure parenting strategies for problem behaviour in ASD. We then examined links between child behaviour and parenting in a sample of 222 predominantly-UK parents of ASD children exhibiting behaviour found difficult or challenging. Analysis revealed three parenting subscales: Accommodation, Reinforcement Approaches and Reducing Uncertainty. Both Accommodation and Reducing Uncertainty were linked to child problem behaviour. Child factors explained up to 29% of the variance in Accommodation, with Socially Inflexible Non-compliance the strongest predictor, and up to 24% of the variance in Reducing Uncertainty, with Intolerance of Uncertainty the strongest predictor. Child factors were not related to Reinforcement Approaches. Longitudinal studies investigating these relationships are needed.

The Measurement of Adult Pathological Demand Avoidance Traits.

Pathological ("extreme") demand avoidance (PDA) involves obsessively avoiding routine demands and extreme emotional variability. It is clinically linked to autism spectrum disorder (ASD). The observer-rated EDA Questionnaire (EDA-Q) for children was adapted as an adult self-report (EDA-QA), and tested in relation to personality and the short-form Autism Screening Questionnaire (ASQ). Study 1 (n = 347) found the EDA-QA reliable, univariate, and correlated with negative affect, antagonism, disinhibition, psychoticism, and ASQ scores. Study 2 (n = 191) found low agreeableness, greater Emotional Instability, and higher scores on the full ASQ predicted EDA-QA. PDA can screened for using this tool, occurs in the general population, and is associated with extremes of personality. Future studies will examine if PDA occurs in other clinical populations.

An fMRI investigation of empathic processing in boys with conduct problems and varying levels of callous-unemotional traits.

The ability to empathise relies in part on using one's own affective experience to simulate the affective experience of others. This process is supported by a number of brain areas including the anterior insula (AI), anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and the amygdala. Children with conduct problems (CP), and in particular those with high levels of callous-unemotional traits (CP/HCU) present with less empathy than their peers. They also show reduced neural response in areas supporting empathic processing when viewing other people in distress. The current study focused on identifying brain areas co-activated during affective introspection of: i) One's own emotions ('Own emotion'); ii) Others' emotions ('Other emotion'); and iii) One's feelings about others' emotions ('Feel for other') during fearful vs neutral scenarios in typically developing boys (TD; n = 31), boys with CP/HCU (n = 31), and boys with CP and low levels of CU (CP/LCU; n = 33). The conjunction analysis across conditions within the TD group revealed significant clusters of activation in the AI, ACC/mPFC, and occipital cortex. Conjunction analyses across conditions in the CP/HCU and CP/LCU groups did not identify these areas as significantly activated. However, follow-up analyses were not able to confirm statistically significant differences between groups across the whole network, and Bayes-factor analyses did not provide substantial support for either the null or alternate hypotheses. Post-hoc comparisons indicated that the lack of conjunction effects in the CP/HCU group may reflect reduced affective introspection in the 'Other emotion' and 'Feel for other' conditions, and by reduced affective introspection in the 'Own emotion' condition in the CP/LCU group. These findings provide limited and ultimately equivocal evidence for altered affective introspection regarding others in CP/HCU, and altered affective introspection for own emotions in CP/LCU, and highlight the need for further research to systematically investigate the precise nature of empathy deficits in children with CP.

Commentary: Conceptualising demand avoidance in an ASD context - a response to Osman Malik & Gillian Baird (2018).

Malik and Baird (this issue) have raised a number of important points drawing on our study of parent-reported dimensions of difficulty in children with features of extreme/'pathological' demand avoidance. In particular, they highlight the pressing need to understand why some children exhibit problematic demand avoidance, and identify factors that promote and maintain these behaviours. As Green et al. () note, children with ASD often show a strong reactivity to the environment. As such, stimuli, activities or interactions that present no problems for typically developing children may unexpectedly provoke extremes of affect. Both Green and colleagues (2018) and Malik & Baird (this issue) highlight a number of possible contributory factors, including sensory sensitivities, difficulty in predicting outcomes, need for sameness, poor tolerance of uncertainty, and fluctuations in autonomic arousal.

Dimensions of difficulty in children reported to have an autism spectrum diagnosis and features of extreme/'pathological' demand avoidance.

BACKGROUND: A subset of individuals with autism spectrum disorder (ASD) resemble descriptions of extreme/'pathological' demand avoidance, displaying obsessive avoidance of everyday demands and requests, strategic or 'socially manipulative' behaviour and sudden changes in mood. Investigating challenging presentations using dimensional description may prove preferable to identifying subgroups. However, there remains an imperative to explore which behavioural traits appear most problematic to inform quantitative investigation. This study provides an in-depth exploration of parent perspectives on maladaptive behaviour in children reported to have an autism spectrum diagnosis and features of extreme/'pathological' demand avoidance. METHOD: Parents completed a tailored semistructured interview about their child's behaviour, focusing on difficulties relevant to descriptions of extreme/'pathological' demand avoidance. The 26 interviews rated as scoring above threshold for 'substantial' features of extreme/'pathological' demand avoidance on relevant indicators were analysed qualitatively using a general inductive approach. RESULTS: New themes that emerged from these data included attempts by the child to control situations and others' activities. Avoidance behaviours in this sample could be described as 'strategic' rather than 'manipulative'. A range of factors, including a negative emotional response to demands, but also phobias, novelty, and uncertainty, were perceived to play a role in triggering extreme behaviour. CONCLUSIONS: These descriptions highlight the importance of systematically measuring noncompliance, attempts to control situations and others' activities, and extreme mood variability in individuals with ASD. These dimensions represent important targets for intervention, given their considerable impact on daily life.

How do Parents Manage Irritability, Challenging Behaviour, Non-Compliance and Anxiety in Children with Autism Spectrum Disorders? A Meta-Synthesis.

Although there is increasing research interest in the parenting of children with ASD, at present, little is known about everyday strategies used to manage problem behaviour. We conducted a meta-synthesis to explore what strategies parents use to manage irritability, non-compliance, challenging behaviour and anxiety in their children with ASD. Approaches included: (1) accommodating the child; (2) modifying the environment; (3) providing structure, routine and occupation; (4) supervision and monitoring; (5) managing non-compliance with everyday tasks; (6) responding to problem behaviour; (7) managing distress; (8) maintaining safety and (9) analysing and planning. Results suggest complex parenting demands in children with ASD and problem behaviour. Findings will inform the development of a new measure to quantify parenting strategies relevant to ASD.

Reduced Laughter Contagion in Boys at Risk for Psychopathy.

Humans are intrinsically social animals, forming enduring affiliative bonds [1]. However, a striking minority with psychopathic traits, who present with violent and antisocial behaviors, tend to value other people only insofar as they contribute to their own advancement [2, 3]. Extant research has addressed the neurocognitive processes associated with aggression in such individuals, but we know remarkably little about processes underlying their atypical social affiliation. This is surprising, given the importance of affiliation and bonding in promoting social order and reducing aggression [4, 5]. Human laughter engages brain areas that facilitate social reciprocity and emotional resonance, consistent with its established role in promoting affiliation and social cohesion [6-8]. We show that, compared with typically developing boys, those at risk for antisocial behavior in general (irrespective of their risk of psychopathy) display reduced neural response to laughter in the supplementary motor area, a premotor region thought to facilitate motor readiness to join in during social behavior [9-11]. Those at highest risk for developing psychopathy additionally show reduced neural responses to laughter in the anterior insula. This region is implicated in auditory-motor processing and in linking action tendencies with emotional experience and subjective feelings [10, 12, 13]. Furthermore, this same group reports reduced desire to join in with the laughter of others-a behavioral profile in part accounted for by the attenuated anterior insula response. These findings suggest that atypical processing of laughter could represent a novel mechanism that impoverishes social relationships and increases risk for psychopathy and antisocial behavior.