Previous studies have reported reduced quality of life in autism. Improving quality of life for autistic people is, therefore, a key priority for clinical research and practice. However, the relative ...impact of core autism traits (e.g. social-communication difficulties), as compared to associated mental health symptoms (e.g. anxiety, depression) on quality of life remains poorly understood. This is despite at least 20%–50% of autistic individuals experiencing associated anxiety and/or depression symptoms. Hence, we measured subjective quality of life in 573 six to thirty-year-olds (autism spectrum disorder N = 344), using two widely validated questionnaires. Adults self-reported on the World Health Organization Quality of Life–Brief instrument. Parents of children/adolescents completed the Child Health and Illness Profile. We assessed individual variability across both measures and modelled associations between quality of life, core autism traits, anxiety, and depression symptoms. Across both age groups and quality of life measures, autistic individuals scored lower than comparison individuals, on average, particularly for physical health in adults (d = −1.24, 95% confidence interval: −1.56, −0.93) and school achievement for children/adolescents (d = −1.06, 95% confidence interval: −1.29, −0.84). However, a notable proportion of autistic individuals (36%–71% across quality of life domains) did not have reduced quality of life. Across ages and quality of life measures, severity of associated symptoms was significantly related to reduced quality of life on several domains, after accounting for core autism traits. Most notably, depression symptoms were related to reduced physical/psychological well-being in both adults (β ⩾ −0.34) and children/adolescents (β = −0.29, 95% confidence interval: −0.36, −0.14). For children/adolescents, anxiety symptoms (β ⩾ −0.28) and core social-communication difficulties (β ⩾ −0.22) were also related to subjective quality of life outcomes. Overall, findings indicate that not all autistic individuals experience reduced subjective quality of life. Variability in quality of life is significantly influenced by associated symptoms, across developmental stage. This may provide a tractable target for mental health services to improve quality of life for autistic individuals over the lifespan.
Lay abstract
Previous studies suggest that some autistic individuals report lower satisfaction, or well-being, with different aspects of everyday life than those without autism. It is unclear whether this might be partly explained by symptoms of anxiety and/or depression, which affect at least 20%–50% of autistic people. In this study, we measured individual differences in well-being in 573 six to thirty-year-olds with and without a diagnosis of autism. We investigated whether individual differences in well-being were explained by autism traits (e.g. social-communication difficulties) and/or anxiety and depression symptoms. We showed that, though well-being was lower for some autistic individuals, compared to those without autism, many autistic individuals reported good well-being. Where well-being was reduced, this was particularly explained by depression symptoms, across all ages. For children/adolescents, anxiety and social-communication difficulties were also related to some aspects of well-being. Our study suggests that support and services for improving mental health, especially depression symptoms, may also improve broader outcomes for autistic people.
Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of ...tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.
Flexible behavior is critical for everyday decision-making and has been implicated in restricted, repetitive behaviors (RRB) in autism spectrum disorder (ASD). However, how flexible behavior changes ...developmentally in ASD remains largely unknown. Here, we used a developmental approach and examined flexible behavior on a probabilistic reversal learning task in 572 children, adolescents, and adults (ASD N = 321; typical development TD N = 251). Using computational modeling, we quantified latent variables that index mechanisms underlying perseveration and feedback sensitivity. We then assessed these variables in relation to diagnosis, developmental stage, core autism symptomatology, and associated psychiatric symptoms. Autistic individuals showed on average more perseveration and less feedback sensitivity than TD individuals, and, across cases and controls, older age groups showed more feedback sensitivity than younger age groups. Computational modeling revealed that dominant learning mechanisms underpinning flexible behavior differed across developmental stages and reduced flexible behavior in ASD was driven by less optimal learning on average within each age group. In autistic children, perseverative errors were positively related to anxiety symptoms, and in autistic adults, perseveration (indexed by both task errors and model parameter estimates) was positively related to RRB. These findings provide novel insights into reduced flexible behavior in relation to clinical symptoms in ASD.
Brain function is a product of the balance between excitatory and inhibitory (E/I) brain activity. Variation in the regulation of this activity is thought to give rise to normal variation in human ...traits, and disruptions are thought to potentially underlie a spectrum of neuropsychiatric conditions (e.g., Autism, Schizophrenia, Downs' Syndrome, intellectual disability). Hypotheses related to E/I dysfunction have the potential to provide cross-diagnostic explanations and to combine genetic and neurological evidence that exists within and between psychiatric conditions. However, the hypothesis has been difficult to test because: (1) it lacks specificity-an E/I dysfunction could pertain to any level in the neural system- neurotransmitters, single neurons/receptors, local networks of neurons, or global brain balance - most researchers do not define the level at which they are examining E/I function; (2) We lack validated methods for assessing E/I function at any of these neural levels in humans. As a result, it has not been possible to reliably or robustly test the E/I hypothesis of psychiatric disorders in a large cohort or longitudinal patient studies. Currently available, in vivo markers of E/I in humans either carry significant risks (e.g., deep brain electrode recordings or using Positron Emission Tomography (PET) with radioactive tracers) and/or are highly restrictive (e.g., limited spatial extent for Transcranial Magnetic Stimulation (TMS) and Magnetic Resonance Spectroscopy (MRS). More recently, a range of novel Electroencephalography (EEG) features has been described, which could serve as proxy markers for E/I at a given level of inference. Thus, in this perspective review, we survey the theories and experimental evidence underlying 6 novel EEG markers and their biological underpinnings at a specific neural level. These cheap-to-record and scalable proxy markers may offer clinical utility for identifying subgroups within and between diagnostic categories, thus directing more tailored sub-grouping and, therefore, treatment strategies. However, we argue that studies in clinical populations are premature. To maximize the potential of prospective EEG markers, we first need to understand the link between underlying E/I mechanisms and measurement techniques.
•We use the visual world paradigm to examine the time-course with which people are able to infer and use perspectives online.•Specifically, we examine for the first time how task constraints ...influence the ease and timing of perspective-taking.•We distinguish the process of making a ToM inference from actively using that knowledge in a given situation.•We discuss the mental representations that might underlie predictions based on false beliefs.
Interpreting other peoples’ actions relies on an understanding of their current mental states (e.g. beliefs, desires and intentions). In this paper, we distinguish between listeners’ ability to infer others’ perspectives and their explicit use of this knowledge to predict subsequent actions. In a visual-world study, two groups of participants (passive observers vs. active participants) watched short videos, depicting transfer events, where one character (‘Jane’) either held a true or false belief about an object’s location. We tracked participants’ eye-movements around the final visual scene, time-locked to related auditory descriptions (e.g. “Jane will look for the chocolates in the container on the left”.). Results showed that active participants had already inferred the character’s belief in the 1s preview period prior to auditory onset, before it was possible to use this information to predict an outcome. Moreover, they used this inference to correctly anticipate reference to the object’s initial location on false belief trials at the earliest possible point (i.e. from “Jane” onwards). In contrast, passive observers only showed evidence of a belief inference from the onset of “Jane”, and did not show reliable use of this inference to predict Jane’s behaviour on false belief trials until much later, when the location (“left/right”) was auditorily available. These results show that active engagement in a task activates earlier inferences about others’ perspectives, and drives immediate use of this information to anticipate others’ actions, compared to passive observers, who are susceptible to influences from egocentric or reality biases. Finally, we review evidence that using other peoples’ perspectives to predict their behaviour is more cognitively effortful than simply using one’s own.
Competition between simultaneously presented visual stimuli lengthens reaction time and reduces both the BOLD response and neural firing. In contrast, conditions of sequential presentation have been ...assumed to be free from competition. Here we manipulated the spatial proximity of stimuli (Near versus Far conditions) to examine the effects of simultaneous and sequential competition on different measures of working memory (WM) for colour. With simultaneous presentation, the measure of WM precision was significantly lower for Near items, and participants reported the colour of the wrong item more often. These effects were preserved when the second stimulus immediately followed the first, disappeared when they were separated by 500 ms, and were partly recovered (evident for our measure of mis-binding but not WM precision) when the task was altered to encourage participants to maintain the sequentially presented items together in WM. Our results show, for the first time, that competition affects the measure of WM precision, and challenge the assumption that sequential presentation removes competition.
Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the ...link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABA
) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABA
activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.
Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to ...identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses.
Between 255 and 488 participants aged 6-30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task.
We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup.
Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication.
We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals.
Difficulties in socio-emotional functioning are proposed to contribute to the development and maintenance of anorexia nervosa (AN). This study aimed to examine emotion recognition abilities in ...individuals in the acute and recovered stages of AN compared to healthy controls (HCs). A second aim was to examine whether attention to faces and comorbid psychopathology predicted emotion recognition abilities. The films expressions task was administered to 148 participants (46 AN, 51 recovered AN, 51 HC) to assess emotion recognition, during which attention to faces was recorded using eye-tracking. Comorbid psychopathology was assessed using self-report questionnaires and the Autism Diagnostic Observation Schedule-2nd edition (ADOS-2). No significant differences in emotion recognition abilities or attention to faces were found between groups. However, individuals with a lifetime history of AN who scored above the clinical cut-off on the ADOS-2 displayed poorer emotion recognition performance than those scoring below cut-off and HCs. ADOS-2 scores significantly predicted emotion recognition abilities while controlling for group membership and intelligence. Difficulties in emotion recognition appear to be associated with high autism spectrum disorder (ASD) traits, rather than a feature of AN. Whether individuals with AN and high ASD traits may require different treatment strategies or adaptations is a question for future research.
Throughout the rapid and intense changes that adolescents experience, their parents retain important influence over how they interact with the complex factors that shape their development. How ...parents care for their adolescent children has a deep and lasting impact on their well-being and development. Yet, parents often require support to meet their own and their adolescent children's needs, which can be achieved through parenting support programmes. Parenting support programmes are delivered to parents of younger children across different contexts and populations, but the benefit of these programmes for parents of adolescents is not well-recognised or prioritised. Given the clear need for these interventions during adolescence and the substantial evidence for effectiveness in this age group, it is time to move the field forward. Increased resources to support parents of adolescents would maximise adolescents' developmental potential and promote their well-being. We highlight four pressing areas for action: including parents of adolescents in parenting initiatives; involving parents in adolescent programming; strengthening efforts to address poverty and inequality, violence, and gender inequality; and engaging in strategic research to intensify the impact of programming.
PDF
