Age, not autism, influences multisensory integration of speech stimuli among adults in a McGurk/MacDonald paradigm.

Differences between autistic and non-autistic individuals in perception of the temporal relationships between sights and sounds are theorized to underlie difficulties in integrating relevant sensory information. These, in turn, are thought to contribute to problems with speech perception and higher level social behaviour. However, the literature establishing this connection often involves limited sample sizes and focuses almost entirely on children. To determine whether these differences persist into adulthood, we compared 496 autistic and 373 non-autistic adults (aged 17 to 75 years). Participants completed an online version of the McGurk/MacDonald paradigm, a multisensory illusion indicative of the ability to integrate audiovisual speech stimuli. Audiovisual asynchrony was manipulated, and participants responded both to the syllable they perceived (revealing their susceptibility to the illusion) and to whether or not the audio and video were synchronized (allowing insight into temporal processing). In contrast with prior research with smaller, younger samples, we detected no evidence of impaired temporal or multisensory processing in autistic adults. Instead, we found that in both groups, multisensory integration correlated strongly with age. This contradicts prior presumptions that differences in multisensory perception persist and even increase in magnitude over the lifespan of autistic individuals. It also suggests that the compensatory role multisensory integration may play as the individual senses decline with age is intact. These findings challenge existing theories and provide an optimistic perspective on autistic development. They also underline the importance of expanding autism research to better reflect the age range of the autistic population.

Navigating adolescence: pubertal development in autism spectrum conditions and its relation to mental health.

Adolescence is a period of social, psychological, and physiological change, including the onset of puberty. Differential pubertal onset has been linked to a myriad of problems, including mental health problems. Therefore, we aim to investigate deviating pubertal development in autism, and whether this is more pronounced in girls than in boys. A total of 68 individuals (nASC = 34, nCOM (comparisons) = 34) aged 12 to 16 years were administered test concerning pubertal development and mental health (i.e., sensory sensitivity, autistic traits, depression, anxiety, and externalizing problems). Frequentist and Bayesian ANOVA was used to examine deviations in pubertal development in ASC and possible sex effects. Regression analyses was used to test whether this asynchronicity was linked to mental health problems. Our (frequentist and Bayesian) analyses revealed earlier onset and slower development of pubertal development in ASC but we did not find any sex differences. Maturation disparity was linked to higher mental health problems in ASC, but not in COM. No sex differences in the relation with mental health outcomes was found. We found evidence for a slower development of "true" puberty in those with ASC compared to those without. Moreover, we show that disparities in pubertal development are related to mental health in ASC, suggesting a greater impact on mental health in autistic than in non-autistic teens. Longitudinal studies are necessary to elucidate important developmental trajectories in puberty in neurodiverse populations.

Schema therapy for personality disorders in autistic adults: Results of a multiple case series study.

BACKGROUND: To our knowledge, treatment of personality disorder (PD) comorbidity in autistic adults is understudied and is still in its infancy. We investigated the effectiveness of schema therapy (ST) for autistic adults with PD. METHOD: A multiple case series design with 12 adults (aged 19-62 years) was used with baseline, exploration, ST (with cognitive behavioural and experiential techniques) and follow-up conditions. Participants rated dysfunctional core beliefs (primary outcome) weekly during baseline and treatment and monthly during follow-up. Schema modes, general mental health symptoms, social responsiveness, PD traits and common Axis-I mental disorders were assessed. RESULTS: Mixed model analyses indicated significant effects of ST with medium to large effect sizes for dysfunctional core beliefs, functional schema modes, PD traits, general mental health symptoms and social responsiveness. Results remained stable during follow-up. CONCLUSION: The results of this study indicate that ST might be effective in decreasing dysfunctional core beliefs, PD traits and general mental health symptoms and in increasing functional schema modes and social responsiveness. Improvements persisted over time. ST seems effective in treating PD in autistic individuals.

Autistic traits in psychotic disorders: prevalence, familial risk, and impact on social functioning.

BACKGROUND: Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD. METHODS: In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16-50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS). RESULTS: For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms. CONCLUSIONS: Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

Age-related differences in autism: The case of white matter microstructure.

Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which white matter abnormalities are already present early on in life. However, it is unknown if and to which extent these abnormalities are hard-wired in (older) adults with ASD and how this interacts with age-related white matter changes as observed in typical aging. The aim of this first cross-sectional study in mid- and late-aged adults with ASD was to characterize white matter microstructure and its relationship with age. We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-74 years), who also completed a Flanker task. Intra-individual variability of reaction times (IIVRT) measures based on performance on the Flanker interference task were used to assess IIVRT-white matter microstructure associations. We observed primarily higher mean and radial diffusivity in white matter microstructure in ASD, particularly in long-range fibers, which persisted after taking head motion into account. Importantly, group-by-age interactions revealed higher age-related mean and radial diffusivity in ASD, in projection and association fiber tracts. Subtle dissociations were observed in IIVRT-white matter microstructure relations between groups, with the IIVRT-white matter association pattern in ASD resembling observations in cognitive aging. The observed white matter microstructure differences are lending support to the structural underconnectivity hypothesis in ASD. These reductions seem to have behavioral percussions given the atypical relationship with IIVRT. Taken together, the current results may indicate different age-related patterns of white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017. © 2016 Wiley Periodicals, Inc.

Autism Characteristics in Older Adults with Depressive Disorders.

OBJECTIVE: To study the prevalence of autism spectrum disorder (ASD) characteristics in older adults with and without depressive disorders and the social network and past negative life events in those with a high number of ASD characteristics and those without a large number of these characteristics. METHODS: This large, multisite, naturalistic, prospective cohort study used data from the Netherlands Study of Depression in Older persons (aged 60-90 years) with (N = 259) and without (N = 114) a depressive disorder according to DSM-IV criteria. ASD characteristics were measured with the abbreviated Autism Spectrum Quotient with a cutoff score of 70. Additional measures were the Composite International Diagnostic Interview, the Inventory of Depressive Symptomatology, the Becks Anxiety Inventory, the Close Person Inventory, and the life events questionnaire. RESULTS: Of the older adults with a depressive disorder, 31% showed elevated ASD characteristics, which is much higher than the observed 6% in the comparison group. High ASD characteristics were associated with elevated depression and anxiety symptoms and more comorbid anxiety disorders. Those with a high number of ASD characteristics did not differ in the size of their social network or the number of negative life events as compared with those with less ASD characteristics. CONCLUSION: ASD might be overlooked in older adults, especially within geriatric psychiatry. When diagnosing and treating depression and anxiety in older patients, one should be attentive to ASD.

One-year follow-up of two novel CBTs for adolescents with ADHD.

Long-term effects of two CBTs for adolescents with ADHD are explored: One aimed at improving planning skills (Plan My Life; PML), the other a solution-focused therapy (SFT) without focusing on planning skills. In a RCT, adolescents with ADHD (n = 159) were assigned to PML or SFT and improved significantly between pre- and posttest with large effect sizes Boyer et al (Eur Child Adolesc Psychiatry. doi: 10.1007/s00787-014-0661-5 ), with marginal differences in favor of PML. One-year follow-up data were gathered. Initial improvements remained stable or continued to improve from posttest to 1-year follow-up. 25.9 % of adolescents showed normalized functioning. However, no treatment differences were found. These results are consistent with the finding that treatment of ADHD improves long-term outcomes, but not to the point of normalization. Earlier found differences at 3-month follow-up in favor of PML disappeared, indicating that focusing treatment on planning skills is not necessary for improvement or that a more prolonged planning-focused treatment is needed.

Working memory and cognitive flexibility-training for children with an autism spectrum disorder: a randomized controlled trial.

BACKGROUND: People with autism spectrum disorders (ASDs) experience executive function (EF) deficits. There is an urgent need for effective interventions, but in spite of the increasing research focus on computerized cognitive training, this has not been studied in ASD. Hence, we investigated two EF training conditions in children with ASD. METHODS: In a randomized controlled trial, children with ASD (n = 121, 8-12 years, IQ > 80) were randomly assigned to an adaptive working memory (WM) training, an adaptive cognitive flexibility-training, or a non-adaptive control training (mock-training). Braingame Brian, a computerized EF-training with game-elements, was used. Outcome measures (pretraining, post-training, and 6-week-follow-up) were near-transfer to trained EFs, far-transfer to other EFs (sustained attention and inhibition), and parent's ratings of daily life EFs, social behavior, attention deficit hyperactivity disorder (ADHD)-behavior, and quality of life. RESULTS: Attrition-rate was 26%. Children in all conditions who completed the training improved in WM, cognitive flexibility, attention, and on parent's ratings, but not in inhibition. There were no significant differential intervention effects, although children in the WM condition showed a trend toward improvement on near-transfer WM and ADHD-behavior, and children in the cognitive flexibility condition showed a trend toward improvement on near-transfer flexibility. CONCLUSION: Although children in the WM condition tended to improve more in WM and ADHD-behavior, the lack of differential improvement on most outcome measures, the absence of a clear effect of the adaptive training compared to the mock-training, and the high attrition rate suggest that the training in its present form is probably not suitable for children with ASD.

Two novel CBTs for adolescents with ADHD: the value of planning skills.

Adolescents with ADHD have planning problems, often affecting school- and social functioning. Evidence-based treatments for adolescents with ADHD are scarce and treatment drop-out rates are substantial. The effectiveness of two new, individual, short-term cognitive behavioral therapies (CBT) was investigated: One with an aim on improving planning skills and one solution-focused treatment (SFT) without such an aim. Motivational Interviewing elements were added to both treatments to enhance treatment compliance. In a multi-center randomized clinical trial, 159 adolescents (12-17 years) with ADHD were randomly assigned to one of both treatments. Pre-, post- and 3-month follow-up data were gathered on five domains: Parent-rated ADHD, planning problems and executive functioning (primary outcomes), neuropsychological measures of planning, comorbid symptoms, general functioning, and teacher measures. Attrition was low in both treatments (5%). Adolescents improved significantly between pre- and post-test with large effect sizes on all domains. Improvements remained stable or continued to improve from post-test to follow-up, also when controlling for medication use. Marginally significant differences were found in favor of the planning-focused treatment: parents and therapists evaluated this treatment more positively than SFT and the planning-focused treatment showed more reduction of parent-rated planning problems. Two new CBTs with integrated motivational components were feasible and attrition was low. ADHD symptoms and co-existing problems of the adolescents improved from pre-test to 3 months after treatment. As the planning-focused treatment was evaluated more positive and had marginal additional beneficial effects to SFT, especially planning-focused CBT seems promising to fill the gap in available treatments for adolescents with ADHD.

Beyond individual differences: are working memory and inhibition informative specifiers within ASD?

Findings on working memory (WM) and inhibition in children with autism spectrum disorders (ASD) are contradictory and earlier studies largely ignored individual differences. As WM and inhibition seem to be related, children who experience WM deficits might also experience inhibition deficits. Moreover, these children possibly form a distinct subgroup, differing on other variables, such as cognitive functioning, symptom severity, behavior, and attention deficit hyperactivity disorder (ADHD) characteristics. We studied a large sample of children with and without ASD (8-12 years, IQ > 80) with classic experimental tasks (n-back task, ASD n = 77, control n = 45; stop task, ASD n = 74, control n = 43), and explored individual differences. The ASD group made more errors on the n-back task with increasing WM load, and had longer stop signal reaction times on the stop task when compared with controls. However, only 6 % of the ASD group showed both WM and inhibition deficits, and 71 % showed no deficits. Parents of children with WM and/or inhibition deficits tended to report more conduct problems on the disruptive behavior disorder rating scale. ADHD characteristics did not influence performance. Some children used medication during testing, which seemingly influenced stop task performance, but excluding these data did not change the main findings. Large individual differences in cognitive functioning are present, even within children with ASD with average or above average intelligence. However, whether individual differences in specific cognitive domains, such as WM and inhibition are as informative as individual differences in diagnosis, comorbidity, and general cognitive functioning, calls for future research.

Annual research review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype.

BACKGROUND: Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. SCOPE AND METHODOLOGY: Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. FINDINGS: Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63-0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. CONCLUSION: We underscore the importance of considering the interactions between top-down control, state regulation (e.g., arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders.

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design.

BACKGROUND: Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different approaches to determine whether there are related findings in humans. METHODS/DESIGN: Animal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques. In addition, we set up two double-blind placebo controlled clinical trials with MPH in 50 boys (10-12 years) and 50 young men (23-40 years) suffering from ADHD (ePOD-MPH) and with FLX in 40 girls (12-14 years) and 40 young women (23-40 years) suffering from depression and anxiety disorders (ePOD-SSRI). Trial registration numbers are: Nederlands Trial Register NTR3103 and NTR2111. A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX (ePOD-Pharmo) is also ongoing. The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition, behavior and emotion. All assessments take place before, during (only in case of MPH) and after chronic treatment. DISCUSSION: The combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development.

Two validation studies of a performance validity test for autistic adults.

In two studies we examined the potential of a simple emotion recognition task, the Morel Emotional Numbing Test (MENT), as a performance validity test (PVT) for autism-related cognitive difficulties in adulthood. The aim of a PVT is to indicate non-credible performance, which can aid the interpretation of psychological assessments. There are currently no validated PVTs for autism-related difficulties in adulthood. In Study 1, non-autistic university students (aged 18-46 years) were instructed to simulate that they were autistic during a psychological assessment (simulation condition; n = 26). These students made more errors on the MENT than those instructed to do their best (control condition; n = 26). In Study 2, we tested how well autistic adults performed on the MENT. We found that clinically diagnosed autistic adults and non-autistic adults (both n = 25; 27-57 years; IQ > 80) performed equally well on the MENT. Moreover, autistic adults made significantly fewer errors than the instructed simulators in Study 1. The MENT reached a specificity of ≥98% (identifying 100% of non-simulators as non-simulator in Study 1 and 98% in Study 2) and a sensitivity of 96% (identifying 96% of simulators as simulator). Together these findings provide the first empirical evidence for the validity of the MENT as a potential PVT for autism-related cognitive difficulties.

How do primary care providers and autistic adults want to improve their primary care? A Delphi-study.

LAY ABSTRACT: Autistic adults often encounter different types of healthcare barriers. Because autistic adults also have an increased risk for health problems, the aim of this study was to evaluate barriers and to explore how primary care providers and autistic adults want to improve their primary healthcare. In this co-created study, semi-structured interviews with three autistic adults, two parents of autistic children and six care providers were performed to evaluate barriers in Dutch healthcare. Next, in the survey-study (using the Delphi-method including controlled feedback in three consecutive questionnaires), 21 autistic adults and 20 primary care providers rated the impact of barriers and the usefulness and feasibility of recommendations to improve primary healthcare. In the interviews, 20 barriers in Dutch healthcare for autistic people were found. In the survey-study, the primary care providers rated the negative impact of most barriers lower than the autistic adults. This survey-study resulted in 22 recommendations to improve primary healthcare focused on: primary care providers (including education in collaboration with autistic people), autistic adults (including improvement of preparation for general practitioner-appointments) and organization of general practice (including improvement of continuity in care). In conclusion, primary care providers seem to view healthcare barriers as less impactful than autistic adults. In this co-created study, recommendations to improve primary healthcare for autistic adults were identified, based on the needs of autistic adults and primary care providers. These recommendations provide a basis for primary care providers, autistic adults and their support network to start conversations about, for example, strategies to improve primary care providers' knowledge, autistic adults' preparation for a general practitioner-appointment and organization of primary care.

When mind and measurement diverge; the interplay between subjective cognitive complaints (SCCs), objective cognition, age, and depression in autistic adults.

While the increased incidence of dementia and subjective cognitive complaints (SCCs) suggests that autistic adults may face cognitive challenges at older age, the extent to which SCCs predict (future) cognitive functioning remains uncertain. This uncertainty is complicated by associations with variables like depression. The current study aims to unravel the interplay of age, depression, cognitive performance, and SCCs in autism. Using a large cross-sectional cohort of autistic (n=202) and non-autistic adults (n=247), we analyzed associations of SCCs with age, depression, and cognitive performance across three domains (visual memory, verbal memory, and fluency). Results showed a strong significant association between depression and SCCs in both autistic and non-autistic adults. Cognitive performance was not significantly associated with SCCs, except for a (modest) association between visual memory performance and SCCs in autistic adults only. Follow-up regression tree analysis indicated that depression and being autistic were considerably more predictive of SCCs than objective cognitive performance. Age nor sex was significantly associated with SCCs. These findings indicate that self-reported cognitive functioning does not equal cognitive performance, and should be interpreted with care, especially in individuals with high rates of depression. Longitudinal investigations are needed to understand SCCs' role in dementia and cognitive health in autism.

Perception of temporal synchrony not a prerequisite for multisensory integration.

Temporal alignment is often viewed as the most essential cue the brain can use to integrate information from across sensory modalities. However, the importance of conscious perception of synchrony to multisensory integration is a controversial topic. Conversely, the influence of cross-modal incongruence of higher level stimulus features such as phonetics on temporal processing is poorly understood. To explore the nuances of this relationship between temporal processing and multisensory integration, we presented 101 participants (ranging from 19 to 73 years of age) with stimuli designed to elicit the McGurk/MacDonald illusion (either matched or mismatched pairs of phonemes and visemes) with varying degrees of stimulus onset asynchrony between the visual and auditory streams. We asked them to indicate which syllable they perceived and whether the video and audio were synchronized on each trial. We found that participants often experienced the illusion despite not perceiving the stimuli as synchronous, and the same phonetic incongruence that produced the illusion also led to significant interference in simultaneity judgments. These findings challenge the longstanding assumption that perception of synchrony is a prerequisite to multisensory integration, support a more flexible view of multisensory integration, and suggest a complex, reciprocal relationship between temporal and multisensory processing.

Neuropsychological assessment of aggressive offenders: a Delphi consensus study.

Objective: This study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression. Methods: An international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability. Results: The panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed. Conclusions: This research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.

The relationship between camouflaging and mental health: Are there differences among subgroups in autistic adults?

LAY ABSTRACT: When autistic people use strategies to hide their autistic characteristics, we call this camouflaging. Autistic adults suggested that camouflaging can result in mental health difficulties. That is, people who report to camouflage also report mental health difficulties. However, since there are many differences between autistic people, this relationship may also differ between subgroups. Therefore, in this study we investigated whether camouflaging and mental health difficulties are related and whether this relationship is equal for all autistic adults. For this study, 352 autistic adults aged 30-84 years filled in the Dutch Camouflaging Autistic Traits Questionnaire to measure camouflaging and the Symptom Checklist-90 Revised to measure mental health difficulties. We found that camouflaging was moderately related to mental health difficulties. This means that people who report more camouflaging also report more mental health difficulties. When we looked closer, we found that this relationship was strong for only a small subgroup of autistic adults. In most other autistic adults, there was a small or no relationship between camouflaging and mental health difficulties. Therefore, it is important that clinicians are aware of camouflaging and its possible relationship with mental health difficulties, but that they do not generalize the negative consequences to everyone.

The clinical relevance of subgroups of autistic adults: Stability and predictive value.

Autism in adulthood is characterized by heterogeneity, complicating the provision of tailored support. In previous work, we aimed to capture this heterogeneity by determining subgroups of autistic adults that differed in clinical outcomes: cognitive failures, psychological difficulties, and quality of life (QoL). Two subgroups were identified: a "Feelings of Low Grip" subgroup characterized by experiencing a lower sense of mastery and a higher susceptibility to difficulties in daily life, and a "Feelings of High Grip" subgroup characterized by a higher sense of mastery and lower susceptibility to difficulties in daily life. The current pre-registered study involves a longitudinal extension to determine (a) stability and (b) predictive value of the previously identified two subgroups. Subgroups were identified using community detection based on 14 self-report measures related to demographic, psychological, and lifestyle characteristics in two samples (aged 31-86 years) that were analyzed separately: Sample 1 (NAutism = 80) measured 5 years after baseline and Sample 2 (NAutism = 241, NComparison = 211) measured 2 years after baseline. The stability over time was assessed based on (a) the number of subgroups, (b) subgroup profiles, and (c) subgroup membership. Predictive validity was assessed for cognitive failures, psychological difficulties, and QoL. Results indicated that autistic and non-autistic adults formed distinct subgroups. Within both autism samples, the two previously identified autism subgroups were replicated at follow-up. Subgroup profiles were similar for >50% of the variables at two-year follow-up, and 21% at five-year follow-up. Moreover, ≥76% remained in the same subgroup at two-year follow-up, and ≥ 57% after 5 years. Subgroup membership was predictive of external clinical outcomes up to 5 years. Thus, this study demonstrated the stability and predictive value of the autism subgroups, especially for the two-year follow-up. A further focus on their clinical utility might increase the aptness of support, and may provide more insight into the aging process when being autistic.

Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study.

Background: Stimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood. Purpose: Investigate the long-term age-dependent effects of stimulant medication use on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD. Methods: This prospective study included the baseline and 4-year follow-up assessment of the "effects of Psychotropic drugs On the Developing brain-MPH" ("ePOD-MPH") project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness. Results: A total of 32 male adolescents (aged mean ± SD, 11.2 ± 0.9 years at baseline) and 24 men (aged mean ± SD, 29.9 ± 5.0 years at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and more improvement of ADHD symptoms was associated with higher medication use in adults (P=0.001). Conclusion: We found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development.