Maternal immune activation during pregnancy is associated with more difficulties in socio-adaptive behaviors in autism spectrum disorder.

Autism spectrum disorder (ASD) are neurodevelopmental conditions characterised by deficits in social communication and interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in ASD, their strengths and difficulties. In this study, we hypothesised that ASD individual with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA-). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used supervised and unsupervised machine learning algorithms. We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ affect persistently the socio-adaptive behavioral trajectories of individuals with ASD. The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results. Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of ASD and for the development of specific immunomodulatory strategies.

Sleep and emotionality in adolescents with anorexia nervosa during the Covid-19 pandemic.

PURPOSE: The recent Covid-19 pandemic and its lockdown measures raised concerns about people's mental health, leading to an increased interest in identifying vulnerable groups especially at risk for mental distress. This cross-sectional study investigated the impact of this unprecedented situation on sleeping patterns and emotionality in adolescents with anorexia nervosa (AN). METHODS: Variations in sleeping patterns and emotionality of two groups of adolescents with AN, assessed before (N = 50) and during (N = 51) the Covid-19 lockdown were analysed. We further investigated these variations over time, considering the two lockdown periods in France. RESULTS: Adolescents self-reported significantly more sleep difficulties and lower rates of positive emotions during lockdown, compared to those evaluated before it. Furthermore, present findings overall suggest that as the lockdown progresses, adolescents with AN show an increased deterioration of sleep quality, as indicated by greater insomnia severity levels. They also show a significant decrease in the subjective experience of positive emotionality, in particular in feelings of tenderness. CONCLUSIONS: These sleep and emotionality alterations may have amplified the severity and the incidence of AN in adolescents during the Covid-19 pandemic. These features may therefore represent therapeutic targets to optimise care of adolescents with AN. This is particularly urgent, considering kinetics of the deterioration. Tools such as those provided by cognitive behavioural therapy for insomnia and by the positive psychology framework seem appropriate to guide clinicians in this context. LEVEL OF EVIDENCE: Level V, descriptive study (evaluation data retrospectively studied).

Gender differences in psychosocial function and self-reported health status in late-diagnosed autistic adults: results from the FACE-ASD national cohort.

BACKGROUND: While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status - an approach that could inform on potential gender differences. METHODS: We investigated gender differences in two aspects of outcome related to health-status, i.e. general functioning and self-perceived health status, and co-occurring health conditions in a large multi-center sample of autistic adults. Three hundred and eighty-three participants were consecutively recruited from the FondaMental Advanced Centers of Expertise for ASD cohort (a French network of seven expert centers) between 2013 and 2020. Evaluation included a medical interview, standardized scales for autism diagnosis, clinical and functional outcomes, self-perceived health status and verbal ability. Psychosocial function was measured using the Global Assessment of Functioning scale. RESULTS: While autistic women in this study were more likely than men to have socially valued roles, female gender was associated with poorer physical and mental health (e.g. a 7-fold risk for having three or more co-occurring physical health conditions) and a poorer self-perceived health status. Psychosocial function was negatively associated with depression and impairment in social communication. Half of the sample had multiple co-occurring health conditions but more than 70% reported that their visit at the Expert Center was their first contact with mental health services. CONCLUSIONS: To improve objective and subjective aspects of health outcome, gender differences and a wide range of co-occurring health conditions should be taken into account when designing healthcare provision for autistic adults.

Dissociable effects of positive feedback on the capture and inhibition of impulsive behavior in adolescents with ADHD versus typically developing adolescents.

The present study investigated how enhancing motivation by delivering positive feedback (a smiley) after a successful trial could affect interference control in adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and in their typically developing (TD) peers. By using a Simon task within the theoretical framework of the "activation-suppression" model, we were able to separately investigate the expression and the inhibition of impulsive motor behavior. The experiment included 19 adolescents with ADHD and 20 TD adolescents in order to explore whether data found in adolescents with ADHD were similar to those found in TD adolescents. Participants performed the Simon task in two conditions: a condition with feedback delivered after each successful trial and a condition with no feedback. The main findings were that increasing motivation by delivering positive feedback increased impulsive response in both groups of adolescents. It also improved the efficiency of impulsive motor action inhibition in adolescents with ADHD but deteriorated it in TD adolescents. We suggest that 1/increased motivation could lead adolescents to favor fast responses even if incorrect, and 2/the differential effect of feedback on the selective suppression of impulsive motor action in both groups could be due to different baseline DA levels.

Comparing executive functions profiles in anorexia nervosa and autism spectrum disorder in adolescence.

OBJECTIVE: Executive functions (EFs) inefficiencies in anorexia nervosa (AN), especially in set-shifting and central coherence, suggest a link between AN and autism spectrum disorders (ASDs). This study aimed at comparing EF profiles in AN and ASD, and investigating clinical variables associated with the identified EF difficulties. METHOD: One hundred and sixty-two adolescents with AN or ASD completed self-report questionnaires assessing depression, anxiety and autism symptoms. Parents completed the behaviour rating of executive functions parent-form (BRIEF-P). Besides comparing EFs in AN and ASD, we also analysed clinical variables scoring below and above the mean age score across the all sample. We additionally examined the relationship between clinical variables and the BRIEF-P indexes in AN. RESULTS: Participants with ASD had greater EF difficulties than participants with AN on all BRIEF-P scales. In the whole sample, higher autistic features were related to poorer EF. In AN, lower body mass index and particularly higher autism-spectrum quotient (BRI: Beta = 0.55; p < 0.001 and GEC: Beta = 0.50; p < 0.001) were most strongly associated with poorer EF. CONCLUSION: Although participants with ASD showed greater difficulties, autistic traits were related to alter EFs in AN. Exploring further this dimension can undeniably allow better adaptive cognitive remediation programs.

Clinical features of children and adolescents with anorexia nervosa and problematic physical activity.

PURPOSE: Problematic physical activity (PPA) is a symptom commonly present in patients suffering from anorexia nervosa (AN). This study aims to refine the clinical description of children with early-onset AN and adolescents with standard-onset AN and associated PPA, in order to better understand their associated features, and to offer them adapted care and physical activity programs. METHODS: 107 participants treated at the Salvator University Hospital Centre of Marseille for AN were retrospectively evaluated by the Exercise Dependence Scale Revised concerning PPA. Other self-report questionnaires were used to evaluate eating disorder, anxiety and depressive symptoms, quality of life, emotions, sleep, and attention deficit disorder with or without hyperactivity. RESULTS: In the entire sample, the presence of PPA was associated with significantly higher levels of eating disorder (EDI-2: p = 0.001) and body image concerns (p = 0.002), anxiety (STAI-Y-trait: p = 0.013) and depression (p = 0.006), as well as significantly lower psychological well-being (p < 0.001) and quality of life (p < 0.001) and impaired sleep (PSQI: p = 0.008). The early-onset group showed a lower prevalence of PPA than the standard-onset group (p < 0.05) but their clinical symptomatology, when this symptom was present, was significantly more severe (EDI-2: p < 0.01; BSQ: p < 0.05; CDI: p < 0.05; STAI-Y-trait: p < 0.05). CONCLUSION: PPA appears to be associated with more severe features in patients with early-onset AN, which seems to differ from standard-onset. It seems necessary to refine our knowledge on the involvement of PPA in the severity of AN, especially in patients with early-onset AN who remain little studied so far. LEVEL OF EVIDENCE: Level V, descriptive study (evaluation data retrospectively studied).

Cohort profile: demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe.

PURPOSE: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. PARTICIPANTS: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. FUTURE PLANS: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. TRIAL REGISTRATION NUMBER: NCT03013595.

Differential response to pharmacological intervention in ADHD furthers our understanding of the mechanisms of interference control.

The deficit in "interference control" found in children with Attention Deficit Hyperactivity Disorder (ADHD) could be due to two distinct processes, which are not disentangled in most studies: a larger susceptibility to activating prepotent response impulses and a deficit in suppressing them. Here, we investigated the effect of 1/ADHD and 2/ methylphenidate (MPH), on these two components of interference control. We compared interference control between untreated children with ADHD, children with ADHD under MPH, and typically developing children performing a Simon task. The main findings were that 1/ children with ADHD were more susceptible to reacting impulsively and less efficient at suppressing impulsive actions, and 2/ MPH improved the selective inhibition of impulsive actions but did not modify the strength of response impulse. This work provides an example of how pharmacological interventions and selective responses to them can be used to investigate and further our understanding of cognitive processing.

Sleep disturbances in anorexia nervosa subtypes in adolescence.

PURPOSE: This retrospective study investigated, for the first time, sleep characteristics in anorexia nervosa (AN) subtypes and the clinical profile in adolescents, as well as the quality of life (QoL) and emotionality in these patients with poor sleep. METHODS: The sample included 111 adolescents with AN. First, restrictive AN (ANR) and binge eating/purging AN (ANB/P) groups were compared in terms of self-reported sleep characteristics, sleepiness and chronotype. Second, the clinical profile, QoL, and emotionality of good sleepers (GS) and poor sleepers (PS) were compared. RESULTS: Compared to the ANR group, participants with ANB/P showed significantly greater sleep disturbances and sleepiness, and also a higher preference for an eveningness chronotype. Results also showed a clinical profile significantly more severe in PS than in GS. After adjustment, only the ANB/P subtype and the EDI-2 ineffectiveness subscale remained significantly linked to poor sleep. Moreover, the QoL was lower and emotionality more negative in PS with respect to GS. CONCLUSION: Findings suggest that subjective sleep disturbances may be used as a clinical marker for AN severity and for ANB/P subtype. Importantly, findings suggest that improving sleep quality in adolescents with AN may help managing their ED and their comorbidities, but also improve their QoL. LEVEL OF EVIDENCE: Level V, descriptive study (evaluation data retrospectively studied).

Acting on observed social exclusion and pro-social behaviour in autism spectrum disorder.

Humans are commonly motivated towards cooperation and prosociality. In this study, we examined this motivational predisposition in autistic individuals. Using an adaptation of the Cyberball paradigm, we investigated subsequent pro-social behaviour after witnessing social exclusion. Participants witnessed and played a series of Cyberball games, rated their affective state and valued emotional faces with respect to their approachability. Results showed that participants from both groups were aware of the social exclusion. However, while neurotypically developing participants engaged in pro-social behaviour in reaction to the exclusion, autistic participants showed less alterations, in terms of either behaviour or affective state. The current findings suggest a distinct motivational drive and processing of social reward stimuli in autism, which may result in behavioural responses divergent from typical development when engaging in the social world.

The quality of life and the future of young adults with Asperger syndrome.

Purpose: This pilot study describes the socio-professional development and quality of life of young adults with Asperger syndrome in France.Methods: Those young adults, between 18 and 30 years old, receiving care in a child psychiatry department for autistic spectrum disorder, were requested to respond to the Ad Hoc, World Health Organization Quality Of Life - Bref and Copenhagen psychosocial questionnaires regarding their socio-professional background and feelings about their future.Results: Of the 79 eligible subjects, 24 were selected to participate in our study. Their average age at the time of the pilot study was 22.2 years (standard deviation 3.4 years), and their average age when they were diagnosed was 17.5 years (standard deviation 3.7 years.). There were 54% who reported a psychiatric comorbidity anxiety disorder. Half stated they had completed secondary school and benefitted from being professionally employed. During this study, only six were employed, while the others remained financially dependent on their parents. The group's quality of life self-assessment scores were significantly lower compared to the French general population in overall psychology (43.6 versus 68.7) and social relationships (48.9 versus 76.5). However, the study's participants perceived work as an important means to their personal development. Hence, in order to cope with their difficulties, they hoped to benefit from customized support adapted to their autistic disorder and for their workplace colleagues to be better informed about Asperger syndrome.Conclusions: Our results are in line with international data. Additional studies need to be done in order to determine socio-professional integration factors and, in particular, the integration of potential contributions by occupational health departments with those social and medical teams supporting these young adults.Implications for rehabilitationYoung adults with Asperger syndrome benefit from the support of their family in determining their professional goals.Support may be required to enhance social and communicative abilities to help integration.Employees would benefit from information on the syndrome and how best to support.

Comparison of body image evaluation by virtual reality and paper-based figure rating scales in adolescents with anorexia nervosa: retrospective study.

PURPOSE: Assessment of the symptoms of body image disorder (BID) is crucial in anorexia nervosa (AN). Recent technological advancements such as virtual reality (VR) have improved the visual perception with 3D avatars and the feeling to be the avatar with the immersive conditions. This retrospective study examines the hypothesis that VR with standardized 3D avatars would improve body image perception and then body image evaluation by adolescents with AN, compared to the paper-based figure rating scales (FRS). METHODS: Data of 31 female adolescents with AN were retrospectively studied. Paired data of perceived and desired body forms in addition to body perception index (BPI) (p = 0.2) and body dissatisfaction (p = 0.6), obtained by both VR and FRS were compared. Furthermore, correlation with validated psychometric questionnaires was also studied. Head-tracking technology allowed for the implicit measurement of explicit choices of patients. RESULTS: Participants with AN overestimated own body size regardless of the assessment tool used. BPI and body dissatisfaction did not differ significantly between FRS and VR. VR-based evaluation was correlated with the psychometric parameters BID and body dissatisfaction. Head tracking revealed significantly longer participant engagement with avatars representing malnutrition and underweight states, while those least engaged corresponded to obesity. CONCLUSIONS: Results of BID evaluation by VR standardized 3D avatars are comparable to those obtained by paper-based FRS. These findings suggest that comparable results obtained by both tools of evaluation reflect primarily the role of affective-cognitive perturbation in BID. The perceptive component could be better evaluated using biometric-enhanced assessment tools. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study (evaluation data retrospectively studied).

Altered sleep architecture during the first months of life in infants born to depressed mothers.

OBJECTIVE: This study investigated sleep architecture in newborn and six-month-old infants who were born to depressed mothers. METHOD: Sixty-four healthy full-term infants (32 males and 32 females) participated in the study. Of these, 32 were high-risk infants who were born to mothers diagnosed with depression, and 32 were low-risk infants born to mothers without a personal history of depression. 24-hour polysomnography was recorded at zero and six months of age (M0 and M6). Sleep macro-structural parameters (total sleep time, TST; awake time; non-rapid eye movement, NREM sleep (%); rapid eye movement, REM sleep %; arousal index; and sleep efficiency) were analysed at M0 and M6. Micro-architectural sleep features (slow-wave activity, SWA; delta sleep ratio, DSR; spindle density; and rapid eye movement density) were calculated at M6. The data between high-risk and low-risk groups were compared using Student's t-tests. RESULTS: At M0 and M6, the high-risk infants showed more awake time and fewer arousals than the low-risk infants. However, the high-risk group had less NREM% at M0 and a shorter TST as well as less REM% at M6 than the low-risk group. At M6, the high-risk group showed higher SWA, higher DSR and lower spindle density in comparison with the low-risk group. CONCLUSIONS: Altered sleep structure was observed during their first months of life in infants born from depressed mothers, thereby suggesting that the prenatal environment could enhance the depression vulnerability of the child and potentially decrease their neuroplasticity.

Behavioral characterization of prediction and internal models in adolescents with autistic spectrum disorders.

Autism has been considered as a deficit in prediction of the upcoming event or of the sensory consequences of our own movements. To test this hypothesis, we recorded eye movements from high-functioning autistic adolescents and from age-matched controls during a blanking paradigm. In this paradigm, adolescents were instructed to follow a moving target with their eyes even during its transient disappearance. Given the absence of visual information during the blanking period, eye movements during this period are solely controlled on the basis of the prediction of the ongoing target motion. Typical markers of predictive eye movements such as the number and accuracy of predictive saccades and the predictive reacceleration before target reappearance were identical in the two populations. In addition, the synergy of predictive saccades and smooth pursuit observed during the blanking periods, which is a marker for the quality of internal models about target/eye motions, was comparable between these two populations. These results suggest that, in our large population of high-functioning autistic adolescent, both predictive abilities and internal models are left intact in Autism, at least for low-level sensorimotor transformations.

Localized Misfolding Within Broca's Area as a Distinctive Feature of Autistic Disorder.

BACKGROUND: Recent neuroimaging studies suggest that autism spectrum disorder results from abnormalities in the cortical folding pattern. Usual morphometric measurements have failed to provide reliable neuroanatomic markers. Here, we propose that sulcal pits, which are the deepest points in each fold, are suitable candidates to uncover this atypical cortical folding. METHODS: Sulcal pits were extracted from a magnetic resonance imaging database of 102 children (1.5-10 years old) distributed in three groups: children with autistic disorder (n = 59), typically developing children (n = 22), and children with pervasive developmental disorder not otherwise specified (n = 21). The geometrical properties of sulcal pits were compared between these three groups. RESULTS: Fold-level analyses revealed a reduced pit depth in the left ascending ramus of the Sylvian fissure in children with autistic disorder only. The depth of this central fold of Broca's area was correlated with the social communication impairments that are characteristic of the pathology. CONCLUSIONS: Our findings support an atypical gyrogenesis of this specific fold in autistic disorder that could be used for differential diagnosis. Sulcal pits constitute valuable markers of the cortical folding dynamics and could help for the early detection of atypical brain maturation.

Effects of motor action on affective preferences in autism spectrum disorders: different influences of embodiment.

In the embodied cognition framework, sensory, motor and emotional experiences are encoded along with sensorimotor cues from the context in which information was acquired. As such, representations retain an initial imprint of the manner in which information was acquired. The current study reports results indicating a lack of embodiment effects in ASD and, further, an association between embodiment differences and ASD symptomatology. The current results are consistent with an embodied account of ASD that goes beyond social experiences and could be driven by subtle deficits in sensorimotor coordination.

Anthropomorphic bias found in typically developing children is not found in children with autistic spectrum disorder.

The anthropomorphic bias describes the finding that the perceived naturalness of a biological motion decreases as the human-likeness of a computer-animated agent increases. To investigate the anthropomorphic bias in autistic children, human or cartoon characters were presented with biological and artificial motions side by side on a touchscreen. Children were required to touch one that would grow while the other would disappear, implicitly rewarding their choice. Only typically developing controls depicted the expected preference for biological motion when rendered with human, but not cartoon, characters. Despite performing the task to report a preference, children with autism depicted neither normal nor reversed anthropomorphic bias, suggesting that they are not sensitive to the congruence of form and motion information when observing computer-animated agents' actions.

Mental Disorders among Children and Adolescents Admitted to a French Psychiatric Emergency Service.

The aim of this study was to describe the characteristics of children and adolescents admitted to the psychiatric emergency department (ED) of a French public teaching hospital over a six-year study period (2001-2006). Data for all episodes of care in the psychiatric ED from January 1, 2001, to December 31, 2006, delivered to adolescents aged less than 18 years were retrospectively analyzed. During the six-year study period, 335 episodes of care in the psychiatric ED were experienced by 264 different adolescents. They accounted for 2.0% of the 16,754 care episodes of the ED; 164 patients (62.1) were female and the average age was 16.5 (SD = 1.6). The neurotic, stress-related, and somatoform disorders were the most frequent (25.4%) and concerned mainly anxiety disorders (15.2%). The frequency of the absence of psychiatric diagnosis (22.7%) was high. A total of 48 children and adolescents (18.2%) benefited from more than one episode of care. Several factors were associated to a higher number of visits to the ED: substance use, schizophrenia, disorders of adult personality and behaviour, disorders occurring in childhood and adolescence, and dual diagnosis. In conclusion, mental health disorders in children and adolescents are a serious problem associated with several potentially modifiable factors.

How do we think machines think? An fMRI study of alleged competition with an artificial intelligence.

Mentalizing is defined as the inference of mental states of fellow humans, and is a particularly important skill for social interactions. Here we assessed whether activity in brain areas involved in mentalizing is specific to the processing of mental states or can be generalized to the inference of non-mental states by comparing brain responses during the interaction with an intentional and an artificial agent. Participants were scanned using fMRI during interactive rock-paper-scissors games while believing their opponent was a fellow human (Intentional agent, Int), a humanoid robot endowed with an artificial intelligence (Artificial agent, Art), or a computer playing randomly (Random agent, Rnd). Participants' subjective reports indicated that they adopted different stances against the three agents. The contrast of brain activity during interaction with the artificial and the random agents didn't yield any cluster at the threshold used, suggesting the absence of a reproducible stance when interacting with an artificial intelligence. We probed response to the artificial agent in regions of interest corresponding to clusters found in the contrast between the intentional and the random agents. In the precuneus involved in working memory, the posterior intraparietal suclus, in the control of attention and the dorsolateral prefrontal cortex, in executive functions, brain activity for Art was larger than for Rnd but lower than for Int, supporting the intrinsically engaging nature of social interactions. A similar pattern in the left premotor cortex and anterior intraparietal sulcus involved in motor resonance suggested that participants simulated human, and to a lesser extend humanoid robot actions, when playing the game. Finally, mentalizing regions, the medial prefrontal cortex and right temporoparietal junction, responded to the human only, supporting the specificity of mentalizing areas for interactions with intentional agents.

Just another social scene: evidence for decreased attention to negative social scenes in high-functioning autism.

The adaptive threat-detection advantage takes the form of a preferential orienting of attention to threatening scenes. In this study, we compared attention to social scenes in 15 high-functioning individuals with autism (ASD) and matched typically developing (TD) individuals. Eye-tracking was recorded while participants were presented with pairs of scenes, either emotional positive-neutral, emotional negative-neutral or neutral-neutral scenes. Early allocation of attention, the first image fixated in each pair, differed between groups: contrary to TD individuals who showed the typical threat-detection advantage towards negative images, the ASD group failed to show a bias toward threat-related scenes. Later processing of stimuli, indicated by the total fixation to the images during the 3-s presentation, was found unaffected in the ASD group. These results support the hypothesis of an early atypical allocation of attention towards natural social scenes in ASD, that is compensated in later stages of visual processing.