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Introduction Autism spectrum disorders (ASD) are associated with high services use, but European data on costs are scarce. Objectives Utilisation and annual costs of 385 individuals with ASD (aged 4-67 years; 18.2% females; 37.4% IQ < 85) from German outpatient clinics were assessed. Methods Client Service Receipt Inventory Results Average annual costs per person were 3287 EUR, with psychiatric inpatient care (19.8%), pharmacotherapy (11.1%), and occupational therapy (11.1%) being the largest cost components. Females incurred higher costs than males (4864 EUR vs. 2936 EUR). In a regression model, female sex (Cost Ratio: 1.65), lower IQ (1.90), and Asperger syndrome (1.54) were associated with higher costs. Conclusions In conclusion, ASD-related health costs are comparable to those of schizophrenia, thus underlining its public health relevance. Higher costs in females demand further research. Disclosure No significant relationships.

LkCa 15 is an extensively studied star in the Taurus region, known for its pre-transitional disk with a large inner cavity in the dust continuum and normal gas accretion rate. The most popular hypothesis to explain the LkCa 15 data invokes one or more planets to carve out the inner cavity, while gas continues to flow across the gap from the outer disk onto the central star. We present spatially unresolved HCO+ observations of the LkCa 15 disk from the James Clerk Maxwell telescope (JCMT) and model the data with the ProDiMo code. We find that: (1) HCO+ line-wings are clearly detected, certifying the presence of gas in the cavity within ≲50 au of the star. (2) Reproducing the observed line-wing flux requires both a significant suppression of cavity dust (by a factor ≳104 compared to the interstellar medium (ISM)) and a substantial increase in the gas scale-height within the cavity (H0/R0 ∼ 0.6). An ISM dust-to-gas ratio (d:g = 10−2) yields too little line-wing flux, regardless of the scale-height or cavity gas geometry, while a smaller scale-height also under-predicts the flux even with a reduced d:g. (3) The cavity gas mass is consistent with the surface density profile of the outer disk extended inwards to the sublimation radius (corresponding to mass Md ∼ 0.03 M⊙), and masses lower by a factor ≳10 appear to be ruled out. [ABSTRACT FROM AUTHOR]

We present calculated rate coefficients for ro-vibrational transitions of CO in collisions with H atoms for a gas temperature range of 10 K ≤ T ≤ 3000 K, based on the recent three-dimensional ab initio H–CO interaction potential of Song et al. Rate coefficients for ro-vibrational transitions were obtained from scattering cross sections previously computed with the close-coupling (CC) method by Song et al. Combining these with the rate coefficients for vibrational quenching obtained with the infinite-order sudden approximation, we propose a new extrapolation scheme that yields the rate coefficients for ro-vibrational de-excitation. Cross sections and rate coefficients for ro-vibrational transitions calculated with the CC method confirm the effectiveness of this extrapolation scheme. Our calculated and extrapolated rates are very different from those that have been adopted in the modeling of many astrophysical environments. The current work provides the most comprehensive and accurate set of ro-vibrational de-excitation rate coefficients for the astrophysical modeling of the H–CO collision system. The application of the previously available and new data sets in astrophysical slab models shows that the line fluxes typically change by 20%–70% in high temperature environments (800 K) with an H/H2 ratio of 1; larger changes occur for lower temperatures. [ABSTRACT FROM AUTHOR]

Background: Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum., Methods: In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis., Results: Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity., Limitations: Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits., Conclusions: Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity., (© 2024. The Author(s).)

Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical 1,2 . Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios 3 . However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity 4 . Isotope ratios, such as deuterium to hydrogen and 14 N/ 15 N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System 5-7 . For exoplanets, only a handful of constraints on 12 C/ 13 C exist, pointing to the accretion of 13 C-rich ice from beyond the CO iceline of the disks 8,9 . Here we report on the mid-infrared detection of the 14 NH 3 and 15 NH 3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14 N/ 15 N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15 N isotope 10 , we expect that 15 NH 3 will be detectable in several cold, wide-separation exoplanets., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks 1 . Water plays a key role in their formation 2-4 , although it is yet unclear whether water molecules are formed in situ or transported from the outer disk 5,6 . So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks 7 , similar to PDS 70, the first system with direct confirmation of protoplanet presence 8,9 . Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk 10,11 . Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H 2 and/or OH, and survival through water self-shielding 5 . This is also supported by the presence of CO 2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir 12 . Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry., (© 2023. The Author(s).)

Background: Against the background of missing culturally sensitive mental health care services for refugees, we developed a group intervention (Empowerment ) for refugees at level 3 within the stratified Stepped and Collaborative Care Model of the project Mental Health in Refugees and Asylum Seekers (MEHIRA). We aim to evaluate the effectiveness of the Empowerment group intervention with its focus on psychoeducation, stress management, and emotion regulation strategies in a culturally sensitive context for refugees with affective disorders compared to treatment-as-usual (TAU)., Method: At level 3 of the MEHIRA project, 149 refugees and asylum seekers with clinically relevant depressive symptoms were randomized to the Empowerment group intervention or TAU. Treatment comprised 16 therapy sessions conducted over 12 weeks. Effects were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MÅDRS). Further scales included assessed emotional distress, self-efficacy, resilience, and quality of life., Results: Intention-to-treat analyses show significant cross-level interactions on both self-rated depressive symptoms (PHQ-9; F (1,147)  = 13.32, p  < 0.001) and clinician-rated depressive symptoms (MÅDRS; F (1,147)  = 6.91, p  = 0.01), indicating an improvement in depressive symptoms from baseline to post-intervention in the treatment group compared to the control group. The effect sizes for both scales were moderate ( d  = 0.68, 95% CI 0.21-1.15 for PHQ-9 and d  = 0.51, 95% CI 0.04-0.99 for MÅDRS)., Conclusion: In the MEHIRA project comparing an SCCM approach versus TAU, the Empowerment group intervention at level 3 showed effectiveness for refugees with moderately severe depressive symptoms.

Background: Refugees and asylum seekers (RAS) in Germany need tailored and resource-oriented mental healthcare interventions., Aims: To evaluate the cost-effectiveness of group psychotherapy for RAS with moderate depressive symptoms., Method: This is a post hoc cost-effectiveness analysis of Empowerment group psychotherapy that was embedded in a stratified stepped and collaborative care model (SCCM) from the multicentre randomised controlled MEHIRA trial. One hundred and forty-nine participants were randomly assigned to SCCM or treatment as usual (TAU) and underwent Empowerment (i.e. level 3 of the SCCM for adults) or TAU. Effects were measured with the nine-item Patient Health Questionnaire (PHQ-9) and quality adjusted life-years (QALY) post-intervention. Health service and intervention costs were measured. Incremental cost-effectiveness ratios (ICER) were estimated and net monetary benefit (NMB) regressions with 95% confidence intervals were performed. Cost-effectiveness was ascertained for different values of willingness to pay (WTP) using cost-effectiveness acceptability curves for probable scenarios. Trial registration number: NCT03109028 on ClinicalTrials.gov., Results: Health service use costs were significantly lower for Empowerment than TAU after 1 year. Intervention costs were on average €409.6. Empowerment led to a significant change in PHQ-9 scores but not QALY. Bootstrapped mean ICER indicated cost-effectiveness according to PHQ-9 and varied considerably for QALY in the base case. NMB for a unit reduction in PHQ-9 score at WTP of €0 was €354.3 (€978.5 to -€269.9). Results were confirmed for different scenarios and varying WTP thresholds., Conclusions: The Empowerment intervention was cost-effective in refugees with moderate depressive symptoms regarding the clinical outcome and led to a reduction in direct healthcare consumption. Concerning QALYs, there was a lack of confidence that Empowerment differed from TAU.

Background: Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders., Methods: Within the German research network for mental disorders, 895 participants ( n  = 476 female, n  = 602 anxiety disorder, n  = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP)., Results: The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: β = -0.35; NVS: β = 0.39; CS: β = -0.12; SP: β = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association., Limitations: The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for., Conclusion: Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways., Competing Interests: FP is a member of the European Scientific Advisory Board of Brainsway Inc., Jerusalem, Israel, and the International Scientific Advisory Board of Sooma, Helsinki, Finland. He has received speaker’s honoraria from Mag&More GmbH, the neuroCare Group, Munich, Germany, and Brainsway Inc. His lab has received support with equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More GmbH and Brainsway Inc. TB served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Förstner, Böttger, Moldavski, Bajbouj, Pfennig, Manook, Ising, Pittig, Heinig, Heinz, Mathiak, Schulze, Schneider, Kamp-Becker, Meyer-Lindenberg, Padberg, Banaschewski, Bauer, Rupprecht, Wittchen, Rapp and Tschorn.)

This review investigates the association between neurodevelopmental disorders (NDD) and variations of the gene HNF1B. Heterozygous intragenetic mutations or heterozygous gene deletions (17q12 microdeletion syndrome) of HNF1B are the cause of a multi-system developmental disorder, termed renal cysts and diabetes syndrome (RCAD). Several studies suggest that in general, patients with genetic variation of HNF1B have an elevated risk for additional neurodevelopmental disorders, especially autism spectrum disorder (ASD) but a comprehensive assessment is yet missing. This review provides an overview including all available studies of patients with HNF1B mutation or deletion with comorbid NDD with respect to the prevalence of NDDs and in how they differ between patients with an intragenic mutation or 17q12 microdeletion. A total of 31 studies was identified, comprising 695 patients with variations in HNF1B, (17q12 microdeletion N  = 416, mutation N  = 279). Main results include that NDDs are present in both groups (17q12 microdeletion 25.2% vs. mutation 6.8%, respectively) but that patients with 17q12 microdeletions presented more frequently with any NDDs and especially with learning difficulties compared to patients with a mutation of HNF1B. The observed prevalence of NDDs in patients with HNF1B variations seems to be higher than in the general population, but the validity of the estimated prevalence must be deemed insufficient. This review shows that systematical research of NDDs in patients with HNF1B mutations or deletions is lacking. Further studies regarding neuropsychological characteristics of both groups are needed. NDDs might be a concomitant of HFN1B-related disease and should be considered in clinical routine and scientific reports., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nittel, Dobelke, König, Konrad, Becker, Kamp-Becker, Weber and and for the NEOCYST consortium.)

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.e., ASD, ADHD, ASD + ADHD, ND = no diagnosis). We found that a subset of five features from both ADOS (clinical observation) and ADI-R (parental interview) reliably differentiated between ASD groups (ASD & ASD + ADHD) and non-ASD groups (ADHD & ND), and these features corresponded to the social-communication but also restrictive and repetitive behavior domains. In conclusion, the results of the current study support the idea that detecting ASD in individuals with suspected signs of the diagnosis, including those with co-occurring ADHD, is possible with considerably fewer items relative to the original ADOS/2 and ADI-R algorithms (i.e., 92% item reduction) while preserving relatively high diagnostic accuracy. Clinical implications and study limitations are discussed., (© 2022. The Author(s).)

Background: Current evidence points towards a high prevalence of psychological distress in refugee populations, contrasting with a scarcity of resources and amplified by linguistic, institutional, financial, and cultural barriers. The objective of the study is to investigate the overall effectiveness and cost-effectiveness of a Stepped Care and Collaborative Model (SCCM) at reducing depressive symptoms in refugees, compared with the overall routine care practices within Germany's mental healthcare system (treatment-as-usual, TAU)., Methods: A multicentre, clinician-blinded, randomised, controlled trial was conducted across seven university sites in Germany. Asylum seekers and refugees with relevant depressive symptoms with a Patient Health Questionnaires score of ≥ 5 and a Refugee Health Screener score of ≥ 12. Participants were randomly allocated to one of two treatment arms (SCCM or TAU) for an intervention period of three months between April 2018 and March 2020. In the SCCM, participants were allocated to interventions tailored to their symptom severity, including watchful waiting, peer-to-peer- or smartphone intervention, psychological group therapies or mental health expert treatment. The primary endpoint was defined as the change in depressive symptoms (Patient Health Questionnaire-9, PHQ-9) after 12 weeks. The secondary outcome was the change in Montgomery Åsberg Depression Rating Scale (MADRS) from baseline to post-intervention., Findings: The intention-to-treat sample included 584 participants who were randomized to the SCCM (n= 294) or TAU (n=290). Using a mixed-effects general linear model with time, and the interaction of time by randomisation group as fixed effects and study site as random effect, we found significant effects for time (p < .001) and time by group interaction (p < .05) for intention-to-treat and per-protocol analysis. Estimated marginal means of the PHQ-9 scores after 12 weeks were significantly lower in SCCM than in TAU (for intention-to-treat: PHQ-9 mean difference at T 1 1.30, 95% CI 1.12 to 1.48, p < .001; Cohen's d=.23; baseline-adjusted PHQ-9 mean difference at T 1 0.57, 95% CI 0.40 to 0.74, p < .001). Cost-effectiveness and net monetary benefit analyses provided evidence of cost-effectiveness for the primary outcome and quality-adjusted life years. Robustness of results were confirmed by sensitivity analyses., Interpretation: The SSCM resulted in a more effective and cost-effective reduction of depressive symptoms compared with TAU. Findings suggest a suitable model to provide mental health services in circumstances where resources are limited, particularly in the context of forced migration and pandemics., Funding: This project is funded by the Innovationsfond and German Ministry of Health [grant number 01VSF16061]. The present trial is registered under Clinical-Trials.gov under the registration number: NCT03109028. https://clinicaltrials.gov/ct2/show/NCT03109028., Competing Interests: Dr. Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Takeda, and Infectopharm. He received conference support or speaker's fee from Lilly, Medice, and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. Alkomiet Hasan has been invited to scientific meetings by Lundbeck, Janssen, and Pfizer, and he received paid speakerships from Desitin, Janssen, Otsuka, and Lundbeck. He was a member of Roche, Otsuka, Lundbeck, and Janssen advisory boards. Paul Plener was involved in clinical trials of Lundbeck and Servier. He received a speaker's honorarium from Shire and Infectopharm. Frank Padberg is a member of the European Scientific Advisory Board of Brainsway Inc., Jerusalem, Israel, and has received speaker's honoraria from Mag&More GmbH and the neuroCare Group. His lab has received support with equipment from neuroConn GmbH, Ilmenau, Germany, and Mag&More GmbH and Brainsway Inc., Jerusalem, Israel. The other authors declare no competing interests., (© 2022 The Author(s).)

Introduction: In order to identify more refined dimensions of social-communication impairments in autism spectrum disorder (ASD) a previous study applied exploratory and confirmatory factor analyses to diagnostic algorithm scores of the autism diagnostic observation schedule (ADOS), Module 3. A three-factor model consisting of repetitive behaviors, impairments in 'Basic Social-Communication' and in 'Interaction quality' (IQ) was established and confirmed. The current study aimed to replicate this model in an independent sample. To advance our understanding of the latent structure of social communication deficits, previous work was complemented by a probabilistic approach., Methods: Participants ( N  = 1363) included verbally fluent children and young adults, diagnosed as ASD or non-ASD based on "gold standard" best-estimate clinical diagnosis. Confirmatory factor analysis examined the factor structure of algorithm items from the ADOS Module 3 and correlations with individual characteristics (cognitive abilities, age) were analyzed. Linear Regressions were used to test the contribution of each latent factor to the prediction of an ASD diagnosis. To tackle large inter-correlations of the latent factors, a Bayesian exploratory factor analysis (BEFA) was applied., Results: Results confirmed the previously reported observation of three latent dimensions in the ADOS algorithm reflecting 'Restricted, Repetitive Behaviors', 'Basic Social-Communication' behaviors and 'Interaction Quality'. All three dimensions contributed independently and additively to the prediction of an ASD diagnosis., Conclusion: By replicating previous findings in a large clinical sample our results contribute to further conceptualize the social-communication impairments in ASD as two dimensional., Competing Interests: The authors have declared that they have no competing or potential conflicts of interest., (© 2022 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Autism spectrum disorder (ASD) is characterized as a very heterogeneous child-onset disorder, whose heterogeneity is partly determined by differences in intelligence quotient (IQ). Older epidemiological studies suggested that the IQ-related spectrum tends to be skewed to the left, i.e., a larger proportion of individuals with ASD have below average intelligence, while only few individuals with ASD may have an IQ above average. This picture changed over time with broadening the spectrum view. Within the present perspective article, we discuss discrepancies in IQ profiles between epidemiological and clinical studies and identify potential underlying aspects, for example, the influence of external factors such as sample biases or differences in availability of autism health services. Additionally, we discuss the validity and reciprocal influences of ASD diagnostics and IQ measurement. We put the impact of these factors for diagnostic as well as care and support situations of patients into perspective and want to encourage further research to contribute to the conceptualization of "autism" more comprehensively including the IQ as well as to examine broader (life) circumstances, interacting factors and diagnostic requirements of given diagnoses in childhood as compared to adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wolff, Stroth, Kamp-Becker, Roepke and Roessner.)

Background: Although autism spectrum disorder (ASD) is a common developmental disorder, our knowledge about a behavioral and neurobiological female phenotype is still scarce. As the conceptualization and understanding of ASD are mainly based on the investigation of male individuals, females with ASD may not be adequately identified by routine clinical diagnostics. The present machine learning approach aimed to identify diagnostic information from the Autism Diagnostic Observation Schedule (ADOS) that discriminates best between ASD and non-ASD in females and males., Methods: Random forests (RF) were used to discover patterns of symptoms in diagnostic data from the ADOS (modules 3 and 4) in 1057 participants with ASD (18.1% female) and 1230 participants with non-ASD (17.9% % female). Predictive performances of reduced feature models were explored and compared between females and males without intellectual disabilities., Results: Reduced feature models relied on considerably fewer features from the ADOS in females compared to males, while still yielding similar classification performance (e.g., sensitivity, specificity)., Limitations: As in previous studies, the current sample of females with ASD is smaller than the male sample and thus, females may still be underrepresented, limiting the statistical power to detect small to moderate effects., Conclusion: Our results do not suggest the need for new or altered diagnostic algorithms for females with ASD. Although we identified some phenotypic differences between females and males, the existing diagnostic tools seem to sufficiently capture the core autistic features in both groups., (© 2022. The Author(s).)

Objective: Although autism spectrum disorder (ASD) is a relatively common, well-known but heterogeneous neuropsychiatric disorder, specific knowledge about characteristics of this heterogeneity is scarce. There is consensus that IQ contributes to this heterogeneity as well as complicates diagnostics and treatment planning. In this study, we assessed the accuracy of the Autism Diagnostic Observation Schedule (ADOS/2) in the whole and IQ-defined subsamples, and analyzed if the ADOS/2 accuracy may be increased by the application of machine learning (ML) algorithms that processed additional information including the IQ level., Methods: The study included 1,084 individuals: 440 individuals with ASD (with a mean IQ level of 3.3 ± 1.5) and 644 individuals without ASD (with a mean IQ level of 3.2 ± 1.2). We applied and analyzed Random Forest (RF) and Decision Tree (DT) to the ADOS/2 data, compared their accuracy to ADOS/2 cutoff algorithms, and examined most relevant items to distinguish between ASD and Non-ASD. In sum, we included 49 individual features, independently of the applied ADOS module., Results: In DT analyses, we observed that for the decision ASD/Non-ASD, solely one to four items are sufficient to differentiate between groups with high accuracy. In addition, in sub-cohorts of individuals with (a) below (IQ level ≥4)/ID and (b) above average intelligence (IQ level ≤ 2), the ADOS/2 cutoff showed reduced accuracy. This reduced accuracy results in (a) a three times higher risk of false-positive diagnoses or (b) a 1.7 higher risk for false-negative diagnoses; both errors could be significantly decreased by the application of the alternative ML algorithms., Conclusions: Using ML algorithms showed that a small set of ADOS/2 items could help clinicians to more accurately detect ASD in clinical practice across all IQ levels and to increase diagnostic accuracy especially in individuals with below and above average IQ level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wolff, Eberlein, Stroth, Poustka, Roepke, Kamp-Becker and Roessner.)

Background: Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. As intranasal oxytocin has been shown to modulate activation of the brain's reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties., Methods: In this randomized, double-blind, placebo-controlled, crossover functional magnetic resonance imaging study, we examined effects of a 24-IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards., Results: Nonsignificant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo., Conclusions: Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD., (© 2021 The Authors.)

Diagnosing autism spectrum disorder (ASD) requires extensive clinical expertise and training as well as a focus on differential diagnoses. The diagnostic process is particularly complex given symptom overlap with other mental disorders and high rates of co-occurring physical and mental health concerns. The aim of this study was to conduct a data-driven selection of the most relevant diagnostic information collected from a behavior observation and an anamnestic interview in two clinical samples of children/younger adolescents and adolescents/adults with suspected ASD. Via random forests, the present study discovered patterns of symptoms in the diagnostic data of 2310 participants (46% ASD, 54% non-ASD, age range 4-72 years) using data from the combined Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) and ADOS data alone. Classifiers built on reduced subsets of diagnostic features yield satisfactory sensitivity and specificity values. For adolescents/adults specificity values were lower compared to those for children/younger adolescents. The models including ADOS and ADI-R data were mainly built on ADOS items and in the adolescent/adult sample the classifier including only ADOS items performed even better than the classifier including information from both instruments. Results suggest that reduced subsets of ADOS and ADI-R items may suffice to effectively differentiate ASD from other mental disorders. The imbalance of ADOS and ADI-R items included in the models leads to the assumption that, particularly in adolescents and adults, the ADI-R may play a lesser role than current behavior observations., Competing Interests: LP has received payment for consulting or speaking fees from Shire, Takeda, Roche, and InfectoPharm. She receives research funding from the BMBF, DFG, and EU and royalties from Hogrefe, Kohlhammer and Schattauer. VR has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals, lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma, and support for research from Shire Pharmaceuticals and Novartis. He has carried out clinical trials in cooperation with the Novartis, Shire, Servier, and Otsuka companies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kamp-Becker, Tauscher, Wolff, Küpper, Poustka, Roepke, Roessner, Heider and Stroth.)

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD. However, evidence linking oxytocin treatment to social behavior and brain function in ASD is limited and heterogeneous effects might depend on variations in the oxytocin-receptor gene (OXTR). We examined 25 male ASD patients without intellectual disability in a double-blind, cross-over, placebo-controlled fMRI-protocol, in which a single dose of oxytocin or placebo was applied intranasally. Patients performed three experiments in the MRI examining empathy for other's physical pain, basic emotions, and social pain. All participants were genotyped for the rs53576 single-nucleotide polymorphism of the OXTR. Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli. Other than that, there were no effects of oxytocin treatment. OXTR genotype did not significantly interact with oxytocin treatment. Our results contribute to the growing body of empirical literature suggesting heterogenous effects of oxytocin administration in ASD. To draw clinically relevant conclusions regarding the usefulness of oxytocin treatment, however, empirical studies need to consider methods of delivery, dose, and moderating individual factors more carefully in larger samples., (© 2021. The Author(s).)

Background: Diagnosing autism spectrum disorder (ASD) is complex and time-consuming. The present work systematically examines the importance of items from the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) in discerning children with and without ASD. Knowledge of the most discriminative features and their underlying concepts may prove valuable for the future training tools that assist clinicians to substantiate or extenuate a suspicion of ASD in nonverbal and minimally verbal children., Methods: In two samples of nonverbal ( N  = 466) and minimally verbal ( N  = 566) children with ASD ( N  = 509) and other mental disorders or developmental delays ( N  = 523), we applied random forests (RFs) to (i) the combination of ADI-R and ADOS data versus (ii) ADOS data alone. We compared the predictive performance of reduced feature models against outcomes provided by models containing all features., Results: For nonverbal children, the RF classifier indicated social orientation to be most powerful in differentiating ASD from non-ASD cases. In minimally verbal children, we find language/speech peculiarities in combination with facial/nonverbal expressions and reciprocity to be most distinctive., Conclusion: Based on machine learning strategies, we carve out those symptoms of ASD that prove to be central for the differentiation of ASD cases from those with other developmental or mental disorders (high specificity in minimally verbal children). These core concepts ought to be considered in the future training tools for clinicians., Competing Interests: Prof. Dr. Poustka has received payment for consulting or speaking fees from Shire, Takeda, Roche,and InfectoPharm. She receives research funding from the BMBF, DFG, and EU and royalties from Hogrefe, Kohlhammer, and Schattauer. Prof. Dr. Roessner has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals; lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma; and support for research from Shire Pharmaceuticals and Novartis. He has carried out clinical trials in cooperation with the Novartis, Shire, Servier, and Otsuka companies. The remaining authors declare no potential conflict of interest., (© 2021 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: In total numbers, Germany has faced the largest number of refugees and asylum seekers (RAS) in Europe in the past decade. Although a considerable proportion have experienced traumatic and stressful life events, there is no systematic review to date examining the prevalence of depressive symptoms and post-traumatic stress disorder (PTSD) symptoms in RAS in Germany., Aims: To calculate the prevalence of depressive symptoms and PTSD symptoms in the general population of RAS living in Germany after the year 2000 and explore the impact of study- and participant-related characteristics on prevalence estimates., Method: We systematically searched PubMed, CINAHL, PsycINFO, PSYNDEX, Academic Search Complete, Science Direct and Web of Science from January 2000 to May 2020 to identify articles reporting prevalence of depressive symptoms and PTSD in RAS in Germany (PROSPERO registration number: CRD42020182796)., Results: In total, 31 different surveys met inclusion criteria with 20 surveys reporting prevalence estimates of depressive symptoms and 25 surveys symptoms of PTSD. Based on screening tools, the pooled prevalence estimate of PTSD symptoms was 29.9% (95% CI 20.8-38.7%) and of depressive symptoms 39.8% (95% CI 29.8-50.1%). Heterogeneity was large within and between subgroups. In multivariate meta-regressions on depressive symptoms, heterogeneity was largely explained by survey period, length of field period and study quality., Conclusions: Prevalence rates of depressive symptoms and PTSD symptoms in RAS are notably large. They exceed the prevalence in the general German population. As a result of high heterogeneity, however, pooled prevalence rates should be interpreted with caution.

Background: Previous case-control studies of autistic spectrum disorder (ASD) have identified altered brain structure such as altered frontal and temporal cortex volumes, or decreased fractional anisotropy (FA) within the inferior fronto-occipital fasciculus in patients. It remains unclear whether subclinical autistic-like traits might also be related to variation in these brain structures., Methods: In this study, we analyzed magnetic resonance imaging (MRI) data of 250 psychiatrically healthy subjects phenotyped for subclinical autistic-like traits using the Autism Spectrum Quotient (AQ). For data analysis, we used voxel-based morphometry of T1-MRIs (Computational Anatomy Toolbox) and tract-based spatial statistics for diffusion tensor imaging data., Results: AQ attention switching subscale correlated negatively with FA values in the bilateral uncinate fasciculus as well as the bilateral inferior fronto-occipital fasciculus. Higher AQ attention switching subscale scores were associated with increased mean diffusivity and radial diffusivity values in the uncinate fasciculus, while axial diffusivity values within this tract show a negative correlation. AQ attention to detail subscale correlated positively with gray matter volume in the right pre- and postcentral gyrus., Conclusions: We demonstrate that individuals with higher levels of autism-spectrum-like features show decreased white matter integrity in tracts associated with higher-level visual processing and increased cortical volume in areas linked to movement sequencing and working memory. Our results resemble regional brain structure alterations found in individuals with ASD. This offers opportunities to further understand the etiology and pathogenesis of the disorder and shows a subclinical continuum perspective.

Face processing is mediated by a distributed neural network commonly divided into a "core system" and an "extended system." The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area, VWFA) and the FFA for common neural resources. In the present pilot study, we assessed the neural face processing network in 12 children (aged 7-9 years) and 10 adults with functional magnetic resonance imaging (fMRI). The hemispheric lateralization of the core face regions was compared between both groups. The study had two goals: First, we aimed to establish an fMRI paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level. Second, we planned to collect data for a power analysis to calculate the necessary group size for a large-scale cross-sectional imaging study assessing the ontogenetic development of the lateralization of the face processing network, with focus on the FFA. It was possible to detect brain activity in the core system of 75% of children at the single subject level. The average scan-to-scan motion of the included children was comparable to adults, ruling out that potential activation differences between groups are caused by unequal motion artifacts. Hemispheric lateralization of the FFA was 0.07 ± 0.48 in children (indicating bilateral activation) and -0.32 ± 0.52 in adults (indicating right-hemispheric dominance). These results thus showed, as expected, a trend for increased lateralization in adults. The estimated effect size for the FFA lateralization difference was d = 0.78 (indicating medium to large effects). An adequately powered follow-up study (sensitivity 0.8) testing developmental changes of FFA lateralization would therefore require the inclusion of 18 children and 26 adults., (Copyright © 2020 Hildesheim, Debus, Kessler, Thome, Zimmermann, Steinsträter, Sommer, Kamp-Becker, Stark and Jansen.)

Diagnosing autism spectrum disorders (ASD) is a complicated, time-consuming process which is particularly challenging in older individuals. One of the most widely used behavioral diagnostic tools is the Autism Diagnostic Observation Schedule (ADOS). Previous work using machine learning techniques suggested that ASD detection in children can be achieved with substantially fewer items than the original ADOS. Here, we expand on this work with a specific focus on adolescents and adults as assessed with the ADOS Module 4. We used a machine learning algorithm (support vector machine) to examine whether ASD detection can be improved by identifying a subset of behavioral features from the ADOS Module 4 in a routine clinical sample of N = 673 high-functioning adolescents and adults with ASD (n = 385) and individuals with suspected ASD but other best-estimate or no psychiatric diagnoses (n = 288). We identified reduced subsets of 5 behavioral features for the whole sample as well as age subgroups (adolescents vs. adults) that showed good specificity and sensitivity and reached performance close to that of the existing ADOS algorithm and the full ADOS, with no significant differences in overall performance. These results may help to improve the complicated diagnostic process of ASD by encouraging future efforts to develop novel diagnostic instruments for ASD detection based on the identified constructs as well as aiding clinicians in the difficult question of differential diagnosis.

Objective: Despite the fact that autism spectrum disorder (ASD) is a common psychiatric diagnosis, knowledge about the special behavioral and neurobiological female phenotype is still scarce. The present study aimed to investigate neural correlates of empathy for physical and social pain and to assess the impact of egocentric perspective taking on social pain empathy in complex social situations in women and girls with ASD. Methods: Nine female individuals with high functioning ASD were compared to nine matched peers without ASD during two functional magnetic resonance imaging (fMRI) experiments, examining empathy for physical and social pain using well-established paradigms. Participants viewed multiple pictorial stimuli depicting a social target in either physically painful or socially unpleasant situations. In the social situations, the participant either shared the social target's knowledge about the inappropriateness of the situation (observed social target is aware about the embarrassment of the situation; e.g., tripping in public) or not (observed social target is unaware about the embarrassment of the situation; e.g., open zipper). Results: Females with ASD did not rate the physical pain stimuli differently from non-clinical controls. Social pain situations, however, posed a greater challenge to females with ASD: For non-shared knowledge situations, females with ASD rated the social target's embarrassment as more intense. Thus, compared to non-clinical controls, females with ASD had a stronger egocentric perspective of the situation rather than sharing the social target's perspective. On the neural systems level, both groups showed activation of areas of the so-called empathy network that was attenuated in females with ASD during empathy for physical and social pain with a particular reduction in insula activation. Conclusion: Females with high functioning ASD are able to share another person's physical or social pain on the neural systems level. However, hypoactivation of the anterior insula in contrast to individuals without ASD suggests that they are less able to rely on their shared representations of emotions along with difficulties to take over a person's perspective and to make a clear distinction between their own and someone else's experience of embarrassment.

Background: Early identification of autism spectrum disorders (ASD) is a prerequisite for access to early interventions. Although parents often note developmental atypicalities during the first 2 years of life, many children with ASD are not diagnosed until school age. For parents, the long period between first parental concerns and diagnosis is often frustrating and accompanied by uncertainty and worry., Methods: This study retrospectively explored the trajectories of children with a confirmed ASD diagnosis during the diagnostic process, from first parental concerns about their child's development until the definite diagnosis. A survey concerning the diagnostic process was distributed to parents or legal guardians of children with ASD from three specialized ASD outpatient clinics in Germany., Results: The response rate was 36.9%, and the final sample consisted of carers of 207 affected children (83.6% male, mean age 12.9 years). The children had been diagnosed with childhood autism (55.6%), Asperger syndrome (24.2%), or atypical autism (20.3%). On average, parents had first concerns when their child was 23.4 months old, and an ASD diagnosis was established at a mean age of 78.5 months. Children with atypical autism or Asperger syndrome were diagnosed significantly later (83.9 and 98.1 months, respectively) than children with childhood autism (68.1 months). Children with an IQ < 85 were diagnosed much earlier than those with an IQ ≥ 85. On average, parents visited 3.4 different health professionals (SD = 2.4, range 1-20, median: 3.0) until their child received a definite ASD diagnosis. Overall, 38.5% of carers were satisfied with the diagnostic process., Conclusions: In this sample of children with ASD in Germany, the time to diagnosis was higher than in the majority of other comparable studies. These results flag the need for improved forms of service provision and delivery for suspected cases of ASD in Germany., Competing Interests: The authors declare that they have no competing interests.