Using machine learning to improve diagnostic assessment of ASD in the light of specific differential and co-occurring diagnoses.

BACKGROUND: Diagnostic assessment of ASD requires substantial clinical experience and is particularly difficult in the context of other disorders with behavioral symptoms in the domain of social interaction and communication. Observation measures such as the Autism Diagnostic Observation Schedule (ADOS) do not take into account such co-occurring disorders. METHOD: We used a well-characterized clinical sample of individuals (n = 1,251) that had received detailed outpatient evaluation for the presence of an ASD diagnosis (n = 481) and covered a range of additional overlapping diagnoses, including anxiety-related disorders (ANX, n = 122), ADHD (n = 439), and conduct disorder (CD, n = 194). We focused on ADOS module 3, covering the age range with particular high prevalence of such differential diagnoses. We used machine learning (ML) and trained random forest models on ADOS single item scores to predict a clinical best-estimate diagnosis of ASD in the context of these differential diagnoses (ASD vs. ANX, ASD vs. ADHD, ASD vs. CD), in the context of co-occurring ADHD, and an unspecific model using all available data. We employed nested cross-validation for an unbiased estimate of classification performance and made available a Webapp to showcase the results and feasibility for translation into clinical practice. RESULTS: We obtained very good overall sensitivity (0.89-0.94) and specificity (0.87-0.89). In particular for individuals with less severe symptoms, our models showed increases of up to 35% in sensitivity or specificity. Furthermore, we analyzed item importance profiles of the ANX, ADHD, and CD models in comparison with the unspecific model revealing distinct patterns of importance for specific ADOS items with respect to differential diagnoses. CONCLUSIONS: ML-based diagnostic classification may improve clinical decisions by utilizing the full range of information from detailed diagnostic observation instruments such as the ADOS. Importantly, this strategy might be of particular relevance for older children with less severe symptoms for whom the diagnostic decision is often particularly difficult.

Real-life self-control conflicts in anorexia nervosa: An ecological momentary assessment investigation.

BACKGROUND: Individuals with anorexia nervosa (AN) are often thought to show heightened self-control and increased ability to inhibit desires. In addition to inhibitory self-control, antecedent-focused strategies (e.g., cognitive reconstrual-the re-evaluation of tempting situations) might contribute to disorder maintenance and enable disorder-typical, maladaptive behaviors. METHODS: Over a period of 14 days, 40 acutely underweight young female patients with anorexia nervosa (AN) and 40 healthy control (HC) participants reported their affect and behavior in self-control situations via ecological momentary assessment during inpatient treatment (AN) and everyday life (HC). Data were analyzed via hierarchical analyses (linear and logistic modeling). RESULTS: Conflict strength had a significantly lower impact on self-control success in AN compared to HC. While AN and HC did not generally differ in the number or strength of self-control conflicts or in the percentage of self-control success, AN reported self-controlled behavior to be less dependent on conflict strength. CONCLUSIONS: While patients with AN were not generally more successful at self-control, they appeared to resolve self-control conflicts more effectively. These findings suggest that the magnitude of self-control conflicts has comparatively little impact on individuals with AN, possibly due to the use of antecedent-focused strategies. If confirmed, cognitive-behavioral therapy might focus on and help patients to exploit these alternative self-control strategies in the battle against their illness.

Health Services Use and Costs in Individuals with Autism Spectrum Disorder in Germany: Results from a Survey in ASD Outpatient Clinics.

Autism spectrum disorders (ASD) are associated with high services use, but European data on costs are scarce. 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. 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. 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.

Hair-Based Assessment of Sex Steroid Hormones in Patients with Anorexia Nervosa.

Anorexia nervosa (AN) is a complex psychiatric disorder accompanied by a variety of endocrine effects. Altered levels of the sex steroid hormones progesterone and dehydroepiandrosterone (DHEA) have been shown to occur in patients with AN using short-term hormonal measurement methods based on blood, saliva, and urine samples. However, since sex steroid hormone levels fluctuate during the menstrual cycle, these measurement methods require a great deal of effort due to the need to collect multiple samples in order to correctly determine the basal level of sex hormones. In contrast, hair-based assessments provide a marker of accumulated longer-term hormone exposure using a single, non-invasive sample. The aim of this study was to investigate sex steroid hormone levels via hair-based assessments in acutely underweight AN in comparison with healthy, age-matched, female control participants. Additionally, we compared progesterone and DHEA hair levels longitudinally during inpatient treatment in AN. Collected hair samples were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) to determine a monthly hormone level of progesterone and DHEA. Our results indicate that DHEA hair hormone levels were similar across groups but progesterone was suppressed in underweight AN compared with healthy controls. In the longitudinal design, no significant change in hair hormone levels during partial weight restoration in patients with AN was observed. Our findings suggest that hair analysis can be used to detect suppressed progesterone levels in severe AN, and that progesterone does not increase during short-term weight restoration.

The costs of over-control in anorexia nervosa: evidence from fMRI and ecological momentary assessment.

A growing body of evidence suggests that a high level of self-control may, despite its positive effects, influence cognitive processing in an unfavorable manner. However, the affective costs of self-control have only rarely been investigated. Anorexia nervosa (AN) is an eating disorder that is often characterized by excessive self-control. Here, we used fMRI to explore whether over-control in AN may have negative affective consequences. 36 predominantly adolescent female AN patients and 36 age-matched healthy controls (HC) viewed negative and neutral pictures during two separate fMRI sessions before and after 10 min of rest. We tested whether abnormally elevated neural activity during the initial presentation in a brain region broadly implicated in top-down control, the dorsolateral prefrontal cortex (dlPFC), could predict subsequent activation in limbic areas relevant to bottom-up affective processing. Using ecological momentary assessment (EMA), we also tested for associations between the aforementioned neuroimaging markers and negative affective states in the two weeks following the experiment. fMRI data revealed that higher initial activation of the dlPFC in AN predicted increased amygdala reactivity during the second fMRI session, which in turn was related to increased self-reported tension during two weeks following the scan. These data suggest that over-control in AN patients may come at a cost including negative affective states on a short (minutes) as well as a longer time scale (days). This mechanism may significantly contribute to the persistence of AN.

Study protocol of the multi-centre, randomised controlled trial of the Frankfurt Early Intervention Programme A-FFIP versus early intervention as usual for toddlers and preschool children with Autism Spectrum Disorder (A-FFIP study).

BACKGROUND: Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored. METHODS/DESIGN: A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP: 67, EIAU: 67) aged 24-66 months at baseline assessment meeting the criteria for ASD (DSM-5) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored. DISCUSSION: If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula. TRIAL REGISTRATION: German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS); ID: 00016330. Retrospectively registered on 4 January 2019. URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016330.

Affective dysregulation in childhood - optimizing prevention and treatment: protocol of three randomized controlled trials in the ADOPT study.

BACKGROUND: The terms affective dysregulation (AD) and irritability describe transdiagnostic dimensions and are characterized by an excessive reactivity to negative emotional stimuli with an affective (anger) and a behavioral component (aggression). Due to early onset, high prevalence and persistence, as well as developmental comorbidity, AD in childhood is one of the most psychosocially impairing and cost-intensive mental health conditions. AD is especially prevalent in children in the youth welfare service. Despite continuous research, there remains a substantial need for diagnostic approaches and optimization of individualized treatment strategies in order to improve outcomes and reduce the subjective and economic burden. METHODS: The ADOPT (Affective Dysregulation - Optimizing Prevention and Treatment) Consortium integrates internationally established, highly experienced and interdisciplinary research groups. The work program encompasses (a) epidemiology, including prevalence of symptoms and disorders, (b) development and evaluation of screening and assessment tools, (c) stepped care approaches for clinically useful personalized medicine, (d) evaluation of an easily accessible and cost-effective online intervention as indicated prevention (treatment effects, moderation/mediation analysis), and (e) evaluation of an intensive personalized modular outpatient treatment in a cohort of children with AD who live with their parents and in a cohort of children with AD who live in out-of-home care (treatment effects, moderation/mediation analysis). DISCUSSION: The results will lead to significant recommendations for improving treatment within routine clinical care in two cohorts of children with AD and coexisting conditions, especially oppositional-defiant disorder, conduct disorder and disruptive mood dysregulation disorder. TRIAL REGISTRATION: Trial registration ADOPT Online: German Clinical Trials Register (DRKS) DRKS00014963 . Registered 27 June 2018. Trial registration ADOPT Treatment: German Clinical Trials Register (DRKS) DRKS00013317 . Registered 27 September 2018. Trial registration ADOPT Institution: German Clinical Trials Register (DRKS) DRKS00014581 . Registered 04 July 2018.

The real-life costs of emotion regulation in anorexia nervosa: a combined ecological momentary assessment and fMRI study.

Regulation of emotions is necessary for successful attainment of short-term and long-term goals. However, over-regulation may also have its costs. In anorexia nervosa (AN), forgoing food intake despite emaciation and endocrine signals that promote eating is an example of "too much" self-control. Here we investigated whether voluntary emotion regulation in AN patients comes with associated disorder-relevant costs. Thirty-five patients with acute AN and thirty-five age-matched healthy controls (HCs) performed an established emotion regulation paradigm during functional magnetic resonance imaging after an overnight fast. The task required reducing emotions induced by positively valenced pictures via distancing. We calculated a neural regulation score from responses recorded in a reward-related brain region of interest (ventral striatum; VS) by subtracting activation measured on "positive distance" trials from that elicited under the "positive watch" (baseline) condition. Complementing the imaging data, we used ecological momentary assessment (EMA) to probe disorder-related rumination and affect six times/day for 2 weeks following the scanning session. The neural regulation score indicating reduced VS activation during emotion regulation was used as a predictor in hierarchical linear models with EMA measures as outcomes. No group differences in neural activity were found for the main contrasts of the task. However, regulation of VS activity was associated with increased body-related rumination and increased negative affect in AN, but not in HC. In line with this finding, correlational analysis with longitudinal BMI measurements revealed a link between greater VS regulation and poorer treatment outcome after 60 and 90 days. Together, these results identify a neural correlate of altered emotion regulation in AN, which seems to be detrimental to psychological well-being and may interfere with recovery.

May Functional Imaging be Helpful for Behavioral Assessment in Children? Regions of Motor and Associative Cortico-Subcortical Circuits Can be Differentiated by Laterality and Rostrality.

BACKGROUND: Cortico-subcortical circuits are organized into the sensorimotor, associative, and limbic loop. These neuronal preconditions play an important role regarding the understanding and treatment of behavioral problems in children. Differencing evidence argues for a lateralized organization of the sensorimotor loop and a bilateral (i.e., non-lateralized) organization of the associative loop. However, a firm behavioral-neurobiological distinction of these circuits has been difficult, specifically in children. OBJECTIVES: Thus, the aim was a comprehensive functional visualization and differentiation of the sensorimotor and the associative circuit during childhood. As a new approach, laterality and rostrality features were used to distinguish between the two circuits within one single motor task. METHODS: Twenty-four healthy boys performed self-paced index finger tapping with each hand separately during functional magnetic resonance imaging at 3 Tesla. RESULTS: A contrast analysis for left against right hand movement revealed lateralized activation in typical sensorimotor regions such as primary sensorimotor cortex, caudal supplementary motor area (SMA), caudal putamen, and thalamus. A conjunction analysis confirmed bilateral involvement of known associative regions including pre-SMA, rostral SMA, and rostral putamen. CONCLUSION: A functional visualization of two distinct corticostriatal circuits is provided in childhood. Both the sensorimotor and associative circuit may be discriminated by their laterality characteristics already in minors. Additionally, the results support the concept of a modified functional subdivision of the SMA in a rostral (associative) and caudal (motor) part. A further development of this approach might help to nurture behavioral assessment and neurofeedback training in child mental health.

Variability of single trial brain activation predicts fluctuations in reaction time.

Brain activation stability is crucial to understanding attention lapses. EEG methods could provide excellent markers to assess neuronal response variability with respect to temporal (intertrial coherence) and spatial variability (topographic consistency) as well as variations in activation intensity (low frequency variability of single trial global field power). We calculated intertrial coherence, topographic consistency and low frequency amplitude variability during target P300 in a continuous performance test in 263 15-year-olds from a cohort with psychosocial and biological risk factors. Topographic consistency and low frequency amplitude variability predicted reaction time fluctuations (RTSD) in a linear model. Higher RTSD was only associated with higher psychosocial adversity in the presence of the homozygous 6R-10R dopamine transporter haplotype. We propose that topographic variability of single trial P300 reflects noise as well as variability in evoked cortical activation patterns. Dopaminergic neuromodulation interacted with environmental and biological risk factors to predict behavioural reaction time variability.

Trends in psychopharmacologic treatment of tic disorders in children and adolescents in Germany.

Data on medical treatment of children and adolescents with tic disorders are scarce. This study examined the administrative prevalence of psychopharmacological prescriptions in this patient group in Germany. Data of the largest German health insurance fund were analysed. In outpatients aged 0-19 years with diagnosed tic disorder, psychotropic prescriptions were evaluated for the years 2006 and 2011. In 2011, the percentage of psychotropic prescriptions was slightly higher than in 2006 (21.2 vs. 18.6%). The highest prescription prevalence was found in Tourette syndrome (51.5 and 53.0%, respectively). ADHD drugs were most frequently prescribed, followed by antipsychotics. In 2011, prescriptions of second generation antipsychotics (SGA) were higher and prescriptions of first generation antipsychotics (FGA) lower than in 2006. Concerning prescribed antipsychotic substances, in 2011 risperidone prescriptions were higher and tiapride prescriptions lower. Paediatricians issued 37.4%, and child and adolescent psychiatrists issued 37.1% of psychotropic prescriptions. The FGA/SGA ratio was highest in GPs (1.25) and lowest in child and adolescent psychiatrists (0.96). From 2006 to 2011, there was only a slight increase in psychotropic prescriptions for children and adolescents with a diagnosis of tic disorder in Germany, which stands in contrast towards the significant increase in psychotropic prescriptions in other child and adolescent psychiatric disorders (e.g. ADHD). There were marked differences in treatment patterns by tic disorder subgroups, with Tourette syndrome patients receiving most frequently psychopharmacotherapy. Risperidone prescriptions increased, probably reflecting a switch in prescribing practice towards up-to-date treatment guidelines. In primary care physicians, dissemination of current tic disorder treatment guidelines might constitute an important educational goal.

Multicultural assessment of child and adolescent psychopathology with ASEBA and SDQ instruments: research findings, applications, and future directions.

Around the world, cultural blending and conflict pose challenges for assessment and understanding of psychopathology. Economical, evidence-based, culturally robust assessment is needed for research, for answering public health questions, and for evaluating immigrant, refugee, and minority children. This article applies multicultural perspectives to behavioral, emotional, and social problems assessed on dimensions describing children's functioning, as rated by parents, teachers, children, and others. The development of Achenbach System of Empirically Based Assessment (ASEBA) and Strengths and Difficulties Questionnaire (SDQ) forms and their applications to multicultural research are presented. A primary aim of both questionnaires is to identify children at high risk of psychiatric disorders and who therefore warrant further assessment. The forms are self-administered or administered by lay interviewers. ASEBA problem items are scored on 6 DSM-oriented scales and 3 broader band scales, plus 8 syndromes derived statistically as taxonomic constructs and supported by uniform confirmatory factor analyses of samples from many populations. Comparisons of ASEBA scale scores, psychometrics, and correlates are available for diverse populations. SDQ forms are scored on one broad-band scale and 5 a priori behavioral dimensions supported by data from various populations. For both instruments, factor analyses, psychometrics, and correlates are available for diverse populations. The willingness and ability of hundreds of thousands of respondents from diverse groups to complete ASEBA and SDQ forms support this approach to multicultural assessment. Although particular items and scales may have differential relevance among groups and additional assessment procedures are needed, comparable results are found in many populations. Scale scores vary more within than between populations, and distributions of scores overlap greatly among different populations. Ratings of children's problems thus indicate more heterogeneity within populations than distinctiveness between populations. Norms from multiple populations can be used to compare children's scores with relevant peer groups. Multicultural dimensional research can advance knowledge by diversifying normative data; by comparing immigrant children with nonimmigrant compatriots and with host country children; by identifying outlier findings for elucidation by emic research; and by fostering efforts to dimensionalize DSM-V diagnostic criteria.