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Abstract Background The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). Results Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

Abstract Background Individuals with autism spectrum disorders (ASDs) often display symptoms from other diagnostic categories. Studies of clinical and psychosocial outcome in adult patients with ASDs without concomitant intellectual disability are few. The objective of this paper is to describe the clinical psychiatric presentation and important outcome measures of a large group of normal-intelligence adult patients with ASDs. Methods Autistic symptomatology according to the DSM-IV-criteria and the Gillberg & Gillberg research criteria, patterns of comorbid psychopathology and psychosocial outcome were assessed in 122 consecutively referred adults with normal intelligence ASDs. The subjects consisted of 5 patients with autistic disorder (AD), 67 with Asperger's disorder (AS) and 50 with pervasive developmental disorder not otherwise specified (PDD NOS). This study group consists of subjects pooled from two studies with highly similar protocols, all seen on an outpatient basis by one of three clinicians. Results Core autistic symptoms were highly prevalent in all ASD subgroups. Though AD subjects had the most pervasive problems, restrictions in non-verbal communication were common across all three subgroups and, contrary to current DSM criteria, so were verbal communication deficits. Lifetime psychiatric axis I comorbidity was very common, most notably mood and anxiety disorders, but also ADHD and psychotic disorders. The frequency of these diagnoses did not differ between the ASD subgroups or between males and females. Antisocial personality disorder and substance abuse were more common in the PDD NOS group. Of all subjects, few led an independent life and very few had ever had a long-term relationship. Female subjects more often reported having been bullied at school than male subjects. Conclusion ASDs are clinical syndromes characterized by impaired social interaction and non-verbal communication in adulthood as well as in childhood. They also carry a high risk for co-existing mental health problems from a broad spectrum of disorders and for unfavourable psychosocial life circumstances. For the next revision of DSM, our findings especially stress the importance of careful examination of the exclusion criterion for adult patients with ASDs.

Aim: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung., Methods: A qualitative survey derived and adapted from Kotlicka-Antczak et al. (2020) was conducted in large early detection services of three Swiss cantons (Geneva, Basel-Stadt, Vaud) focusing on pathways to care. More specifically, using questionnaires delivered to the heads of participating services, information was collected on referral sources, on activities to implement outreach campaigns and on the use of a pre-screening tool., Results: Main results on referral source indicated that sources were variable but seemed to come primarily from the medical sector and more so from the psychiatric sector. Very few referrals came from non-medical sectors. Outreach activities included the contact to other clinics as well as through brochures and posters. All services but one used the Prodromal Questionnaire - 16 as pre-screening tool., Conclusions: All in all, the results indicate a referral and care pathway system implemented mostly within the medical and particularly mental health sector. Accordingly, the PsyYoung project proposes a procedure for pathways to care which could help overcome the obstacle of referrals being restrained to a narrow field of mental health and to harmonize the referral process within services dedicated to the same aim of helping young people at high risk of developing a psychosis., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Introduction: Clinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population., Method: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis., Results: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c=0.51). Retraining resulted in moderate discrimination (Harrel's c=0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0-23.1%) over two years., Conclusion: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention., (Copyright © 2024 The Author(s). Published by Elsevier España S.L.U. All rights reserved.)

The Autism Behavior Coding System (ABCS) was developed to help evaluating the effectiveness of early intensive interventions in children with autism spectrum disorder (ASD). The video-based ABCS assesses eight core autistic behavioral variables during therapist-child interaction using standardized quantitative criteria, four behaviors according to their frequency of occurrence, four according to their duration. The present study focuses (1) on the correspondence of ABCS scores with scores on two standard clinical instruments (the ADOS-2 and an ASD-adaptation of the Children's Global Assessment Scale, DD-CGAS), (2) on the sensitivity to change of ABCS scores by the end of an intensive 18 days intervention period (EIP) and (c) on the predictability of short- and longer-term changes in social and repetitive behaviors from ABCS scores at baseline and EIP. Data from 51 children (42 M, 9 F; median age 45 months) followed over 1 year were available. There were significant correlations at baseline between several ABCS scores and ADOS-2 as well as DD-CGAS scores. Correlations at EIP between some ABCS and DD-CGAS scores were highly significant. Four ABCS scores reflected significant changes from baseline to EIP. Several baseline ABCS scores were predictive of DD-CGAS and ADOS-2 scores at EIP and Year 1. However, associations between ABCS score changes from baseline to EIP and the clinical scale changes by Year 1 were not significant. It is concluded that several ABCS scores have adequate clinical validity and sensitivity to change. The short-term changes in ABCS scores and their relationship to longer-term clinical changes need further study., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Distinct empathy deficits are often described in patients with conduct disorder (CD) and autism spectrum disorder (ASD) yet their neural underpinnings and the influence of comorbid Callous-Unemotional (CU) traits are unclear. This study compares the cognitive (CE) and affective empathy (AE) abilities of youth with CD and ASD, their potential neuroanatomical correlates, and the influence of CU traits on empathy. Adolescents and parents/caregivers completed empathy questionnaires (N = 148 adolescents, mean age = 15.16 years) and T1 weighted images were obtained from a subsample (N = 130). Group differences in empathy and the influence of CU traits were investigated using Bayesian analyses and Voxel-Based Morphometry with Threshold-Free Cluster Enhancement focusing on regions involved in AE (insula, amygdala, inferior frontal gyrus and cingulate cortex) and CE processes (ventromedial prefrontal cortex, temporoparietal junction, superior temporal gyrus, and precuneus). The ASD group showed lower parent-reported AE and CE scores and lower self-reported CE scores while the CD group showed lower parent-reported CE scores than controls. When accounting for the influence of CU traits no AE deficits in ASD and CE deficits in CD were found, but CE deficits in ASD remained. Across all participants, CU traits were negatively associated with gray matter volumes in anterior cingulate which extends into the mid cingulate, ventromedial prefrontal cortex, and precuneus. Thus, although co-occurring CU traits have been linked to global empathy deficits in reports and underlying brain structures, its influence on empathy aspects might be disorder-specific. Investigating the subdimensions of empathy may therefore help to identify disorder-specific empathy deficits., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Difficulties in face recognition contribute to social-cognitive problems in autistic children. Evidence on behavioral interventions targeting this cognitive domain is limited. In non-autistic individuals, a single exercise session is known to elicit temporary benefits for several cognitive functions. Our study investigates whether acute aerobic exercise influences face recognition in autistic children. In a randomized order, 29 participants completed a 20-min moderately-intense cycling bout on an ergometer and a control condition. Before and after each condition, participants categorized Mooney faces and instruments during a computerized cognitive task. Simultaneously, the N170 component of event-related potentials and pupil size were recorded using electroencephalography and eyetracking, respectively. As indicated by a greater increase of reaction time in the exercise compared to the control condition, the results revealed impaired face recognition following aerobic exercise. This effect was accompanied by a lower decrease of the positive N170 amplitude and a trend towards a greater constriction of the pupil size in the exercise compared to the control condition. Our findings highlight the interplay of the physiological state and face recognition in autistic children. Exercise-induced impairments in this social-cognitive ability may be due to an interference with the learning effect that is typically seen for the structural encoding of faces., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Aims: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments. It investigates the effects of service changes on the referrals and outcomes of young people with ARMS or a FEP., Methods: Six psychiatric outpatient clinics in three cantons (Basel-Stadt, Vaud, and Geneva) participated in the project. They passed through an implementation phase including service changes and the adaptation of a standardized stepped care model for diagnosis and assessment, in addition to measures for increasing the awareness, networking and training of local professionals., Preliminary Results: All participating cantons had entered the implementation phase. By March 2023, there were 619 referrals to participating sites. A total of 163 patients (37% FEP and 31% ARMS) and 15 close relatives had participated in individual longitudinal assessments, and 26 patients participated in qualitative interviews., Conclusion: This national collaborative project addresses the issue of early intervention for emerging psychoses, and creates spaces for fruitful reflections and collaboration in Switzerland. The ultimate aim of PsyYoung is to harmonize clinical practices in early intervention of psychosis on a national level.

Approximately 2% of adolescents and young adults display symptoms indicating a high risk for psychotic disorders. Apart from a risk of 20-35% of developing a psychotic disorder, these individuals show high rates of persisting mental health problems and functional impairment, even in the absence of a psychotic transition. Treatment in specialized centers can improve outcomes in these patients, but the need to provide timely access to care needs to be balanced against the risks of premature psychiatrization, stigmatization and unnecessary medication treatment. The transcantonal project PsyYoung aims to optimize early detection in young people, while at the same time minimizing unnecessary psychiatrization. This will be achieved through improved networking across the entire care chain and a stepped-care intervention approach., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Comprehensive behaviorally or developmentally based early intervention programs have been shown to be effective in improving cognitive, social communicative, and adaptive skills of children with autism spectrum disorder (ASD). Besides the definition of relevant outcome predictors, the question of whether early intensive intervention positively changes core autism symptoms in children, as well as their long-term outcome, is an important issue for current research. The primary objective of the current study was to examine whether symptomatic and behavioral changes in children up to 4.5 years with ASD were sustained one and two years after an initial 18 days of intensive FIAS (Frühintervention bei autistischen Störungen) intervention., Methods: We analyzed the data of 32 young children with moderately severe to severe ASD who had been treated at the FIAS center between January 2011 and July 2017 and who had completed their 2-year follow-up in summer 2019., Results: ADOS total scores decreased significantly from baseline to the 1-year follow-up and from baseline to the 2-year follow-up (p < 0.01), with the most prominent change being from baseline to 2-year follow-up. The DD-C-GAS, a global scale used to assess four areas of everyday functioning, showed highly significant improvements on all subdomains. We found mostly significant correlations between results on both rating instruments at all time points, yet mostly no meaningful correlation between their changes over time. There was a close and statistically significant relationship between parents' treatment adherence and ADOS scores, indicating that the better parents' treatment adherence, the lower the children scored on the ADOS at 1- and 2-year follow-up. Overall, improvement on both scales was virtually independent of age and autism symptom severity at baseline, suggesting that older (>43 months) and more severely affected children (ADOS total score >20) may benefit from the FIAS intervention to the same extent as younger children do., Conclusions: The results of the study indicate that the FIAS approach of providing an initial highly intensive 18-day intervention period, followed by 2 years of less intensive follow-up care had an impact on the core autism symptoms as well as the adaptive functioning of children with ASD., (Copyright © 2020 Herbrecht, Lazari, Notter, Kievit, Schmeck and Spiegel.)

The development of sensitive measures to capture changes in core autism symptoms is crucial in early intervention research. The study examines the sensitivity to change of the Autism Behavior Coding System (ABCS), a video-based instrument to assess core autism symptoms during therapist-child interaction. Video sequences of 40 young children treated in the Frühintervention bei Autistischen Störungen center were analyzed with regard to the question of whether short-term changes during an 18 day period of early intervention could be captured, and whether these results are reflected in an independent clinical assessment (Developmental Disorders-Child-Global Assessment Scale [DD-C-GAS]). ABCS results showed statistically significant improvements on behavioral domains such as "expression of wishes" and "social cooperative behavior" (P < 0.01), less pronounced on "eye contact." Improvements on the DD-C-GAS were highly significant on all subdomains. Both scales showed high correlations within their subdomains, yet no significant correlations between the changes in both instruments' scores were found. An additional analysis between the DD-C-GAS scores at day 18 and the changes in the ABCS scores showed statistically significant associations in the expected direction between the changes in the variable "eye contact" and all DD-C-GAS subdomains. The correspondence of the two levels of assessment is low, but the specifics of this relationship deserve further study. The ABCS may prove useful in addition to standard assessment tools, especially in early intervention research settings, as it allows reliable analysis of core behavioral elements in young children with autism. Autism Res 2019, 12: 1817-1828. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: The study examined the sensitivity of an autism-specific video coding system (ABCS) in assessing changes after an 18 day period of intensive early intervention. Video sequences of therapist-child-interaction of 40 young children with autism spectrum disorder (ASD) were analyzed. Children's behavior improved in expression of wishes, social cooperativity and eye contact. A therapist-based global assessment scale also showed important improvement after 18 days, yet both assessment instruments showed weak correlations between their respective changes. We showed that the ABCS may prove useful in capturing short-term changes in autism-related behaviors, especially in early intervention research., (© 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.)

The aims of this paper are to present the Autism Behaviour Coding System (ABCS), a novel, video-based observational instrument for assessing core autism symptoms during intensive early interventions in autism spectrum disorder (ASD), to provide preliminary data on its psychometric characteristics and to discuss its clinical utility. Video recordings of child-therapist interactions during the 'Frühintervention bei autistischen Störungen' (FIAS) were coded by treatment-independent raters who were blind with respect to the temporal order of the sequences. We assessed inter-rater reliability using intra-class correlations (ICCs). Mean ICCs ranged from 0.85 to 0.90. We analysed the sensitivity of the ABCS to change by comparing the change in ABCS scores with the change in a validated external measure of level of functioning (Developmental Disorder-Child-Global Assessment of functioning Scale, DD-C-GAS) in a sample of 15 children who received intensive treatment. Both the ABCS and DD-C-GAS indicated that the intervention improved symptoms. The ABCS has promise as a research instrument and has good to excellent inter-rater agreement and sensitivity to intervention-related changes. This pilot study suggests that the ABCS may be useful as an objective method of assessing the proximal effects of therapy in young children with ASD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: In autism spectrum disorders (ASDs), impairments in fundamental social abilities and a lack of interest in social stimuli become apparent early in life. These impairments are thought to negatively affect further brain and behavioural development. Early intensive interventions can help to attenuate social-development and other risk factors and, thus, to ameliorate the deficits associated with ASDs. We present FIAS, an intensive early intervention approach for young children with ASD, which aims at developing children's social motivation. During 18 days, therapists work continuously for 6 h a day with the affected child, involving the whole family in a day care setting. Follow-up care at home over 1 year as well as fresh-up interventions and inclusion in kindergarten or a play group should stabilise the effects and help to respond to further challenges., Material and Methods: Here, we present observations from the first 12 patients (25-48 months of age) treated according to the FIAS approach. We evaluated changes in core autistic symptoms and level of functioning after the 18 days of intensive intervention. Beyond standardised assessment, two innovative video-based instruments (Autism Behaviour Coding System and Evaluationsfragebogen) have been developed to assess autistic symptoms and interaction parameters during intervention., Results: Improvements were noted in most core autistic symptom domains, with the highest effect sizes in domains like eye contact, communication, repetitive behaviour, imitation, motivation and reciprocity. In addition, the level of functioning significantly improved., Conclusions: The first evaluation of the FIAS approach shows promising results, as the FIAS intervention appears to improve core autistic symptom domains as well as the level of everyday functioning. Limitations of this study are the small sample size and the lack of a control group. A more comprehensive and longitudinal evaluation is in progress; this will focus on the stability of the observed effects and will attempt to identify potential predictors of treatment response. © 2015 S. Karger AG, Basel.

Background: Autism spectrum disorders (ASD) are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate., Methodology/principal Findings: We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP), complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls., Conclusions/significance: Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

The objective of this pilot study was to evaluate the effectiveness of a group-based intervention aiming at improving social and communication skills in individuals with autism spectrum disorder. Over a period of 11 months, N = 17 children and adolescents received treatment according to the manualised Frankfurt Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert ratings were assessed to judge outcome regarding peer interaction, autistic behaviours, adaptive functioning and family burden. The participants exhibited improvements pre to follow-up treatment, particularly in the area of autistic symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69. Among other things, regression models showed a positive influence of IQ and language skills on gains in social skills. Findings indicate that KONTAKT might be useful for enhancing social skills and reducing autism-related psychopathology over time in different contexts. Nevertheless, controlled trials are needed to reassure its effectiveness.

Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Objective: Despite the recognition of the need for group-based training programmes for children and adolescents with autistic disorders, there are only very few specific German-speaking training programmes available. Since 2003, a structured group training programme on social skills for children and adolescents with high-functioning autism or Asperger syndrome has been developed and conducted at our department. The training programme focuses on the main deficits of those disorders. Thus, the primary goal is to improve communication and interaction skills., Method: Participants are children and adolescents without significant cognitive and language delays. Principles of intervention include structured formats, combination of theoretical and practical elements, predictable rules, consideration of individual difficulties, and sequential and progressive learning. Techniques range from structured games, the training of affect recognition, group activities, role play, team discussions, and feedback to homework using a newly designed manual on our group-based social skill training programme and curriculum. Generally, three groups of 5-7 participants each and of different age range (children, adolescents) meet weekly/biweekly for 1-1.5 hours (excluding the holidays). Two trainers--who change during the programme--carry out each of the sessions. Trainers meet regularly with the parents to discuss experiences and to provide details of the programme., Results: Acceptance by and satisfaction with the programme are high among participants, as is the mutual recognition of and tolerance of their respective problems. Both feedback from parents and trainers' clinical impressions indicate distinct improvement of verbalization and contact abilities. Participants seem to benefit particularly from role play., Conclusions: Qualtitative measures (impressions of the participants, their parents and their trainers with regard to change in behaviour skills) suggest mounting interaction, communication, and problem-solving skills during the group treatment. An ongoing pilot evaluation also includes measurements of effects in everyday settings. Depending on the results, the training subsequently could be conducted and evaluated in groups with both pervasive developmental, as well as other psychiatric disorders.