Adverse Childhood Experiences Among Inpatient Youths with Severe and Early-Onset Psychiatric Disorders: Prevalence and Clinical Correlates.

This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2 years) and 81 for a manic or mixed episode (average age 15.7 years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58 %) and from catatonia (57 %), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group.

Treatment use in a prospective naturalistic cohort of children and adolescents with catatonia.

We aimed to (1) describe the treatment used in a large sample of young inpatients with catatonia, (2) determine which factors were associated with improvement and (3) benzodiazepine (BZD) efficacy. From 1993 to 2011, 66 patients between the ages of 9 and 19 years were consecutively hospitalized for a catatonic syndrome. We prospectively collected sociodemographic, clinical and treatment data. In total, 51 (77%) patients underwent a BZD trial. BZDs were effective in 33 (65%) patients, who were associated with significantly fewer severe adverse events (p = 0.013) and resulted in fewer referrals for electroconvulsive therapy (ECT) (p = 0.037). Other treatments included ECT (N = 12, 18%); antipsychotic medications, mostly in combination; and treatment of an underlying medical condition, when possible. For 10 patients, four different trials were needed to achieve clinical improvement. When all treatments were combined, there was a better clinical response in acute-onset catatonia (p = 0.032). In contrast, the response was lower in boys (p = 0.044) and when posturing (p = 0.04) and mannerisms (p = 0.008) were present as catatonic symptoms. The treatment response was independent of the underlying psychiatric or systemic medical condition. As in adults, BZDs should be the first-line symptomatic treatment for catatonia in young patients, and ECT should be a second option. Additionally, the absence of an association between the response to treatment and the underlying psychiatric condition suggests that catatonia should be considered as a syndrome.

French version of the Brief Infant-Toddler Social and Emotional Assessment questionnaire-BITSEA.

OBJECTIVE: The aim of the present study was to examine the psychometric properties of the French version of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). METHODS: The sample consisted of 589 low-risk infants aged 12-36 months and their parents. Parents completed the BITSEA, the Child Behavior Checklist 1½-5 (CBCL - 18 months to 5 years version), and the Parenting Stress Index - Short Form (PSI-SF). RESULTS: Multitrait-multimethod and confirmatory factor analyses revealed adequate psychometric properties for the French version of the BITSEA. Scores on the BITSEA Problem scale were positively correlated to all CBCL and PSI-SF subscales, whereas negative correlations were found between BITSEA Competence scale and CBCL and PSI-SF subscales. The BITSEA Problem score significantly increased with level of parental worry, examined through a single-item question that is part of the BITSEA. CONCLUSION: Findings support the validity of the French version of the BITSEA. However, additional work on the clinical validity of the BITSEA, including with at-risk children, is warranted.

Infant's engagement and emotion as predictors of autism or intellectual disability in West syndrome.

West syndrome (WS) is a rare epileptic encephalopathy with early onset and a high risk of autistic outcome. The PréAut grid assesses this risk following WS onset by taking into account synchrony and emotion in interactions and by evaluating the baby's active desire to engage in pleasant interactions (especially the infant's early active behaviors that encourage being gazed at or kissed by the mother or to share joy with her). We followed a sample of 25 WS patients prospectively from disease onset and assessed whether the PréAut grid before 9 months, and the checklist for autism in toddlers (CHAT) at 18 and 24 months predicted autism or intellectual disability (ID) outcomes at 4 years. We found that the PréAut grid at 9 months (sensitivity = 0.83; specificity = 1) had similar prediction parameters as the CHAT at 18 months (sensitivity = 0.90; specificity = 0.83) and 24 months (sensitivity = 0.92; specificity = 1). WS patients with a positive PréAut screening at 9 months had a risk of having autism or ID at 4 years, which is 38 times that of children with a negative PréAut grid [OR = 38.6 (95 % CI 2.2-2961); p = 0.006]. We conclude that the PréAut grid could be a useful tool for the early detection of autism or ID risk in the context of WS. Further research is needed to assess the PréAut grid in other contexts (e.g. infants at high-risk for non-syndromic autism).

Impact of the COVID-19 health crisis on psychotropic drug use in children and adolescents in France.

BACKGROUND: In 2019, the world faced a pandemic brought about by a severe acute respiratory infection caused by SARS-CoV-2 virus. The spread of this virus has profoundly affected societies, particularly in terms of their economic, human and social dimensions, as well as their healthcare systems. Several restrictive measures (reduced social interaction, periodic school closures,…) had to be taken to contain the spread of the virus. These measures have had an impact on the psychological well-being of both adults and children. The aim of this study was to assess the changes in psychotropic drugs prescriptions for children and adolescents living in Limousin, a French region, over the period 2018 to 2021. METHODS: The consumption of psychotropic drugs was studied using a national database of drug reimbursement. These data were extracted and supplied from the nationwide French reimbursement healthcare system database (SNDS). The following therapeutic classes were studied: N05A (antipsychotics), N05B (anxiolytics), N05C (hypnotics and sedatives), N06A (antidepressants) and N06B (psychostimulants). Data were collected for insured persons under the age of 18 who received at least one reimbursement for a psychotropic drug between 2018 and 2021. RESULTS: Over a 4-year period, 7949 patients under the age of 18 were included with an average age of 12.1 years and a sex ratio of 0.97 M/F. The number of patients increased from 2018 to 2021, as did the number of reimbursements. We observed a statistically significant difference of means of patients reimbursed per week for on five therapeutic classes, with the greatest difference in 2021 (p < 0.0001). An increase in the number of patients of between + 20.7% and + 689% was observed, depending on the drug classes studied. Comparisons between the COVID-19 and pre-COVID-19 periods showed a significantly higher COVID average for psychotropic drugs reimbursements in general and individually for all classes except psychostimulants. CONCLUSION: The results show a significant increase in the consumption of psychotropic drugs among youth. The increase in psychotropic drug use was continuous and progressive throughout the pandemic. All five classes were increased, but particularly anxiolytics and antidepressants. The COVID-19 context may have been at the origin of a deterioration in the mental health of children and adolescents, or of a heightened awareness of psychiatric care among young people.

Electroconvulsive therapy in adolescents with intellectual disability and severe self-injurious behavior and aggression: a retrospective study.

Efficacious intervention for severe, treatment-refractory self-injurious behavior and aggression (SIB/AGG) in children and adolescents with intellectual disability and concomitant psychiatric disorders remains a complex and urgent issue. The aim of this study is to assess the efficacy of electroconvulsive therapy (ECT) on severe and treatment-resistant SIB/AGG in young people with intellectual disability and current psychiatric disorder. We reviewed the charts of all patients (N = 4) who received ECT in the context of SIB/AGG with resistance to behavioral interventions, milieu therapy and pharmacotherapy from 2007 to 2011. We scored the daily rate of SIB/AGG per patient for each hospital day. Inter rater reliability was good (intraclass correlations = 0.91). We used a mixed generalized linear model to assess whether the following explanatory variables (time, ECT) influenced the course of SIB/AGG over time, the dependant variable. The sample included two girls and two boys. The mean age at admission was 13.8 years old [range 12-14]. The patients had on average 19 ECT sessions [range 16-26] and one patient received maintenance ECT. There was no effect of time before and after ECT start. ECT was associated with a significant decrease in SIB/AGG scores (p < 0.001): mean aggression score post-ECT was half the pre-ECT value. ECT appears beneficial in severe, treatment-resistant SHBA in adolescents with intellectual disability.

Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis.

In adults, second-generation antipsychotics (SGAs) have a low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess short-term adverse effects of SGAs in children and adolescents. We searched for relevant studies in MEDLINE and EMBASE (1996-2010), Food and Drug Administration and European Medicines Agency clinical trial registries, and reference lists of review articles. We found 41 were short-term (3-12 weeks) controlled studies that evaluated SGA adverse effects in youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole, 10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25 (n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was assessed only for weight gain and somnolence. Compared with placebo, significant treatment-related increases were observed for weight gain with olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg), clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19-4.62 kg), risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39-2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99-2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26-1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08-6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13-4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6-14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24-7.73 mg/dL); triglyceride levels with olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL) and quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL); hyperprolactinemia with risperidone (OR, 38.63; 95% credible interval, 8.62-125.6), olanzapine (OR, 15.6; 95% credible interval, 4.39-41.1), and ziprasidone (OR, 9.35; 95% credible interval, 1.24-37.03); and EPS with ziprasidone (OR, 20.56; 95% credible interval, 3.53-68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84), aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17), and risperidone (OR, 3.71; 95% credible interval, 2.18-6.02). All SGAs increased the risk of somnolence/sedation. We conclude that short-term metabolic effects and EPS are frequent in children treated with SGAs. Second-generation antipsychotics have distinct profiles of secondary effects, which should be considered in making treatment decisions.

Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1.

AIM: To investigate the psychiatric and cognitive phenotype in young individuals with the childhood form of myotonic dystrophy type 1 (DM1). METHOD: Twenty-eight individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6, range 7-24y) were assessed using standardized instruments and cognitive testing of general intelligence, visual attention, and visual-spatial construction abilities. RESULTS: Nineteen patients had repeated a school grade. The mean (SD) Full-scale IQ was 73.6 (17.5) and mean Verbal IQ was significantly higher than the mean Performance IQ: 80.2 (19.22) versus 72.95 (15.58), p=0.01. Fifteen patients had one or more diagnoses on the DSM-IV axis 1, including internalizing disorders (phobia, n=7; mood disorder, n=6; other anxiety disorders, n=5) and attention-deficit-hyperactivity disorder, inattentive subtype (n=8). Twelve out of 22 patients had alexithymia (inability to express feelings with words and to recognize and share emotional states). Cognitive testing found severe impairments in visual attention and visual-spatial construction abilities in four out of 18, and 14 out of 24 patients respectively. No diagnosis was correlated with the transmitting parent's sex or with cytosine-thymine-guanine (CTG) repeat numbers. Patients with severe visual-spatial construction disabilities had a significantly longer CTG expansion size than those with normal visual-spatial abilities (p=0.04). INTERPRETATION: Children and adolescents with childhood DM1 have frequent diagnoses on DSM-IV axis 1, with internalizing disorders being the most common type of disorder. They also have borderline low intelligence and frequent impairments in attention and visual-spatial construction abilities.

Pre-, peri- and neonatal risk factors for autism.

OBJECTIVE: To identify pre-, peri- and neonatal risk factors for pervasive developmental disorders (PDD). METHODS: We searched the Medline database through March 2011 for relevant case-control and population-based studies on pre-, peri- and neonatal hazards related to PDD, including autism. We identified 85 studies for this review. Data were extracted systematically and organized according to risk factors related to family history, pregnancy, gestational age, delivery, birth milestones and the neonate's condition at birth. RESULTS: During the prenatal period, risk factors for PDD were advanced maternal or paternal ages, being firstborn vs. third or later, maternal prenatal medication use and mother's status as foreign born. During the perinatal and neonatal periods, the risk factors for PDD were preterm birth, breech presentation, planned cesarean section, low Apgar scores, hyperbilirubinemia, birth defect and a birthweight small for gestational age. The influence of maternal pre-eclampsia, diabetes, vomiting, infections and stress during pregnancy requires further study in order to determine risk for PDD. DISCUSSION: Despite evidence for the association of some pre-, peri- and neonatal risk factors associated with PDD, it remains unclear whether these risks are causal or play a secondary role in shaping clinical expression in individuals with genetic vulnerability. A plausible hypothsesis is that improvements in obstetric and neonatal management have led to an increased rate of survivors with pre-existing brain damage. Given the variety of risk factors, we propose that future studies should investigate combinations of multiple factors, rather than focusing on a single factor.

Impact of the Timing of Maternal Peripartum Depression on Infant Social and Emotional Development at 18 Months.

The study assessed how the timing of maternal perinatal depressive symptoms affects infant socio-emotional characteristics at age 18 months. The study was a longitudinal cohort study that included six assessment points from the third trimester of pregnancy up to age 18 months (±1 month). Assessment of mothers included the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory, while assessments of infant included the Infant Toddler Social and Emotional Assessment (ITSEA) at 18 months. Mothers were categorized into one of the following groups: mothers who presented postnatal depression only (n = 19); mothers who presented both prenatal and postnatal depression (n = 14), and mothers who never showed perinatal depression symptoms (n = 38). Mothers who presented both prenatal and postnatal depression showed significantly higher levels of depressive score, reactivity to stress and level of anxiety trait compared to mothers of the two other groups. Infants of prenatally and postnatally depressed mothers had higher scores on the internalizing subscore of the ITSEA. The number of depression episodes during the study period was positively correlated with the externalizing and internalizing subscores of the ITSEA. These findings support the need to provide specific screening to identify women with prenatal depression.

A randomized controlled trial of 25 sessions comparing music therapy and music listening for children with autism spectrum disorder.

BACKGROUND: Music therapy is based on the use of musical elements by a trained and qualified therapist. Clinical researches have suggested that children with Autism Spectrum Disorders (ASD) may benefit from MT. In this regard, this study examines if MT is more effective than simply listening to music for children with ASD. METHOD: A 8-month RCT has been carried out comparing music therapy (MT) to music listening (ML) for children with ASD aged from 4 to 7 years old. Thirty-seven participants were randomly assigned to one of the two groups (MT vs. ML). The outcome measures were the Clinical Global Impression (CGI), the Childhood Autism Rating Scale (CARS) and the Aberrant Behavior Checklist (ABC) in each condition (MT and ML). RESULTS: CGI scores decreased more for participants in the MT than in the ML condition. This clinical improvement was associated with an improvement of autistic symptoms on lethargy and stereotypy ABC subscales. CONCLUSION: Our findings suggest that music therapy is more efficient than music listening for children with ASD. The present study thus supports the consideration of MT as a rightful add-on to ASD healthcare programs.

Pre-linguistic infants employ complex communicative loops to engage mothers in social exchanges and repair interaction ruptures.

Language has long been identified as a powerful communicative tool among humans. Yet, pre-linguistic communication, which is common in many species, is also used by human infants prior to the acquisition of language. The potential communicational value of pre-linguistic vocal interactions between human infants and mothers has been studied in the past decades. With 120 dyads (mothers and three- or six-month-old infants), we used the classical Still Face Paradigm (SFP) in which mothers interact freely with their infants, then refrain from communication (Still Face, SF), and finally resume play. We employed innovative automated techniques to measure infant and maternal vocalization and pause, and dyadic parameters (infant response to mother, joint silence and overlap) and the emotional component of Infant Directed Speech (e-IDS) throughout the interaction. We showed that: (i) during the initial free play mothers use longer vocalizations and more e-IDS when they interact with older infants and (ii) infant boys exhibit longer vocalizations and shorter pauses than girls. (iii) During the SF and reunion phases, infants show marked and sustained changes in vocalizations but their mothers do not and (iv) mother-infant dyadic parameters increase in the reunion phase. Our quantitative results show that infants, from the age of three months, actively participate to restore the interactive loop after communicative ruptures long before vocalizations show clear linguistic meaning. Thus, auditory signals provide from early in life a channel by which infants co-create interactions, enhancing the mother-infant bond.

Analysis of Psychiatric Disorders by Age Among Children Following a Mass Terrorist Attack in Nice, France, on Bastille Day, 2016.

This cross-sectional study examines psychiatric disorders among children after a mass terrorist attack in Nice, France, in 2016.

Catatonia in Children and Adolescents: A High Rate of Genetic Conditions.

Pediatric catatonia is a rare and severe neuropsychiatric syndrome. We previously reported, in 58 children and adolescents with catatonia, a high prevalence (up to 20%) of medical conditions, some of which have specific treatments.1 Here we extend the cohort inclusion and report the first systematic molecular genetic data for this syndrome. Among the 89 patients consecutively admitted for catatonia (according to the pediatric catatonia rating scale)2 between 1993 and 2014, we identify 51 patients (57.3%) who had genetic laboratory testing, of whom 37 had single nucleotide polymorphism (SNP) microarray tests for CNVs and 14 had routine genetic explorations (karyotyping and searches for specific chromosomal abnormalities by fluorescence in situ hybridization [FISH]) or a specific diagnosis test based on clinical history. To assess the causality of observed genetic findings in each patient, we used a causality assessment score (CAUS)3 including 5 causality-support criteria on a 3-point scale (0 = absent; 1 = moderate; 2 = high): the existence of similar cases in the literature; the presence of a clinical contributing factor; the presence of a biological contributing factor; the presence of other paraclinical symptoms; and response to a specific treatment related to the suspected genetic or medical condition.

Hormonal Risk Factors for Osteoporosis: Different Profile Among Antipsychotics.

Objectives: Osteoporosis is a major risk factor for fracture and treatment is mainly preventive. Patients with severe psychiatric condition and treated with antipsychotics are at risk for vitamin D deficiency and iatrogenic hyperprolactinemia, two serious risk factors of osteoporosis. We aim to determine whether all antipsychotics are similar regarding the risk of osteoporosis in young patients. Methods: From January 2009 to March 2015, we determined the vitamin D blood level (VDBL) among 484 inpatients and from January 2012 to March 2015, we determined the prolactin blood level (PBL) among 205 inpatients. We systematically recorded well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and suspected risk factors (e.g., disease type or antipsychotic treatment). Results: Up to 89% of the inpatients had a VDBL under the recommended threshold. Up to 60% of the inpatients had hyperprolactinemia. The multivariate model found a significant effect on VDBL for seasonality (higher VDBL in summer), ethnicity (lower VDBL in Black individuals), and treatment exposure. The multivariate model found a significant effect on PBL for gender and treatment exposure. In both models, aripiprazole had a safer profile compared with other antipsychotics. Conclusion: Because adolescence is a period of bone construction and a critical window of opportunity for maximizing bone mass, we recommend vitamin D supplementation in young patients with severe mental condition. It could be interesting to reconsider to regularly monitor PBL among youth patients treated with antipsychotic, with the exception of aripiprazole.

A causality algorithm to guide diagnosis and treatment of catatonia due to autoimmune conditions in children and adolescents.

OBJECTIVES: Pediatric catatonia is a rare and life-threatening syndrome. Around 20% of juvenile catatonia is associated with organic condition (Consoli et al., 2012). Autoimmune conditions represent a diagnostic and therapeutic challenge since specific antibodies can be missed. To facilitate decision making, we recently formulated a causality assessment score (CAUS) using a stepwise approach and an immunosuppressive therapeutic challenge (Ferrafiat et al., 2016). Our objectives were to validate retrospectively CAUS and to define its threshold for an accurate distinction between organic catatonia and non-organic catatonia, and specifically between autoimmune catatonia and non-organic catatonia. METHOD: To obtain a sufficient number of cases with organic catatonia, we pooled two samples (N=104) - one from a child psychiatry center, the other from neuro-pediatrics center - expert in catatonia and autoimmune conditions. Organic conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. Given the binary classification needs, we used receiver operating characteristic (ROC) analysis (Peacock and Peacock, 2010) to calculate the best classification threshold. RESULTS: The cohort included 67 cases of non-organic catatonia and 37 cases of organic catatonia. ROC analysis showed that the CAUS performance in discriminating both organic catatonia vs. non-organic catatonia, and autoimmune catatonia vs. non-organic catatonia was excellent (Area Under the Curve=0.99). In both analyses, for a CAUS threshold≥5, accuracy equaled to 0.96. CONCLUSION: Regarding juvenile catatonia, the use of the CAUS score algorithm combining a therapeutic challenge and a threshold≥5 may help to diagnose and treat autoimmune conditions even without formal identification of auto-antibodies.

GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study.

BACKGROUND: To meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study. METHODS: From two specialized clinics, we included 14 children (age range 5-8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models. RESULTS: Children and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time × group interaction. CONCLUSIONS: Despite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform. Trial registration Clinicaltrials.gov NCT02560415.

Infant and dyadic assessment in early community-based screening for autism spectrum disorder with the PREAUT grid.

BACKGROUND: The need for early treatment of autism spectrum disorders (ASD) necessitates early screening. Very few tools have been prospectively tested with infants of less than 12 months of age. The PREAUT grid is based on dyadic assessment through interaction and shared emotion and showed good metrics for predicting ASD in very-high-risk infants with West syndrome. METHODS: We assessed the ability of the PREAUT grid to predict ASD in low-risk individuals by prospectively following and screening 12,179 infants with the PREAUT grid at four (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of age. Children who were positive at one screening (N = 100) were proposed a clinical assessment (including the Children Autism Rating Scale, a Developmental Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third year of life. A randomly selected sample of 1,100 individuals who were negative at all screenings was followed by the PMI team from three to five years of age to identify prospective false negative cases. The clinical outcome was available for 45% (N = 45) of positive children and 52.6% (N = 579) of negative children. RESULTS: Of the 100 children who screened positive, 45 received a diagnosis at follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed with ASD, seven with intellectual disability (ID), and six had another developmental disorder. Thus, 50% of infants positive at one screening subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were significantly associated with medium and high ASD risk status on the CHAT at 24 months (odds ratio of 12.1 (95%CI: 3.0-36.8), p < 0.001, at four months and 38.1 (95%CI: 3.65-220.3), p < 0.001, at nine months). Sensitivity (Se), specificity, negative predictive values, and positive predictive values (PPVs) for PREAUT at four or nine months, and CHAT at 24 months, were similar [PREAUT-4: Se = 16.0 to 20.6%, PPV = 25.4 to 26.3%; PREAUT-9: Se = 30.5 to 41.2%, PPV = 20.2 to 36.4%; and CHAT-24: Se = 33.9 to 41.5%, PPV = 27.3 to 25.9%]. The repeated use of the screening instruments increased the Se but not PPV estimates [PREAUT and CHAT combined: Se = 67.9 to 77.7%, PPV = 19.0 to 28.0%]. CONCLUSIONS: The PREAUT grid can contribute to very early detection of ASD and its combination with the CHAT may improve the early diagnosis of ASD and other neurodevelopmental disorders.

A Developmental and Sequenced One-to-One Educational Intervention for Autism Spectrum Disorder: A Randomized Single-Blind Controlled Trial.

INTRODUCTION: Individuals with autism spectrum disorder (ASD) who also exhibit severe-to-moderate ranges of intellectual disability (ID) still face many challenges (i.e., less evidence-based trials, less inclusion in school with peers). METHODS: We implemented a novel model called the "Developmental and Sequenced One-to-One Educational Intervention" (DS1-EI) in 5- to 9-year-old children with co-occurring ASD and ID. The treatment protocol was adapted for school implementation by designing it using an educational agenda. The intervention was based on intensity, regular assessments, updating objectives, encouraging spontaneous communication, promoting skills through play with peers, supporting positive behaviors, providing supervision, capitalizing on teachers' unique skills, and providing developmental and sequenced learning. Developmental learning implies that the focus of training is what is close to the developmental expectations given a child's development in a specific domain. Sequenced learning means that the teacher changes the learning activities every 10-15 min to maintain the child's attention in the context of an anticipated time agenda. We selected 11 French institutions in which we implemented the model in small classrooms. Each institution recruited participants per dyads matched by age, sex, and developmental quotient. Patients from each dyad were then randomized to a DS1-EI group or a Treatment as usual (TAU) group for 36 months. The primary variables - the Childhood Autism Rating scale (CARS) and the psychoeducational profile (PEP-3) - will be blindly assessed by independent raters at the 18-month and 36-month follow-up. DISCUSSION AND BASELINE DESCRIPTION: We enrolled 75 participants: 38 were randomized to the DS1-EI and 37 to the TAU groups. At enrollment, we found no significant differences in participants' characteristics between groups. As expected, exposure to school was the only significant difference [9.4 (±4.1) h/week in the DS1-EI group vs. 3.4 (±4.5) h/week in the TAU group, Student's t-test, t = 5.83, p < 0.001]. ETHICS AND DISSEMINATION: The protocol was authorized by the competent national regulatory authority (Agence nationale de sécurité du médicament et des produits de santé) and approved by the local Ethics Committee (Comité de Protection des Personnes) at the University Hospital Saint-Antoine (May 7, 2013). The findings will be disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION NUMBERS: ANSM130282B-31 (April 16 2013) and ACTRN12616000592448 (May 6 2016).

Validation of the Pediatric Catatonia Rating Scale (PCRS).

INTRODUCTION: Despite the increased recognition of catatonia in children and adolescents, no specific assessment instrument has been validated in this population. METHOD: Within the context of a prospective study on catatonia, we developed the Pediatric Catatonia Rating Scale (PCRS, maximum score=60), adapted from the Bush and Francis Catatonia Rating Scale for its use in child and adolescent inpatients. We assessed the psychometric properties of the PCRS by measuring its internal consistency, construct validity, and factor structure. Bivariate analyses were performed to compare the different diagnostic patient groups across the extracted factors. RESULTS: Internal consistency was moderate (Cronbach's α for total score=0.67) suggesting multidimensionality. Multiple factors underlie the PCRS items, as revealed by factor analysis. Four distinct dimensions of catatonic symptoms were identified and accounted for 44% of total variance: a "negative withdrawal" factor (with mutism, negativism, and social withdrawal), a "catalepsy" factor (with posturing and waxy flexibility), an "abnormal movements" factor (with mannerisms and stereotypes) and an "echo phenomenon" factor (with echolalia and echopraxia). Receiver operating characteristic (ROC) analysis showed that the PCRS performance in discriminating individuals with catatonia vs. those without catatonia was excellent for a threshold≥9 (Area Under the Curve=0.983) in this sample. DISCUSSION: These results support the validity of the PCRS among children and adolescent inpatients. With regard to such analyses, the internal structure of catatonic syndrome in children and adolescents is roughly comparable with the adult form, except the lack of a "hyperactive/excitement" dimension.