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

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

Digital Phenotyping: Data-Driven Psychiatry to Redefine Mental Health.

The term "digital phenotype" refers to the digital footprint left by patient-environment interactions. It has potential for both research and clinical applications but challenges our conception of health care by opposing 2 distinct approaches to medicine: one centered on illness with the aim of classifying and curing disease, and the other centered on patients, their personal distress, and their lived experiences. In the context of mental health and psychiatry, the potential benefits of digital phenotyping include creating new avenues for treatment and enabling patients to take control of their own well-being. However, this comes at the cost of sacrificing the fundamental human element of psychotherapy, which is crucial to addressing patients' distress. In this viewpoint paper, we discuss the advances rendered possible by digital phenotyping and highlight the risk that this technology may pose by partially excluding health care professionals from the diagnosis and therapeutic process, thereby foregoing an essential dimension of care. We conclude by setting out concrete recommendations on how to improve current digital phenotyping technology so that it can be harnessed to redefine mental health by empowering patients without alienating them.

Development of a suspicion index for secondary schizophrenia using the Delphi method.

AIM: The aim of this study was to develop a suspicion index that aids diagnosis of secondary schizophrenia spectrum disorders in regular clinical practice. METHOD: We used the Delphi method to rate and refine questionnaire items in consecutive rounds. Differences in mean expert responses for schizophrenia spectrum disorders and secondary schizophrenia spectrum disorders populations allowed to define low/middle/high predictive items, which received different weights. Algorithm performance was tested in 198 disease profiles by means of sensitivity and specificity. RESULTS: Twelve experts completed the Delphi process, and consensus was reached in 19/24 (79.2%) items for schizophrenia spectrum disorders and 17/24 (70.8%) for secondary schizophrenia spectrum disorders. We assigned rounded values to each item category according to their predictive potential. A differential distribution of scores was observed between schizophrenia spectrum disorders and secondary schizophrenia spectrum disorders when applying the suspicion index for validation to 198 disease profiles. Sensitivity and specificity analyses allowed to set a >8/10/16 risk prediction score as a threshold to consider medium/high/very high suspicion of secondary schizophrenia spectrum disorders. CONCLUSION: Our final outcome was the Secondary Schizophrenia Suspicion Index, the first paper-based and reliable algorithm to discriminate secondary schizophrenia spectrum disorders from schizophrenia spectrum disorders with the potential to help improve the detection of secondary schizophrenia spectrum disorder cases in clinical practice.

Prevention of Suicidal Relapses in Adolescents With a Smartphone Application: Bayesian Network Analysis of a Preclinical Trial Using In Silico Patient Simulations.

BACKGROUND: Recently, artificial intelligence technologies and machine learning methods have offered attractive prospects to design and manage crisis response processes, especially in suicide crisis management. In other domains, most algorithms are based on big data to help diagnose and suggest rational treatment options in medicine. But data in psychiatry are related to behavior and clinical evaluation. They are more heterogeneous, less objective, and incomplete compared to other fields of medicine. Consequently, the use of psychiatric clinical data may lead to less accurate and sometimes impossible-to-build algorithms and provide inefficient digital tools. In this case, the Bayesian network (BN) might be helpful and accurate when constructed from expert knowledge. Medical Companion is a government-funded smartphone application based on repeated questions posed to the subject and algorithm-matched advice to prevent relapse of suicide attempts within several months. OBJECTIVE: Our paper aims to present our development of a BN algorithm as a medical device in accordance with the American Psychiatric Association digital healthcare guidelines and to provide results from a preclinical phase. METHODS: The experts are psychiatrists working in university hospitals who are experienced and trained in managing suicidal crises. As recommended when building a BN, we divided the process into 2 tasks. Task 1 is structure determination, representing the qualitative part of the BN. The factors were chosen for their known and demonstrated link with suicidal risk in the literature (clinical, behavioral, and psychometrics) and therapeutic accuracy (advice). Task 2 is parameter elicitation, with the conditional probabilities corresponding to the quantitative part. The 4-step simulation (use case) process allowed us to ensure that the advice was adapted to the clinical states of patients and the context. RESULTS: For task 1, in this formative part, we defined clinical questions related to the mental state of the patients, and we proposed specific factors related to the questions. Subsequently, we suggested specific advice related to the patient's state. We obtained a structure for the BN with a graphical representation of causal relations between variables. For task 2, several runs of simulations confirmed the a priori model of experts regarding mental state, refining the precision of our model. Moreover, we noticed that the advice had the same distribution as the previous state and was clinically relevant. After 2 rounds of simulation, the experts found the exact match. CONCLUSIONS: BN is an efficient methodology to build an algorithm for a digital assistant dedicated to suicidal crisis management. Digital psychiatry is an emerging field, but it needs validation and testing before being used with patients. Similar to psychotropics, any medical device requires a phase II (preclinical) trial. With this method, we propose another step to respond to the American Psychiatric Association guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03975881; https://clinicaltrials.gov/ct2/show/NCT03975881.

The MEOPAeDent trial protocol-an observational study of the Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) effects in paediatric dentistry.

BACKGROUND: Many studies were conducted to assess the benefit/risk ratio of EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) in France before it was authorized for use outside the hospital setting in 2009. The main objective of this project is to evaluate the effects sought and felt by children when EMONO is used in paediatric dentistry. The secondary objectives are to (i) evaluate the appreciation of EMONO by the children, (ii) characterize children who experience both analgesia and anxiolysis, (iii) evaluate children's appetite for EMONO and characterize children with a high appetite and (iv) evaluate the impact of the difference in practice among the French dental service university hospitals on anxiety. The maintenance of a framework for the safe use of this drug, whose place in dental care is fundamental, is essential. Twelve of the 16 French dental service university hospitals agreed to participate in this study. METHODS: MEOPAeDent is an observational, descriptive, transversal study that aims to evaluate the effects sought and felt by children when EMONO is used in paediatric dentistry. Subjects requiring dental care under EMONO are recruited by 12 French dental service university hospitals. Patients aged from 3 to 15 years are recruited for the study when they visit a dental service of a French university hospital requiring dental care under EMONO. The investigator collects the necessary data from the child's medical records, from his own observations and from questions posed to the child and his/her parents. A survey is completed at the first and final sessions of dental care under EMONO. DISCUSSION: This study will provide an evaluation of the effects of EMONO on the French paediatric population in need of dental care as well as evaluate the appetite for the use of this substance. The results will first be used to provide additional data that is essential to monitor the use of a product with an authorization to use it outside of hospitals from 2009 in France, confirm its safety for use and justify its framework of application. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03453411 registered 2 March 2018.

Autism spectrum disorder: an early and frequent feature in cerebrotendinous xanthomatosis.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism (IEM) due to mutations in the CYP27A1 gene. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenile-onset cataract are the earliest symptoms in childhood. In the current study, we evaluated the presence of autism spectrum disorder (ASD) in a large cohort of CTX patients. METHODS: We performed a retrospective patient file study in 77 genetically confirmed Dutch CTX patients to determine the frequency of ASD. In addition, we compared plasma cholestanol levels in CTX patients with and without a diagnosis of ASD and tried to establish a relation between CYP27A1 genotype and ASD. RESULTS: In our CTX cohort, 10 patients (13%; nine pediatric and one adult) with ASD were identified. At the time of diagnosis of ASD, most patients only exhibited symptoms of diarrhea and/or intellectual disability without signs of cataract or neurological symptoms. No correlation was found between the presence of ASD and the level of cholestanol or CYP27A1 genotype. The behavioral problems stabilized or improved after treatment initiation with chenodeoxycholic acid (CDCA) in all pediatric patients. CONCLUSIONS: We conclude that ASD is an early and probably underestimated frequent feature in CTX. Metabolic screening for CTX should be performed in patients with ASD when accompanied by diarrhea, intellectual disability, juvenile cataract, and/or neurological involvement. Early recognition allows for earlier initiation of specific treatment and will improve clinical outcome. Our results add CTX to the list of treatable IEMs associated with ASD.

Influence of socioeconomic status on antipsychotic prescriptions among youth in France.

BACKGROUND: Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs. METHOD: Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013-June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician). RESULTS: There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X 2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%). CONCLUSIONS: Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions. First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this population, and this discrepancy should be addressed with informational campaigns targeted to medical practitioners.

PHEDRE trial protocol - observational study of the prevalence of problematic use of Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) and analgesics in the French sickle-cell disease population.

BACKGROUND: The use of analgesics can lead to cases of drug abuse and dependence. It can also cause pseudo-addiction in patients suffering from pain. What is the actual situation in patients suffering from severe sickle-cell disease, exposed to acute pain during vaso-occlusive crises? Evaluation of the use of analgesics, on the basis of Diagnostic and Statistical Manual of Mental Disorders criteria for substance abuse and dependence, makes it possible to differentiate the symptoms occurring only in a context of pain, in the aim of managing the pain, and thus describing pseudo-addiction, from symptoms also occurring when there is no pain, and more in favour of true addiction. Currently there is no data available in France on this problem, and no studies have been carried out in children or adolescents with sickle-cell disease. The purpose of the study is to evaluate the prevalence of problematic use of equimolar mixture of oxygen and nitrous oxide and other analgesic drugs in a population of subjects with severe sickle-cell disease in France. METHODS/DESIGN: PHEDRE (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease) is an observational, descriptive and transversal study. Patients under the age of 26 with sickle-cell disease are included in the study by the doctors looking after them in sickle-cell disease centres. The patients are then contacted by a trained researcher for a telephone interview, including an evaluation of the Diagnostic and Statistical Manual of Mental Disorders criteria for abuse and dependence to equimolar mixture of oxygen and nitrous oxide and for each of the analgesic drugs taken by the patient. The data are also completed using the subject's medical record. DISCUSSION: This study will make it possible to provide an initial quantitative and qualitative evaluation of problematic use of equimolar mixture of oxygen and nitrous oxide and analgesic drugs in the sickle-cell disease population. The results will be used firstly to provide additional data essential for monitoring the risk of overdose, abuse, dependence and misuse of these products, and to begin awareness-raising and to provide information for health care professionals, in order to significantly improve the management of sickle-cell disease-related pain. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT02580565 registered 16 October 2015 Unique Protocol ID: RC14_0344.

Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges.

In children and adolescents with conduct disorder (CD), pharmacotherapy is considered when non-pharmacological interventions do not improve symptoms and functional impairment. Risperidone, a second-generation antipsychotic is increasingly prescribed off-label in this indication, but its efficacy and tolerability is poorly studied in CD, especially in young people with normal intelligence. The Paediatric European Risperidone Studies (PERS) include a series of trials to assess short-term efficacy, tolerability and maintenance effects of risperidone in children and adolescents with CD and normal intelligence as well as long-term tolerability in a 2-year pharmacovigilance. In addition to its core studies, secondary PERS analyses will examine moderators of drug effects. As PERS is a large-scale academic project involving a collaborative network of expert centres from different countries, it is expected that results will lead to strengthen the evidence base for the use of risperidone in CD and improve standards of care. Challenging issues faced by the PERS consortium are described to facilitate future developments in paediatric neuropsychopharmacology.

[Schizophrenic disorders in adolescence]. / Troubles schizophréniques de l'adolescence.

This article provides a brief overview of Early Onset Schizophrenia (EOS). Schizophrenia is a severe, devastating and common psychiatric disorder (around 1% of general population). EOS is defined as onset before 18 years with a Childhood Onset Schizophrenia (COS) sub-category beginning before 13. COS is rare representing 1% of all schizophrenia, with a prevalence of 1 in 10000 births. Prevalence increases remarkably during adolescence with 4% of all schizophrenic disorders before 10 and 12-34% before 18. DSM-IV criteria for EOS are the same as for adult onset schizophrenia. Interestingly, compared to cases with adult onset, EOS shows the following characteristics: 1) it is more frequent in males; 2) onset is more often insidious; 3) minor neurological signs, negative symptoms and catatonia are more frequent; 3) a history of developmental problems (ranging from minor motor coordination disorder to autism spectrum disorders) occurs in up to 50% of the cases; 4) the disease process has a greater impact on cognition and brain anatomic markers; 5) comorbid organic and genetic risk factors, including mental retardation, are more prevalent. Gold standard treatments are antipsychotic medications, which are approved by administration until 13 years old in France. It is of particular importance to search for side effects which may have different profile in pediatric populations.

The neuropsychiatry of inborn errors of metabolism.

A number of metabolic disorders that affect the central nervous system can present in childhood, adolescence or adulthood as a phenocopy of a major psychiatric syndrome such as psychosis, depression, anxiety or mania. An understanding and awareness of secondary syndromes in metabolic disorders is of great importance as it can lead to the early diagnosis of such disorders. Many of these metabolic disorders are progressive and may have illness-modifying treatments available. Earlier diagnosis may prevent or delay damage to the central nervous system and allow for the institution of appropriate treatment and family and genetic counselling. Metabolic disorders appear to result in neuropsychiatric illness either through disruption of late neurodevelopmental processes (metachromatic leukodystrophy, adrenoleukodystrophy, GM2 gangliosidosis, Niemann-Pick type C, cerebrotendinous xanthomatosis, neuronal ceroid lipofuscinosis, and alpha mannosidosis) or via chronic or acute disruption of excitatory/inhibitory or monoaminergic neurotransmitter systems (acute intermittent porphyria, maple syrup urine disease, urea cycle disorders, phenylketonuria and disorders of homocysteine metabolism). In this manuscript we review the evidence for neuropsychiatric illness in major metabolic disorders and discuss the possible models for how these disorders result in psychiatric symptoms. Treatment considerations are discussed, including treatment resistance, the increased propensity for side-effects and the possibility of some treatments worsening the underlying disorder.

Psychotropic drugs consumption during 2020 COVID-19 pandemic and lockdowns: Evidence of a surprising resilience of the drugs delivery system in France.

The COVID-19 pandemic imposed two lockdowns of eight and six weeks in France. While access to care was reduced during lockdown periods, these stressful situations with the pandemic and lockdown periods may have a negative impact on mental health, especially in vulnerable subgroups. Monitoring of psychotropic drugs consumption in France is a comprehensive and reliable tool for indirectly analyzing the mental health of French people. This historical cohort study (n = 767 147) investigated the short-term and long-term evolution of the weekly trend of psychotropic drugs users in 2020 by performing a Seasonal Trend decomposition time series analysis. Rate of progression of consumers per week increased from 186 in the last week of 2019 to 261 per week in the last week of 2020 (+40.3%). Our results did not show a significant break in psychotropic drugs consumption trends during the year 2020 and its two lockdowns. The increase in trend regarding psychotropic drugs consumptions was greatest in young people (<15 years) and patients not being socially deprived. Despite the increase in consumers with restrictive health measures, the French drugs delivery system has been able to adapt with the support of government and pharmacy network. This point should be kept in mind as the necessary reforms to the health care system are undertaken. The COVID-19 pandemic has a negative impact on mental health and two lockdowns occurred in France with reduced access to care. In this context, monitoring of psychotropic drugs consumption is a comprehensive and reliable tool for analyzing the mental health of French people. We hypothesized that the psychotropic drugs consumption has increased during the 2020 COVID-19 pandemic, testifying to French people mental health deterioration, with psychotropic drugs consumption breaks during lockdowns, especially during the first "grand national lockdown", due to the closure or difficulties for accessing to health care structures. By carrying out a historical cohort study among Pays de la Loire residents (n = 767 147), we investigated evolution of the weekly trend of psychotropic drugs users in 2020 compared to 2019 by performing a Seasonal Trend decomposition time series analysis. Between 2019 to 2020, we found a + 40.3% rate of progression of consumers per week. During the year 2020, changes in trend regarding psychotropic drugs consumptions was observed in various sub-groups, e.g. greater in the youngest (< 15 years), which may indicate a vulnerable group strongly impacted by COVID-19 negative consequences, and patients not being socially deprived, which may indicate a group with probably an easier access to care. Lockdown periods were not associated with a significant change in psychotropic drug use, suggesting a form of resilience in the French health care system to maintain its capacity to deliver psychotropic treatments. We mainly discussed that despite the increase in consumers and the policies of restricting access to care during lockdown periods, the French drugs delivery system has been able to adapt thanks to supportive policy actions (extension of the prescriptions validity without the need for a renewal by a physician during periods of lockdowns), an efficient pharmacy network with a collaborative practice of health actors that need to be developed and/or conserved to face potential future health crises.

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

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

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.

Emergence of psychiatric adverse events during antipsychotic treatment in AP-naïve children and adolescents.

BACKGROUND: Over the last decades, antipsychotic prescriptions in children have increased worldwide. However, adverse events are frequently observed, with some such as psychiatric adverse events remaining poorly documented. METHOD: The French ETAPE study is a 12-month naturalistic prospective multisite study that included 190 antipsychotic-naïve pediatric patients (mean age = 12 ± 3 years), treated by antipsychotic for psychotic or non-psychotic symptoms. From the ETAPE database, we performed additional analyses focusing on psychiatric adverse events. RESULTS: Children received mainly second-generation antipsychotic for conditions out of regulatory approval, with risperidone and aripiprazole being the most frequent (respectively 52.5% and 30.83%). Clinicians reported 2447 adverse events, mainly non-psychiatric (n = 2073, 84.72%), including neuromuscular, metabolic, gastroenterological, and (n = 374, 15.28%) psychiatric. 55.88% of psychiatric adverse events were attributable to antipsychotic by the clinician, compared to 89% of non-psychiatric adverse events (p < 0.001). 63.2% (n = 120) of the 190 children and adolescents presented at least one psychiatric adverse event. The most frequent were externalized behaviors such as aggressiveness or agitation (22.7%), mood changes (18.4%) and suicidal ideas or behaviors (11.8%). Half of psychiatric adverse events occurred during the first quarter, 49.46%, compared to 23.79% during the second, 15.77% during the third, and 10.96% during the fourth. CONCLUSION: This additional analysis from the French ETAPE study emphasizes that psychiatric adverse events might be more frequent than expected in the pediatric population. Also, the potential risk of psychiatric adverse events should be part of the benefit-risk evaluation and sub-sequent follow-up.

Efficacy, Tolerability, and Acceptance of Long-Lasting Antipsychotics in Children and Adolescents: A Systematic Review.

Objectives: While long-lasting antipsychotics (LLA) were specifically developed to address the problem of adherence in patients with chronic psychiatric disorders, their role in pediatric populations is not clear. Methods: To document the efficacy, tolerance, and acceptance of LLAs in children and adolescents, a literature search was conducted using several databases for published studies (PubMed, PsycINFO) from January 1965 to December 2020. Twenty-two studies were identified (16 case reports/series, 3 open label studies, 2 controlled studies, and 1 retrospective analysis of national database). Results: Demographic features were widely heterogeneous across studies (total N = 480, 58% male, mean age = 15.0 ± 1.8). Case reports/series presented positive therapeutic outcomes in noncompliant youths with severe mental illness. Three open-label one-arm studies supported the clinical efficacy of risperidone long-acting injection in patients previously stabilized with oral risperidone. One study showed lower clinical symptoms and higher functioning at 12 months in youths treated for an acute psychotic episode with paliperidone palmitate compared to oral risperidone. The types and rates of side effects of LLA were comparable to those observed for oral antipsychotics. Two studies suggested better metabolic and neurological tolerance of LLA compared to an oral form. Preliminary evidence supported a satisfactory level of treatment satisfaction in patients treated with LLA and their families, while concerns were raised regarding practical administration in outpatient services. However, the average quality of the evidence based on the RoB2 tool was low. Conclusions: The level of evidence was low for the efficacy of LLA in pediatric populations and very low for the tolerance and acceptance. It concerned mostly the effect of risperidone long-acting injection in adolescents with psychotic disorders. Randomized maintenance clinical trials using noninferiority analysis would be more appropriate for further research.

Digital phenotype of mood disorders: A conceptual and critical review.

Background: Mood disorders are commonly diagnosed and staged using clinical features that rely merely on subjective data. The concept of digital phenotyping is based on the idea that collecting real-time markers of human behavior allows us to determine the digital signature of a pathology. This strategy assumes that behaviors are quantifiable from data extracted and analyzed through digital sensors, wearable devices, or smartphones. That concept could bring a shift in the diagnosis of mood disorders, introducing for the first time additional examinations on psychiatric routine care. Objective: The main objective of this review was to propose a conceptual and critical review of the literature regarding the theoretical and technical principles of the digital phenotypes applied to mood disorders. Methods: We conducted a review of the literature by updating a previous article and querying the PubMed database between February 2017 and November 2021 on titles with relevant keywords regarding digital phenotyping, mood disorders and artificial intelligence. Results: Out of 884 articles included for evaluation, 45 articles were taken into account and classified by data source (multimodal, actigraphy, ECG, smartphone use, voice analysis, or body temperature). For depressive episodes, the main finding is a decrease in terms of functional and biological parameters [decrease in activities and walking, decrease in the number of calls and SMS messages, decrease in temperature and heart rate variability (HRV)], while the manic phase produces the reverse phenomenon (increase in activities, number of calls and HRV). Conclusion: The various studies presented support the potential interest in digital phenotyping to computerize the clinical characteristics of mood disorders.

Early Detection of Neurodevelopmental Disorders of Toddlers and Postnatal Depression by Mobile Health App: Observational Cross-sectional Study.

BACKGROUND: Delays in the diagnosis of neurodevelopmental disorders (NDDs) in toddlers and postnatal depression (PND) in mothers are major public health issues. In both cases, early intervention is crucial. OBJECTIVE: We aimed to assess if a mobile app named Malo can reduce delay in the recognition of NDD and PND. METHODS: We performed an observational, cross-sectional, data-based study in a population of young parents with a minimum of 1 child under 3 years of age at the time of inclusion and using Malo on a regular basis. We included the first 4000 users matching the criteria and agreeing to participate between November 11, 2021, and January 14, 2022. Parents received monthly questionnaires via the app, assessing skills on sociability, hearing, vision, motricity, language of their infants, and possible autism spectrum disorder. Mothers were also requested to answer regular questionnaires regarding PND, from 4-28 weeks after childbirth. When any patient-reported outcomes matched predefined criteria, an in-app notification was sent to the user, recommending the booking of an appointment with their family physician or pediatrician. The main outcomes were the median age of the infant at the time of notification for possible NDD and the median time of PND notifications after childbirth. One secondary outcome was the relevance of the NDD notification for a consultation as assessed by the physicians. RESULTS: Among 4242 children assessed by 5309 questionnaires, 613 (14.5%) had at least 1 disorder requiring a consultation. The median age of notification for possible autism spectrum, vision, audition, socialization, language, or motor disorders was 11, 9, 17, 12, 22, and 4 months, respectively. The sensitivity of the alert notifications of suspected NDDs as assessed by the physicians was 100%, and the specificity was 73.5%. Among 907 mothers who completed a PND questionnaire, highly probable PND was detected in 151 (16.6%) mothers, and the median time of detection was 8-12 weeks. CONCLUSIONS: The algorithm-based alert suggesting NDD was highly sensitive with good specificity as assessed by real-life practitioners. The app was also efficient in the early detection of PND. Our results suggest that the regular use of this multidomain familial smartphone app would permit the early detection of NDD and PND. TRIAL REGISTRATION: ClinicalTrials.gov NCT04958174; https://clinicaltrials.gov/ct2/show/NCT04958174.

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports.

Introduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future.

Mobile App for Parental Empowerment for Caregivers of Children With Autism Spectrum Disorders: Prospective Open Trial.

BACKGROUND: Conflicting data emerge from literature regarding the actual use of smartphone apps in medicine; some considered the introduction of smartphone apps in medicine to be a breakthrough, while others suggested that, in real-life, the use of smartphone apps in medicine is disappointingly low. Yet, digital tools become more present in medicine daily. To empower parents of a child with autism spectrum disorder, we developed the Smartautism smartphone app, which asks questions and provides feedback, using a screen with simple curves. OBJECTIVE: The purpose of this study was to evaluate usage of the app by caregivers of individuals with autism spectrum disorders. METHODS: We conducted a prospective longitudinal exploratory open study with families that have a child with autism spectrum disorder. Data were recorded over a period of 6 months, and the outcome criteria were (1) overall response rates for a feedback screen and qualitative questionnaires, and (2) response rates by degree of completion and by user interest, based on attrition. RESULTS: Participants (n=65) had a very high intent to use the app during the 6-month period (3698/3900 instances, 94.8%); however, secondary analysis showed that only 46% of participants (30/65) had constant response rates over 50%. Interestingly, these users were characterized by higher use and satisfaction with the feedback screen when compared to low (P<.001) and moderate (P=.007) users. CONCLUSIONS: We found that real or perceived utility is an important incentive for parents who use empowerment smartphone apps. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2016-012135.