Somatic and Posttraumatic Stress Symptoms in Children and Adolescents in France.

Importance: Somatic symptoms are a major concern among the pediatric population because of frequency and burden. The association between adverse childhood experiences and somatic symptoms in adults is well established but less is known concerning somatic symptoms in young people. Objective: To explore the frequency and intensity of somatic symptoms in children and adolescents exposed to traumatic events. Design, Setting, and Participants: This cross-sectional study was conducted from January 1 to December 31, 2021, at the Nice Pediatric Psychotrauma Referral Center in Nice, France. Participants included pediatric outpatients, aged 7 to 17 years, who were referred to the center. Statistical analysis was performed in January 2022. Exposure: All participants experienced at least 1 traumatic event during life. Main Outcome and Measure: Somatic and posttraumatic stress symptoms were assessed using the Patient Health Questionnaire-13 (PHQ-13) and Child PTSD Checklist (CPC). Posttraumatic stress disorder (PTSD) and non-PTSD groups were defined based on CPC symptoms severity score. In the hypothesized association between somatic symptoms and posttraumatic stress symptoms (PTSS), PTSD and non-PTSD groups were compared, correlations between PTSS and severity of CPC were analyzed, and a regression model was performed. Results: There were 363 participants included (mean [SD] age, 13.58 [0.25] years; 174 [47.9%] female, 189 [52.1%] male). Compared with the non-PTSD group, the PTSD group presented with a higher mean (SD) number of somatic symptoms (7.0 [2.5] vs 4.0 [2.5] symptoms; t360 = 11.7; P < .001), and higher mean (SD) intensity (10.4 [4.6] vs 4.8 [3.7] points; t360 = 12.6; P < .001). Most of the explored somatic symptoms positively correlated with the intensity of PTSS and their functional alterations (eg, PTSS intensity correlated with stomach pain symptoms [r = .30; P < .001]; and with headaches symptoms [r = .44; P < .001]). In the regression model, the combination of migraines, palpitation, nausea, tiredness, and sleep disorders explained 6.5% of the variance in the PTSD group. (F1,341 = 22.651; P < .001). Conclusions and Relevance: In this cross-sectional study, somatic symptoms were positively correlated with PTSS both in frequency and intensity among youths. These results suggest that the systematic screening for somatic symptoms in youths with traumatic exposure should be a routine evaluation procedure.

Psychiatric outcomes in outpatients affected by long COVID: A link between mental health and persistence of olfactory complaint.

BACKGROUND: Anosmia was one of the main symptoms of coronavirus disease 2019 (COVID-19). A psychiatric history (i.e., depression) may be an independent contributor to the risk of COVID-19 diagnosis, and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae (bidirectional association). AIM: To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory complaints. METHODS: We conducted a prospective case control study from March 2020 to May 2021. Patients recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint (visual analogue scale) for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by serology. Post-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology department. Psychiatric medical histories were collected by a psychiatrist during the assessments. RESULTS: Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the study. Fifty percent of the patients were female (n = 17). The group's mean age was 40.5 ± 12.9 years. The control group included 32 participants, of which 34.4% were female (n = 11), and had a mean age of 61.2 ± 12.2 years. The rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher (41.7%) than among patients without (18.8%) (χ2 = 5.9, P = 0.015). CONCLUSION: The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent anosmia. It therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk patients. Further prospective, translational, and collaborative studies are needed to extrapolate these results to the general population.

Cardiac and metabolic safety profile of antipsychotics in youths: A WHO safety database analysis.

A significant heterogeneity prevails in antipsychotics (APs) safety monitoring recommendations. Youths are deemed more vulnerable to cardiometabolic side effects. We aimed to assess age-dependent reporting of cardiac and metabolic disorders in youths, relying on the WHO safety database (VigiBase®). VigiBase® was queried for all reports of cardiac, glucose, lipid and nutritional disorders involving APs. Patients <18 years were classified as pediatric population. Disproportionality analyses relied on the Information Component (IC): the positivity of the lower end of its 95 % confidence interval was required to suspect a signal. We yielded 4,672 pediatric reports. In disproportionality analysis, nutritional disorders were leading in youths (IC 3.9 [3.9-4.0]). Among healthcare professionals' reports, stronger signals were detected in youths than in adults. Children had the greatest signal with nutritional disorders (IC 4.7 [4.6-4.8]). In adolescents, aripiprazole was ascribed to non-alcoholic steatohepatitis (NASH). Our findings, based on real-world data, support the hypothesis of a greater propensity for nutritional disorders in youths, despite limitations of pharmacovigilance studies. We suggest specific safety profiles, such as aripiprazole and NASH. Pending more answers from population-based studies, a careful anamnesis should seek for risk factors before AP initiation. A cautious monitoring is warranted to allow earlier identification of side effects.

July 14th 2016 Nice Terrorist Attack Court Trial: A Protocol on Sleep Quality and Somatic Symptoms as Markers of Risk for Traumatic Reactivation in Adolescents Exposed to This Attack.

The court trial of the 14th of July 2016 terrorist attack in Nice (France) opened in September 2022 and ended in December 2022. Engaging in court proceedings, whether as a victim or a witness, can lead to a significant risk of traumatic reactivation (i.e., the re-emergence of post-traumatic stress symptoms). The present protocol aimed to improve knowledge of the pathophysiology of traumatic reactivation due to the media coverage of the trial by assessing sleep disturbances and somatic symptoms that could reappear if there is a traumatic reactivation. Method and Analysis: This is a monocentric longitudinal study, with recruitment solely planned at the Nice Pediatric Psychotrauma Center (NPPC). We intended to include 100 adolescents aged 12 to 17 years who were directly or indirectly exposed to the attack and included in the "14-7" program). Assessments began one month before the trial, in August 2022, and were scheduled once a month until the end of the trial. A smartwatch recorded sleep activity. Somatic and PTSD symptoms and sleep were assessed through validated questionnaires. The main analyses comprised the variance and regression analyses of predictors of clinical evolution over time. Ethics and Dissemination: The National Ethics Committee "NORD OUEST III" approved the "14-7" program protocol (number 2017-A02212-51). The specific amendment for this research was approved in April 2022 by the same national ethical committee. Inclusions started in August 2022.

Impact of the 7/14/2016 Nice terrorist attack on pediatric emergency department visits thanks to syndromic surveillance: a descriptive study.

Objective: Study the impact of 14th July 2016 Nice terrorist attack on Pediatric Emergency Department (PED) visits by youth under 18 years of age. Methods: PED visits diagnoses (ICD10) were clustered and analyzed based on retrospective data from the syndromic surveillance system of the Children's university hospital of Nice (Southern France). The studied period ranges from 2013 to 2019, i.e., 3 years before and after the terrorist attack of 14th July 2016. Results: Among 416,191 PED visits, the number of visits for stress in 4-17 years old appeared to increase in the 3 years after the attack compared to the 3 years before, particularly in September 2016 (acute effect) with 11 visits compared to an average of 2.3 visits per month from September 2013 to 2016 (p = 0.001827). In September 2017, we noticed 21 visits compared to an average of 4.8 visits per month during the following period (2013-2019). In 2017, PED visits for stress among 4-17 year olds were higher in comparison to the other years of the study: 107 visits compared to an annual average of 57. Conclusion: To our knowledge, this is the first study of the use of the pediatric care system before and after a terrorist attack involving syndromic surveillance. This suggests acute and long-term effects of the terrorist attack on PED use by youth for mental health issues. Further studies of the pediatric care system involving syndromic surveillance are needed in the context of mass violent events, such as terrorist attacks.

Early-onset schizophrenia: studying the links between cognitive and clinical dimensions.

BACKGROUND: Early-onset schizophrenia (EOS), a rare and severe chronic psychiatric condition, is defined by an onset of schizophrenia symptoms before the age of 18. Core symptoms also include cognitive impairments. However, little is known about links between psychiatric symptoms of EOS and cognitive abilities. OBJECTIVE: To explore the clinical and neurocognitive profiles of EOS patients and their links. METHOD: EOS patients have been phenotyped using standardised psychiatric assessments for DSM-5 diagnoses (K-SADS-PL) and for symptoms (PANSS and SANS), together with neurocognitive evaluations. RESULTS: The EOS sample (n = 27, 12.4 +/-3.2 years) presented hallucinations (83%), negative symptoms (70%) and delusion (59%). 81% of patients presented comorbidities such as anxiety disorders (33%), autism spectrum disorder (26%) and attention-deficit hyperactivity disorder (26%). Patients presented borderline intellectual deficiency (total IQ = 72.5 +/-4.7), with low performances in working memory subtest. We highlight a positive correlation between the IQ and intensity of positive symptoms (PANSS) and between the IQ and a first treatment being administered at an older age. We also highlight a negative correlation between the IQ and attention items of SANS. CONCLUSION: Cognitive skills are correlated with symptom intensity in EOS patients. An older age of onset seems to be a protective factor for cognitive development.

Iatrogenic triggers for anorexia nervosa and bulimia nervosa: A WHO safety database disproportionality analysis.

Eating disorders, characterized by abnormal eating, weight control behaviors or both include anorexia nervosa (AN) and bulimia nervosa (BN). We investigated their potential iatrogenic triggers, using real-world data from the WHO safety database (VigiBase®). VigiBase® was queried for all AN and BN reports. The reports were classified as `pediatric' or `adult' according to age. Disproportionality analyses relied on the Information Component (IC), in which a 95% confidence interval lower-end positivity was required to suspect a signal. Our queries yielded 309 AN and 499 BN reports. Isotretinoin was disproportionately reported in pediatric AN (IC 3.6; [2.6-4.3]), adult AN (IC 3.1; [1.7-4.0]), and pediatric BN (IC 3.9; [3.0-4.7]). Lamivudine (IC 4.2; [3.2-4.9]), nevirapine (IC 3.7; [2.6-4.6]), and zidovudine (IC 3.4; [2.0-4.3]) had the highest ICs in adult AN. AN was associated with isotretinoin, anticonvulsants in minors, and antiretroviral drugs in adults. In adults, BN was related to psychotropic and hormonally active drugs. Before treatment initiation, an anamnesis should seek out mental health conditions, allowing the identification of patients at risk of developing or relapsing into AN or BN. In addition to misuse, the hypothesis of iatrogenic triggers for AN and BN should also be considered.

Drug-related catatonia in youths: real-world insights from the WHO Safety Database.

Catatonia is characterized by psychomotor alterations and reduced contact with the environment. Initially linked to schizophrenia, it also occurs in mood disorders or organic conditions. In children, catatonia remains poorly delineated, despite dramatically increasing the risk of premature death. As data on pediatric drug-induced catatonia bears many uncertainties, we aimed to characterize its age-dependent patterns, using real-world data from the WHO safety database (VigiBase®).VigiBase® was queried for all reports of catatonia registered up to December 8th 2022. Reports involving patients <18 years were classified into 3 groups: ≤23 months, 2-11 years, and 12-17 years. Disproportionality analyses relied on the Reporting Odds Ratio (ROR), and the positivity of the lower end of the 95% confidence interval of the Information Component (IC) was required to suspect a signal. Catatonia was evoked in 421 pediatric reports. In infants, vaccines were leading. In children, the main signals involved haloperidol (ROR 104.3; 95% CI 45.6-238.5), ondansetron (ROR 40.5; 95% CI 16.5-99.5), and ciclosporin (ROR 27.4; 95% CI 13.8-54.1). In adolescents, chlorpromazine (ROR 199.1; 95% CI 134.8-294.1), benzatropine (ROR 193; 95% CI 104.1-361.6), and olanzapine (ROR 135.7; 95% CI 104.6-175.9) reached the highest RORs. In infants, catatonia was related to vaccines, it was ascribed to multiple drugs in children, and mainly to psychotropic drugs in adolescents. Less suspected drugs, such as ondansetron, were highlighted. Despite limitations inherent in spontaneous reporting systems, this study supports that a careful anamnesis is warranted to separate catatonia associated with medical conditions from drug-induced catatonia in pediatric patients.

Study protocol: how does parental stress measured by clinical scales and voice acoustic stress markers predict children's response to PTSD trauma-focused therapies?

INTRODUCTION: Post-traumatic stress disorder (PTSD) symptoms in youth are influenced by parental anxiety and stress. When parents have high levels of stress or have developed PTSD themselves, children tend to show more anxiety symptoms. Parental stress can affect the severity of children's PTSD and lower the success of recovery. However, the influence of parental stress on the effectiveness of trauma-focused therapies (eye movement desensitisation and reprocessing and cognitive behavioural therapy) has not yet been investigated to our knowledge. Hence, we will measure parental stress (using both validated scales and vocal acoustic markers) and investigate how it influences children's PTSD recovery. METHOD AND ANALYSIS: Sixty children between the ages of 7 and 15 years who experienced type 1 trauma will be recruited at the Nice Pediatric Psychotrauma Center in France. We plan to measure stress using two different approaches. We will ask parents to answer validated scales of stress and mood in general. Stress will also be measured using vocal acoustic markers. Parents will be recorded while narrating their child's trauma and during the narrative of a positive and neutral recall of events. Child participants will have to complete anxiety, PTSD and depression scales before the beginning of the trauma-focused therapy and after 3 months of treatment.Linear mixed effects models and differential statistics, such as significance testing corrected for multiple testing, will be used to determine the validity of speech features for the proposed hypotheses. Repeated measures analysis of variance will be performed on the clinical scales scores according to parental stress. Correlations will be performed between clinical scales of parents and children according to time of assessment. ETHICS AND DISSEMINATION: This study was approved by the Committee for the Protection of Individuals of the University of Nice Sophia Antipolis (CERNI) on 21 February 2022, under the number CER2022-015.All participants will be informed that this is an observational study and their consent taken prior to the experiment. Participants will be informed that they can withdraw from the study at any time and that it would not affect the care provided. TRIAL REGISTRATION NUMBER: CER AVIS n° 2022-015.

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.

A 3-year retrospective study of 866 children and adolescent outpatients followed in the Nice Pediatric Psychotrauma Center created after the 2016 mass terror attack.

Background: The mass terrorist attack in Nice, France, in July 2016 caused deaths and injuries in a local population, including children and adolescents. The Nice Pediatric Psychotrauma Center (NPPC) was opened to provide mental health care to the pediatric population (0-18 years) who experienced traumatic events. Objectives: This study describes the specificity of the care pathway for young trauma victims, with an explanation of how the NPPC works during the first three years. Methods: In this retrospective study, we conducted quantitative and qualitative data collection about new and follow-up consultations, primary and comorbid diagnoses, and the kind of trauma (terrorist attack versus other kinds of trauma). Ethics approval was obtained from the local Ethics committee. Results: 866 children and adolescents were followed in the NPPC. We found a high rate of Post-Traumatic Stress Disorder (PTSD; 71%) in this population with a high rate of comorbidities (67%), mainly sleep disorders (34.7%) and mood and anxiety disorders (16.2%). A high number of children and adolescents impacted by the terrorist attack required follow-up consultations after exposure to the mass terrorist attack, the first care-seeking requests continued to occur three years later, although at a slower rate than in the first and second years. New consultations for other kinds of trauma were observed over time. Discussion: This study supports previous findings on the significant impact of mass trauma in the pediatric population showing even a higher level of PTSD and a high rate of comorbidities. This may be explained by the brutality of the traumatic event, particularly for this age group. The findings of this study have implications for early interventions and long-term care for children and adolescents to prevent the development of chronic PTSD into adulthood.

Antipsychotic Abuse, Dependence, and Withdrawal in the Pediatric Population: A Real-World Disproportionality Analysis.

Antipsychotic drugs (APs) aim to treat schizophrenia, bipolar mania, and behavioral symptoms. In child psychiatry, despite limited evidence regarding their efficacy and safety, APs are increasingly subject to off-label use. Studies investigating addictology-related symptoms in young people being scarce, we aimed to characterize the different patterns of AP misuse and withdrawal in children and adolescents relying on the WHO pharmacovigilance database (VigiBase®, Uppsala Monitoring Centre, Sweden). Using the standardized MedDRA Query 'drug abuse, dependence and withdrawal', disproportionality for each AP was assessed with the reporting odds ratio and the information component. A signal was detected when the lower end of the 95% confidence interval of the information component was positive. Results revealed mainly withdrawal symptoms in infants (under 2 years), intentional misuse in children (2 to 11 years), and abuse in adolescents (12 to 17 years). Olanzapine, risperidone, aripiprazole, and quetiapine were disproportionately reported in all age groups, with quetiapine being subject to a specific abuse signal in adolescents. Thus, in adolescents, the evocation of possible recreational consumption may lead to addiction-appropriate care. Further, in young patients with a history of AP treatment, a careful anamnesis may allow one to identify misuse and its role in the case of new-onset symptoms.

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.

Remote training as a common tool for the different professionals involved in the acute phase after terror attacks across Europe: Perspectives from an expert panel.

The acute response after a terror attack may have a crucial impact on the physical and psychological wellbeing of the victims. Preparedness of the professionals involved in the acute response is a key element to ensure effective interventions, and can be improved through trainings. Today in Europe there is a recognized lack of inter-professional and international trainings, which are important, among others, to respond to the needs and the rights of victims affected by a terrorist attack in another country than their home country. In this paper we report the perspectives of an expert panel composed by different categories of professionals on the possible role of interprofessional trainings provided remotely. The experts discussed the pertinence of remote trainings for professionals involved in the acute response of a terror attack, and highlighted their Strengths, Weaknesses, Opportunities and Threats (SWOT analysis). We concluded that, while remote trainings cannot replace in-person trainings, they may be useful to share knowledge about the role and the organization of the different categories of professionals, thus potentially improving response coordination, and to easily share good practices across professionals and countries.

[Child psychiatry in pediatric intensive care unit]. / Pédopsychiatrie en unité de soins intensifs pédiatriques.

A study was conducted in the pediatric intensive care and resuscitation unit of the Nice pediatric hospitals, University Hospital Center Lenval (06) from January to March 2015. Its objective was to describe the events and child psychiatric interventions experienced by young patients. Of the 181 individuals managed during the research, 63 met the inclusion criteria.

Adverse Drug Reactions of Olanzapine, Clozapine and Loxapine in Children and Youth: A Systematic Pharmacogenetic Review.

Children and youth treated with antipsychotic drugs (APs) are particularly vulnerable to adverse drug reactions (ADRs) and prone to poor treatment response. In particular, interindividual variations in drug exposure can result from differential metabolism of APs by cytochromes, subject to genetic polymorphism. CYP1A2 is pivotal in the metabolism of the APs olanzapine, clozapine, and loxapine, whose safety profile warrants caution. We aimed to shed some light on the pharmacogenetic profiles possibly associated with these drugs' ADRs and loss of efficacy in children and youth. We conducted a systematic review relying on four databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations and checklist, with a quality assessment. Our research yielded 32 publications. The most frequent ADRs were weight gain and metabolic syndrome (18; 56.3%), followed by lack of therapeutic effect (8; 25%) and neurological ADRs (7; 21.8%). The overall mean quality score was 11.3/24 (±2.7). In 11 studies (34.3%), genotyping focused on the study of cytochromes. Findings regarding possible associations were sometimes conflicting. Nonetheless, cases of major clinical improvement were fostered by genotyping. Yet, CYP1A2 remains poorly investigated. Further studies are required to improve the assessment of the risk-benefit balance of prescription for children and youth treated with olanzapine, clozapine, and/or loxapine.