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.

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.

A novel microduplication in INPP5A segregates with schizophrenia spectrum disorder in the family of a patient with both childhood onset schizophrenia and autism spectrum disorder.

Childhood-Onset Schizophrenia (COS) is a very rare and severe psychiatric disorder defined by adult schizophrenia symptoms occurring before the age of 13. We report a microduplication in the 10q26.3 region including part of the Inositol Polyphosphate-5-Phosphatase A (INPP5A) gene that segregates with Schizophrenia Spectrum Disorders (SSDs) in the family of a female patient affected by both COS and Autism Spectrum Disorder (ASD). Phenotyping and genotyping (including CGH-array) were performed for mother, healthy sister, and affected child according to the GenAuDiss protocol (NCT02565524). The duplication size is 324 kb and is present in a patient with COS and in her mother with SSD, but not in the patient's healthy sister. INPP5A encodes a membrane-associated 43 kDa type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. This protein is found both in mouse and human brains and we found that its Drosophila homologue 5PtaseI is specifically expressed in the central nervous system. Hydrolyzed products from InsP3 5-phosphatases mobilize intracellular calcium, which is relevant for dendritic spine morphogenesis in neurons and altered in both schizophrenia and ASD. These may constitute arguments in favor of this gene alteration in the pathophysiology of COS.

Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports.

BACKGROUND: Phelan-Mc Dermid syndrome is a contiguous disorder resulting from 22q13.3 deletion implicating the SHANK3 gene. The typical phenotype includes neonatal hypotonia, moderate to severe intellectual disability, absent or delayed speech, minor dysmorphic features and autism or autistic-like behaviour. Recently, point mutations or micro-deletions of the SHANK3 gene have been identified, accompanied by a phenotype different from the initial clinically description in Phelan McDermid syndrome. CASE PRESENTATION: Here we present two case studies with similar psychiatric and genetic diagnosis as well as similar clinical history and evolution. The two patients were diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioural disorders after a stressful event during adolescence. Interestingly, both patients presented mutation/microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and methylphenidate) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioural symptoms and allowed patients to recover their pre-catatonia level of functioning, without significant side effects. CONCLUSION: These cases support the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to catatonia-like deterioration for which lithium use could be an efficient treatment. Therefore, these cases provide an important contribution to the field of autism research, clinical genetics and possible pharmacological answers.

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.

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.

Shame and guilt in the suicidality related to traumatic events: A systematic literature review.

Background: Shame and guilt are involved in suicidality and in post-traumatic stress disorder. However, few studies have explored the implication of those emotions in the suicidality of patients exposed to traumatic events. Objective: The objective of this literature review was to examine the implication of shame and guilt in the suicidality of individuals who have experienced potentially traumatic events or been diagnosed with post-traumatic stress disorder. These two emotions are part of post-traumatic stress disorder and suicidality. Moreover, when individuals perceive that their coping strategies are inadequate, they may view suicide as a relief from suffering. Method: This review was conducted according to PRISMA method. We used combinations of search words for traumatization, suicide ideation and behavior and shame and guilt to search for empirical studies in common databases in psychology and medicine. Results: Among 137 identified articles, 9 full texts were retained. Results suggest that shame and guilt were involved in all aspects of suicidality in patients who had experienced traumatic events or been diagnosed with post-traumatic stress disorder. The degree of shame and guilt differed with the type of traumatic event, notably affecting individuals who had experienced military combat, physical or sexual abuse, or emotional or physical neglect. Conclusion: Shame and guilt are implicated in suicide's risk. Future research is now needed to determine whether greater attention to these two emotions would enhance our understanding and anticipation of suicidal behavior in those who have experienced a potentially traumatic event or been diagnosed with post-traumatic stress disorder.

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.

Case Report: Anti-NMDAR Encephalitis Presenting With Catatonic Symptoms in an Adolescent Female Patient With a History of Traumatic Exposure.

INTRODUCTION: Catatonia is a severe syndrome associated with a high proportion of underlying organic conditions including autoimmune encephalitis. The link between catatonia and psychiatric conditions such as mood disorders and schizophrenia spectrum disorders is well established while the causative effect of Post-Traumatic Stress Disorders and stress related disorders remains speculative. CASE REPORT: Here we describe the clinical case of a 14-year-old female patient presenting to the Emergency Department of a Pediatric University Hospital with acute changes in behavior five days after a sexual abuse. Acute stress reaction was suspected. Afterwards she developed catatonic symptoms alternating from stupor to excitement, resistant to the usual treatment with benzodiazepines. The first line examinations (PE, MRI, EEG) were inconclusive. The final diagnosis of anti-NMDARE was made 22 days after her admission in a University Department of Child and Adolescent Psychiatry. Her state improved after first- and second-line immunotherapy, with no signs of relapse at this day (8 months of clinical follow-up). DISCUSSION: The diagnosis of anti-NMDARE is challenging, involving a multidisciplinary approach. The neuropsychiatric features are complex, with no specific psychiatric phenotype. Several hypotheses are discussed to determine the role of an acute environmental stressors in the emergence of such complex neuropsychiatric clinical presentation (i.e., shared vulnerability, precipitators, consequences of preexisting psychiatric symptoms). CONCLUSION: Child and adolescent psychiatrists and pediatricians should be aware of the overlap between neurological and psychiatric features in the setting of anti-NMDARE. Catatonia should not be dismissed as a primary psychiatric disorder even in the context of recent traumatic exposure.

Storm Alex: acute stress responses in the pediatric population.

Introduction: On 2 October 2020, a violent storm (Alex) reached the French Riviera and caused significant damage in three inhabited valleys in the hinterland of the city of Nice. Entire populations were exposed to prolonged stress (no means of communication, electricity nor water) and were particularly at risk of suffering from psychological consequences. We first hypothesized that a majority of children would experience an acute stress reaction. However, we also hypothesized that their clinical expression would differ depending on their developmental age. Thus, we aimed to evaluate, according to the child's level of development, the presence of acute stress symptoms. Methods: Consecutive interviews with the child/adolescent and his/her parents were conducted by child and adolescent psychologists and psychiatrists to assess symptomatology following storm Alex (from day 1 to day 3). Each interview assessed nine classes of symptoms that have been compared according to age-groups. Results: 116 children have been evaluated (0.2-17.6 years, mean 9.1). The 0-5-years-old showed more agitation as well as developmental regression than children aged 6-11 (p = .011, p = .045) and 12-18 years (p < .001, p < .001). Anxiety was reported more frequently among the 6-11 years old than the 0-5 years children (p = .018). Overall, the interviewed children presented at least one manifestation of acute stress after the storm (94% for the 0-5 years; 83% for the 6-11 years and 74% for the 12-18 years). Discussion: The results highlight the high rate of acute stress symptoms in a natural disaster context, their specificity depending on children's age. Therefore; it emphasizes the need to develop, improve and validate specific assessment tools. Scheduled follow-up evaluations will help to understand, after a natural disaster, the long-term stress response in children, paving the way for targeting early, intensive, specific and multidisciplinary symptomatic treatment approaches.Trial registration: ClinicalTrials.gov identifier: NCT04850924. HIGHLIGHTS: Acute stress symptoms in children and adolescents are very frequent in the context of exposure to a natural disaster with specifications depending on the developmental age.

Drug-Associated Parosmia: New Perspectives from the WHO Safety Database.

Parosmia is a qualitative distortion of smell perception. Resulting from central causes, sinonasal diseases, and infections, parosmia has also been associated with medications. Therefore, we aimed to investigate potential signals for drugs associated with parosmia. VigiBase® (the WHO pharmacovigilance database) was queried for all reports of "Parosmia" (MedDRA Preferred Term), registered up to 23 January 2022. Disproportionality analysis relied on the reporting odds ratio and the information component. A signal is detected when the lower end of the 95% confidence interval of the information component is positive. We found 14,032 reports of parosmia, with a median patient age of 53 years. Most reported drugs were antiinfectives, among which COVID-19 vaccines accounted for 27.1% of reports. Antibiotics and corticosteroids were involved in 6.8% and 4.6% of reports. Significant disproportionate reporting was detected for corticosteroids, antibiotics, drugs used in nicotine dependence, COVID-19 and HPV vaccines, serotonin-norepinephrine reuptake inhibitors (SNRI), and incretin mimetics. We suggest potential safety signals involving nicotine replacement therapies and vaccines. We also highlight the potential role of less suspected classes, such as SNRIs and incretin mimetics. An iatrogenic etiology should be evoked when parosmia occurs, especially in the elderly.

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.

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.

Validation of the French Version of the Child Posttraumatic Stress Checklist in French School-Aged Children.

Background: The child posttraumatic stress disorder checklist (CPC) updated to DSM-5 is a questionnaire aimed to assess posttraumatic stress disorder (PTSD) symptoms in children. It is available in both parents and child versions. The back-translation method has been used for the French translation of the CPC. It has not been yet validated in French-speaking populations. The aim of this study was to assess the psychometric properties and the validity of the CPC in a sample of French-speaking schoolchildren and their parents. Methods: The sample was composed by 176 children outpatients implicated in the Nice terrorist attack (14 July 2016) aged 7-17 (mean = 11.68 years, SD = 2.63 months) and 122 parents. Cronbach's alpha was used to test CPC internal consistency. The Spearman-correlation coefficient was performed between the French version of the CPC and the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime version (K-SADS-PL) to assess the convergent validity. An ROC curve was constructed to verify the validity of the cutoff scores. An evaluation of the sensitivity and specificity of each score and a comparison with the diagnosis of the K-SADS-PL were made. Finally, a principal component analysis with varimax rotation was computed to analyze the structure of the French version of the CPC. Results: Cronbach's alpha coefficient was 0.90 for child version and 0.91 for parent version of the CPC. There was a statistical correlation between the K-SADS-PL for PTSD and the total score of CPC for the child version (r = 0.62; p < 0.001) and for the parent version (r = 0.55; p < 0.001). The sensitivity and specificity of the children version with a threshold of >20 were 73.1 and 84.7%, respectively, using the K-SADS-PL as the diagnostic reference for PTSD. Concerning the parent version, using the same recommended cutoff score, the sensitivity, and specificity were 77 and 80.5%, respectively. Conclusions: The psychometric properties of the French CPC are good. This questionnaire appears to be valid and should be used in French-speaking children.

In-Person and Remote Workshops for People With Neurocognitive Disorders: Recommendations From a Delphi Panel.

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders.

Different clinical presentation in siblings with mitochondrial acetoacetyl-CoA thiolase deficiency and identification of two novel mutations.

Mitochondrial acetoacetyl-CoA thiolase (T2) catalyzes 2-methylacetoacetyl-CoA cleavage into acetyl-CoA and propionyl-CoA in isoleucine catabolism and interconversion between acetyl-CoA and acetoacetyl-CoA in ketone body metabolism. T2 deficiency is a rare metabolic disease of autosomal recessive inheritance. The disorder is characterized by intermittent ketoacidotic episodes. The onset of clinical symptoms is in the infant or toddler period. The frequency of episodes declines with age, stopping before adolescence. Here we report two siblings with this disorder. The proband (GK65) is a French girl born from non-consanguineous parents. She presented several ketoacidotic episodes with 5 hospitalizations from age 2 to 4 years, the first of them complicated by ketoacidotic coma. Minor episodes, which are generally provoked by infections or high protein intake, still persist at age of 16 years. Molecular analysis of the T2 gene has revealed the compound heterozygosity of c.578T>C (M193T) and IVS8+5g>t. The latter mutation results in skipping of exon 8. In contrast, the younger brother (GK65b) had a unique ketoacidotic crisis at the age of 6 years that is the oldest-age first crisis among T2-deficient patients reported thus far. Despite the mild phenotype, he carried the same T2 gene mutations as his sister (GK65). Furthermore, T2 catalytic activity and T2 protein were not detected in the fibroblasts derived from GK65 and GK65b. In conclusion, the siblings with the same T2 gene mutations present different clinical severity. Diagnostic testing for asymptomatic siblings is important in the management of T2-deficient families.

Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype.

Depression is a devastating illness with a lifetime prevalence of up to 20%. The neurotransmitter serotonin or 5-hydroxytryptamine (5-HT) is involved in the pathophysiology of depression and in the effects of antidepressant treatments. However, molecular alterations that underlie the pathology or treatment of depression are still poorly understood. The TREK-1 protein is a background K+ channel regulated by various neurotransmitters including 5-HT. In mice, the deletion of its gene (Kcnk2, also called TREK-1) led to animals with an increased efficacy of 5-HT neurotransmission and a resistance to depression in five different models and a substantially reduced elevation of corticosterone levels under stress. TREK-1-deficient (Kcnk2-/-) mice showed behavior similar to that of naive animals treated with classical antidepressants such as fluoxetine. Our results indicate that alterations in the functioning, regulation or both of the TREK-1 channel may alter mood, and that this particular K+ channel may be a potential target for new antidepressants.

[Review of the prescription of antipsychotics in children]. / État des lieux de la prescription des antipsychotiques chez l'enfant.

Review of the prescription of antipsychotics in children. In France, as in the rest of the world, prescribing of antipsychotic drugs increases in children and adolescentsIndeed, antipsychotics are frequently prescribed in children and adolescents for both psychotic and non-psychotic disorders, with 36 to 93%o fprescriptionsbeingoff-label in this population. In addition, a high number of adverse events have been reported in the literature under antipsychotic treatment. The consequences of these adverse events are still poorly documented. In France, a 12-months national prospective study (ETAPE) observed a high incidence rate, severity and persistence of adverse events during first-time antipsychotic treatment in pediatric patients. Therefore, a careful and continuous clinical and biological monitoring all over the treatment period is required to adapt treatment decisions based on benefice-risk-analysis.

État des lieux de la prescription des antipsychotiques chez l'enfant. En France, comme dans le reste du monde, les prescriptions d'antipsychotiques augmentent chez l'enfant et l'adolescent. Les antipsychotiques sont fréquemment prescrits chez l'enfant et l'adolescent pour des troubles psychotiques et non psychotiques. Le taux de prescription effectué hors autorisation de mise sur le marché (AMM) s'étend de 36 à 93 % dans cette population. De plus, un nombre important d'effets secondaires sous antipsychotiques ont été rapportés dans la littérature. Les conséquences de ces effets secondaires sont encore insuffisamment documentées. En France, une étude nationale prospective sur 12 mois (ETAPE) réalisée en population pédiatrique exposée pour la première fois à un antipsychotique a montré un taux d'incidence d'effets secondaires élevé, une sévérité et la persistance de ces effets pendant toute la durée du suivi. Aussi une surveillance attentive et régulière, clinique et biologique, pendant toute la durée d'exposition au traitement est nécessaire afin d'adapter les décisions thérapeutiques en fonction de la balance bénéfice-risque.