Neurodevelopmental Disorders and Suicide: A Narrative Review

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study

Objective: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. Methods: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children’s-Sleep-Habits-Questionnaire (CSHQ). Results: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. Conclusion: Our findings support that sleep-problems are common in ADHD, but don’t suggest significant negative long-term effects of MPH on sleep

Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood:Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects)

Pandemic-related emergency psychiatric presentations for self-harm of children and adolescents in 10 countries (PREP-kids): a retrospective international cohort study

To examine the differences in hospital emergency psychiatric presentations for self-harm of children and adolescents during the covid-19 lockdown in March and April 2020 compared with the same period in 2019. Retrospective cohort study. We used electronic patient records from 23 hospital emergency departments in ten countries grouped into 14 areas. We examined data on 2073 acute hospital presentations by 1795 unique children and adolescents through age 18. We examined the total number of emergency psychiatric hospital presentations and the proportion of children and adolescents presenting with severe self-harm as our two main outcome measures. In addition, we examined sociodemographic and clinical characteristics and clinical management variables for those presenting with self-harm. To compare the number of hospital presentations between 2020 and 2019 a negative binomial model was used. For other variables, individual participant data (IPD) meta-analyses were carried out. Emergency psychiatric hospital presentations decreased from 1239 in 2019 to 834 in 2020, incident rate ratio 0.67, 95% CI 0.62-0.73; p < 0.001. The proportion of children and adolescents presenting with self-harm increased from 50% in 2019 to 57% in 2020, odds ratio 1.33, 1.07-1.64; p = 0.009 but there was no difference in the proportion presenting with severe self-harm. Within the subpopulation presenting with self-harm the proportion of children and adolescents presenting with emotional disorders increased from 58 to 66%, odds ratio 1.58, 1.06-2.36; p = 0.025. The proportion of children and adolescents admitted to an observation ward also decreased from 13 to 9% in 2020, odds ratio 0.52, 0.28-0.96; p = 0.036. Service planners should consider that, during a lockdown, there are likely to be fewer emergency psychiatric presentations. Many children and adolescents with psychiatric emergencies might not receive any service. A focus on developing intensive community care services with outreach capabilities should be prioritised

Lockdown stringency and paediatric self-harm presentations during COVID-19 pandemic: retrospective cohort study

Background Lockdown during the pandemic has had significant impacts on public mental health. Previous studies suggest an increase in self-harm and suicide in children and adolescents. There has been little research on the roles of stringent lockdown. Aims To investigate the mediating and predictive roles of lockdown policy stringency measures in self-harm and emergency psychiatric presentations. Method This was a retrospective cohort study. We analysed data of 2073 psychiatric emergency presentations of children and adolescents from 23 hospital catchment areas in ten countries, in March to April 2019 and 2020. Results Lockdown measure stringency mediated the reduction in psychiatric emergency presentations (incidence rate ratio of the natural indirect effect [IRRNIE] = 0.41, 95% CI [0.35, 0.48]) and self-harm presentations (IRRNIE = 0.49, 95% CI [0.39, 0.60]) in 2020 compared with 2019. Self-harm presentations among male and looked after children were likely to increase in parallel with lockdown stringency. Self-harm presentations precipitated by social isolation increased with stringency, whereas school pressure and rows with a friend became less likely precipitants. Children from more deprived neighbourhoods were less likely to present to emergency departments when lockdown became more stringent, Conclusions Lockdown may produce differential effects among children and adolescents who self-harm. Development in community or remote mental health services is crucial to offset potential barriers to access to emergency psychiatric care, especially for the most deprived youths. Governments should aim to reduce unnecessary fear of help-seeking and keep lockdown as short as possible. Underlying mediation mechanisms of stringent measures and potential psychosocial inequalities warrant further research

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.// Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.// Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.// Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents:Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.</p

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents:Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.</p