Psychotic symptoms with and without a primary psychotic disorder in children requiring inpatient mental health admission.

Psychotic symptoms are relatively common in children and adolescents attending mental health services. On most occasions, their presence is not associated with a primary psychotic disorder, and their clinical significance remains understudied. No studies to date have evaluated the prevalence and clinical correlates of psychotic symptoms in children requiring inpatient mental health treatment. All children aged 6 to 12 years admitted to an inpatient children's unit over a 9-year period were included in this naturalistic study. Diagnosis at discharge, length of admission, functional impairment, and medication use were recorded. Children with psychotic symptoms without a childhood-onset schizophrenia spectrum disorder (COSS) were compared with children with COSS and children without psychotic symptoms using Chi-square and linear regressions. A total of 211 children were admitted during this period with 62.4% experiencing psychotic symptoms. The most common diagnosis in the sample was autism spectrum disorder (53.1%). Psychotic symptoms were not more prevalent in any diagnosis except for COSS (100%) and intellectual disability (81.8%). Psychotic symptoms were associated with longer admissions and antipsychotic medication use. The mean length of admission of children with psychotic symptoms without COSS seems to lie in between that of children without psychotic symptoms and that of children with COSS. We concluded that psychotic symptoms in children admitted to the hospital may be a marker of severity. Screening for such symptoms may have implications for treatment and could potentially contribute to identifying more effective targeted interventions and reducing overall morbidity.

Clinical and cost-effectiveness of an adapted intervention for preschoolers with moderate to severe intellectual disabilities displaying behaviours that challenge: the EPICC-ID RCT.

Background: Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship. Objective: To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities. Design, setting, participants: A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n = 155) or treatment as usual arm (n = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle. Intervention: Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic. Main outcome measure: The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge. Results: We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p = 0.014) and -11.53 (95% CI -26.97 to 3.91, p = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively (p = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention. Limitations: There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention. Conclusions: Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks. Future work: Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes. Study registration: This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information.

Research shows that in children without learning disabilities, parenting groups which support parents to develop skills to manage behaviours that challenge in their child can be helpful. The National Institute of Health and Care Excellence recommended that more research was needed to strengthen the evidence for such interventions for children with moderate to severe learning disability who are more likely to display behaviours that challenge in England. In this study, we tested in real-world conditions a programme called level 4 Stepping Stones Triple P, which has shown positive results in trials outside of the United Kingdom. Trained therapists delivered six groups and three individual sessions over 9 weeks to parents of children aged 30­59 months with moderate to severe learning disabilities. Two hundred and sixty-one parents were allocated to one of two arms by chance (randomisation): one received Stepping Stones Triple P and treatment as usual and the other treatment as usual only. Treatment as usual included support and advice by general practitioners or community child development teams. Our primary outcome was parent-reported child behaviour at 12 months after randomisation. We also collected data on other outcomes and carried out interviews with parents, service managers and therapists to find out their views about Stepping Stones Triple P. We did not find that Stepping Stones Triple P reduces behaviours that challenge in the child more than treatment as usual at 12 months. However, when we looked at people who received more than half of the sessions, there was a larger reduction in behaviours which suggests that Stepping Stones Triple P works for families if they attend the full programme. Stepping Stones Triple P seems to be good value for money, as we found that at 12 months (covering 10 months of costs), the Stepping Stones Triple P cost £1058 less than treatment as usual from a health and social care perspective. As such, Stepping Stones Triple P is fairly cheap to deliver and a suitable early intervention for behaviours that challenge especially because of positive feedback from parents. Throughout the trial, we included a Parent Advisory Group that oversaw study materials, interview topic guides and promotion of the study.

Umbrella Review: Atlas of the Meta-Analytical Evidence of Early-Onset Psychosis.

OBJECTIVE: Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in the field of this vulnerable population and to provide evidence-based recommendations. METHOD: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant, pre-registered (PROSPERO: CRD42022350868) systematic review of several databases and registers to identify meta-analyses of studies conducted in EOP individuals to conduct an umbrella review. Literature search, screening, data extraction, and quality assessment were carried out independently. Results were narratively reported, clustered across core domains. Quality assessment was performed with the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. RESULTS: A total of 30 meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% female). Individuals with EOP showed more cognitive impairments compared with controls and individuals with adult/late-onset psychosis. Abnormalities were observed meta-analytically in neuroimaging markers but not in oxidative stress and inflammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest efficacy for overall, positive, and negative symptoms. Tolerance to medication varied among the evaluated antipsychotics. The risk of discontinuation of antipsychotics for any reason or side effects was low or equal compared to placebo. CONCLUSION: EOP is associated with cognitive impairment, involuntary admissions, and poor prognosis. Antipsychotics can be efficacious in EOP, but tolerability and safety need to be taken into consideration. Clozapine should be considered in EOP individuals who are resistant to 2 non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors. STUDY PREREGISTRATION INFORMATION: Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

The impact of the COVID-19 pandemic on children and young people.

In March 2020, the World Health Organization declared the spread of COVID-19 as a global pandemic, and youth worldwide were suddenly confronted with unprecedented consequences. The first line of concern was related to the direct effect of SARS-CoV-2 viral infection. While severe physical health symptomatology including death following infection was found to be less common in children than in adults,1 long-COVID has been identified in the pediatric population with the most prevalent manifestations involving mood symptoms, sleep difficulties, and fatigue.2 Secondly, the measures against COVID-19 carried their own set of risks. Many governments imposed national lockdowns, schools closed, remote learning started operating and social distancing measures prevented families from visiting public places or meeting people from other households. Isolation, disruption of everyday routines, and a sharp and dramatic decrease in physical activity and social interaction levels became the new reality experienced by children and adolescents of all age groups.3 Cross-sectional community studies on children and adolescents conducted early in the course of the pandemic indicated elevated levels of loneliness, anxiety, and behavioral problems in youth samples, even during the initial phases of the outbreak.4 Systematic reviews of mainly cross-sectional studies that followed indicated a significant rise in clinically significant anxiety and depression symptoms among children and adolescents compared to pre-pandemic levels5 and high prevalence estimates for depression, anxiety, posttraumatic stress symptomatology, and sleep disorders.6 A recent systematic review that included data from 55,000 children and adolescents from many countries of the world (mean age 11.3 years) reported that anxiety (range = 1.8­49.5%), depression (range = 2.2­ 63.8%), irritability (range = 16.7­73.2%) and anger (range = 30.0­51.3%) were frequently reported by children and adolescents during the pandemic.7 However, the experience of the pandemic was not homogenous among all youth. Possible risk factors included the presence of mental health problems before the pandemic, excessive exposure to media, and high COVID-19 caseload in the community, while the presence of any kind of family routines and good parent-child communication were identified as protective factors.7 Females and older adolescents were also reported to be at greater risk for adverse mental health outcomes. In most countries, the spread of the infection, on one hand, and the enforcement of lockdowns and other containment measures, on the other, have put health care under tremendous pressure, leaving families with children with mental health disorders with minimal or inadequate support. Nevertheless, differences were also observed within the group of children with psychiatric or developmental disorders diagnosed before the pandemic. Numerous studies that have investigated the impact of the COVID-19 pandemic and related containment measures on children and adolescents with autism spectrum disorders reported a significant increase in parental stress, as well as high levels of anxiety, irritability, hyperactivity, stereotypical behavior, and other behavioral problems among children and adolescents.8 Further studies that investigated the issue of neurodevelopmental disorders showed that the COVID-19 pandemic has disproportionately and adversely affected children with attention-deficit/hyperactivity disorder (ADHD) with a recent meta-analysis pointing to a global increase in ADHD symptoms.9 Finally, early concerns about a possible significant increase in suicidality among youth during the pandemic were followed by contradicting findings from relevant studies. On the whole, though, it is suggested that during the pandemic, as previously, higher rates of suicidal ideation than of suicidal behaviors and suicide events were reported among children and adolescents.10 Similar patterns of mental health difficulties to those described above have also been identified in youth in Greece. During the early stages of the pandemic, one-third (35.1%) of the parents reported that their child's psychological health was considerably affected,11 while a study of final-year high-school students found that the rates of severe depression and anxiety increased significantly during the lockdown.12 Among children and adolescents with pre-existing mental health problems from different parts of the country, no change was found in mood state scores pre- and post-pandemic onset, while several of their daily behaviors worsened during the lockdown, such as reduced sleep or time spent outdoors.13 Such research findings related to the effects of the COVID-19 pandemic and its containment measures should guide the follow-up of children and young people affected by it and inform the design of effective health strategies and policies in the post-pandemic era with the aim to prevent and mitigate further mental health crises.

Trait and State Anxiety Effects on Mismatch Negativity and Sensory Gating Event-Related Potentials.

We used the auditory roving oddball to investigate whether individual differences in self-reported anxiety influence event-related potential (ERP) activity related to sensory gating and mismatch negativity (MMN). The state-trait anxiety inventory (STAI) was used to assess the effects of anxiety on the ERPs for auditory change detection and information filtering in a sample of thirty-six healthy participants. The roving oddball paradigm involves presentation of stimulus trains of auditory tones with certain frequencies followed by trains of tones with different frequencies. Enhanced negative mid-latency response (130-230 ms post-stimulus) was marked at the deviant (first tone) and the standard (six or more repetitions) tone at Fz, indicating successful mismatch negativity (MMN). In turn, the first and second tone in a stimulus train were subject to sensory gating at the Cz electrode site as a response to the second stimulus was suppressed at an earlier latency (40-80 ms). We used partial correlations and analyses of covariance to investigate the influence of state and trait anxiety on these two processes. Higher trait anxiety exhibited enhanced MMN amplitude (more negative) (F(1,33) = 14.259, p = 6.323 × 10-6, ηp2 = 0.302), whereas state anxiety reduced sensory gating (F(1,30) = 13.117, p = 0.001, ηp2 = 0.304). Our findings suggest that high trait-anxious participants demonstrate hypervigilant change detection to deviant tones that appear more salient, whereas increased state anxiety associates with failure to filter out irrelevant stimuli.

Experience of stigmatization in children receiving inpatient and outpatient mental health treatment: a longitudinal study.

Mental health-related stigma is poorly understood, and minimal research has focused on the experience of stigma from children's perspectives. We sought to investigate whether children treated as inpatients and outpatients had different experiences of stigma over time and whether stigma is linked to global functioning cross-sectionally and longitudinally. Children, aged 8-12 years, receiving treatment within a national specialist mental health inpatient unit were matched for age, gender and diagnosis with children receiving outpatient treatment (N = 64). Validated measures of stigma, global functioning and symptom severity were collected at the start of treatment and upon discharge from the ward for inpatients, and a similar timeframe for their individually matched outpatients. Latent change score models and partial correlation coefficients were employed to test our hypotheses. No differences in most aspects of stigma between children treated as inpatients and outpatients were observed, except for personal rejection at baseline and self-stigma at follow-up favouring outpatients. A reduction in stigma was observed in societal devaluation, personal rejection and secrecy for inpatients, and self-stigma and secrecy for outpatients between the two assessments. Societal devaluation declined at a higher rate among inpatients compared to outpatients, albeit reductions in stigma were comparable for all remaining measures. No association was found between the change in stigma and change in global functioning. Future research may offer further insights into the development and maintenance of stigma and identify key targets for anti-stigma interventions to reduce its long-term impact.

Functional neurodevelopment of working memory in early-onset schizophrenia: A longitudinal FMRI study.

Schizophrenia, a debilitating disorder with typical manifestation of clinical symptoms in early adulthood, is characterized by cognitive impairments in executive processes such as in working memory (WM). However, there is a rare case of individuals with early-onset schizophrenia (EOS) starting before their 18th birthday, while WM and its neural substrates are still undergoing maturation. Using the WM n-back task with functional magnetic resonance imaging, we assessed the functional neurodevelopment of WM in adolescents with EOS and age- and gender-matched typically developing controls. Participants underwent neuroimaging in the same scanner twice, once at age 17 and at 21 (mean interscan interval = 4.3 years). General linear model analysis was performed to explore WM neurodevelopmental changes within and between groups. Psychopathological scores were entered in multiple regressions to detect brain regions whose longitudinal functional change was predicted by baseline symptoms in EOS. WM neurodevelopment was characterized by widespread functional reductions in frontotemporal and cingulate brain areas in patients and controls. No between-group differences were found in the trajectory of WM change. Baseline symptom scores predicted functional neurodevelopmental changes in frontal, cingulate, parietal, occipital, and cerebellar areas. The adolescent brain undergoes developmental processes such as synaptic pruning, which may underlie the refinement WM of network. Prefrontal and parietooccipital activity reduction is affected by clinical presentation of symptoms. Using longitudinal neuroimaging methods in a rare diagnostic sample of patients with EOS may help the advancement of neurodevelopmental biomarkers intended as pharmacological targets to tackle WM impairment.

Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.