Detection of copy number variations (CNVs) is a first-tier clinical diagnostic test for children with neurodevelopmental disorders (NDD), which reveals the genetic cause of the disorder in more than ...20%. These are mostly known microdeletion/microduplication syndromes, but variants of unknown clinical significance (VOUS) and ambiguous CNVs can also be detected. An example of the last two are abnormalities in the DOCK8 gene. Conflicting interpretations of CNVs affecting DOCK8 can be found in the literature. Deletions were predicted to have a impact in carriers with variable clinical manifestations, where duplications have been proposed as benign variants. In our study, CNV screening was performed in a cohort involving 439 probands with suspected NDD. We identified known microdeletion/microduplication syndromes in 19% and VOUS CNVs in 8% of patients. Among these, three patients had a CNV encompassing the DOCK8 gene. Although diverse clinical presentations are noted in our three patients, comparison of their phenotypes revealed that abnormalities in cognition and communication, aggressive behaviour and mood swings are common to all of them. Therefore, a clinical relevance, in terms of influencing the psychiatric clinical picture of patients, is proposed for the CNVs disrupting the DOCK8 gene, regardless of whether it is a deletion or duplication.
Most guidelines for the management of aggressive behavior in acute psychiatric patients describe the use of de-escalation as the first-choice method, but the evidence for its effectiveness is ...inconsistent. The aim of the study was to assess the effect of verbal and non-verbal de-escalation on the incidence and severity of aggression and the use of physical restraints in acute psychiatric wards.
A multi-center cluster randomized study was conducted in the acute wards of all psychiatric hospitals in Slovenia. The research was carried out in two phases, a baseline period of five consecutive months and an intervention period of the same five consecutive months in the following year. The intervention was implemented after the baseline period and included training in verbal and non-verbal de-escalation techniques for the staff teams on experimental wards.
In the baseline study period, there were no significant differences in the incidence of aggressive behavior and physical restraints between the experimental and control groups. The incidence rates of aggressive events, severe aggressive events, and physical restraints per 100 treatment days decreased significantly after the intervention. Compared to the control group, the incidence rate of aggressive events was 73% lower in the experimental group (IRR = 0.268, 95% CI 0.221; 0.342), while the rate of severe events was 86% lower (IRR = 0.142, 95% CI 0.107; 0.189). During the intervention period, the incidence rate of physical restraints due to aggression in the experimental group decreased to 30% of the rate in the control group (IRR = 0.304, 95% CI 0.238; 0.386). No reduction in the incidence of restraint used for reasons unrelated to aggression was observed. After the intervention, a statistically significant decrease in the severity of aggressive incidents (
< 0.001) was observed, while the average duration of restraint episodes did not decrease.
De-escalation training is effective in reducing the incidence and severity of aggression and the use of physical restraints in acute psychiatric units.
www.ClinicalTrials.gov, identifier NCT05166278.
Slovenia is a small European country facing rapid changes that also impact child and adolescent psychiatry (CAP) in the country. Looking back, Slovenia had been a part of the Austro-Hungarian Empire ...for almost 600 years. After its collapse at the end of WWI, the country gained its independence as part of the Kingdom of Serbs, Croats, and Slovenes. After WWII, Slovenia became a constituent republic of Yugoslavia and remained part of Yugoslavia until 1991 when it gained its independence. In 2004, Slovenia joined the European Union.Political, social, and economic shifts that Slovenia was facing after the breakup of Yugoslavia were dramatic. Loss of social security and growing unemployment, which was at the time above 15%, changed family dynamics in a very dysfunctional way. The situation improved only 10 years after the breakup of Yugoslavia when Slovenia’s economy finally managed to reach other European counties. However, it worsened again with the world economic crisis in 2008. Today, Slovenia’s economy is growing again. In terms of demographics, Slovenia has 2.1 million inhabitants, 15% of which are aged 0–14 1. Ljubljana is the country’s capital city.
This double-blind pilot randomized placebo-controlled trial examined the possible effect of the probiotic strain
GG ATCC53103 (LGG) on symptoms of attention-deficit/hyperactivity disorder (ADHD), ...health-related quality of life (QoL), and serum levels of cytokines in children and adolescents with ADHD.
This trial evaluated 32 drug-naive children and adolescents aged between four and 17 years with a diagnosis of ADHD. The study subjects were randomly assigned to either the group that received LGG or the group that received the placebo. Assessments, comprising
;
; and the serum cytokines; were compared between the groups at the baseline and after 3 months.
Thirty-five participants were randomized, with 32 completing the study (91.4% retention). There was a significant improvement in the PedsQL Child Self-Report Total Score after 3 months of treatment in the probiotic (
= 0.021, d = 0.53), whereas there was no significant improvement in the placebo group (
= 0.563, d = 0.04). The results of psychometric parameters assessed by parents and teachers were not so straightforward. There were statistically significant differences in the levels of serum cytokines between the groups after the 3-month treatment period: IL-6 in both the probiotic (
= 0.004, d = 0.73) and the placebo groups (
= 0.035, d = 0.94); IL-10 (
= 0.035, d = 0.6); IL-12 p70 (
= 0.025, d = 0.89); and TNF-α (
= 0.046, d = 0.64) in the probiotic group only.
Children and adolescents with ADHD who received LGG supplementation reported better health-related QoL compared to their peers who received the placebo. This suggests that LGG supplementation could be beneficial. But results with psychometric tests conducted by parents and teachers as well as differences in the levels of inflammatory cytokines were ambiguous. Based on these results, we propose some study modifications: a longer observation period (6-12 months); inclusion of more children's self-report assessments; recruitment of non-drug naive patients and the possible omission of serum cytokines measurements.
Medical Ethics Committee (UKC-MB-KME-19-06/16).
Early-onset schizophrenia (EOS) and bipolar disorder (EOB) start before the age of 18 years and have a more severe clinical course, a worse prognosis, and a greater genetic loading compared to the ...late-onset forms. Copy number variations (CNVs) are an important genetic factor in the etiology of psychiatric disorders. Therefore, this study aimed to analyze CNVs in patients with EOS and EOB and to establish genotype-phenotype relationships for contiguous gene syndromes or genes affected by identified CNVs.
Molecular karyotyping was performed in 45 patients, 38 with EOS and seven with EOB hospitalized between 2010 and 2017. The exclusion criteria were medical or neurological disorders or IQ under 70. Detected CNVs were analyzed according to the standards and guidelines of the American College of Medical Genetics.
Molecular karyotyping showed CNVs in four patients with EOS (encompassing the
, and
genes, and the 16p11.2 microduplication syndrome) and in two patients with EOB (encompassing the
and
genes). In one patient with EOB, a chromosomal aneuploidy 47, XYY was found.
Our study is the first study of CNVs in EOS and EOB patients in Slovenia. Our findings support the association of the
, and
genes with schizophrenia and/or bipolar disorder. To our knowledge, this is also the first report of a multiplication of the
gene and the smallest deletion of the
gene in a patient with EOS, and one of the few reports of the 47, XYY karyotype in a patient with EOB.
Autism spectrum disorders (ASD) represent a phenotypically heterogeneous group of patients that strongly intertwine with other neurodevelopmental disorders (NDDs), with genetics playing a significant ...role in their etiology. Whole exome sequencing (WES) has become predominant in molecular diagnostics for ASD by considerably increasing the diagnostic yield. However, the proportion of undiagnosed patients still remains high due to complex clinical presentation, reduced penetrance, and lack of segregation analysis or clinical information. Thus, reverse phenotyping, where we first identified a possible genetic cause and then determine its clinical relevance, has been shown to be a more efficient approach. WES was performed on 147 Slovenian pediatric patients with suspected ASD. Data analysis was focused on identifying ultrarare or “single event” variants in ASD-associated genes and further expanded to NDD-associated genes. Protein function and gene prioritization were performed on detected clinically relevant variants to determine their role in ASD etiology and phenotype. Reverse phenotyping revealed a pathogenic or likely pathogenic variant in ASD-associated genes in 20.4% of patients, with subsequent segregation analysis indicating that 14 were
de novo
variants and 1 was presumed compound heterozygous. The diagnostic yield was further increased by 2.7% by the analysis of ultrarare or “single event” variants in all NDD-associated genes. Protein function analysis established that genes in which variants of unknown significance (VUS) were detected were predominantly the cause of intellectual disability (ID), and in most cases, features of ASD as well. Using such an approach, variants in rarely described ASD-associated genes, such as
SIN3B
,
NR4A2
, and
GRIA1
, were detected. By expanding the analysis to include functionally similar NDD genes, variants in
KCNK9
,
GNE
, and other genes were identified. These would probably have been missed by classic genotype–phenotype analysis. Our study thus demonstrates that in patients with ASD, analysis of ultrarare or “single event” variants obtained using WES with the inclusion of functionally similar genes and reverse phenotyping obtained a higher diagnostic yield despite limited clinical data. The present study also demonstrates that most of the causative genes in our cohort were involved in the syndromic form of ASD and confirms their comorbidity with other developmental disorders.
Autistic traits or autism spectrum disorder (ASD) can be found in 4% to 52% of anorexic patients, which makes the treatment of these patients very challenging. In this review, possible ways to treat ...ASD and anorexia nervosa (AN) comorbidity in children and adolescents are summarized. Over recent years, the focus has shifted from searching for the evidence of connections between these two disorders, which have started with Gillberg's study in 1983, to searching for more effective and holistic treatment of this comorbidity. The latter is known to contribute to more severe courses and worse prognosis, which is probably related to the obstacles in both diagnosing and treating. Since AN usually starts in early adolescence and high-functioning ASD children seem to begin struggling with increased pressure in adolescence, while various comorbidities can occur, it is important to improve the treatment of this comorbidity in young patients and to tailor it specifically in terms of diagnosing. In this paper, a literature review is conducted on common features and promising treatment possibilities. We describe cognitive remediation therapy and the promising pharmacotherapeutic candidate oxytocin with a special focus on adolescents.
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