Aim: To evaluate the incidence, severity and characteristics of aggressive behaviour in patients hospitalized in acute psychiatric wards, as well as the association between patient characteristics and the incidence of recurrent aggressive behaviour. Methods: A multicentre prospective study included all twelve acute wards in Slovenian psychiatric hospitals with a total capacity of 232 beds. Over five consecutive months, data on the number of treatment episodes involving aggressive behaviour and the number of aggressive incidents, their severity and characteristics were obtained using the Staff Observation Aggression Scale-Revised (SOAS-R). Patient- and event-based incident rates of verbal and physical aggression were calculated. The association between patient characteristics and recurrent aggressive behaviour was analysed. Patient characteristics data were extracted from hospital databases. Results: 3,190 treatment episodes were included during a 5-month period. Aggressive behaviour was observed in 13.4% of treatment episodes, and 922 aggressive incidents were recorded, which resulted in 3.98 incidents per 100 occupied bed days and 9.48 incidents per bed per year. 74.1% of incidents were severe, and more than half of incidents included physical aggression. 75.5% of incidents were directed against medical staff. 5.9% of treatment episodes were involved in multiple aggressive incidents. Compared to patients with single incidents, patients with recurrent aggression had a less frequent main diagnosis of substance use disorders and a longer duration of hospitalization. Conclusion: Monitoring the frequency and characteristics of aggressive behaviour allows comparisons with other studies and, more importantly, it is necessary for planning and assessing the effectiveness of preventative aggression management strategies.
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.
Objective: 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. Methods: 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. Results: 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 (p < 0.001) was observed, while the average duration of restraint episodes did not decrease. Conclusion: De-escalation training is effective in reducing the incidence and severity of aggression and the use of physical restraints in acute psychiatric units. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT05166278].
The present study is the first to examine both the implicit and explicit self-concept of identity diffusion in a sample of adolescent patients with borderline personality disorder (BPD). A clinical sample of adolescent girls with diagnosed BPD (N = 30; M age = 15.9 years) and a sample of girls with a healthy personality development (N = 33; M age = 16.6 years) completed an implicit association test (IAT) that was adjusted to identity diffusion, the core of BPD. Common domains of child and adolescent psychopathology and core components of BPD were assessed using self-reports on the Strengths and Difficulties Questionnaire (SDQ), the Borderline Personality Features Scale for Children-11 (BPFSC-11) and the Assessment of Identity Development in Adolescence (AIDA). BPD patients scored significantly higher on explicit measures of borderline pathology than girls with a healthy personality development. A crucial finding for this study was that girls with BPD had a significantly lower implicit preference for stability than their counterparts in the control group. Moreover, explicit measures of borderline personality pathology were significantly correlated with an implicit measure of identity diffusion, the core of BPD. However, when looking at the predictive ability of implicit and explicit measures, only explicit identity diffusion was significantly associated with borderline features. Our data suggests that adolescent girls with BPD differ from healthy individuals not only in their conscious representation but also in their implicit representation of the self with regard to BPD related characteristics, which further advances the need for the identification of at-risk adolescents.
Introduction: 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. Methods: 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. Result: Molecular karyotyping showed CNVs in four patients with EOS (encompassing the PAK2, ADAMTS3, and ADAMTSL1 genes, and the 16p11.2 microduplication syndrome) and in two patients with EOB (encompassing the ARHGAP11B and PRODH genes). In one patient with EOB, a chromosomal aneuploidy 47, XYY was found. Discussion: Our study is the first study of CNVs in EOS and EOB patients in Slovenia. Our findings support the association of the PAK2, ARHGAP11B, and PRODH genes with schizophrenia and/or bipolar disorder. To our knowledge, this is also the first report of a multiplication of the ADAMTSL1 gene and the smallest deletion of the PAK2 gene in a patient with EOS, and one of the few reports of the 47, XYY karyotype in a patient with EOB.
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.
DNA Copy Number Variations , Gene Deletion , Guanine Nucleotide Exchange Factors/genetics , Neurodevelopmental Disorders/genetics , Aggression , Child , Cognition , Communication , Female , Humans , Male , Neurodevelopmental Disorders/pathology , Phenotype
Chromosomal abnormalities involving 2q32q33 deletions are very rare and present with a specific phenotype. This case report describes a 37-year-old female patient with 2q32q33 microdeletion syndrome presenting with the characteristic features, but with the addition of secondary cognitive decline. Molecular karyotyping was performed on the patient and her parents. It revealed an 8.6 megabase deletion with the proximal breakpoint in the chromosome band 2q32.2 and the distal breakpoint in 2q33.1. The deletion encompassed 22 known genes, including theGLS,MYO1B,TMEFF2,PGAP1andSATB2genes. The observed deletion was confirmed using a paralogue ratio test. This case report provides further evidence that theSATB2gene, together withGLS,MYO1B,TMEFF2and possiblyPGAP1,is a crucial gene in 2q32q33 microdeletion syndrome. TheSATB2gene seems to be crucial for the behavioural problems noted in our case, but deletion of theGLS,MYO1BandTMEFF2genes presumably contributed to the more complex behavioural characteristics observed. Our patient is also, to our knowledge, the only patient with 2q32q33 microdeletion syndrome with secondary cognitive decline.
Abnormalities, Multiple/genetics , Aggression/psychology , Cognitive Dysfunction/genetics , Hysteria/physiopathology , Intellectual Disability/genetics , Self-Injurious Behavior/physiopathology , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/physiopathology , Adult , Chromosome Breakpoints , Chromosome Deletion , Chromosomes, Human, Pair 2/genetics , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/physiopathology , Female , Glutaminase/deficiency , Glutaminase/genetics , Humans , Hysteria/psychology , Intellectual Disability/diagnosis , Intellectual Disability/physiopathology , Karyotyping , Matrix Attachment Region Binding Proteins/deficiency , Matrix Attachment Region Binding Proteins/genetics , Membrane Proteins/deficiency , Membrane Proteins/genetics , Myosin Type I/deficiency , Myosin Type I/genetics , Neoplasm Proteins/deficiency , Neoplasm Proteins/genetics , Phenotype , Phosphoric Monoester Hydrolases/deficiency , Phosphoric Monoester Hydrolases/genetics , Self-Injurious Behavior/psychology , Transcription Factors/deficiency , Transcription Factors/genetics
