The clinical course of individuals with 22q11.2 deletion syndrome converting to psychotic disorders: a long-term retrospective follow-up.

OBJECTIVES: This retrospective study aims to investigate the evolution and clinical course of psychotic disorders from three large international cohorts of individuals with 22q11.2 deletion syndrome (22q11.2DS) (Tel Aviv, Philadelphia, and Geneva). METHODS: We followed 118 individuals with 22q11.2DS from several years before the onset to several years after the onset of psychotic disorders. Data from structured baseline assessment of psychiatric disorders, symptoms of prodrome, indicators and types of psychotic disorders were collected. Additionally, cognitive evaluation was conducted using the age-appropriate Wechsler Intelligence Scale. Electronic medical records were reviewed for medication usage, occupational status, living situation, and psychiatric hospitalizations. RESULTS: At baseline evaluation, the most common psychiatric disorders were anxiety disorder (80%) and attention/deficit hyperactivity disorder (50%). The age of onset of prodromal symptoms and conversion to psychotic disorders were 18.6 ± 6.8 and 20.3 ± 7.2, respectively. The most common prodromal symptoms were exacerbation of anxiety symptoms and social isolation. Of the psychotic disorders, schizophrenia was the most common, occurring in 49% of cases. History of at least one psychiatric hospitalization was present in 43% of participants, and the number of psychiatric hospitalizations was 2.1 ± 1.4. Compared to the normalized chart, IQ scores in our cohort were lower after vs. before conversion to psychosis. Following conversion there was a decrease in the use of stimulants and antidepressants and an increase in antipsychotics use, and most individuals with 22q11.2DS were unemployed and lived with their parents. CONCLUSIONS: Our results indicate that 22q11.2DS psychosis is like non-22q11.2DS in its course, symptoms, and cognitive and functional impairments.

Capgras syndrome in children and adolescents: A systematic review.

OBJECTIVES: To improve understanding of Capgras syndrome (CS) in the pediatric population, this study investigates its clinical features and discerns similarities and differences compared to CS in adults. METHODS: We conducted a descriptive systematic review of case reports following PRISMA guidelines, including cases of pediatric patients with CS. Patient demographics, medical and psychiatric history, imposter identity, underlying diagnosis, clinical manifestation, treatments, and outcomes were extracted and analyzed. RESULTS: We included 37 articles comprising 38 cases. The median age of patients was 15, with 23 (60.5%) being male. The most prevalent underlying diagnoses were schizophrenia spectrum and other psychotic disorders (47.3%). Imposter identity involved parents in 32 cases (84.2%). Associated symptoms included persecutory delusions (63.1%), auditory hallucinations (42.1%), aggression (31.5%), and depression (21.0%). CONCLUSION: There is a significant gap in our understanding of CS, particularly in pediatric patients. This is the first systematic review of CS in pediatric patients, encompassing all cases found in English literature since 1923.

Lymphoblast transcriptome analysis in 22q11.2 deletion syndrome individuals with schizophrenia-spectrum disorder.

OBJECTIVES: 22q11.2 deletion is the most prominent risk factor for schizophrenia (SZ). The aim of the present study was to identify unique transcriptome profile for 22q11.2 deletion syndrome (DS)-related SZ-spectrum disorder (SZ-SD). METHODS: We performed RNA-Seq screening in lymphoblasts collected from 20 individuals with 22q11.2DS (10 men and 10 women, four of each sex with SZ-SD and six with no psychotic disorders (Np)). RESULTS: Sex effect in RNA-Seq descriptive analysis led to separating the analyses between men and women. In women, only one differentially expressed gene (DEG), HLA-DQA2, was associated with SZ-SD. In men, 48 DEGs (adjp < 0.05) were found to be associated with SZ-SD. Ingenuity pathway analysis of top 85 DEGs (p < 4.66E - 04) indicated significant enrichment for immune-inflammatory response (IIR) and neuro-inflammatory signalling pathways. Additionally, NFATC2, IFNG, IFN-alpha, STAT1 and IL-4 were identified as upstream regulators. Co-expression network analysis revealed the contribution of endoplasmic reticulum protein processing and N-Glycan biosynthesis. These findings indicate dysregulation of IIR and post-translational protein modification processes in individuals with 22q11.2DS-related SZ-SD. CONCLUSIONS: Candidate pathways and upstream regulators may serve as novel biomarkers and treatment targets for SZ. Future transcriptome studies, including larger samples and proteomic analysis, are needed to substantiate our findings.

Embracing different languages and local differences: Co-constructive patient simulation strengthens host countries' clinical training in psychiatry.

BACKGROUND: Global education in psychiatry is heavily influenced by knowledge from Western, high-income countries, which obscures local voices and expertise. AIM: To adapt a human simulation model to psychiatric education in a context that is specific to local languages and cultures. METHODS: We conducted an observational study consisting of six human simulation sessions with standardized patients from two host countries, speaking their native languages, and following an adaptation of the co-constructive patient simulation (CCPS) model. As local faculty became increasingly familiar with the CCPS approach, they took on the role of facilitators-in their country's native language. RESULTS: Fifty-three learners participated: 19 child and adolescent psychiatry trainees and 3 faculty members in Türkiye (as a group that met online during 3 consecutive months); and 24 trainees and 7 faculty in Israel (divided into 3 groups, in parallel in-person sessions during a single training day). Each of the six cases reflected local realities and clinical challenges, and was associated with specific learning goals identified by each case-writing trainee. CONCLUSION: Human simulation has not been fully incorporated into psychiatric education: The creation of immersive clinical experiences and the strengthening of reflective practice are two areas ripe for development. Our adaptations of CCPS can also strengthen local and regional networks and psychiatric communities of practice. Finally, the model can help question and press against hegemonies in psychiatric training that overshadow local expertise.

Changes in Symptom Severity among Children and Adolescents with Obsessive-Compulsive Disorder during the COVID-19 Pandemic: A 2-year Follow-up.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused significant global turmoil, including changes in social and societal conduct such as lockdowns, social isolation, and extensive regulations. These changes can be major sources of stress. The first wave of the pandemic (April-May 2020) was a time of global uncertainty. We evaluated symptom severity among 29 Israeli children and adolescents with obsessive-compulsive disorder (OCD). Our previous study found that most of these participants did not experience an exacerbation of symptoms. OBJECTIVES: To re-evaluate the OCD symptoms of 18 participants from the original group of 29 children and adolescents during three time points: before the pandemic, during the first wave, and 2 years later. METHODS: Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), a functional questionnaire, and the Obsessive-Compulsive Inventory-child version (OCI-CV). RESULTS: OCS in patients did not change significantly during the three time points. Participants reported minimal changes in their general functioning 2 years after the outbreak of COVID-19 and showed minimal change in OCI-CV scale scores. CONCLUSIONS: Our results indicated clinical stability of OCD symptoms among most of the participants.

Post-traumatic growth correlates among parents of children with chronic illnesses: A systematic review and meta-analysis.

Parenting a child with a chronic illness presents a complex journey marked by various challenges, along with possible personal growth following these challenges. In this systematic review we present three meta-analyses, in order to examine the associations of post-traumatic growth (PTG) among parents of children with diverse chronic illnesses, and psychological distress, social support, and resilience. Analyzing 34 studies encompassing a total of 5328 parents, the results reveal several key findings. First, PTG was found to be prevalent among the parents. Second, there was no significant correlation between PTG and psychological distress, suggesting that these two processes may exist independently. Third, a positive correlation was observed between PTG and both social support and resilience-related factors, underscoring the role of these factors in fostering growth among parents of children with chronic illnesses. Additionally, illness type emerged as a moderator, affecting the strength of the above-mentioned correlations with PTG. Specifically, in the case of psychiatric illnesses, correlations of PTG with social support and resilience were stronger than in the context of other illnesses. Overall, this review emphasizes the significance of recognizing and addressing PTG correlates among parents of children with chronic illnesses, offering insights for clinical practice.

Parents' experience of a shared parent-child stay during the first week of hospitalization in a child psychiatry inpatient ward.

Hospitalization of children in an inpatient psychiatric ward is stressful for both the children and their parents, and separation from the parents during hospitalization is probably one major cause of this stress. We designated one room in a closed inpatient unit to enable a parent to stay with his/her child, including overnight, during the 1st week of hospitalization. We then examined the parents' experience of the shared parent-child stay. Thirty parents of 16 children aged 6-12 years admitted to our inpatient child psychiatry ward completed in-depth semi-structured interviews after that week's experience. The interviews covered the parents' experiences of the 1st week in the larger context of pre-hospitalization period, which also includes the decision to hospitalize the child. The contents of the interviews were analyzed by means of independent coders that identified the following major themes: (1) ambivalence and confusion of the parents as related to their decision to hospitalize their child in the time period just before admission; (2) gradual process of separation from the child during the joint stay at the ward; (3) building confidence and trust toward the staff. Themes 2 and 3 express benefits from the joint hospitalization that may have a strong positive impact on the child's and the parent's recovery. These themes warrant further evaluation of the proposed shared stay during hospitalization in future studies.

Impact of COVID-19 on Lifestyle Habits and Emotional State of Childhood Cancer Survivors and Their Parents.

OBJECTIVE: The COVID-19 pandemic and associated social distancing measures affected the physical and emotional state of children and parents worldwide. Survivors of childhood cancer may be particularly vulnerable to these effects. We aimed to evaluate the lifestyle habits and emotional states of childhood cancer survivors and their parents during the COVID-19 outbreak. METHODS: Lifestyle habits and emotional distress were assessed in 43 childhood cancer survivors (aged 8-21 years) and their parents before and during the COVID-19 lockdown, using the PROMIS anxiety and depression modules and the "Mabat Youth" questionnaire. RESULTS: Most parents (80.5%) reported eating more family meals during home confinement compared to their usual routine. Patients' physical activity levels did not change significantly during confinement, leisure-related screen time nearly doubled (p < 0.001), and sleep duration increased (p = 0.006). Anxiety levels of children (p = 0.045) and parents (p = 0.02) increased during confinement compared to pre-pandemic levels, with no significant changes in depression levels. CONCLUSIONS: Contrary to concerns regarding lifestyle habits during the COVID-19 lockdown, eating behaviors of childhood cancer survivors improved, sleep duration increased, and physical activity remained unchanged. Still, screen time increased significantly. Parents of childhood cancer survivors reported higher anxiety levels for themselves and their children during home confinement. Our findings may assist medical and psycho-social teams in guiding parents of cancer survivors during similar circumstances in the future.

The relationship between oxidative stress and psychotic disorders in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. This condition is associated with a wide range of symptoms including immune and neuropsychiatric disorders. Notably, psychotic disorders including schizophrenia have a prevalence of âˆ¼ 30%. A growing body of evidence indicates that neuroinflammation and oxidative stress (OS) play a role in the pathophysiology of schizophrenia. In this study, we aim to assess the interaction between 22q11.2DS, OS and schizophrenia. METHODS: Blood samples were collected from 125 participants (including individuals with 22q11.2DS [n = 73] and healthy controls [n = 52]) from two sites: Sheba Medical Center in Israel, and University Hospital Gasthuisberg in Belgium. Baseline OS levels were evaluated by measuring Myeloperoxidase (MPO) activity. A sub-sample of the Israeli sample (n = 50) was further analyzed to examine survival of Peripheral Blood Mononuclear Cells (PBMCs) following induction of OS using vitamin K3. RESULTS: The levels of MPO were significantly higher in all individuals with 22q11.2DS, compared to healthy controls (0.346 ± 0.256 vs. 0.252 ± 0.238, p =.004). In addition, when comparing to healthy controls, the PBMCs of individuals with 22q11.2DS were less resilient to induced OS, specifically the group diagnosed with psychotic disorder (0.233 ± 0.206 for the 22q11.2DS individuals with psychotic disorders, 0.678 ± 1.162 for the 22q11.2DS individuals without psychotic disorders, and 1.428 ± 1.359 for the healthy controls, p =.003, η2 = 0.207). CONCLUSIONS: Our results suggest that dysregulation of OS mechanisms may play a role in the pathophysiology of the 22q11.2DS phenotype. The 22q11.2DS individuals with psychotic disorders were more sensitive to induction of OS, but did not present significantly different levels of OS at baseline. These results may be due to the effect of antipsychotic treatment administered to this sup-group. By elucidating novel molecular pathways, early identification of biochemical risk markers for 22q11.2DS and psychotic disorders can be detected. This can ultimately pave the way to the design of early and more precise interventions of individuals with 22q11.2DS.

The contribution of medical burden to 22q11.2 deletion syndrome quality of life and functioning.

PURPOSE: To date, there is no systematic method to quantify the medical burden of individuals with 22q11.2 deletion syndrome (22q11.2DS). This study aimed to design a Medical Burden Scale for 22q11.2DS to evaluate the effect of medical symptoms severity on quality of life (QoL) and functioning in individuals with this syndrome. METHODS: Individuals with 22q11.2DS (n = 76) were included in the study. A multidisciplinary group of physicians determined the severity of symptoms (on a scale of 0 to 4) of 8 major medical systems affected in 22q11.2DS, as well as the level of cognitive deficits and psychiatric morbidity. Regression models were used to evaluate the impact of medical, cognitive, and psychiatric symptoms' severity on global assessment of functioning (GAF) and QoL. RESULTS: The total Medical Burden Scale score was significantly associated with both QoL and GAF scores, beyond the effect of the psychiatric and cognitive deficits. We also found that QoL and GAF scores were associated with the severity scores of specific medical systems, particularly neurological symptoms, but also cardiovascular, ear-nose-throat, endocrinology, and orthopedics. CONCLUSION: Quantifying the medical burden of 22q11.2DS individuals is feasible and indicates the overall and specific contribution of medical symptoms to QoL and functioning of 22q11.2DS individuals.

Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40-50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

A 16-month longitudinal investigation of risk and protective factors for mental health outcomes throughout three national lockdowns and a mass vaccination campaign: Evidence from a weighted Israeli sample during COVID-19.

BACKGROUND: COVID-19 is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. We explored potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel. METHODS: Across the span of 16 months, 2478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). We applied mixed-effects models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, and longitudinally assessed participants who completed at least two consecutive surveys (n = 400). We weighted our sample to increase representativeness of the population. RESULTS: Fatigue was the strongest predictor for depression, anxiety and PTSS at all time points, and predicted deterioration overtime. Financial concerns associated with depression and anxiety at all time points, and with their deterioration overtime. Health related concerns were uniquely associated with anxiety and PTSS at all time points and their deterioration, but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety. Hesitancy towards vaccination was associated to higher financial concerns and lower sense of protection by the authorities. CONCLUSIONS: Our findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the centrality of fatigue in determining mental health outcomes.

Child and Adolescent Mental Health during the COVID-19 Pandemic: Challenges of Psychiatric Outpatient Clinics.

BACKGROUND: Worldwide national surveys show a rising mental health burden among children and adolescents (C&A) during COVID-19. The objective of the current study is to verify the expected rise in visits to psychiatric outpatient clinics of C&A, especially of new patients. METHODS: a cross-sectional study focusing on visits as recorded in electronic medical records of eight heterogeneous C&A psychiatric outpatient clinics. The assessment was based on visits held from March to December of 2019 (before the pandemic) in comparison to visits held in 2020 (during the pandemic). RESULTS: The number of visits was similar for both periods. However, in 2020, 17% of the visits used telepsychiatry (N = 9885). Excluding telepsychiatry reveals a monthly decrease in traditional in-person activities between 2020 and 2019 (691.6 ± 370.8 in 2020 vs. 809.1 ± 422.8 in 2019, mean difference = -117.5, t (69) = -4.07, p = 0.0002, Cohen's d = -0.30). Acceptation of new patients declined during 2020, compared to 2019 (50.0 ± 38.2 in 2020 vs. 62.8 ± 42.9 in 2019; Z = -3.12, p = 0.002, r = 0.44). Telepsychiatry was not used for new patients. CONCLUSIONS: The activity of C&A psychiatric outpatient clinics did not rise but was guarded due to the use of telepsychiatry. The decline in visits of new patients was explained by the lack of use of telepsychiatry for these patients. This calls for expanding the use of telepsychiatry, especially for new patients.

Contribution of Risk and Resilience Factors to Suicidality among Mental Health-Help-Seeking Adolescent Outpatients: A Cross-Sectional Study.

BACKGROUND: Peer victimization is an established risk factor for youth suicidal thoughts and behavior (suicidality), yet most peer-victimized youth are not suicidal. More data are needed pertaining to factors that confer resilience to youth suicidality. AIM: To identify resilience factors for youth suicidality in a sample of N = 104 (Mean age 13.5 years, 56% female) outpatient mental health help-seeking adolescents. METHODS: Participants completed self-report questionnaires on their first outpatient visit, including the Ask Suicide-Screening Questions, a battery of risk (peer victimization and negative life events) and resilience (self-reliance, emotion regulation, close relationships and neighborhood) measures. RESULTS: 36.5% of participants screened positive for suicidality. Peer victimization was positively associated with suicidality (odds ratio [OR] = 3.84, 95% confidence interval [95% CI] 1.95-8.62, p < 0.001), while an overall multi-dimensional measure of resilience factors was inversely associated with suicidality (OR, 95% CI = 0.28, 0.11-0.59, p = 0.002). Nevertheless, high peer victimization was found to be associated with a greater chance of suicidality across all levels of resilience (marked by non-significant peer victimization by resilience interaction, p = 0.112). CONCLUSIONS: This study provides evidence for the protective association of resilience factors and suicidality in a psychiatric outpatient population. The findings may suggest that interventions that enhance resilience factors may mitigate suicidality risk.

Bridging the gap between the emergency department and outpatient care: feasibility of a short-term psychiatric crisis intervention for children and adolescents.

Child and adolescent mental health systems are facing limited resources of available psychosocial interventions, often leading to long waiting lists for acceptance to treatment. We describe the feasibility of a short-term (8-10 sessions) psychological crisis intervention (CI) protocol for children and adolescents aged 8-17 years (n = 30, mean ± standard deviation 12.9 ± 2.4 years) who were referred to an outpatient mental health clinic due to suicidal ideation, aggression, severe anxiety, or extreme family conflict. The participants were assessed before and after the CI, and at a 3-6-months follow-up visit. The psychiatric assessments included clinical evaluation by a senior psychiatrist, and the completion of self-report questionnaires by both the participants and their parents. Following the establishment of the CI unit, the waiting lists for urgent cases were reduced from a median of 84 days in the two preceding years to 23 days in the following 3 years (H[2] = 18.5, p < 0.0001) for patients of the CI unit. A 1-year psychiatric follow-up after the end of the CI revealed that 72% did not require additional psychotherapy. The overall clinical evaluation measures (clinical evaluation, parents-report and child report) improved and had been preserved at the 3-6-months follow-up. Our results demonstrate the feasibility of a short-term CI protocol for expediting admission to treatment for urgent psychiatric cases.

Internalizing symptoms impede adolescents' ability to transition from in-person to online mental health services during the 2019 coronavirus disease pandemic.

INTRODUCTION: Online mental health services were previously found to be effective in many studies. However, this method was not generally used in Israel. By the end of 2019, the coronavirus disease 2019 pandemic erupted, forcing mental health services to transition to online meetings to maintain the standard of care. In this cross-sectional study, we investigated the attitudes of adolescent patients toward this involuntary new mode of care. METHODS: Forty-four adolescents (mean age 14.62 ± 2.12 years, 54.5% females) and 40 of their primary caregivers completed a battery of questionnaires that included the telemedicine satisfaction questionnaire, session evaluation questionnaire, working alliance inventory, and pediatric symptom checklist. RESULTS: Both adolescents and their caregivers reported a reasonable experience with the online medium and a feeling that the meetings were overall powerful, helpful, and comfortable as demonstrated by medium to high scores on the telemedicine satisfaction questionnaire and session evaluation questionnaire questionnaires. A therapeutic alliance was generally maintained according to working alliance inventory scores. However, working alliance inventory scores were negatively correlated with higher levels of internalizing symptoms and parental stress. DISCUSSION: Our findings point to the possibility that anxious/depressed adolescents will have greater difficulties re-establishing therapeutic alliance when transitioned from in-person to online meetings. This may be due to the introduction of an "invisible" third party to the therapeutic setting-the computer. Psychologists and psychiatrists should be aware of these difficulties and respond adequately to maintain the standard of care.

Parental Expressed Emotion, Parenting Stress, and Behavioral Problems of Young Children with 22q11.2 Deletion Syndrome and Idiopathic Autism Spectrum Disorder.

This study examined the associations of parents' expressed emotion (EE) and parenting stress, with behavioral problems of children with 22q11.2 deletion syndrome, idiopathic autism (iASD) and typically developing (TD) children. Parents of children aged 3-8 years completed the five-minute-speech-sample (FMSS), parental stress index and children behavioral checklist. Parents' FMSS-EE-criticism was higher among parents of children with 22q11DS and iASD compared to parents of TD children. FMSS-EE scores predicted children's behavioral problems, above and beyond parenting stress. The associations between FMSS-EE, parenting stress and children's behavioral problems were consistent across 22q11DS, iASD and TD children. These findings highlight the need for targeting parents' EE and parenting stress as integral elements in the screening and prevention of behavioral problems of young children with 22q11DS and iASD.