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.

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.

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.

Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects.

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.

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.

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.

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.

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.

Pediatric psychiatric emergency rooms during COVID-19: a multi-center study.

BACKGROUND: The COVID-19 (SARS-CoV-2) pandemic has been a major stressor for the mental health and well-being of children and adolescents. Surveys and reports from hotlines indicate a significant rise in mental health problems. As the psychiatric emergency room (ER) is a first-line free-of-charge facility for psychiatric emergencies, we expected to see a significant increase in visits, specifically of new patients suffering from anxiety, depression, or stress-related disorders. METHODS: Data from two psychiatric hospital ERs and one general hospital were included. All visits of children and adolescents from the computerized files between March and December of 2019 were analyzed anonymously and compared to the same months in 2020, using multilevel linear modeling. RESULTS: There was a significant decline in the total number of visits (p = .017), specifically among those diagnosed as suffering from stress-related, anxiety, and mood disorder groups (p = .017), and an incline in the proportion of visits of severe mental disorders (p = .029). DISCUSSION: The limited use of child and adolescent psychiatric emergency facilities during the pandemic highlights the importance of tele-psychiatry as part of emergency services. It also suggests the importance of the timeline of the emergence of clinically relevant new psychiatric diagnoses related to the pandemic. Future studies are needed to establish the long-term effects of the pandemic and the expeditious use of tele-psychiatry.

Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome.

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18 years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1 years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.

Clinical Features in a Large Cohort of Patients With 22q11.2 Deletion Syndrome.

OBJECTIVES: To evaluate various clinical aspects, specifically regarding immune status, in a large cohort of patients with DiGeorge syndrome. STUDY DESIGN: Data were collected for 98 patients with DiGeorge syndrome treated at a tertiary medical center. This included general information, laboratory results, and clinical features. RESULTS: The median age at diagnosis was 2.0 years (range, 0.0-36.5 years). The most common symptoms that led to diagnosis were congenital heart defect, speech delay, palate anomalies, and developmental delay. Common clinical features included recurrent infections (76 patients), congenital heart diseases (61 patients), and otorhinolaryngology disorders (61 patients). Twenty patients had anemia; the incidence was relatively high among patients aged 6-59 months. Thrombocytopenia was present in 20 patients. Recurrent chest infections were significantly higher in patients with T cell and T cell subset deficiencies. Decreased T cell receptor excision circles were more common with increasing age (P < .001). Of the 27 patients hospitalized due to infection, pneumonia was a leading cause in 13. CONCLUSIONS: Awareness of DiGeorge syndrome's typical and uncommon characteristics is important to improve diagnosis, treatment, surveillance, and follow-up.

The association between witnessing patient death and mental health outcomes in frontline COVID-19 healthcare workers.

BACKGROUND: Healthcare workers (HCW) treating coronavirus disease 2019 (COVID-19) patients face high levels of psychological stress. We aimed to compare mental health outcomes, risk and protective factors for posttraumatic stress symptoms (PTSS), probable depression, and anxiety between HCW working in COVID-19 and non-COVID-19 wards. METHODS: A self-report survey, administered in a large tertiary hospital in Israel during the peak of the COVID-19 outbreak was completed by 828 HCW (42.2% physicians, 57.8% nurses. Patient-Reported Outcomes Measurement Information System; the Patient Health Questionnaire-9; the Primary Care-Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) were used for assessing anxiety, depression, and PTSS, respectively. Pandemic-related stress factors, negative experiences, and potential protective factors were also assessed. RESULTS: Median PC-PTSD scores differed significantly between study teams (χ2 [5] = 17.24; p = .004). Prevalence of probable depression and anxiety were similar in both groups. Risk factors for mental health outcomes included mental exhaustion, anxiety about being infected and infecting family. Overall, higher proportion of the COVID-19 team witnessed patient deaths as compared to the non-COVID-19 team (50.2% vs. 24.7%). Witnessing patient death at the COVID-19 wards was associated with a four-fold increased likelihood of PTSS (odds ratio [OR] = 3.97; 95% confidence interval [CI], 1.58-9.99; p = .0007), compared with the non-COVID-19 wards (OR 0.91; 95% CI, 0.51-1.61; p = .43). CONCLUSIONS: Witnessing patient death appears to be a risk factor for PTSS unique to HCW directly engaged in treating patients with COVID-19. Our findings suggest that helping HCW cope with COVID-19 related deaths might reduce their risk of posttraumatic stress.

The Feasibility of a Parent Group Treatment for Youth with Anxiety Disorders and Obsessive Compulsive Disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD). Yet CBT is insufficiently effective in approximately half of cases in clinical trials and in a substantial number of cases children refuse to participate in CBT sessions altogether. Parent training offers a promising alternative to direct child therapy. The present study examined the feasibility of a group implementation of SPACE (Supportive Parenting for Anxious Childhood Emotions), a novel parent training approach aimed at reducing parent's accommodation of children's anxiety symptoms. Based on parent reports (N = 25), following treatment there was a significant decrease in parental accommodation, in family power struggles and in parental sense of helplessness, as well as a significant reduction in anxiety and OCD symptom severity. Results support the promise of group SPACE treatment and underscore the need for additional clinical trial research.

Deletion size analysis of 1680 22q11.2DS subjects identifies a new recombination hotspot on chromosome 22q11.2.

Recurrent, de novo, meiotic non-allelic homologous recombination events between low copy repeats, termed LCR22s, leads to the 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome). Although most 22q11.2DS patients have a similar sized 3 million base pair (Mb), LCR22A-D deletion, some have nested LCR22A-B or LCR22A-C deletions. Our goal is to identify additional recurrent 22q11.2 deletions associated with 22q11.2DS, serving as recombination hotspots for meiotic chromosomal rearrangements. Here, using data from Affymetrix 6.0 microarrays on 1680 22q11.2DS subjects, we identified what appeared to be a nested proximal 22q11.2 deletion in 38 (2.3%) of them. Using molecular and haplotype analyses from 14 subjects and their parent(s) with available DNA, we found essentially three types of scenarios to explain this observation. In eight subjects, the proximal breakpoints occurred in a small sized 12 kb LCR distal to LCR22A, referred to LCR22A+, resulting in LCR22A+-B or LCR22A+-D deletions. Six of these eight subjects had a nested 22q11.2 deletion that occurred during meiosis in a parent carrying a benign 0.2 Mb duplication of the LCR22A-LCR22A+ region with a breakpoint in LCR22A+. Another six had a typical de novo LCR22A-D deletion on one allele and inherited the LCR22A-A+ duplication from the other parent thus appearing on microarrays to have a nested deletion. LCR22A+ maps to an evolutionary breakpoint between mice and humans and appears to serve as a local hotspot for chromosome rearrangements on 22q11.2.

Exploring the potential association among sleep disturbances, cognitive impairments, and immune activation in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.DS) is a neurogenetic disorder caused by a microdeletion in chromosome 22. Its phenotype includes high rates of psychiatric disorders, immune system abnormalities, and cognitive impairments. We assessed the quality of sleep in 22q11.2DS and its potential link to inflammatory markers and cognitive deficits. Thirty-three 22q11.2DS individuals and 24 healthy controls were studied. Sleep parameters were assessed by the Pittsburgh sleep quality index (PSQI) questionnaire and correlated with serum cytokine levels and cognitive functioning, measured using the Penn computerized neurocognitive battery (CNB). The 22q11.2DS individuals had significantly worse sleep quality scores than the controls, unrelated to the psychiatric or physical comorbidities common to 22q11.2DS. Interleukin 6 levels were correlated with the overall score of the PSQI questionnaire for nonpsychotic 22q11.2DS participants only. Several domains of the CNB were associated with poorer sleep quality, suggesting that cognitive impairments in 22q11.2DS may be at least partially explained by poor sleep quality. Our findings confirm sleep impairments in individuals with 22q11.2DS, which might negatively affect their cognitive functioning, and corroborate a potential role of immunological pathways in the 22q11.2DS neuro-phenotype.

A three-tier process for screening depression and anxiety among children and adolescents with cancer.

OBJECTIVE: To establish and to evaluate the effectiveness of a three-tier screening process of depressive and anxiety disorders among children and adolescents with cancer based on questionnaires (first tier), semistructured psychiatric interviews (second tier), and referral for psychiatric assessment and recommendations for treatment (third tier). We also aimed to determine the rates of depressive and anxiety disorders among participants. METHODS: Participants and their parents completed the Patient Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety modules. Then, they were interviewed separately using the semistructured Affective and Anxiety Modules of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). PROMIS cutoff values for diagnosing depressive and anxiety disorders, based on the K-SADS, were calculated by receiver-operating characteristics (ROCs). RESULTS: Of 91 participants 34 (37.4%) aged 7 to 21 years with cancer met the K-SADS criteria for depressive and/or anxiety disorders. The results of the ROC analyses were stronger for depressive disorders than for anxiety disorders and for more severe cases. The cutoff of 13 on the child-reported PROMIS for a major depressive episode had a sensitivity of 0.80 and a specificity of 0.82, and a cutoff of 14 on the parent-reported PROMIS for generalized anxiety disorder had a sensitivity of 0.78 and a specificity of 0.79. CONCLUSIONS: Using the K-SADS, we found that anxiety and depressive disorders are very common in youngsters with cancer. The three-tier screening process we developed for depression and anxiety in this population provides practical cutoff values for identifying depressive and anxiety disorders in children with cancer.

Anxiety, pandemic-related stress and resilience among physicians during the COVID-19 pandemic.

BACKGROUND: Physicians play a crucial frontline role in the COVID-19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic-related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians. METHODS: A self-report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID-19 outbreak. Anxiety was measured by the 8-item version of the Patient-Reported Outcomes Measurement Information System. Resilience was evaluated by the 10-item Connor-Davidson Resilience Scale. Stress was assessed using a PRSF inventory. RESULTS: Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores. CONCLUSIONS: Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians.

A retrospective case series of electroconvulsive therapy in the management of comorbid depression and anorexia nervosa.

OBJECTIVE: Major depressive disorder (MDD) is common in anorexia nervosa (AN), associated with worse outcome and greater suicide risk. Electroconvulsive therapy (ECT) is highly effective in the treatment of MDD refractory to antidepressive treatment. We describe a case series of female adolescents with AN receiving ECT for MDD resistant to treatment and/or with severe suicide risk. METHOD: We retrospectively analyzed the files of all 30 adolescent females hospitalized in our department because of AN between 1998 and 2017 and treated with ECT. Severity of eating disorder (ED) and depressive symptoms was retrospectively assessed using the Clinical Global Impression-Severity Scale. RESULTS: Patients were severely depressed and suicidal on admission. All were resistant to antidepressants. A significant deterioration in depression, with severe suicidality, occurred from admission to pre-ECT, with concomitant improvement in ED symptoms and increase in body mass index (BMI). Significant improvement in depressive and ED symptoms and increase in BMI occurred following ECT, continuing to discharge. Adverse effects were mostly minimal. Fifty-three percentage of the patients were rehospitalized within the first year after ECT, mostly because of deterioration of depression and attempted suicide. Several years after discharge, 46.6% of the patients had no evidence of depression, suicidality, and ED-symptomatology, and another 23% had only evidence of ED symptomatology. DISCUSSION: ECT is safe and well tolerated in AN with severe comorbid treatment resistant MDD and/or with increased suicide risk. Many AN patients undergoing ECT may be remitted at long-term follow-up.

eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.

Together with GTP and initiator methionyl-tRNA, translation initiation factor eIF2 forms a ternary complex that binds the 40S ribosome and then scans an mRNA to select the AUG start codon for protein synthesis. Here, we show that a human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2γ (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex. Biochemical studies of human cells overexpressing the eIF2γ mutant and of yeast eIF2γ with the analogous mutation revealed a defect in binding the eIF2ß subunit to eIF2γ. Consistent with this loss of eIF2 integrity, the yeast eIF2γ mutation impaired translation start codon selection and eIF2 function in vivo in a manner that was suppressed by overexpressing eIF2ß. These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function.

Effectiveness and side effects of psychopharmacotherapy in individuals with 22q11.2 deletion syndrome with comorbid psychiatric disorders: a systematic review.

22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans and is associated with high rates of attention deficit/hyperactivity disorder (ADHD), psychotic spectrum disorders and mood and anxiety disorders. The objective of the study was to systematically review studies regarding pharmacological treatments for psychiatric disorders in individuals with 22q11.2DS and to provide practical guidelines for the psychiatric management and side effect monitoring in 22q11.2DS. A literature search was conducted using the databases PubMed, PsycINFO and Embase. Information regarding study population, drug treatment, side effect profile and efficacy for each trial was extracted. Data collection was completed on May 2018. The search identified 705 studies. A total of seven studies, describing 182 individuals, were included. Pharmacological interventions included three studies for antipsychotic treatment, two studies for stimulants, one study for selective serotonin reuptake inhibitors (SSRIs), one study for S-adenosyl-L-methionine (SAMe), and one case series for metyrosine. The presented data support the clinical impression that individuals with 22q11.2DS and comorbid psychiatric disorders are treated in a manner comparable to non-22q11.2DS individuals. However, distinct medical comorbidities common in individuals with 22q11.2DS may complicate the administration of pharmacotherapy. Further trials with RCT design, larger sample sizes and more syndrome-specific pharmacological agents are needed to improve evidence-based psychiatric care of 22q11.2DS individuals with comorbid mental disorders.