Expanding the phenotype of NEDAMSS with a psychiatric perspective: analysis of a new case, and a systematic review of the literature.

Pathogenic variants in the IRF2BPL gene are associated with neurodevelopmental disorders with varying degrees of regression, loss of speech and epilepsy. The phenotype is also known as Neurodevelopmental Disorder with regression, Abnormal Movements, loss of Speech, and Seizures (NEDAMSS). The motor symptoms of this disorder share significant phenotypical characteristics with catatonia, a severe neuropsychiatric psychomotor syndrome. The objective of this article is to expand the knowledge on the presentation of NEDAMSS with a focus on psychiatric symptoms including catatonia. A systematic review of 32 case presentations of NEDAMSS, and a novel case report of a patient with NEDAMSS, exhibiting multiple psychiatric symptoms, including catatonia are presented. Psychiatric symptoms and disorders including affective disorders, psychotic symptoms, catatonia, and developmental disorders are reported in one third of the reviewed cases. Reported effects of pharmacological treatment on motor symptoms of NEDAMSS are very limited. Our case presents improvement in motor symptoms originally attributed to NEDAMSS, after treatment with Lorazepam following diagnosis with catatonia. Patients with NEDAMSS may present with both neurological and psychiatric symptoms. The clinical presentation of NEDAMSS motor symptoms and catatonia have similarities and thus poses significant challenges to the diagnostic process, with risk of incorrect or delayed treatment. The limited experience and the complex phenotype of NEDAMSS complicates pharmacological treatment and encourages caution, especially with the use of antipsychotic drugs in the presence of possible catatonic symptoms.

Psychosocial interventions promoting personal recovery in people with schizophrenia: a scoping review protocol.

INTRODUCTION: Personal recovery is an important aspect for many individuals diagnosed with schizophrenia, as people can live rich, fulfilling lives despite ongoing symptoms. Prior reviews have found several factors to be associated with personal recovery, but a comprehensive overview of the psychosocial interventions aimed at improving personal recovery in schizophrenia is needed. METHODS AND ANALYSIS: Key terms relating to personal recovery and psychosocial interventions to promote personal recovery will be searched for in the following databases: PubMed, EMBASE, PsycINFO, CINAHL, MEDLINE, Google Scholar, Web of Science Core Collection and Cochrane. Additionally, a simple search for grey literature will be conducted in The Networked Digital Library of Theses and Dissertations. Two reviewers will individually screen and extract the data, and the selection of sources will be documented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow chart. A content analysis will be conducted on the data, and the findings will be presented in tables, and narratively synthesised. Lastly, research gaps will be identified, and recommendations for future research will be proposed. ETHICS AND DISSEMINATION: Ethics approval was not required for the development or publishing of this protocol. Findings will be disseminated through conferences, meeting with patient organisations and consumers, and published in a peer-reviewed scientific journal.

Value of gym-based group exercise versus usual care for young adults receiving antipsychotic medication: study protocol for the multicenter randomized controlled Vega trial.

BACKGROUND: Exercise is recommended to protect physical health among people with severe mental illness and holds the potential to facilitate long-term recovery. An inclusive exercise community provides an opportunity for life skill training and social connectedness and may reduce the experience of loneliness and internalized stigmatization which together may improve personal recovery. Using a pragmatic randomized design, we aim to examine the effectiveness of a gym-based exercise intervention tailored to young adults in antipsychotic treatment (i.e., Vega Exercise Community) compared to usual care. It is hypothesized that the Vega Exercise Community will be superior to usual care for personal recovery at four months. METHODS: The trial will be conducted at four sites in Denmark from which 400 participants, aged 18 to 35 years, who are in current treatment with antipsychotic medications for the management of schizophrenia spectrum or affective disorders, will be recruited. Participants will be randomized (2:1) to Vega Exercise Community or usual care. Vega Exercise Community includes three weekly group-based exercise sessions hosted in commercial functional training centers delivered by certified Vega instructors. After four months, participants in Vega Exercise Community will be randomized (1:1) to minimal versus extended support with regards to sustained physical activity. Data will be collected at baseline, four, six and 12 months. The primary outcome is personal recovery assessed by Questionnaire about the Process of Recovery at four months. Behavioral symptoms, health-related quality of life, metabolic health, and program costs will be evaluated to further determine the effectiveness and cost-effectiveness of the Vega Exercise Community. Finally, the quality of life and physical and mental health of the participants' primary relative will be evaluated. DISCUSSION: The results of this trial may have important implications for health, sustained physical activity, and recovery for individuals in treatment with antipsychotics. Given the pragmatic design, positive results may readily be implemented by mental health care professionals to promote exercise as an integrated part of treatment of severe mental illness. TRIAL REGISTRATION: Clinical Trials.gov (NCT05461885, initial registration June 29th, 2022). WHO Universal Trial Number (UTN): U1111-1271-9928.

Tapered discontinuation vs. maintenance therapy of antipsychotic medication in patients with first-episode schizophrenia: Obstacles, findings, and lessons learned in the terminated randomized clinical trial TAILOR.

Aim: Evidence is insufficient regarding the consequences of discontinuing vs. maintaining antipsychotic medication in patients with first-episode schizophrenia. Our aim was to examine tapered discontinuation vs. maintenance treatment regarding remission of psychotic symptoms and impact on other areas. Methods: Patients included had a diagnosis of schizophrenia, were treated with antipsychotic medication, and were in remission of psychotic symptoms. Participants were randomized to tapered discontinuation or maintenance treatment with antipsychotic medication. Assessments were undertaken at baseline and after 1-year. The primary outcome was remission of psychotic symptoms without antipsychotic medication. Results: The trial was terminated due to insufficient recruitment. In total, 29 participants were included: 14 in the tapering/discontinuation group and 15 in the maintenance group. Adherence to maintenance treatment was poor. At 1-year follow-up, remission of psychotic symptoms without antipsychotic medication for 3 months was observed in five participants in the tapering/discontinuation group and two in the maintenance group. Conclusion: Due to insufficient recruitment this study does not provide a conclusion on whether unfavorable outcomes or advantages follow tapering of antipsychotic medication. Recruitment and adherence to maintenance treatment encountered obstacles. Based on experiences from this trial, we discussed alternative study designs as consistent evidence is still needed on whether to continue or discontinue antipsychotic medication in remitted patients with first-episode schizophrenia. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000565-23/DK, EU Clinical Trials Register-EudraCT no. 2016-000565-23.

Long-term outcome of early-onset compared to adult-onset schizophrenia: A nationwide Danish register study.

OBJECTIVE: Early-onset schizophrenia (EOS) may have worse outcomes than adult-onset schizophrenia (AOS), but data are scarce. We compared outcomes of EOS vs. AOS. METHODS: Longitudinal, register-based study of patients diagnosed with schizophrenia in Denmark between 1996 and 2012, with follow-up until 12/2014. Co-primary outcomes were psychiatric inpatient days during the initial two years after schizophrenia diagnosis and mean number of annual inpatient days for the remaining follow-up. RESULTS: Altogether, 16,337 patients with schizophrenia were included (EOS = 1223, AOS = 15,114, mean follow-up = 9.5 ± 5.0 years). EOS were hospitalized longer during the first two years than AOS (180.9 ± 171.0 vs 163.4 ± 183.1 days, p < 0.005; IRR = 1.27, 95% CI = 1.19-1.35, p < 0.001), but duration and annual rates thereafter did not differ (EOS = 26.8 ± 57.1 days, AOS = 26.6 ± 56.2 days, p = 0.95; IRR = 1.07, 95% CI = 0.94-1.23, p = 0.30). Fewer EOS patients were never psychiatrically hospitalized (EOS = 17.2%, AOS = 20.1%, p < 0.001), but with no difference in re-admissions in patients diagnosed during hospitalization (EOS = 77.1% vs AOS = 78.1%, p = 0.56). More EOS patients were admitted involuntarily (41% vs. 36%, p < 0.02). AOS patients had more often comorbid substance use disorders during follow-up than EOS (EOS = 21.7%, AOS = 34.2%, p < 0.001). Substance use disorders and out-of-home placement were significantly associated with more inpatient days during both short- and long-term follow-up. CONCLUSION: Although EOS was associated with more inpatient days in the first two years after diagnosis, results do not seem to support a generally poorer long-term outcome of EOS compared to AOS. Longer initial hospitalization may be driven by different treatment patterns in child and adolescent vs. adult psychiatry. These data suggest that patient characteristics other than age of onset significantly affect outcomes.

Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register.

The objective of this study is to assess (1) the concordance and validity of schizophrenia register diagnoses among children and adolescents (early onset schizophrenia = EOS) in the Danish Psychiatric Central Research Register (DPCRR), and (2) the validity of clinical record schizophrenia diagnoses. Psychiatric records from 200 patients with a first-time diagnosis of schizophrenia (F20.x) at age < 18 years between 1994 and 2009 in the DPCRR were rated by experienced clinicians according to ICD-10 criteria, using a predefined checklist. We retrieved 178 records, representing 19.6% of all patients diagnosed with EOS from 1994 to 2009. Mean age was 15.2 years and 56.2% were males. The register-based and clinical diagnoses matched in 158 cases (88.8%). Raters' diagnoses confirmed the DPCRR schizophrenia diagnoses in 134 cases, rendering a diagnostic validity of 75.3% of DPCRR schizophrenia, while 149 cases were confirmed as being in the schizophrenia spectrum (83.7%). When removing records with registration errors, 83.5% of cases were confirmed as schizophrenia and 91.8% as being in the schizophrenia spectrum. Interrater reliability was substantial with Cohen's kappa > 0.78-0.83 depending on classification. Compared to diagnoses made in outpatient settings, EOS diagnoses during hospitalizations were more likely to be valid and had fewer registration errors. Diagnosed in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge, it is possible to reduce the number of false-positives in register-based research of EOS.

Attenuated psychotic and basic symptom characteristics in adolescents with ultra-high risk criteria for psychosis, other non-psychotic psychiatric disorders and early-onset psychosis.

While attenuated psychotic symptoms (APS) and basic symptoms (BS) are the main current predictors of psychosis in adults, studies in adolescents are scarce. Thus, we (1) described the prevalence and severity of positive, negative, disorganization, general, and basic symptoms in adolescent patients at ultra-high risk for psychosis (UHR), with other non-psychotic psychiatric disorders (PC) and with early-onset psychosis (EOP); and (2) investigated BS criteria in relation to UHR criteria. Sixty-nine 12-18-year-old adolescents (15.3 ± 1.7 years, female = 58.0 %, UHR = 22, PC = 27, EOP = 20) were assessed with the structured interview for prodromal syndromes (SIPS) and the schizophrenia proneness instrument-child and youth version (SPI-CY). Despite similar current and past 12-month global functioning, both UHR and EOP had significantly higher SIPS total and subscale scores compared to PC, with moderate-large effect sizes. Expectedly, UHR had significantly lower SIPS positive symptom scores than EOP, but similar SIPS negative, disorganized, and general symptom scores. Compared to PC, both EOP and UHR had more severe basic thought and perception disturbances, and significantly more often met cognitive disturbances criteria (EOP = 50.0 %, UHR = 40.9 %, PC = 14.8 %). Compared to UHR, both EOP and PC significantly less often met cognitive-perceptive BS criteria (EOP = 35.0 %, UHR = 68.2 %, PC = 25.9 %). BS were significantly more prevalent in both EOP and UHR than PC, and UHR were similar to EOP in symptom domains. Given the uncertain outcome of adolescents at clinical high-risk of psychosis, future research is needed to determine whether the combined assessment of early subjective disturbances with observable APS can improve the accuracy of psychosis prediction.

Risk of diabetes in children and adolescents exposed to antipsychotics: a nationwide 12-year case-control study.

OBJECTIVE: Antipsychotics are associated with weight gain and diabetes. The risk and rate of diabetes in children and adolescents treated with antipsychotics is unclear. METHOD: A longitudinal register linkage case-control study of diabetes in all psychiatric patients aged <18 years in Denmark was performed from January 1999 through the end of June 2010. Patients with and without antipsychotic exposure were compared regarding the occurrence of type 2 diabetes, defined as the prescription of oral antidiabetic medication. Regression analyses with type 2 diabetes as the dependent variable were conducted with sex, age, and diagnoses as covariates. RESULTS: We compared the risk of diabetes in 48,299 psychiatrically ill youth. Of 7,253 youth exposed to antipsychotics, 52 (0.72%; 95% CI = 0.52% - 0.91%) developed type 2 diabetes. Of 41,046 youth without exposure to antipsychotics, 111 (0.27%; 95% CI = 0.22% - 0.32%) developed type 2 diabetes. In a 25,033 + 16,013 logistic regression analysis, type 2 diabetes development was associated with antipsychotic drug exposure (odds ratio [OR] = 1.60; 95% CI = 1.08 - 2.36, p < .05) female sex, (OR = 4.48; 95% CI = 2.90 - 6.91, p < 0.001) and older age at first psychiatric diagnosis (OR = 1.19; 95% CI = 1.12 - 1.27, p < 0.001), but not with psychiatric diagnosis. In a Cox-regression analysis, shorter time to type 2 diabetes onset was associated with female sex (Hazard Ratio (HR) = 4.83; 95% CI = 3.05-7.66, p = 0.001), and older age at first psychiatric diagnosis (HR = 1.19; 95% CI = 1.12-1.28, p = 0.001), while antipsychotic exposure (HR) = 1.41; 95% CI = 0.92-2.16, p = 0.11) trended towards increasing the rate of diabetes. CONCLUSION: Antipsychotic treatment, female sex, and older age at psychiatric diagnosis were associated with a significantly more frequent type 2 diabetes onset in children and adolescents. Strict indications for antipsychotic treatment and routine cardiometabolic monitoring are crucial.

Quetiapine versus aripiprazole in children and adolescents with psychosis--protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial.

BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. DISCUSSION: Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01119014.

A systematic review of the long-term outcome of early onset schizophrenia.

BACKGROUND: The current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies in 1980. METHODS: A systematic search of articles published in the English-language literature after 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS) or both EOS and other psychotic disorders (MIX). The authors of the current review scored the outcome as either "good," "moderate," or "poor." The mean age of onset in these studies was <18 years. RESULTS: In general, the outcome in studies with EOS is worse than the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus 19.6% of the patients in MIX studies experienced a "good" outcome. In contrast, 24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a "moderate" outcome, and 60.1% in EOS studies versus 46.8% in MIX studies experienced a "poor" outcome. The authors identified various significant effects on outcome. In EOS, the findings were significantly affected by sample attrition, indicating that in studies with a high dropout rate, fewer patients experienced a "moderate" outcome, and more patients experienced a "poor" outcome; however, the effect sizes were small. Furthermore, the effects were also small and more favourable for specific functioning measures, as opposed to more global measures, small to moderate in terms of worse outcomes for follow-up periods >10 years, small to moderate for more unfavourable outcomes in males, and small to large for worse outcomes in studies including patients diagnosed before 1970. CONCLUSIONS: In contrast to the adult manifestation, the early manifestation of schizophrenia in childhood and adolescence still carries a particularly poor prognosis. According to these aggregated data analyses, longer follow-up periods, male sex, and patients having been diagnosed before 1970 contribute predominantly to the rather poor course of EOS.