Clinical utility of magnetic resonance imaging in first-episode psychosis.

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR)=3.1, 95% CI 1.26-7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.

Adverse Childhood Experiences Among Inpatient Youths with Severe and Early-Onset Psychiatric Disorders: Prevalence and Clinical Correlates.

This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2 years) and 81 for a manic or mixed episode (average age 15.7 years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58 %) and from catatonia (57 %), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group.

Treatment use in a prospective naturalistic cohort of children and adolescents with catatonia.

We aimed to (1) describe the treatment used in a large sample of young inpatients with catatonia, (2) determine which factors were associated with improvement and (3) benzodiazepine (BZD) efficacy. From 1993 to 2011, 66 patients between the ages of 9 and 19 years were consecutively hospitalized for a catatonic syndrome. We prospectively collected sociodemographic, clinical and treatment data. In total, 51 (77%) patients underwent a BZD trial. BZDs were effective in 33 (65%) patients, who were associated with significantly fewer severe adverse events (p = 0.013) and resulted in fewer referrals for electroconvulsive therapy (ECT) (p = 0.037). Other treatments included ECT (N = 12, 18%); antipsychotic medications, mostly in combination; and treatment of an underlying medical condition, when possible. For 10 patients, four different trials were needed to achieve clinical improvement. When all treatments were combined, there was a better clinical response in acute-onset catatonia (p = 0.032). In contrast, the response was lower in boys (p = 0.044) and when posturing (p = 0.04) and mannerisms (p = 0.008) were present as catatonic symptoms. The treatment response was independent of the underlying psychiatric or systemic medical condition. As in adults, BZDs should be the first-line symptomatic treatment for catatonia in young patients, and ECT should be a second option. Additionally, the absence of an association between the response to treatment and the underlying psychiatric condition suggests that catatonia should be considered as a syndrome.

Catatonia in neurodevelopmental disorders: assessing catatonic deterioration from baseline.

Despite the inclusion of catatonia as a specifier of autism spectrum disorder in DSM-5, we-a team of child and adolescent neuropsychiatrists who specialise in paediatric catatonia and neurodevelopmental disorders-have identified a number of issues with the diagnosis and clinical management of catatonia in our patients. In this Personal View, we summarise the literature regarding catatonia in people with neurodevelopmental disorders, including autism spectrum disorder, describe our concerns, and offer a novel approach to addressing important issues with current diagnostic and treatment paradigms. We emphasise the need for a measure to diagnose and monitor people with catatonia and their history of neurodevelopmental disorders. This measure should consider previous complex and underlying motor, medical, functional, and neurobehavioural symptoms. We propose two concepts for understanding catatonia that relate to the baseline status of an individual: the personalised score at baseline, an estimate of premorbid neurobehavioral and motor symptoms, and the catatonic deterioration from baseline, an estimate of current features that are due to catatonia rather than an underlying neurodevelopmental disorder. We hope this measure will provide a practical tool for clinicians and researchers working with this underserved and high-risk population.

Relevance of Brain 18F-FDG PET Imaging in Probable Seronegative Encephalitis With Catatonia: A Case Report.

Autoimmune encephalitis (AIE) is a rare, severe, and rapidly progressive encephalopathy, and its diagnosis is challenging, especially in adolescent populations when the presentation is mainly psychiatric. Currently, cerebral 18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging is not included in the diagnosis algorithm. We describe a 16-year-old patient with probable seronegative encephalitis with catatonia for which several cerebral PET scans were relevant and helpful for diagnosis, treatment decision making, and follow-up monitoring. The patient recovered after 2 years of treatment with etiologic treatment of AIE and treatment of catatonia. This case suggests a more systematic assessment of the clinical relevance of 18F-FDG-PET imaging in probable seronegative AIE.

Psychiatric autoimmune conditions in children and adolescents: Is catatonia a severity marker?

OBJECTIVES: Patients with autoimmune encephalitis (AE) are likely to exhibit an acute onset of severe psychiatric features, including psychosis and/or catatonia. Based on the high prevalence of catatonia in AE and our clinical experience, we hypothesized that catatonia might be a marker of severity requiring more aggressive treatment approaches. METHODS: To reach a sufficient number of cases with brain-autoimmune conditions, we pooled two samples (N = 58): the first from the French National Network of Rare Psychiatric diseases and the second from the largest Italian neuro-pediatrics center for encephalopathies. Autoimmune conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. We retrospectively compared patients with and without catatonia for psychiatric and non-psychiatric clinical features, biological and imaging assessments, type of immunotherapy used and outcomes. RESULTS: The sample included 25 patients (43%) with catatonia and 33 (57%) without catatonia. Forty-two patients (72.4%) had a definite AE (including 27 anti-NMDA receptor encephalitis) and 16 (27.6%) suspected autoimmune encephalitis. Patients with catatonia showed significantly more psychotic features [18 (72%) vs 9 (27.3%), p < 0.001)] and more movement disorders [25 (100%) vs 20 (60.6%), p < 0.001] than patients without catatonia. First line (corticoids, immunoglobulin and plasma exchanges) and second line (e.g., rituximab) therapies were more effective in patients with catatonia, with 24 (96%) vs 22 (66.7%) (p = 0.006) and 17 (68%) vs 9 (27.3%) (p = 0.002), respectively. However, those with catatonia received more combinations of first and second line treatments and had more relapses during outcomes. CONCLUSION: Despite its exploratory design, the study supports the idea that autoimmune catatonia may be a marker of severity and morbidity in terms of initial presentation and relapses, requiring the need for early and aggressive treatment.

Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study.

Prader-Willi Syndrome (PWS) is a rare genetic syndrome leading to severe behavioural disorders and mild cognitive impairment. The objective of this double-blind randomised placebo-controlled trial was to study the efficacy and tolerance of topiramate on behavioural disorders in patients with PWS. Participants (aged 12-45 years) had genetically confirmed PWS and severe irritability/impulsivity, eating disorders and/or obesity, and skin picking. Thirty-two participants received a placebo (PBO), and 30 participants received topiramate (TOP) (50-200 mg/day) for 8 weeks. The primary outcome was the rate of responders using the Clinical Global Impression-Improvement (CGI-I) scale. The secondary outcome measures included the Aberrant Behaviour Checklist, the Dykens Hyperphagia Questionnaire (DHK), the Self-Injurious Behaviour Scale (SIBS) and the body mass index (BMI). We found no significant difference in the primary outcome (the CGI-I): 9 (30%) patients were very much or much improved in the TOP group compared to 7 (22.6%) patients in the PBO group. However, the DHK behaviour and severity scores improved significantly more over time in patients treated with topiramate versus those receiving a placebo, with a significant dose-effect relationship. DHK scores were also significantly associated with genetic subtypes and hospitalisation status. The effects of topiramate on eating behaviours remained significant after adjusting for genetic subtype and hospitalisation. Topiramate had therefore a significant effect on eating disorders, with a dose-effect relationship. Given the burden of eating disorders in PWS, we believe that topiramate may become the first psychotropic option within the global care of obesity in individuals with PWS.

Catatonia in children and adolescents: New perspectives.

INTRODUCTION: Catatonia is a rare and severe psychomotor condition in children and adolescents. In the current report, we aimed to review the recent literature. METHOD: Using a PRISMA approach, we searched MEDLINE between 1982 and 2017 using the keywords 'CATATONIA' and 'CHILD' or 'ADOLESCENT'. In total, we reviewed 130 reports (controlled study, N=4; clinical chart, N=23; case report, N=54; and editorial/review, N=42). RESULTS: Several aspects seem to be age specific: (1) although the clinical presentation resembles that in adults, some symptoms are important in children and adolescents (e.g., psychomotor regression). (2) Associated disorders are similar to that found in adults; however, schizophrenia is more frequently observed than mood disorder. Additionally, a history of neurodevelopmental disorders maybe encountered. (3) Morbidity and mortality are among the worst in child psychiatry. (4) Underlying organic conditions are highly prevalent (>20% of the cases), and their search is warranted because some diagnoses may result in specific treatments (e.g., immune-suppressor therapy for autoimmune conditions). (5) Symptomatic approaches - high dose of benzodiazepines and electroconvulsive therapy (ECT) - are as efficient in children or adolescents as they are in adults, but this finding needs to be acknowledged because a resistance against the use of ECT or high-dose medication exists among child psychiatrists. DISCUSSION: Recent advances in child and adolescent catatonia research have offered major improvements in understanding catatonia and in new therapeutic opportunities. The syndrome is rare, but these advances need to be acknowledged in order to direct patients to centers that have developed a specific expertise.

Flow cytometry-based evaluation of the bacterial removal efficiency of a blackwater reuse treatment plant and the microbiological changes in the associated non-potable distribution network.

The study evaluated the changes in bacterial numbers across a full-scale membrane bioreactor (MBR) blackwater reuse system. Flow cytometry was used to quantify total and intact bacterial concentrations across the treatment train and during distribution of the recycled water. Membrane passage reduced bacterial numbers by up to 5-log units resulting in coliform-free permeate. A 2-log increase in bacterial cell concentration was subsequently observed after the granular activated carbon unit followed by a reduction in intact cells after chlorination, which corresponds to an overall intact bacteria removal of 3.4-log units. In the distribution network, the proportion of intact cells greatly depended on the free chlorine residual, with decreasing residual enabling regrowth. An initial target of 0.5 mg L-1 free chlorine ensured sufficient suppression of intact cells for up to 14 days (setting the time intervals for system flushes at times of low water usage). Bacterial regrowth was only observed when the free chlorine concentration was below 0.34 mg L-1. Such loss of residual chlorine mainly applied to distant points in the distribution network from the blackwater reuse treatment plant (BRTP). Flushing these network points for 5 min did not substantially reduce cell numbers. At points closer to the BRTP, on the other hand, flushing reduced cell numbers by up to 1.5-log units concomitant with a decreasing proportion of intact cells. Intact cell concentrations did not correlate with DOC, total nitrogen, or soluble reactive phosphate, but it was shown that dead biomass could be efficiently converted into new biomass within seven days.

An overview of medical risk factors for childhood psychosis: Implications for research and treatment.

OBJECTIVE: Psychotic disorders in childhood and early adolescence often progress to chronic schizophrenia, but in many cases there are diagnosable medical and genetic causes or risk factors. We reviewed our clinical experience and the relevant literature to identify these factors and to define their clinical features, appropriate work-up and treatment. METHOD: We reviewed the results of comprehensive medical evaluations of 160 psychotic children and adolescents in our center. We also searched the Medline database (January 1994 to December 2015) with the following keywords and combinations: early onset schizophrenia, childhood onset schizophrenia, early onset psychosis, first episode psychosis, inborn errors of metabolism (IEM), genetic syndrome, copy number variants, autoimmune disorders, endocrine diseases, nutritional deficiencies, central nervous system infections, movement disorders, and epilepsy. RESULTS: In our center, 12.5% of cases had medical disorders likely to be contributing to psychosis. Based on 66 relevant papers and our experience, we describe the clinical features of multiple genetic syndromes, IEM, and autoimmune, neurological, endocrinological and nutritional disorders that increase the risk of psychotic disorders in childhood and adolescence. We propose an algorithm for systematic laboratory evaluation, informed by clinical examination, emphasizing common and/or treatable factors. CONCLUSIONS: In children and early adolescents with psychotic disorders, systematic medical work-up is warranted to identify medical and genetic factors. Not every rare cause can be worked up, thus careful clinical examinations are required to detect medical, neurological and genetic signs. Comprehensive medical evaluation can detect treatable diseases among cases of early-onset psychosis.

Catatonia in Children and Adolescents: A High Rate of Genetic Conditions.

Pediatric catatonia is a rare and severe neuropsychiatric syndrome. We previously reported, in 58 children and adolescents with catatonia, a high prevalence (up to 20%) of medical conditions, some of which have specific treatments.1 Here we extend the cohort inclusion and report the first systematic molecular genetic data for this syndrome. Among the 89 patients consecutively admitted for catatonia (according to the pediatric catatonia rating scale)2 between 1993 and 2014, we identify 51 patients (57.3%) who had genetic laboratory testing, of whom 37 had single nucleotide polymorphism (SNP) microarray tests for CNVs and 14 had routine genetic explorations (karyotyping and searches for specific chromosomal abnormalities by fluorescence in situ hybridization [FISH]) or a specific diagnosis test based on clinical history. To assess the causality of observed genetic findings in each patient, we used a causality assessment score (CAUS)3 including 5 causality-support criteria on a 3-point scale (0 = absent; 1 = moderate; 2 = high): the existence of similar cases in the literature; the presence of a clinical contributing factor; the presence of a biological contributing factor; the presence of other paraclinical symptoms; and response to a specific treatment related to the suspected genetic or medical condition.

Hormonal Risk Factors for Osteoporosis: Different Profile Among Antipsychotics.

Objectives: Osteoporosis is a major risk factor for fracture and treatment is mainly preventive. Patients with severe psychiatric condition and treated with antipsychotics are at risk for vitamin D deficiency and iatrogenic hyperprolactinemia, two serious risk factors of osteoporosis. We aim to determine whether all antipsychotics are similar regarding the risk of osteoporosis in young patients. Methods: From January 2009 to March 2015, we determined the vitamin D blood level (VDBL) among 484 inpatients and from January 2012 to March 2015, we determined the prolactin blood level (PBL) among 205 inpatients. We systematically recorded well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and suspected risk factors (e.g., disease type or antipsychotic treatment). Results: Up to 89% of the inpatients had a VDBL under the recommended threshold. Up to 60% of the inpatients had hyperprolactinemia. The multivariate model found a significant effect on VDBL for seasonality (higher VDBL in summer), ethnicity (lower VDBL in Black individuals), and treatment exposure. The multivariate model found a significant effect on PBL for gender and treatment exposure. In both models, aripiprazole had a safer profile compared with other antipsychotics. Conclusion: Because adolescence is a period of bone construction and a critical window of opportunity for maximizing bone mass, we recommend vitamin D supplementation in young patients with severe mental condition. It could be interesting to reconsider to regularly monitor PBL among youth patients treated with antipsychotic, with the exception of aripiprazole.

A causality algorithm to guide diagnosis and treatment of catatonia due to autoimmune conditions in children and adolescents.

OBJECTIVES: Pediatric catatonia is a rare and life-threatening syndrome. Around 20% of juvenile catatonia is associated with organic condition (Consoli et al., 2012). Autoimmune conditions represent a diagnostic and therapeutic challenge since specific antibodies can be missed. To facilitate decision making, we recently formulated a causality assessment score (CAUS) using a stepwise approach and an immunosuppressive therapeutic challenge (Ferrafiat et al., 2016). Our objectives were to validate retrospectively CAUS and to define its threshold for an accurate distinction between organic catatonia and non-organic catatonia, and specifically between autoimmune catatonia and non-organic catatonia. METHOD: To obtain a sufficient number of cases with organic catatonia, we pooled two samples (N=104) - one from a child psychiatry center, the other from neuro-pediatrics center - expert in catatonia and autoimmune conditions. Organic conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. Given the binary classification needs, we used receiver operating characteristic (ROC) analysis (Peacock and Peacock, 2010) to calculate the best classification threshold. RESULTS: The cohort included 67 cases of non-organic catatonia and 37 cases of organic catatonia. ROC analysis showed that the CAUS performance in discriminating both organic catatonia vs. non-organic catatonia, and autoimmune catatonia vs. non-organic catatonia was excellent (Area Under the Curve=0.99). In both analyses, for a CAUS threshold≥5, accuracy equaled to 0.96. CONCLUSION: Regarding juvenile catatonia, the use of the CAUS score algorithm combining a therapeutic challenge and a threshold≥5 may help to diagnose and treat autoimmune conditions even without formal identification of auto-antibodies.

Pattern of activation during delayed matching to sample task predicts functional outcome in people at ultra high risk for psychosis.

BACKGROUND: Clinical outcomes in people identified as at ultra-high risk (UHR) for psychosis are remarkably heterogeneous, and are difficult to predict on the basis of the presenting clinical features. Individuals at UHR are at risk of poor functional outcome regardless of development of psychotic disorder. The aim of the present study was to assess whether there is a relationship between functional neuroimaging measures at presentation and functional outcome as measured by the GAF three years after scanning. METHODS: Functional magnetic resonance imaging (fMRI) data were collected during an object working memory task in 34 ultra-high risk (UHR) subjects and 20 healthy controls. On the basis of their GAF scores at follow up, the UHR participants were divided into subgroups with good and poor functional outcomes, respectively. RESULTS: At baseline, the UHR group differed from controls in showing altered frontal and cuneus/posterior cingulate activation. Significant group x task interactions were found in the left cuneus and posterior cingulate gyrus, reflecting differential responses to the task conditions. Within the UHR sample, the subgroup with a poor functional outcome exhibited altered activation in frontal, temporal and striatal regions, and reduced deactivation within default-mode network regions, relative to those with a good outcome. Within the whole UHR sample, in these regions the local task response was correlated with the GAF score at follow up. CONCLUSIONS: The findings suggest a potential role of functional neuroimaging in the prediction of outcomes in people at high clinical risk of psychosis.

Catatonia and Autoimmune Conditions in Children and Adolescents: Should We Consider a Therapeutic Challenge?

OBJECTIVE: Catatonia as a result of autoimmune conditions offers new therapeutic opportunities for patients that child and adolescent psychiatrists should consider. However, the diagnosis is sometimes challenging when an autoimmune signature is not identified. METHODS: In this study, we aim to summarize seven cases from a 20-year series of 84 youths with catatonia, including three cases that represented a diagnostic challenge because of the absence of positive autoimmune testing. RESULTS: Immunosuppressive/modulatory treatment improved catatonic and psychotic features in all cases. CONCLUSION: To facilitate treatment decision-making, we propose a causality assessment score and a treatment algorithm, which may help clinicians consider whether an autoimmune condition is associated with catatonia.

Validation of the Pediatric Catatonia Rating Scale (PCRS).

INTRODUCTION: Despite the increased recognition of catatonia in children and adolescents, no specific assessment instrument has been validated in this population. METHOD: Within the context of a prospective study on catatonia, we developed the Pediatric Catatonia Rating Scale (PCRS, maximum score=60), adapted from the Bush and Francis Catatonia Rating Scale for its use in child and adolescent inpatients. We assessed the psychometric properties of the PCRS by measuring its internal consistency, construct validity, and factor structure. Bivariate analyses were performed to compare the different diagnostic patient groups across the extracted factors. RESULTS: Internal consistency was moderate (Cronbach's α for total score=0.67) suggesting multidimensionality. Multiple factors underlie the PCRS items, as revealed by factor analysis. Four distinct dimensions of catatonic symptoms were identified and accounted for 44% of total variance: a "negative withdrawal" factor (with mutism, negativism, and social withdrawal), a "catalepsy" factor (with posturing and waxy flexibility), an "abnormal movements" factor (with mannerisms and stereotypes) and an "echo phenomenon" factor (with echolalia and echopraxia). Receiver operating characteristic (ROC) analysis showed that the PCRS performance in discriminating individuals with catatonia vs. those without catatonia was excellent for a threshold≥9 (Area Under the Curve=0.983) in this sample. DISCUSSION: These results support the validity of the PCRS among children and adolescent inpatients. With regard to such analyses, the internal structure of catatonic syndrome in children and adolescents is roughly comparable with the adult form, except the lack of a "hyperactive/excitement" dimension.

Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data.

The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p < 0.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (p < 0.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis.