Debate: Involuntary treatment - not whether, but when and what else is needed.

Involuntary treatment is a complex dialectic balancing self-autonomy and the individual's right to consent to treatment with society's duty to protect those suffering from severe mental illness who are at risk of causing harm to themselves or others. When necessary, involuntary treatment should provide evidence-based and medically justified care, with sufficient oversight and due process to protect the rights of patients. Clinically, the issue is not whether involuntary treatment should ever be used, but rather what other services are needed to enhance the quality of care within comprehensive community systems of care, thus limiting or preventing the need for involuntary interventions while also improving the outcomes of individuals affected by severe mental illness.

An evolutionary perspective on complex neuropsychiatric disease.

The forces of evolution-mutation, selection, migration, and genetic drift-shape the genetic architecture of human traits, including the genetic architecture of complex neuropsychiatric illnesses. Studying these illnesses in populations that are diverse in genetic ancestry, historical demography, and cultural history can reveal how evolutionary forces have guided adaptation over time and place. A fundamental truth of shared human biology is that an allele responsible for a disease in anyone, anywhere, reveals a gene critical to the normal biology underlying that condition in everyone, everywhere. Understanding the genetic causes of neuropsychiatric disease in the widest possible range of human populations thus yields the greatest possible range of insight into genes critical to human brain development. In this perspective, we explore some of the relationships between genes, adaptation, and history that can be illuminated by an evolutionary perspective on studies of complex neuropsychiatric disease in diverse populations.

Strategies for Managing Impairing Emotional Outbursts.

This Viewpoint discusses the important role pediatricians play in assessment, prevention, and early intervention for children who display impairing emotional outbursts.

Practitioner Review: Psychosis in children and adolescents.

Psychotic symptoms, including hallucinations, delusions, and disorganized thinking and behaviors, are the hallmarks of schizophrenia; but may also present in the context of other psychiatric and medical conditions. Many children and adolescents describe psychotic-like experiences, which can be associated with other types of psychopathology and past experiences (e.g., trauma, substance use, and suicidality). However, most youth reporting such experiences do not have, nor will ever develop, schizophrenia or another psychotic disorder. Accurate assessment is critical because these different presentations have different diagnostic and treatment implications. For this review, we focus primarily on the diagnosis and treatment of early onset schizophrenia. In addition, we review the development of community-based first-episode psychosis programming, and the importance of early intervention and coordinated care.

An Optimized Version of the Positive and Negative Symptoms Scale (PANSS) for Pediatric Trials.

OBJECTIVE: The accepted primary outcome measure for evaluating psychotic symptoms is decades old, long, and initially designed for adults. Surprisingly, the psychometric properties of primary outcome measures have never been reported for a pediatric sample using modern methods. The present study's aim is to use a pediatric sample to evaluate the psychometrics of the most used primary outcome measure in pediatric schizophrenia trials, the Positive and Negative Syndrome Scale (PANSS). METHOD: To evaluate the factor structure, item characteristics, and treatment sensitivity of the PANSS in a pediatric sample, secondary analyses of PANSS data at baseline and weekly throughout an 8-week randomized double-blind study of 3 antipsychotic agents (registered and previously published) were conducted. Subjects were 118 youths receiving outpatient psychiatric treatment for schizophrenia spectrum disorders (mean age = 14.26 years, SD = 2.41 years). RESULTS: A 10-item short form, keeping 2 strongest items for each factor, had r = 0.89 with the full-length scale. Each of the five 2-item subscales has alphas ranging from 0.66 to 0.84. Item Response Theory (IRT) found that the 10-item scale and 2-item subscores had high reliability across the severity range typical of those for clinical trials. Criterion validity was high, with equal sensitivity to clinical changes over time. CONCLUSION: A 10-item PANSS version eliminates weaker items in the pediatric population while preserving coverage of 5 factors and similar sensitivity to clinical changes over time. It thus may be more appropriate for subsequent pediatric trials, and for clinical use when time and efficiency are paramount.

Narrative Review: Impairing Emotional Outbursts: What They Are and What We Should Do About Them.

OBJECTIVE: Impairing emotional outbursts, defined by extreme anger or distress in response to relatively ordinary frustrations and disappointments, impact all mental health care systems, emergency departments, schools, and juvenile justice programs. However, the prevalence, outcome, and impact of outbursts are difficult to quantify because they are transdiagnostic and not explicitly defined by current diagnostic nosology. Research variably addresses outbursts under the rubrics of tantrums, anger, irritability, aggression, rage attacks, or emotional and behavioral dysregulation. Consistent methods for identifying and assessing impairing emotional outbursts across development or systems of care are lacking. METHOD: The American Academy of Child and Adolescent Psychiatry Presidential Task Force (2019-2021) conducted a narrative review addressing impairing emotional outbursts within the limitations of the existing literature and independent of diagnosis. RESULTS: Extrapolating from the existing literature, best estimates suggest that outbursts occur in 4%-10% of community children (preschoolers through adolescents). Impairing emotional outbursts may respond to successful treatment of the primary disorder, especially for some children with attention-deficit/hyperactivity disorder whose medications have been optimized. However, outbursts are generally multi-determined and often represent maladaptive or deficient coping strategies and responses. CONCLUSION: Evidence-based strategies are necessary to address factors that trigger, reinforce, or excuse the behaviors and to enhance problem-solving skills. Currently available interventions yield only modest effect sizes for treatment effect. More specific definitions and measures are needed to track and quantify outbursts and to design and assess the effectiveness of interventions. Better treatments are clearly needed.

Commentary: Getting kids what they need, where they are, when they need it: home-based services in a continuum of care - a commentary on Boege et al. (2021).

In this edition of CAMH, Boege and colleague's 4-year follow-up study supports intensive home-based treatment as a viable alternative to inpatient hospitalization. Youth receiving home-based multimodal treatment fared just as well as those who remained hospitalized longer, with higher parental satisfaction. This study contributes to a sparse evidence base regarding longitudinal outcomes of psychiatric inpatient and intensive outpatient treatments for children and adolescents. Although mental illness is prevalent and increasing among youth, existing systems of care are often inadequate to provide flexible, effective, interdisciplinary team-based treatments, and supports for children and their families. Innovative approaches to providing evidence-based care and tracking outcomes are needed to strengthen the continuum of care.

Adaptation and validation of a computerized neurocognitive battery in the Xhosa of South Africa.

OBJECTIVE: Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa. METHOD: Individuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined. RESULTS: Tests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed. CONCLUSIONS: Results support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A tipping point in neuropsychiatric genetics.

Severe neuropsychiatric disorders are so genetically heterogeneous that virtually every unrelated patient harbors different clinically significant alleles. By studying schizophrenia in the Ashkenazi Jewish founder population, Lencz and co-authors identified rare severe alleles each shared by a few patients. Experimental evaluation of an implicated protocadherin allele revealed failure to form homophilic cellular aggregates as a possible mechanism for defective development of neural circuits.

Debate: Putting psychiatric hospitalization for children and adolescents in its place: it is time to create a system of care that works.

Inpatient psychiatric care is the most expensive resource within the pediatric mental health system and is too often justified based on the lack of more appropriate and effective services. Rates of readmission are high, and data regarding long-term benefits are lacking. The continuum of care needs to be realigned to meet the needs of children and families, with investments in intensive community-based services and evidence-based training while limiting the use of acute inpatient care to those patients whose clinical presentations require and benefit from that level of service.

Emotional and Behavioral Dysregulation in Severe Mental Illness.

Emotional and behavioral dysregulation are common in severe mental illnesses, including schizophrenia, bipolar disorder, and borderline personality disorder. Emotional instability and behavioral outbursts can be driven by internal processes and/or environmental triggers and interpersonal interactions. Understanding the underlying diagnosis is important in determining the best course of treatment. Disorder-specific treatments are important in addressing underlying drivers of emotional dysregulation, irritability, and aggression. Coping skills training and behavioral modification strategies have broad applicability and are useful for aggression and irritability. Treatment planning to address emotion dysregulation and aggression in severe mental illness should address psychiatric comorbidities, substance use, and medication adherence.

Impact of tobacco, alcohol and cannabis use on treatment outcomes among patients experiencing first episode psychosis: Data from the national RAISE-ETP study.

AIM: The primary aim of this study was to examine the effect of recent tobacco, alcohol and cannabis use on treatment outcomes among participants experiencing first episode psychosis (FEP). METHODS: Secondary data analyses were conducted on 404 participants enrolled in the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study. RAISE-ETP investigated the effectiveness of a coordinated specialty care (CSC) intervention for FEP in community mental health agencies in the United States. Generalized estimating equations were used to examine whether recent tobacco smoking, alcohol, and cannabis use at baseline were associated with illness severity, number of antipsychotic pills missed, psychiatric symptoms and quality of life during the 24-month treatment period, after controlling for duration of untreated psychosis and treatment group. RESULTS: At baseline, roughly 50% (n = 209) of participants reported recent tobacco, 28% (n = 113) alcohol and 24% (n = 95) cannabis use. Tobacco smokers had higher levels of illness severity (ß = .24; P < .005), a higher number of missed pills (ß = 2.89; P < .05), higher psychiatric symptoms and lower quality of life during treatment relative to non-smokers. Alcohol users had a higher number of missed pills (ß = 3.16; P < .05) during treatment and cannabis users had higher levels of illness severity (ß = .18; P < .05) and positive symptoms (ß = 1.56; P < .05) relative to non-users. CONCLUSIONS: Tobacco, alcohol and cannabis use are common in youth seeking treatment for FEP. Tobacco smoking was associated with more negative clinical outcomes. These findings have implications for including interventions targeting these areas of substance use within current CSC models.

Racial-Ethnic Disparities in First-Episode Psychosis Treatment Outcomes From the RAISE-ETP Study.

OBJECTIVE: This study examined racial and ethnic differences in treatment outcomes among participants in a randomized controlled trial of an intervention for first-episode psychosis called NAVIGATE. METHODS: Secondary data analyses were conducted for participants randomly assigned to usual community care (N=181) and NAVIGATE (N=223). Generalized estimating equations assessed whether race and ethnicity were associated with psychiatric symptoms and service use (medication management, family psychoeducation, and individual therapy) over a 24-month treatment period, accounting for baseline symptoms, duration of untreated psychosis, and insurance status. RESULTS: Among persons in usual community care, non-Hispanic blacks scored significantly higher throughout treatment on measures of positive symptoms (ß=2.15, p=.010), disorganized thoughts (ß=1.15, p=.033), and uncontrolled hostility (ß=.74, p=.027), compared with non-Hispanic whites, and non-Hispanic blacks were less likely than non-Hispanic whites to receive individual therapy (OR=.45, p=.001). Families of Hispanic participants in usual community care were less likely than non-Hispanic white families to receive family psychoeducation (OR=.20, p=.01). For NAVIGATE participants, race and ethnicity were not associated with differences in psychiatric symptoms over time; families of non-Hispanic black participants were less likely than those of non-Hispanic white participants to receive family psychoeducation (OR=.53, p=.009). Hispanic participants in NAVIGATE were more likely than non-Hispanic white participants to receive medication management (OR=2.93, p=.001). CONCLUSIONS: In usual community care, non-Hispanic blacks scored higher on measures of psychiatric symptoms and were less likely to receive important services, compared with non-Hispanic whites. In NAVIGATE, racial and ethnic differences in psychiatric symptoms were not evident, although non-Hispanic blacks were less likely than non-Hispanic whites to receive family psychoeducation.

Psychosis in Children and Adolescents.

Psychosis is characterized by overt disruptions in thought, perceptions, and behavior. Complex syndromes presenting with psychosis, including schizophrenia spectrum disorders, mood disorders, and medical illnesses, are differentiated by characteristic patterns of symptom presentation and course of illness. Accurate diagnosis is important to guide treatment and to avoid inaccurate labeling, because most youth reporting psychotic-like experiences do not have a true psychotic disorder.

De novo mutation in RING1 with epigenetic effects on neurodevelopment.

RING1 is an E3-ubiquitin ligase that is involved in epigenetic control of transcription during development. It is a component of the polycomb repressive complex 1, and its role in that complex is to ubiquitylate histone H2A. In a 13-year-old girl with syndromic neurodevelopmental disabilities, we identified a de novo mutation, RING1 p.R95Q, which alters a conserved arginine residue in the catalytic RING domain. In vitro assays demonstrated that the mutant RING1 retains capacity to catalyze ubiquitin chain formation, but is defective in its ability to ubiquitylate histone H2A in nucleosomes. Consistent with this in vitro effect, cells of the patient showed decreased monoubiquitylation of histone H2A. We modeled the mutant RING1 in Caenorhabditis elegans by editing the comparable amino acid change into spat-3, the suggested RING1 ortholog. Animals with either the missense mutation or complete knockout of spat-3 were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance. Relevant to our patient, animals heterozygous for either the missense or knockout allele also showed neuronal defects. Our results support three conclusions: mutation of RING1 is the likely cause of a human neurodevelopmental syndrome, mutation of RING1 can disrupt histone H2A ubiquitylation without disrupting RING1 catalytic activity, and the comparable mutation in C. elegans spat-3 both recapitulates the effects on histone H2A ubiquitylation and leads to neurodevelopmental abnormalities. This role for RING1 adds to our understanding of the importance of aberrant epigenetic effects as causes of human neurodevelopmental disorders.

Gene Discovery for Complex Traits: Lessons from Africa.

The genetics of African populations reveals an otherwise "missing layer" of human variation that arose between 100,000 and 5 million years ago. Both the vast number of these ancient variants and the selective pressures they survived yield insights into genes responsible for complex traits in all populations.