Navigating Neurogenetics for Child and Adolescent Psychiatry Practice.

Neurodevelopmental disorders (NDDs) are a group of conditions characterized by impairments of brain processes that impact cognition, communication, motor abilities, and/or behavior during development. These conditions typically have significant effects across the life span and impact personal, social, academic, or occupational functioning. The US Centers for Disease Control and report that 1 in 6 children has a developmental disability, making it highly likely for child and adolescent psychiatrists to encounter children with NDDs in daily practice.1 While the etiologies of NDDs are broad, genetic syndromes are a common cause of NDDs. The diagnostic yield of thorough genetic testing for NDDs as a group is about 40% based on meta-analysis, including 30% to 50% yield in patients with global developmental delay (GDD) or intellectual disability (ID) and 15% to 20% yield in patients with in autism spectrum disorder.1-3 The findings are extremely heterogeneous, including chromosomal copy number variants (CNVs) and more than 2,000 known monogenic disorders associated with NDDs.3 Diagnostic yields will increase over time with advances in technology and disease gene discovery.3.

Impact of the COVID-19 Pandemic on the Behavioral Health of People With Intellectual and Developmental Disabilities.

OBJECTIVE: The authors examined how the COVID-19 pandemic affected the behavioral health of people with intellectual and developmental disabilities (IDD). METHODS: A modified version of the Coronavirus Health Impact Survey-Adapted for Autism and Related Neurodevelopmental Conditions was sent to the authors' clinical networks and IDD-affiliated organizations from March to June 2021. RESULTS: In total, 437 people with IDD or their caregivers responded to the survey. Diagnoses included intellectual disability (51%) and autism spectrum disorder (48%). More than half (52%) of respondents reported worsened mental health. Losing access to services correlated with declining mental health. Interventions suggested to improve behavioral health included more time with friends and family (68%), more time outdoors (61%), and access to community activities (59%). CONCLUSIONS: COVID-19 affected the behavioral health of individuals with IDD. Survey results highlight the opportunity to leverage physical activity and pandemic-safe social supports as accessible means to mitigate gaps in services.

Epilepsy Benchmarks Area IV: Limit or Prevent Adverse Consequence of Seizures and Their Treatment Across the Life Span.

Epilepsy represents a complex spectrum disorder, with patients sharing seizures as a common symptom and manifesting a broad array of additional clinical phenotypes. To understand this disorder and treat individuals who live with epilepsy, it is important not only to identify pathogenic mechanisms underlying epilepsy but also to understand their relationships with other health-related factors. Benchmarks Area IV focuses on the impact of seizures and their treatment on quality of life, development, cognitive function, and other aspects and comorbidities that often affect individuals with epilepsy. Included in this review is a discussion on sudden unexpected death in epilepsy and other causes of mortality, a major area of research focus with still many unanswered questions. We also draw attention to special populations, such as individuals with nonepileptic seizures and pregnant women and their offspring. In this study, we review the progress made in these areas since the 2016 review of the Benchmarks Area IV and discuss challenges and opportunities for future study.

Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy.

Cognitive, psychiatric, psychosocial, and behavioral difficulties are common in youth with epilepsy. Collectively, these comorbidities can be referred to as mental health problems as they reflect brain and behavioral function. Detection and treatment of mental health problems remain an unmet need in epilepsy care that can impact epilepsy, psychosocial, scholastic, and quality-of-life outcomes. Given limited resources in everyday pediatric epilepsy practice, this targeted review provides a stratified plan and suggested tools for screening school-aged youth with epilepsy for the presence of mental health problems. Comanagement of epilepsy and associated comorbidities is a newer concept that may help address the complex, long-term needs of patients by using a multidisciplinary team approach and by engaging primary care providers.

Brief cognitive and behavioral screening in children with new-onset epilepsy: a pilot feasibility trial.

BACKGROUND: Minimal work has used psychometrically robust measures in a systematic fashion to identify and monitor children at risk for cognitive and behavioral comorbidities in current epilepsy care. We piloted a computerized cognitive battery and behavioral questionnaire for children with newly diagnosed epilepsy to determine clinical feasibility and acceptability to parents and patients. METHODS: We recruited medication-naïve children (ages 8-17 years) with recent-onset seizures and typical developmental history from an outpatient child neurology clinic. Children completed the CNS Vital Signs computerized battery, whereas parents completed the Strengths and Difficulties Questionnaire. Post-test interviews with parents and patients were completed regarding the acceptability of the assessment procedures. RESULTS: Forty-four families were eligible, and 39 agreed to participate (89%). All assessments were completed in less than 45 minutes. Parents rated testing in clinic as convenient and important, expressing strong interest in the cognitive and behavioral impact of epilepsy and medication. Children also rated the testing procedure as acceptable and agreed that they would recommend it to peers. CONCLUSIONS: Our brief battery was tolerated and well received by children and their parents. Computerized testing of children along with a parent questionnaire is a psychometrically viable approach that is acceptable to families. Our protocol is time efficient for clinical use with the potential to detect early cognitive and behavioral difficulties related to epilepsy. Ongoing longitudinal study will provide further information regarding the success of our screening methods in monitoring for disease- or treatment-related changes.

Investigating inhibitory control in children with epilepsy: an fMRI study.

OBJECTIVE: Deficits in executive function are noted increasingly in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional magnetic resonance imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. METHODS: This cross-sectional study consisted of 34 children aged 8-17 years: 17 with well-controlled epilepsy and 17 age- and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood oxygen level-dependent (BOLD) activation. RESULTS: Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (nonreward) and reward trials, but exhibited significant task improvement during reward trials. Post hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. SIGNIFICANCE: Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation.

Clinicians' views on antiepileptic medication management in nonepileptic seizures.

Discontinuation of antiepileptic drugs should be a first step in treatment of nonepileptic seizures without comorbid epilepsy. However, clinical practices vary and standardized guidelines are not available. The aim of this study was to survey members of the American Epilepsy and Child Neurology Societies about factors that influence their decision about antiepileptic drug management in patients with nonepileptic seizures. A total of 236 respondents completed this survey, of whom 84% were academic pediatric neurologists and 96.2% were very willing to discontinue antiepileptic drugs in these patients. Clinicians with sufficient knowledge about nonepileptic seizures had fewer concerns about the potential for medical errors, were less influenced by requests made by patients or parents to continue antiepileptic drugs, and were comfortable making this decision if patients receive ongoing psychiatric care. Results of this survey highlight the need to examine if the same factors are involved in a large sample of community clinicians.

White matter development in adolescence: diffusion tensor imaging and meta-analytic results.

BACKGROUND: In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. METHODS: DTI was performed in 78 healthy subjects aged 8-21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence. RESULTS: In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age. CONCLUSIONS: These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.

Deficits in oculomotor performance in pediatric epilepsy.

PURPOSE: Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition--including speed of processing, response inhibition, and spatial working memory--supporting executive function in pediatric epilepsy patients and matched controls. METHODS: A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. KEY FINDINGS: Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology, but comorbidity did not predict worse functioning compared to patients with no Attention Deficit Hyperactivity Disorder (ADHD). Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing, which was correlated with inhibitory control and antisaccade accuracy. SIGNIFICANCE: Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory, and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development.

Pediatric psychogenic nonepileptic seizures: a study of assessment tools.

The goal of this study was to identify assessment tools and associated behavioral domains that differentiate children with psychogenic nonepileptic seizures (PNES) from those with epilepsy. A sample of 24 children with PNES (mean age 14.0 years, 14 female), 24 children with epilepsy (mean age 13.6 years, 13 female), and their parents were recruited from five epilepsy centers in the United States. Participants completed a battery of behavioral questionnaires including somatization, anxiety, and functional disability symptoms. Children with PNES had significantly higher scores on the Childhood Somatization and Functional Disability Inventories, and their parents reported more somatic problems on the Child Behavior Checklist (CBCL). Depression, anxiety, and alexithymia instruments did not differentiate the groups. Measures of somatization and functional disability may be promising tools for differentiating the behavioral profile of PNES from that of epilepsy. Increased somatic awareness and perceived disability emphasize the similarity of PNES to other pediatric somatoform disorders.

Adolescent and caregiver experiences with epilepsy.

Epilepsy during adolescence can impede the development of psychosocial independence and typical biological maturational processes. We examined in parallel the experiences and perceptions of adolescent patients with epilepsy and their caregivers. Specifically, we focused on frequency and type of seizures, comorbid conditions, adherence to therapies, productivity, clinical and quality of life consequences of seizures, estimated use and content of seizure emergency plans, and the patient-physician relationship. Two cross-sectional online surveys were conducted among 153 adolescent patients with epilepsy and their respective caregivers. A total of 35% of adolescents indicated that they had been nonadherent to antiepileptic medications in the prior month. Adolescents scored significantly lower compared with their peers on quality-of-life measures. Adolescents and caregivers reported similarly on nearly all domains. An adolescent-centered epilepsy management program may help alleviate concerns and also help the adolescent independently manage their epilepsy as they transition into adulthood.

Neuromyelitis optica in a young child with positive serum autoantibody.

Relapsing neuromyelitis optica is rare in children. The identification of a highly specific serum autoantibody marker (neuromyelitis optica-immunoglobulin G) differentiates neuromyelitis optica from other demyelinating disorders, particularly in clinically challenging cases. We present a child with multiple episodes of transverse myelitis and optic neuritis with positive neuromyelitis optica-immunoglobulin G titers, consistent with a diagnosis of relapsing neuromyelitis optica. Serial titers of neuromyelitis optica-immunoglobulin G normalized during remission.

Seizure emergency plans: patient results from a cross-sectional epilepsy survey.

Guidance for seizure emergency plans exists, although their impact and extent of use in patients with epilepsy are undetermined. This study's primary purpose was to measure the estimated use and content of seizure emergency plans. Secondary objectives included measuring: disease severity, quality of life, productivity, and adherence among patients with and without a plan. An online survey was conducted among 408 patients with epilepsy (ages 18-64) who took one or more antiepileptic drugs. Only 30% of patients reported having a plan, which included avoiding injury, notifying a physician, resting/relaxing, and seeking emergency assistance. Those with a plan were more likely to have experienced more seizures in the past year, to have missed school/work, to have incurred injury, to have visited the ER, to have been hospitalized, to fear additional seizures, and to have lost a job. Seizure emergency plans appear to be reserved for adults with more severe disease, but there may be clinical benefits to developing a plan for all adult patients with epilepsy.

Association of non-adherence to antiepileptic drugs and seizures, quality of life, and productivity: survey of patients with epilepsy and physicians.

Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical outcomes, although few studies have examined this relationship. This study assessed barriers and drivers to adherence, its impact on quality of life, and the importance of the patient-physician relationship to adherence. Two cross-sectional online surveys were conducted among 408 adult patients with epilepsy and 175 neurologists who treat epilepsy patients. Twenty-nine percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents. Patient-oriented epilepsy treatment programs and clear communication strategies to promote self-management and patients' understanding of epilepsy are essential to maximizing treatment and quality of life outcomes while also minimizing economic costs.

Cognitive processes in the development of TOL performance.

Components of executive function continue to develop through adolescence. There is limited knowledge of how these cognitive components impact complex cognitive function requiring their integration. This study examines the development of response planning, a complex cognitive function, and the contributions of selected cognitive processes, including speed of processing, response inhibition, and working memory to its development. We tested 100 healthy 8-30 year old individuals with a computerized version to the Tower of London (TOL) task and cognitive oculomotor tests including the visually guided saccade, oculomotor delayed response, and antisaccade tasks. Speed of processing, response inhibition, working memory, and TOL performance all demonstrated maturation in adolescence. While all processes were correlated with the development of TOL performance, antisaccade performance showed the strongest association indicating an important role for response inhibition in planning. These results indicate that the development of converging cognitive processes in adolescence, including response inhibition and working memory, support response planning and may serve as a model for the development of performance in other complex problem solving tasks.

Neuropsychiatric problems in tuberous sclerosis complex.

Tuberous sclerosis complex is an autosomal dominant disorder characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. It is a disease affecting multiple organ systems and typically has brain involvement, causing severe disabilities. This article reviews the literature of the commonly associated neuropsychiatric complications, including mental retardation, autism-like features, and other behavior problems, which are discussed in the context of the neuropathology and epilepsy observed in tuberous sclerosis complex. The potential pathogenesis of neuropsychiatric problems is explored, including links to the genetics, neuropathology, neurotrophins, and epilepsy factors associated with tuberous sclerosis complex. Treatment of neuropsychiatric symptoms, including autism-like features, attention deficits, and sleep disorders, is also discussed.