Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients.

OBJECTIVE: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. METHOD: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). RESULTS: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. CONCLUSION: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing.

Differences in cognitive and academic performance during the COVID-19 pandemic in child psychiatric outpatients.

This study examined the impact of the COVID-19 pandemic on cognitive and academic functioning in 574 youth presenting for outpatient clinical neuropsychiatric evaluations. We extended the prior literature by (a) determining the extent to which academic difficulties documented in population and community samples also occurred in child psychiatric outpatients; (b) evaluating the impact of the pandemic on neuropsychological functions relevant to academic performance (overall cognition, executive functions, and graphomotor skill); and (c) investigating the moderating impact of attention deficit hyperactivity disorder (ADHD) diagnosis. We compared cross-sectional scores on standardized measures for groups of youth evaluated at three time periods related to the COVID-19 pandemic: (a) prior to onset (PRIOR; N = 198), (b) during Year 1 (Y1; N = 149), and (c) during Year 2 (Y2; N = 227). Relative to overall cognitive ability, math scores were lower in Y1 and Y2 and reading scores were lower in Y2. Additionally, relative to overall cognitive ability, youth showed lower working memory in Y1 and lower processing speed in Y1 and Y2. Graphomotor skill and parent-rated executive functions (EF) did not vary significantly across the three time periods. ADHD status did not moderate psychometric test scores but did moderate parent-rated EF. These data suggest that the COVID-19 pandemic has negatively impacted academic and executive functions in child psychiatry outpatients. More research is needed to understand the long-term implications for development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prevalence of ADHD Symptomatology in Adult Population in the Czech Republic: A National Study.

BACKGROUND: ADHD is a common neurodevelopmental disorder frequently diagnosed between the ages 7 and 10 years. We measured ADHD symptomatology in a representative sample of the Czech population. MATERIAL AND METHODS: Data collection was performed in January 2019 through the European National Panel. The respondents completed a demographic questionnaire focusing on ADHD history and a standardized questionnaire, the Adult ADHD Self-Report Scale (ASRS) screener for ADHD symptomatology in adulthood. RESULTS: From the sample of 1,518 respondents, 3% of the respondents reported having been diagnosed with ADHD/hyperkinetic disorder in their lifetime. According to ASRS scoring, 119 respondents were classified as suspected ADHD. Overall, more males than females reported ADHD symptomatology. Age was also significantly associated with ASRS. Education status yielded no significant results. CONCLUSION: Our study documents that the prevalence of ADHD symptomatology in adults is comparable with that in Western countries despite the different historical and health care backgrounds.

Behavior ratings of executive functions index multiple domains of psychopathology and school functioning in child psychiatric outpatients.

Behavior rating scales of executive functions (EFs) are convenient and associate with academic and other outcomes; however, prior studies indicate limited correlations with psychometric tests of EFs. To better understand their potential for clinical utility, we examined the extent to which parent ratings on the Behavior Rating Inventory of Executive Function (BRIEF) related to psychopathology constructs and psychometric test scores in a sample of N = 692 psychiatric outpatients aged 8-17. Then, in a subsample of the youth (N = 261), we related the BRIEF, psychopathology constructs, and psychometric test scores to teacher ratings of school functioning. BRIEF scales were significantly associated with multiple types of psychopathology including ADHD, autism spectrum, mood, anxiety, conduct, oppositional defiant, and psychotic disorders. While the BRIEF showed limited associations with psychometric EF tests, its Global Executive Composite score explained additional variance in teacher-reported functioning beyond what was predicted by clinical diagnoses (additional explained variance of 9.9% in study skills) and psychometric tests (additional explained variance of 2.1% in learning problems and 4.5% in study skills). The Global Executive Composite was not significantly related to teacher-rated school functioning after psychiatric symptoms were accounted for. These findings support further investigation of the unique contribution of the BRIEF in clinical practice.

Distinct patterns of emotional and behavioral change in child psychiatry outpatients during the COVID-19 pandemic.

BACKGROUND: Studies are documenting the impact of the COVID-19 pandemic on youth mental health. We extended this literature by characterizing a child psychiatric outpatient sample in the United States during the middle of the 2020-2021 school year. We also used a computational strategy to identify distinct patterns of psychopathology symptom change and examined correlates and predictors of such change. Among potential predictors were cognition and clinical diagnoses, which have not been studied in this context previously. METHODS: Participants were 171 youth (aged 10.6 ± 3.1) referred for neuropsychiatric evaluation who enrolled in research and whose parents filled out a survey on COVID-19. The questionnaire included eight psychiatric and six psychosocial domains rated retrospectively prior to the pandemic and currently at the time of evaluation. We examined change in severity of individual domains with Wilcoxon signed-rank tests. We used a latent profile analysis (LPA) to identify groups with distinct symptom change profiles. Using multinomial logistic regression, we examined potential predictors and correlates of LPA-derived groups. Models controlled for age, sex, and assessment date and corrected for multiple testing. RESULTS: Although the majority of individual psychopathology domains were worse on average during the 2020-2021 school year, youth showed distincive patterns of symptom change. In addition to a large group (72.2%) with relatively stable symptoms and a small group (6.4%) that improved on most symptoms, there were two groups with different constellations of worsening symptoms. These latter groups both showed increased sadness, anxiety and oppositionality; however, one had increased hyperactivity/impulsivity and no change in hopelessness while the other showed greater hopelessness and no change in hyperactivity. Symptoms related to the distinguishable domains of these groups predicted group membership, and changes in screen time, conflict with parents and social isolation were correlates of worsening. Cognition and lifetime clinical diagnoses failed to predict group membership. CONCLUSIONS: In youth outpatients, psychiatric and psychosocial difficulties were worse on average during the school year following the spring 2020 COVID-19 lockdown; yet, some youth experienced greater and distinctive symptom change. A personalized approach to support may be needed as youth emerge from this period.

Neuropsychological Profile of an Adolescent Female With Ectodermal Dysplasia With Hypohidrosis.

The ectodermal dysplasias are a group of rare genetic disorders that are caused by abnormalities in cell and tissue development of the embryonic ectoderm. A paucity of research has systematically examined the cognitive, academic, and psychological phenotype of individuals with ectodermal dysplasia. We describe the neuropsychological profile of a female adolescent with ectodermal dysplasia with hypohidrosis. Using a battery of standardized tests, we assessed the adolescent's intellectual functioning, language processing, visuospatial and visuomotor functioning, perceptual reasoning, sensory-motor functioning, memory, executive functioning, academic functioning, emotional and behavioral functioning, and adaptive functioning. Results from the testing indicated that the adolescent possessed relative verbal strengths, with scores generally falling in the low average to average range. However, she exhibited severe deficits in visuospatial functioning, visuomotor construction/organization, visuomotor integration, visual memory, executive functioning, reading, and math. She also presented with symptoms of anxiety and depression but had relatively strong adaptive skills. Based on the testing results from our evaluation, the adolescent met the criteria for specific learning disorders with impairment in reading and math, generalized anxiety disorder, and major depressive disorder. To our knowledge, this is the first case report to comprehensively characterize the full neuropsychological and academic profile of an adolescent female with ectodermal dysplasia with hypohidrosis. Recommendations from the evaluation are presented to inform clinical practice with, and future research of, this population.

Prevalence of ADHD Symptomatology in Adult Population in the Czech Republic-A National Study.

Background: Attention deficit/hyperactivity disorder is a common neurodevelopmental disorder frequently diagnosed between the ages 7 and 10 years. We measured ADHD symptomatology in a representative sample of the Czech population. Material and Methods: Data collection was performed in January 2019 through the European National Panel. The respondents completed a demographic questionnaire focusing on ADHD history and a standardized questionnaire, the Adult ADHD Self-Report Scale (ASRS) screener for ADHD symptomatology in adulthood. Results: From the sample of 1,518 respondents, 3% of the respondents reported having been diagnosed with ADHD/hyperkinetic disorder in their lifetime. According to ASRS scoring, 119 respondents were classified as suspected ADHD. Overall, more males than females reported ADHD symptomatology. Age was also significantly associated with ASRS. Education status yielded no significant results. Conclusion: Our study documents that the prevalence of ADHD symptomatology in adults is comparable with that in Western countries despite the different historical and health care backgrounds.

ADHD Symptoms in Adults and Time Perspectives - Findings From a Czech National Sample.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting individuals in all stages of their lives and leading to a variety of negative quality of life outcomes. The disorder is associated with marked differences related to time perception and time perspectives, and this area of research is currently becoming more prominent and gaining ground in showing new aspects of ADHD that were considered secondary (i.e., time perception differences, affective differences). In this study, we looked at ADHD symptoms in adults, correlated lifestyles, and time perspectives as defined by the Zimbardo Time Perspective Inventory (ZTPI). The ZTPI is a useful standardized scale to measure one's time perspective anchoring in the categories of past positive, past negative, present fatalistic, present hedonistic, and future oriented. This is the first study on adult ADHD and time perspectives conducted in the Czechia. METHODOLOGY: A national representative sample of Czech adults aged 18-65 was recruited by the STEM/MARK Agency. The individuals were assessed for ADHD symptoms with the Adult ADHD Self-Report Scale (ASRS v.1.1). Furthermore, a demographic and lifestyle questionnaire was administered along with the ZTPI to assess time perspectives. Statistical calculations were conducted to find correlations between ADHD symptoms as assessed by the ASRS and the various categories of the ZTPI. RESULTS: ADHD symptoms were found to be positively correlated with the present hedonistic perspective along with the past negative perspective. Gender was a strong factor in both ADHD symptoms, with males being more likely to show symptoms and to have a present hedonistic perspective. In females, the past negative perspective was most prominent. Education and age were negatively correlated with ADHD symptomatology and the present hedonistic perspective also decreased with age unlike the past negative perspective. Other time perspectives such as future orientation was seen in individuals with lower ADHD symptoms and higher levels of educational achievement. CONCLUSION: Researching ADHD symptoms and their connection to time perspectives can increase knowledge of both the disorder and how time perspectives tie into it. We wish to also raise awareness of the possible utility of the ZTPI scale when working with individuals with ADHD.

Characteristics of child psychiatric outpatients with slow processing speed and potential mechanisms of academic impact.

While slow processing speed (PS) is well documented in youth with ADHD, growing evidence suggests that this difficulty affects children with other neuropsychiatric conditions. Clarifying the relationship between slow PS and different forms of psychopathology is important clinically, given the potential impact of PS on academic functioning, and conceptually. In 751 youth, ages 6-21, consecutively referred for neuropsychiatric evaluation, we examined the association between slow PS (i.e., Wechsler PS Index < 85) and seven neuropsychiatric diagnostic groups. In 492 of these youth, we also related slow PS to eight psychopathology symptom dimensions. Finally, we modeled the relationship between PS, other cognitive functions and academic achievement. Data are from the Longitudinal Study of Genetic Influences on Cognition. Analyses included one-sample t tests, ANOVA, logistic regression, mixed modeling, and structural equation modeling (SEM), controlling for age, sex, and medication. Compared to normative data, all clinical groups showed PS decrements. Compared to referred youth without full diagnoses and accounting for other psychopathology, risk for slow PS was elevated in youth with autism spectrum disorder (OR = 1.8), psychotic disorders (OR = 3.4) and ADHD-inattentive type (OR = 1.6). Having multiple comorbidities also increased risk for slow PS. Among dimensions, inattention (OR = 1.5) associated with slow PS but did not fully explain the association with autism or psychosis. In SEM, PS had direct effects on academic achievement and indirect effects through working memory. Findings extend evidence that PS relates to multiple aspects of child psychopathology and associates with academic achievement in child psychiatric outpatients.

Translating Discoveries in Attention-Deficit/Hyperactivity Disorder Genomics to an Outpatient Child and Adolescent Psychiatric Cohort.

OBJECTIVE: Genomic discoveries should be investigated in generalizable child psychiatric samples in order to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRSs) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRSs with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRSs manifest a distinctive clinical profile. METHOD: Participants were 433 youth, ages 7-18 years, from the Longitudinal Study of Genetic Influences on Cognition. We used logistic/linear regression and mixed effects models to examine associations with ADHD-related polygenic variation from the largest ADHD genome-wide association study to date. We replicated key findings in 5,140 adult patients from a local health system biobank. RESULTS: Among referred youth, ADHD PRSs were associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (odds ratios ∼1.4; R2 values ∼2%-3%), as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRSs were associated with ADHD and phenotypes beyond the condition that have public health implications. Finally, youth with a high ADHD polygenic burden showed a more severe clinical profile than youth with a low burden (ß coefficients ∼.2). CONCLUSION: Among child and adolescent outpatients, ADHD polygenic risk was associated with ADHD and related phenotypes as well as clinical severity. These results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research.

Reliability and validity of the Thinking Skills Inventory, a screening tool for cross-diagnostic skill deficits underlying youth behavioral challenges.

Deficits in a range of skill domains (including executive functioning, emotion regulation, social cognition and language/communication) are associated with disrupted youth behavior and functioning across mental health diagnoses. The identification of skill deficits are important for effective treatment planning, particularly for personalized interventions. While there are multiple ways to assess these skills, parent/caregiver reports represent an important information source. To date, no single, brief measure has been developed that gathers parent/caregiver ratings across this range of constructs. We have developed a short caregiver-report questionnaire (the Thinking Skills Inventory; TSI), to screen for skill deficits. Here, we examine the reliability and validity of this rating scale in 384 youth who were consecutively referred for neuropsychiatric evaluation. A primary caregiver completed the TSI as well as other established measures. Exploratory and confirmatory factor analyses support five subscales on the TSI: Attention and Working Memory, Language and Communication, Emotion Regulation, Cognitive Flexibility, and Social Thinking Skills. The subscales showed moderate to high internal consistency (Cronbach's alphas range from 0.84 to 0.91). Correlations with established caregiver-report measures confirm their convergent and discriminant validity, and associations with multiple clinical diagnoses and cross-diagnostic aggressive behavior further support the utility of the scale for our intended purpose. In sum, this free, brief measure is a valid and reliable way to identify variation in skill domains relevant to a range of psychopathology. The TSI may be useful in youth mental health settings to assist with treatment planning and to inform referral for further evaluation.

Slow Processing Speed and Sluggish Cognitive Tempo in Pediatric Attention-Deficit/Hyperactivity Disorder: Evidence for Differentiation of Functional Correlates.

The association between slow processing speed and sluggish cognitive tempo (SCT), a phenotype described within attention-deficit/hyperactivity disorder (ADHD) samples over the past decade, remains unclear. We examined whether SCT and processing speed predict different functional correlates within children and adolescents with ADHD. Participants were 193 clinically-referred youth meeting DSM ADHD criteria without comorbid conditions (mean age = 9.9 years, SD = 2.5; age range 6-16). The incremental utility of SCT and processing speed to predict (1) adaptive functioning and (2) academic achievement, after controlling for age, sex, medication status, and ADHD symptom burden, was assessed using hierarchical multiple regressions. SCT symptoms significantly predicted adaptive functioning, accounting for 6% of the variance, but did not predict academic achievement. Processing speed did not add incrementally to the prediction of adaptive functioning, but did predict academic achievement, accounting for 4% of the variance. Results suggest that SCT and processing speed differentially predict functional abilities not accounted for by ADHD symptom burden.

Clinical Implications of the Perception of Time in Attention Deficit Hyperactivity Disorder (ADHD): A Review.

Attention deficit hyperactivity disorder (ADHD) is a lifelong neurodevelopmental disorder that can affect many areas of the daily life of individuals and is associated with poor health outcomes and with debilitating deficits in executive function. Recently, increasing numbers of research studies have begun to investigate the associations between neural and behavioral manifestations of ADHD. This review summarizes recent research on the perception of time in ADHD and proposes that this symptom is a possible diagnostic characteristic. Controlled studies on time perception have compared individuals with ADHD with typically developing controls (TDCs) and have used methods that include the Zimbardo Time Perspective Inventory (ZTPI). Practical approaches to time perception and its evaluation have shown that individuals with ADHD have difficulties in time estimation and discrimination activities as well as having the feeling that time is passing by without them being able to complete tasks accurately and well. Although ADHD has been associated with neurologic abnormalities in the mesolimbic and dopaminergic systems, recent studies have found that when individuals with ADHD are treated medically, their perception of time tends to normalize. The relationship between ADHD and the perception of time requires greater attention. Further studies on time perception in ADHD with other abnormalities, including executive function, might be approaches that refine the classification and diagnosis of ADHD and should include studies on its varied presentation in different age groups.

Characteristics of Child Psychiatric Outpatients at Highest Risk for Suicidal Thoughts and Behaviors.

On average, compared to non-referred youth, child psychiatric outpatients show elevated rates of suicidal thoughts and behaviors (STBs), which are predictors of completed suicide. Determining the psychopathology features that associate with highest risk for STBs among youth outpatients may yield opportunities for targeted prevention/intervention. Yet, outpatient studies are limited and have not systematically examined comorbidity and dimensional psychopathology. In 758 youth, aged 6-18, consecutively referred for neuropsychiatric evaluation, we examined the extent to which diagnostic groups, comorbid subgroups and dimensional symptoms associated with STBs. After controlling for comorbidity, mood, anxiety and conduct disorders associated with elevated STB risk. Regarding dimensions, symptoms of depression, aggression and psychosis all contributed to higher STB risk. Although ADHD (as a diagnosis or dimension) did not associate with elevated STB risk independently, ADHD that was comorbid with other conditions did. Suicide prevention/intervention efforts should be investigated in youth outpatients with the highest risk for STBs.

Clinical and functional correlates of processing speed in pediatric Attention-Deficit/Hyperactivity Disorder: a systematic review and meta-analysis.

It is well established that processing speed is negatively impacted in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Unfortunately, exactly how processing speed vulnerabilities manifest in daily functioning has not been well established. To support clinical care of youth with ADHD, it is important to better understand the functional consequences and relevant outcomes associated with processing speed deficits. This systematic review and meta-analysis sought to identify the association between processing speed and clinical or functional correlates among children or adolescents diagnosed with ADHD. A total of 409 abstracts were screened, of which, 60 full-text articles were identified as potentially relevant, and 8 of these studies met inclusion criteria. Domains evaluated across these studies included reading skills, mathematics skills, written expression, anxiety, self-appraisals of competence, and adaptive functioning. Six studies reported an association between processing speed and reading skills, allowing for meta-analysis. Processing speed difficulties among youth with ADHD appear strongly associated with several clinical and functional correlates including weaker academic skills, poorer adaptive skills, increased self-reported anxiety, and overestimates of social competence. Meta-analytic results for studies reporting the association between processing speed and reading skills indicate a medium overall weighted mean effect size (r = 0.33, 95% CI = 0.28 -0.39) with minimal heterogeneity (I2 = 0.17). Clinical implications of these findings, limitations in the current knowledge base, and suggestions for future research are discussed.

Cross-Disorder Cognitive Impairments in Youth Referred for Neuropsychiatric Evaluation.

OBJECTIVES: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity. METHODS: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders. RESULTS: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants' own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders. CONCLUSIONS: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91-103).

Extending the 'cross-disorder' relevance of executive functions to dimensional neuropsychiatric traits in youth.

BACKGROUND: Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with 'cross-disorder' relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. METHODS: Data are from 393 participants, ages 8-17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of the autism spectrum disorder, bipolar illness, and schizophrenia (including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively). RESULTS: We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits, but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting that it related to a general increase in psychopathology symptoms across those dimensions. CONCLUSIONS: Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relates to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability.

Cryptic and complex chromosomal aberrations in early-onset neuropsychiatric disorders.

Structural variation (SV) is a significant component of the genetic etiology of both neurodevelopmental and psychiatric disorders; however, routine guidelines for clinical genetic screening have been established only in the former category. Genome-wide chromosomal microarray (CMA) can detect genomic imbalances such as copy-number variants (CNVs), but balanced chromosomal abnormalities (BCAs) still require karyotyping for clinical detection. Moreover, submicroscopic BCAs and subarray threshold CNVs are intractable, or cryptic, to both CMA and karyotyping. Here, we performed whole-genome sequencing using large-insert jumping libraries to delineate both cytogenetically visible and cryptic SVs in a single test among 30 clinically referred youth representing a range of severe neuropsychiatric conditions. We detected 96 SVs per person on average that passed filtering criteria above our highest-confidence resolution (6,305 bp) and an additional 111 SVs per genome below this resolution. These SVs rearranged 3.8 Mb of genomic sequence and resulted in 42 putative loss-of-function (LoF) or gain-of-function mutations per person. We estimate that 80% of the LoF variants were cryptic to clinical CMA. We found myriad complex and cryptic rearrangements, including a "paired" duplication (360 kb, 169 kb) that flanks a 5.25 Mb inversion that appears in 7 additional cases from clinical CNV data among 47,562 individuals. Following convergent genomic profiling of these independent clinical CNV data, we interpreted three SVs to be of potential clinical significance. These data indicate that sequence-based delineation of the full SV mutational spectrum warrants exploration in youth referred for neuropsychiatric evaluation and clinical diagnostic SV screening more broadly.

Neuropsychological function in a child with 18p deletion syndrome: a case report.

We report the neuropsychological profile of a 4-year-old boy with the rare 18p deletion syndrome. We used a battery of standardized tests to assess his development in intellect, language, visuomotor integration, academic readiness, socialization, and emotional and behavioral health. The results showed borderline intellectual function except for low average nonverbal reasoning skills. He had stronger receptive than expressive language skills, although both were well below his age group. He had impaired visuomotor integration and pre-academic skills such as letter identification. Emotional and behavioral findings indicated mild aggressiveness, anxiety, low frustration tolerance, and executive function weaknesses, especially at home. Interestingly, he showed social strengths, responding to joint attention and sharing enjoyment with his examiner. With its assessment of development in many domains, this case report is among the first to characterize the neuropsychological and psychiatric function of a young child with 18p deletion syndrome. We discuss the implications of our findings for clinical practice.

Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States network.

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.